Clinical Topic A-Z Clinical Speciality

Opioid dependence

Opioid dependence
D009293Opioid-Related Disorders
D009021Morphine Dependence
D006556Heroin Dependence
Drugs and devicesMental health
2008-02-18Last revised in February 2008

Opioid dependence - Summary

An opioid is either a natural derivative of opium or a synthetic substance with agonist, partial agonist, or mixed agonist and antagonist activity at opioid receptors.

All opioids have dependence potential to varying degrees. Of the opioids, heroin (diamorphine) has the greatest potential for dependency, especially when injected. Physical and psychological dependence can develop within 2–10 days of continuous use.

The key elements of opioid dependence include a strong desire to take the substance, difficulty in controlling use, a physiological withdrawal state, tolerance, and persistence of use despite harm to oneself and others.

Complications include death, overdose, infection, and social problems such as homelessness and crime.

Key features of the initial assessment include assessing: the person's degree of dependency (past and current); level of motivation to change; medical, psychiatric, social, and forensic history; and past contact with treatment services.

The need for substitution therapy should be assessed and a decision made (with the person) whether to opt for maintenance therapy or detoxification. If substitution is being considered, opioid use must be confirmed by testing for the presence of opioids in oral fluids or urine.

The goal of maintenance therapy is harm reduction and stabilization of lifestyle. At least initially, it is likely to be a better option than detoxification for most people, particularly those who have been addicted for longer periods of time, who often inject, or who have high levels of drug use.

The goal of detoxification is to come off opioids altogether. It is suitable for people who are highly motivated and wish to detoxify from all opioids and whose circumstances are stable and conducive to maintaining abstinence.

It is important that there is a clear distinction between maintenance and detoxification in order to avoid a situation whereby a lower level of substitute drug is reached and the person stays on this dose long-term, using illicit drugs 'on top' and deluding themselves that they are still in detoxification.

Advice should be offered on safer sex, the dangers of sharing needles and other equipment, the risks of acquiring blood-borne viruses, and immunization (e.g. tetanus, hepatitis A and B).

A report should be made to the National Drug Treatment Monitoring System (NDTMS) when a person first starts treatment for drug misuse (patient consent must be obtained).

GPs should not prescribe beyond their experience. Expert advice should be sought, or referral to the local drug services arranged, if necessary.

For maintenance treatment, if methadone or buprenorphine are equally suitable, methadone is preferred (the need for supervised consumption should be considered). Dihydrocodeine, slow-release oral morphine and injectable opioid treatments are not recommended.

For detoxification from maintenance therapy, methadone or buprenorphine should be offered as first-line treatment. Naltrexone may be an option in some people. Suboxone, dihydrocodeine, and clonidine are not routinely recommended.

For detoxification from street heroin, buprenorphine is the drug of choice although lofexidine is sometimes used. Methadone is not recommended.

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This CKS topic covers the management of opioid dependence in adults. It is based on the following guidelines and publications:

Guidance for the use of methadone for the treatment of opioid dependence in primary care (2005), Guidance for the use of buprenorphine for the treatment of opioid dependence in primary care (2004), and Guidance for hepatitis A and B vaccination of drug users in primary care and criteria for audit, published by Royal College of General Practitioners (RCGP).

Naltrexone for the management of opioid dependence, Methadone and buprenorphine for the management of opioid dependence, and Drug misuse: psychosocial interventions, published by the National Institute for Health and Care Excellence (NICE).

Guidance on prescribing benzodiazepines to drug users in primary care, published by the Substance Misuse management in General Practice (SMMGP).

Models of care for treatment of adult drug misusers: update 2006, published by the National Treatment Agency for Substance Misuse (NTA), and Drug misuse and dependence: UK guidelines on clinical management (2007), published by the UK Department of Health.

This CKS topic does not cover the management of drug dependence in neonates or in those aged under 16 years (who must be referred to specialist services); the management of people mildly dependent on weak opioids (e.g. codeine, co-codamol); the detailed management of misuse of other illicit drugs (e.g. cocaine/crack); or the prevention of drug dependence.

There are separate CKS topics on Alcohol - problem drinking and Benzodiazepine and z-drug withdrawal.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in February 2008

September 2013 — minor update to the text to reflect current recommendations regarding metoclopramide [EMA, 2013].

July 2013 — minor update. Links to the DVLA website have been updated.

June 2012 - minor update. Minor typographical error corrected.

October 2011 — minor update. Relevant recommendations from the NICE guideline Needle and syringe programmes: providing people who inject drugs with injecting equipment [NICE, 2009] have been incorporated into this topic. Issued in December 2011.

May 2011 — minor update. Relevant recommendations from the NICE guideline Psychosis with coexisting substance misuse have been incorporated into this topic. Issued in June 2011.

October 2010 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

October 2008 — minor update to reflect changes in the Home Office Application for personal import/export licence form. Issued in October 2008.

October 2007 to February 2008 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

There are no major changes to the recommendations.

Previous changes

March 2007 — minor update to include NICE technology appraisal guidance on methadone and buprenorphine [NICE, 2007b] and NICE technology appraisal guidance on naltrexone [NICE, 2007a] for the management of opioid dependence. Issued in March 2007.

January–March 2006 — reviewed. Validated in June 2006 and issued in July 2006.

This guidance has been reviewed and updated following a full literature review.The guidance now incorporates recommendations from the Royal College of General Practitioners, the Royal Pharmaceutical Society of Great Britain and the National Treatment Agency. A more detailed evidence section to support the recommendations has been included.

May 2003 — updated to include the Royal College of General Practitioners' publication of Guidance for the use of buprenorphine for the treatment of opioid dependence in primary care. Validated in September and issued in February 2004.

October 2002 — rewritten and validated in March 2003.

June 2001 — updated to include the directive from the Chief Medical Officer and Chief Pharmaceutical Officer allowing the daily dispensing of buprenorphine for the management of drug dependence.

May 1999 — written.

Update

New evidence

Evidence-based guidelines

Guidelines published since the last revision of this topic:

Management of Opioid Therapy for Chronic Pain Working Group (2010) Clinical practice guideline. Management of opioid therapy for chronic pain. Department of Veterans Affairs and Department of Defense. www.healthquality.va.gov [Free Full-text]

NICE (2009) Needle and syringe programmes: providing people who inject drugs with injecting equipment (NICE public health guidance 18). National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

WHO (2009) Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. World Health Organization. www.who.int [Free Full-text (pdf)]

HTAs (Health Technology Assessments)

No new HTAs since 1 September 2007.

Economic appraisals

No new economic appraisals relevant to England since 1 September 2007.

Systematic reviews and meta-analyses

Systematic reviews published since the last revision of this topic:

Amato, L., Miozzi, S., Davoli, M., et al. (2008) Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Amato, L., Minozzi, S., Davoli, M., et al. (2008) Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Castells, X., Casas, M., Perez-Maria, C., et al. (2010) Efficacy of psychostimulant drugs for cocaine dependence (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Castells, X., Kosten, T.R., Capella, D., et al. (2009) Efficacy of opiate maintenance therapy and adjunctive interventions for opioid dependence with comorbid cocaine use disorders: a systematic review and meta-analysis of controlled clinical trials. American Journal of Drug & Alcohol Abuse 35(5), 339-346. [Abstract]

Ferri, M., Minozzi, S., Bo, A., and Amato, L. (2013) Slow-release oral morphine as maintenance therapy for opioid dependence (Cochrane Review). The Cochrane Library. Issue 6. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Gowing, L., Ali, R., and White, J.M. (2009) Buprenorphine for the management of opioid withdrawal (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Gowing, L., Farrell, M., Ali, R., and White, J.M. (2009) Alpha2-adrenergic agonists for the management of opioid withdrawal (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Gowing, L., Farrell, M., Bornemann, R., et al. (2008) Substitution treatment of injecting opioid users for prevention of HIV infection (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Lobmaier, P., Kornor, H., Kunoe, N., and Bjorndal, A. (2008) Sustained-release naltrexone for opioid dependence (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Mattick, R.P., Kimber, J., Breen, C., and Davoli, M. (2008) Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Minozzi, S., Amata, L., and Davoli, M. (2009) Detoxification treatments for opiate dependent adolescents (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Minozzi, S., Amato, L., and Davoli, M. (2009) Maintenance treatments for opiate dependent adolescents (Cochrane Review). The Cochrane Library. Issue 2. John WIley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Minozzi, S., Amato, L., and Davoli, M. (2012) Development of dependence following treatment with opioid analgesics for pain relief: a systematic review. Addiction 108(4), 688-98. [Abstract]

Minozzi, S., Amato, L., Vecchi, S., and Davoli, M. (2008) Maintenance agonist treatment for opiate dependent pregnant women (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Nicholson, A.B. (2007) Methadone for cancer pain (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Pani, P.P., Trogu, E., Vacca, R., et al. (2010) Disulfiram for the treatment of cocaine dependence (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Pani, P.P., Vacca, R., Trogu, E., et al. (2010) Pharmacological treatment for depression during opioid agonist treatment for opioid dependence (Cochrane Review). The Cochrane Library. Issue 9. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Pani, P.P., Trogu, E., Maremmani, I., and Pacini, M. (2013) QTc interval screening for cardiac risk in methadone treatment of opioid dependence (Cochrane Review). The Cochrane Library. Issue 6. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Rahimi-Movaghar, A., Amin-Esmaeili, M., Hefazi, M., and Yousefi-Nooraie, R. (2013) Pharmacological therapies for maintenance treatments of opium dependence (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Strand, M.C., Fjeld, B., Arnestad, M., and Morland, J. (2013) Can patients receiving opioid maintenance therapy safely drive? A systematic review of epidemiological and experimental studies on driving ability with a focus on concomitant methadone or buprenorphine administration. Traffic Injury Prevention 14(1), 26-38. [Abstract]

Primary evidence

Randomized controlled trials published since the last revision of this topic:

Magura, S., Lee, J.D., Hershberger, J., et al. (2009) Buprenorphine and methadone maintenance in jail and post-release: a randomized clinical trial. Drug and Alcohol Dependence 99(1-3), 222-230. [Abstract] [Free Full-text]

Oviedo-Joekes, E., Brissette, S., March, D.C. et al. (2009) Diacetylmorphine versus methadone for the treatment of opioid addiction. New England Journal of Medicine 361(8), 777-786. [Abstract] [Free Full-text]

Schottenfeld, R.S., Chawarski, M.C., and Mazlan, M. (2008) Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial. Lancet 371(9631), 2192-2200. [Abstract]

Sheard, L., Wright, N.M.J., El-Sayeh, H.G., et al. (2009) The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project: a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification. Substance Abuse Treatment, Prevention and Policy 4, 1. [Abstract] [Free Full-text]

Strang, J., Metrebian, N., Lintzeris, N., et al. (2010) Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial. Lancet 375(9729), 1885-1895. [Abstract]

Tassinari, D., Sartori, S., Tamburini, E., et al. (2009) Transdermal fentanyl as a front-line approach to moderate-severe pain: a meta-analysis of randomized clinical trials. Journal of Palliative Care 25(3), 172-180. [Abstract]

Wolstein, J., Gastpar, M., Finkbeiner, T., et al. (2009) A randomized, open-label trial comparing methadone and Levo-Alpha-Acetylmethadol (LAAM) in maintenance treatment of opioid addiction. Pharmacopsychiatry 42(1), 1-8. [Abstract]

Woody, G.E., Poole, S.A., Subramaniam, G., et al. (2008) Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. Journal of the American Medical Association 300(17), 2003-2011. [Abstract] [Free Full-text]

Observational studies published since the last revision of this topic:

Alford, D.P., LaBelle, C.T., Kretsch, N., et al. (2011) Collaborative care of opioid-addicted patients in primary care using buprenorphine: five-year experience. Archives of Internal Medicine 171(5), 425-431. [Abstract] [Free Full-text]

Kuepper, R., van Os, J., Lieb, R., et al. (2011) Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ 342, d738. [Abstract] [Free Full-text]

Marsden, J., Eastwood, B., Bradbury, C., et al (2009) Effectiveness of community treatments for heroin and crack cocaine addiction in England: a prospective, in-treatment cohort study. Lancet 374(9697), 1262-1270. [Abstract]

McCowan, C., Kidd, B., and Fahey, T. (2009) Factors associated with mortality in Scottish patients receiving methadone in primary care: retrospective cohort study. BMJ 338, b2225. [Abstract] [Free Full-text]

New policies

No new national policies or guidelines since 1 September 2007.

New safety alerts

No new safety alerts since 1 September 2007.

Changes in product availability

No changes in product availability since 1 September 2007.

Goals and outcome measures

Goals

To support primary healthcare professionals:

To help a person with opioid dependence to remain healthy

To reduce the harm associated with illicit drug misuse

To reduce the dangers associated with injecting and sharing equipment (hepatitis A, B, and C; HIV; other blood-borne infections; streptococcal and staphylococcal infections; and deep vein thrombosis)

To help a person with opioid dependence to achieve a stable life

To help a person overcome their dependence and move to recovery when they are ready

If abstinence is not possible, to establish the person on maintenance treatment at a sufficient dose to prevent or avoid withdrawal effects, reduce illicit drug misuse, and reduce the chance of future episodes of drug misuse

To reduce the adverse social consequences associated with illegal drug misuse (e.g. unemployment, marital problems, criminal activity, diversion of prescribed drugs onto the illegal market)

Background information

Definition

What is it?

For the purpose of this CKS topic, the meanings of the terms 'opioid' and 'opiate' can be considered as largely synonymous, with opioid being used, as it has a broader definition [Sweetman, 2005]:

An opioid is either a natural derivative of opium (e.g. heroin) or a synthetic substance (e.g. methadone, buprenorphine) with agonist, partial agonist, or mixed agonist and antagonist activity at opioid receptors. An opioid antagonist is a drug that blocks the activity of a drug with agonist activity.

An opiate is either a natural derivative or a semi-synthetic constituent of opium.

All opioids have dependence potential to varying degrees [Swadi et al, 1990]. Of the opioids, heroin (diamorphine) has the greatest potential for dependency, especially when injected [DH, 1999].

Physical and psychological dependence can develop within a relatively short period of continuous use (2–10 days) [NICE, 2007b].

The World Health Organization (WHO) states that the key elements of opioid dependence are [WHO et al, 2006]:

A strong desire or sense of compulsion to take the substance.

Difficulty in controlling use.

A physiological withdrawal state.

Tolerance.

Neglect of alternative pleasures and interests.

Persistence of use despite harm to oneself and others.

The WHO states: 'Opioid dependence develops after a period of regular use of opioids, with the time required varying according to the quantity, frequency and route of administration, as well as factors of individual vulnerability and the context in which drug use occurs. Opioid dependence is not just a heavy use of opioids but a complex health connotation that has social, psychological and biological determinants and consequences, including changes in the brain. It is not a weakness of character or will' [WHO et al, 2006].

Opioid dependence should be viewed as a chronic relapsing-remitting disorder and treated using a medical model: 'For decades opiate addiction has been viewed as a problem of motivation, willpower, or strength of character. Through careful study of its natural history and through research at the genetic, molecular, neuronal, and epidemiological levels, it has been proven that opiate addiction is a medical disorder characterized by predictable symptoms and signs' [National Institutes of Health, 1997; Connock et al, 2007].

Heroin, methadone, cocaine, and diamorphine are Class A drugs and buprenorphine is a Class C drug. For further information, see a list of Controlled Drugs (CD),

Prevalence

How common is it?

Data from the National Drugs Treatment Monitoring system suggests that [National Collaborating Centre for Mental Health, 2007a; NTA, 2007]:

There were an estimated 195,464 people in contact with treatment services in England in 2006–2007, and the majority were primary opioid users.

Men comprise over 70% of new presentations for treatment.

It is estimated that there are about 280,000 opioid users in the UK.

National prevalence estimates, which combine local prevalence data and routinely available indicator data, suggest that in the UK the prevalence of problem drug use is 9.35 per 1000 of the population aged 15–64 years, with a total drug-use population estimated at 360,811. It is estimated that 3.2 per 1000 people aged 15–64 years inject drugs (123,498 people) [NICE, 2007b]. Almost one fifth of injecting drug users share needles and syringes [HPA, 2010].

The histories of people using illicit diamorphine who attend treatment services suggest that most people develop dependence in their late teens and early twenties, and continue use over the next 10–20 years [NICE, 2007b].

A survey of drug use amongst 11–15-year-olds in England in 2004 found that 18% had taken drugs within the past year [National Centre for Social Research and National Foundation for Educational Research, 2006]. Prevalence increased with age, from 5% of 11-year-olds to 32% of 15-year-olds. Of all those surveyed, 11% had taken cannabis, 1% had taken heroin, and 1% had taken cocaine.

Drug use is more common in vulnerable young people aged 16–24 years: in one survey 24% of vulnerable young people reported using illicit drugs frequently compared with 5% of their less vulnerable peers. The authors defined five vulnerable groups (those who have ever been in care, those who have ever been homeless, truants, those expelled from school, and serious or frequent offenders) and found that drug use was significantly higher in people who belonged to more than one vulnerable group [Home Office, 2005; NICE, 2007e].

The British Crime Survey 2003/2004 estimated that 4 million people aged 16–59 years in England and Wales have used a Class A drug in their lifetime: just over 1 million have used them in the last year and over 500,000 in the last month. It is estimated that 50,000 people have taken opioids in the past year [Chivite-Matthews et al, 2005].

Many people dependent on opioids are likely to be polydrug users — about two-thirds (67%) presenting for treatment reported heroin as their main drug of misuse, followed by cannabis (9%), methadone (8%), cocaine (7%), and amphetamines (3%) [DH, 2002].

Complications

What are the complications?

Death. Drug-related death (i.e. deaths caused directly by the consumption of one or more drugs and, generally, occurring shortly after the consumption of the substance/s) accounted for more than 7% of all deaths amongst those aged 15–39 years in 2003–2004 in the UK. There were 7000 drug-related deaths in Europe in 2003, with opioids being found in about 70% of them [EMCDDA, 2006]:

The four main causes of drug-related deaths are [DH and Devolved Administrations, 2007]:

Overdose.

Suicide.

Accidents.

Physical health complications of drug misuse.

One study found that injecting drug misusers were 22 times more likely to die than people of the same age who did not misuse drugs [Frischer et al, 1997]. The risk of death among people who inject drugs is over 1% per year [NICE, 2009].

Many deaths appear to be due to multiple drug toxicity, especially the presence of central nervous system depressants (e.g. alcohol and benzodiazepines), rather than an 'overdose': people whose deaths are attributed to overdose are likely to have morphine levels no higher than those who survive, or than heroin users who die from other causes [Darke and Zador, 1996].

In 2005, there were 1608 deaths in England and Wales related to drug misuse. Heroin or morphine were mentioned on the death certificate in 842 deaths, and methadone was mentioned in 220 deaths [National Statistics, 2007].

Although women are a minority in terms of the number of deaths, the number had risen to its highest level in 2005 (346 women compared with 1042 men) [O'Dowd, 2005].

Overdose.

Infection [HPA, 2005; HPA, 2006b]:

Staphylococcus aureus causes infection varying from minor skin and soft-tissue infections to life-threatening invasive disease (e.g. bacteraemia and endocarditis). Meticillin-resistant S. aureus is often reported.

Group A streptococci cause skin sepsis, bacteraemia, and necrotic infections.

HIV prevalence among injecting drug users is about 1 in 50 in England and Wales, and about 1 in 25 in London [HPA, 2006b].

Hepatitis [HPA, 2006b]:

Hepatitis A: Figures from 2005 suggest that outbreaks of hepatitis A among injecting drug users are declining.

Hepatitis B: In 2004, 19% of injecting drug users who took part in a survey in England, Wales, and Northern Ireland had antibodies to hepatitis B core antigen (a marker of previous or current infection).

Hepatitis C: Nearly half of injecting drug users in England are infected with hepatitis C (46%). There is a marked regional variation in the prevalence of hepatitis C: 20% in the North east (111 of 552) and 55% (703 of 1273) in London.

Clostridium infections may cause rapid deterioration. Such infections are associated with injecting into the skin or muscle ('popping') [Beeching and Crowcroft, 2005].

Clostridium tetani: occurred in 25 injecting drug users in England and Wales between 2003 and 2004 (possibly because of contamination of heroin with tetanus spores) and resulted in three deaths [HPA, 2006b].

Clostridium novyi: caused an outbreak of necrotizing fasciitis with overwhelming sepsis and death in 2000 [HPA, 2005].

Clostridium botuli: between March 2000 and December 2002, there were 33 clinically diagnosed cases in the UK and Republic of Ireland [HPA, 2004]. Cases continue to occur and there were 25 suspected cases in England in 2005 [HPA, 2006b].

Bacillus anthracis (anthrax) is rare but potentially fatal. In England in 2010 there were four deaths as a result of anthrax among heroin users. For more information, see http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Anthrax/.

Human T-cell lymphotropic virus, type 11. This is rare, but likely to be under-diagnosed [HPA, 2006b].

There is a greater prevalence of tuberculosis among drug misusers compared with the general population [DH and Devolved Administrations, 2007].

Venous and arterial thrombosis can result from poor injecting technique, especially in people injecting into the groin [DH and Devolved Administrations, 2007]:

Deep vein thrombosis and pulmonary emboli are more prevalent amongst drug misusers [DH and Devolved Administrations, 2007].

Superficial thrombophlebitis [Samlaska and James, 1990]:

Dependent users are susceptible to superficial thrombophlebitis because of repetitive trauma, unsterilized techniques, and irritation caused by the drug mixtures.

Street drugs are often cut with substances that promote thrombosis (e.g. lactose, sucrose, dextrose). Cocaine in particular seems to promote thrombosis.

Poor nutrition and dental disease [DH and Devolved Administrations, 2007].

Social:

Crime: it is estimated that half of all recorded crime is drug related, with associated costs to the criminal justice system in the UK estimated at £1 billion per annum in 1996 [Connock et al, 2007]. A study in 2001 of 1435 people who had been arrested found that the average weekly spend on illegal drugs was £290 and the main sources of illegal income were theft, burglary, robbery, handling stolen goods, and fraud [National Collaborating Centre for Mental Health, 2007a].

Imprisonment [National Collaborating Centre for Mental Health, 2007a].

Effect on partner and children. Child protection issues [National Collaborating Centre for Mental Health, 2007a]. See Child protection issues.

Deprivation and social exclusion [National Collaborating Centre for Mental Health, 2007a].

Involvement in the sex trade [Coid et al, 2004].

Homelessness [National Collaborating Centre for Mental Health, 2007a].

Loss of driving licence. See Advice about driving.

Psychological:

Craving and fear of withdrawal.

Guilt.

Anxiety [NICE, 2007e].

Loss of memory or cognitive skills [NICE, 2007e].

Roles in dealing with people with substance misuse

What is the hierarchy of roles for GPs depending on their level of competence in dealing with people with substance misuse?

It is essential that in all situations practitioners should only treat and prescribe within their expertise and specialist advice should be sought where needed.

Depending on the GP's skills and experience there is a hierarchy of roles for GPs [NTA, 2005; NTA, 2006b]:

Core services only: The GP provides general medical care only to substance misusers.

Enhanced services: The GP provides basic medical care, plus care to substance misusers in accordance with locally agreed shared care guidelines.

Enhanced services provided by GPs with a special clinical interest: GPs with special clinical interest (GPwSI) have received specific higher level training in the management of substance misusers in primary care, usually the GP Certificate in Management of Drug Use Part 2. GPwSIs are able to work more autonomously and take responsibility for more complex cases in substance misuse than other GPs.

Substance misuse specialist (primary care): A doctor with a general practice background and an extensive postgraduate training in substance misuse working as a specialist GP lead or director employed by a Primary Care Trust or mental health trust. These doctors are able to take on most complex cases and have responsibility for the full range of clinical governance activities and service development.

Tiers of care in the practice

What are the different tiers of care that a GP practice may provide?

Many drug users' initial or main contact with drug treatment is through primary care. GPs and primary healthcare teams can choose to provide a level of care appropriate to their competence [NTA, 2006b]:

Tier 1 interventions — screening people using drugs and referring them on to other service providers; provision of general medical services. All GPs must provide Tier 1 interventions.

Tier 2 interventions — assessment to determine the seriousness and urgency of a person's problems and the most appropriate type of treatment. All practices can provide at least some Tier 2 interventions via the primary healthcare team as a whole (e.g. simple harm minimization advice, brief interventions, and immunizations).

Tier 3 interventions — prescribing for drug users within the context of a care plan. Many GPs provide Tier 3 services under specific contractual arrangements.

Tier 4 interventions — medical monitoring of residential rehabilitation or detoxification services, provided by a few GPs where there is local need.

A number of different contractual arrangements may be used to commission appropriate primary care–based drug treatments including shared care to meet local needs [NTA, 2006b]. These include contracts for nationally enhanced services (NES) or locally enhanced services (LES) under the new GP Contract for GPs in shared care schemes with specialist support:

NES for drug misusers have nationally negotiated specifications and payments.

LES for drug misusers allow wide flexibility in determining service specifications.

Practices providing enhanced service

What is expected of a practice providing an enhanced service for drug misusers?

It is useful for a practice to nominate or identify a lead clinician for substance misuse. The clinician who is the drugs lead in a practice must have competence in managing substance misuse, either through experience or training or both, and should undergo any further training identified in their personal development plan to update their skills where appropriate.

The following elements of the service would need to be in place in the practice already in order for it to be part of the national enhanced service [BMA, 2003]:

An accurate register of people on substitute medication.

Regular reviews of substance misusers.

Safety measures and policies appropriate for the provision of such services.

A good knowledge of, and effective liaison with, local drug services and other agencies, including non-statutory (e.g. voluntary) services.

Links with local pharmacies, primary care drug support workers, social services (including the Child Protection Service), and local mental and clinical health teams.

Policy issues for primary care teams

What policy issues should primary care teams consider?

Care for people who have problems with drug misuse needs to be managed by the whole multidisciplinary team.

All people, including drug misusers, may occasionally present with demands, and previously agreed procedures and processes should be in place to cover the most difficult scenarios.

Ideally, all the practice staff should be involved in developing agreed procedures. A useful setting might be a lunchtime meeting with all the staff, facilitated by someone from the local drug service.

In a survey investigating the training needs of primary care team members in contact with substance misusers, the most popular topic for training was handling aggression [Sherratt and Jones, 2003]. Up to 80% of respondents had experienced aggressive behaviour. A meeting for the whole practice team was thought to be the best forum for training.

In the practice policy it is important to have a process for dealing with the following situations when they arise:

Requests for lost prescriptions or medication.

Requests for medication to be prescribed before it is due.

Another drug user or unknown person coming to collect the person's prescription.

The drug misuser attending appointments with groups of friends.

A person arriving either late for an appointment or without an appointment.

Threatening behaviour or shouting at nurses, receptionists, doctors, and others.

Physical violence.

The following points apply to the practice interactions with all people, not only with drug misusers:

Has the whole team decided on a common policy?

If paper prescriptions are used, are they kept in a safe place?

What procedures are in place for potentially higher risk situations (e.g. consulting alone in a late evening surgery or a Saturday surgery)?

What procedures are in place regarding a potentially difficult home visit?

What is the policy/practice for removal of someone from the practice list?

Do all staff feel able to report fears or difficult situations? Whom should they approach?

How and where should incidents be recorded?

In which situations should the police be called?

Should the practice staff have training on handling aggression and violence?

Safety measures

What safety measures should be in place?

All practices should have safety measures in place for dealing with all patients. The existence of this section is not meant to imply that this is a problem particularly related to drug misuse.

Department of Health advice [DH, 1999]:

If a member of staff is working alone, reception staff should check with the staff member if an appointment overruns. Staff should notify reception of anticipated delays.

Avoid seeing a person alone if they have been aggressive or threatening to staff, or are judged by reception staff to be clearly upset or angry while waiting. If this is not possible, ask reception staff to make periodic checks. It is advisable to carry out predictably difficult consultations in an open area or with someone else present.

If it is necessary to see the person alone:

Keep a clear exit route by positioning yourself nearest to the door.

Hide potential weapons (e.g. sharps).

Have a means of requesting help, such as assistance, alarms, or a mobile phone.

Be consistent (e.g. when receptionists are expected to be firm in their application of the policy, they must be supported by more senior staff).

If the behaviour is clearly unmanageable, it becomes a criminal matter. This should be made clear to the person. If they refuse to cooperate, the police should be called to remove them. Where theft or clearly witnessed unacceptable behaviour or injury has taken place, the practice should consider pressing criminal charges.

Yielding to demands is often not helpful, and can undermine the person's expectation of a firm decision. The message of a firm course of action soon gets communicated to other people, making recurrence of unacceptable behaviour much less likely.

Useful contacts:

National Treatment Agency for Substance Misuse (NTA) www.nta.nhs.uk

FRANK (the national drugs information service): provides free and confidential advice, including information on local services. Telephone: 0800 77 66 00. Website: www.talktofrank.com

Prognosis

What is the prognosis?

A longitudinal data collection project in the US found that the average time from the first to the last episode of opioid use was 9.9 years, with 40% of people addicted for over 12 years [Joe et al, 1990].

Mortality in heroin-dependent users is nearly 12 times greater than in the general population [NICE, 2007b].

A long term follow-up study of 581 male opioid users in the US found that after 24 years, 29% were abstinent, 28% had died, 23% had positive urine tests for opioids, and 18% were in prison [Hser et al, 1993].

A quarter to a third of those entering drug treatment are able to achieve long-term abstinence [Gossop et al, 2001].

Detoxification regimens have high relapse rates [DH and Devolved Administrations, 2007]. They are improved when linked to long-term psychosocial support, and are unlikely to succeed if imposed without the patient's consent.

Drug treatment interventions available locally

What sort of drug treatment interventions may be available locally?

Open access interventions. Substance misuse-related advice and information and harm-reduction interventions should be available and accessible to all people with drug problems. However, they might also be component parts of a drug user's care plan and delivered as part of structured treatment. These would include:

Substance use advice and information about:

Different drugs and alcohol and their effects.

Harm reduction.

How to access help for drug problems.

How to access help for other problems (e.g. housing, sexual health).

Drug problems for drug user's partners, family members, and carers.

Harm reduction interventions including:

Needle and syringe programmes .

Advice on safer injecting.

Counselling, testing, and vaccination for blood-borne virus infections.

Structured treatment interventions. These must be delivered as part of a coherent care plan agreed among the drug user, key worker, and any other practitioners involved.

Community prescribing interventions for drug misuse may be carried out:

In a primary care setting through GPs or other primary care staff depending on contractual arrangements. This is usually assisted or supported by a specialist drug team. The patient group in primary care has traditionally been drug users who are stable on substitute medication or whose problem level is mild to moderate. However, the exact nature of the drug users treated and how the prescribing takes place will depend on the skills and competencies of the GP, and the degree of skilled multidisciplinary support. GP prescribing services may also be supported by non-medical prescribers, such as nurses and pharmacists.

In a specialist drug service setting which usually comprises a multidisciplinary drug misuse team. The client group is drug users whose problem level is usually moderate to severe.

Structured day programmes provide a range of interventions and a drug user must attend for 3–5 days a week. Interventions are usually provided via a fixed rolling programme or via an individual timetable.

Structured psychosocial interventions are clearly defined evidence-based psychosocial interventions, delivered as part of a care plan, which assist the person to make changes in their drug and alcohol using behaviour. They include:

Cognitive behavioural therapy.

Coping skills training.

Relapse prevention therapy.

Motivational interventions.

Contingency management.

Community reinforcement approaches.

Behavioural couples therapy.

Family approaches.

'Other structured treatment' describes a package of interventions set out in a care plan which includes as a minimum regular planned therapeutic sessions with the key worker.

Inpatient drug treatment interventions usually involve short episodes of hospital-based drug and alcohol treatment. This usually includes 24-hour medical cover and multidisciplinary team support for treatments, such as:

Stabilization on a substitute medication.

Detoxification/assisted withdrawal from illegal and substitute drugs and alcohol.

Emergency care for drug users in drug-related crisis.

Drug residential rehabilitation consists of a range of treatment delivery models or programmes to address drug and alcohol misuse, including abstinence-orientated drug interventions within the context of residential accommodation.

Aftercare is a package of support planned with the drug user to support them when they leave structured treatment (i.e. when their care plan is complete). The aim of aftercare is to sustain treatment gains and further develop community reintegration. Aftercare may include drug-related interventions, such as open access relapse prevention or harm reduction. It may also include non-drug-related support, such as housing, access to education, and generic health and social care. The aftercare plan should include measures that cover possible relapse and ensure swift access back to treatment if required:

Drug-related support could include open-access relapse prevention, mutual support groups (e.g. Narcotics Anonymous or equivalent user-led groups), and advice and harm-reduction support.

Non-drug-related support can cover a range of issues, such as access to housing, supported accommodation, relationship support, education and training, support to gain employment, and help with parenting and childcare responsibilities.

[NTA, 2006b; DH and Devolved Administrations, 2007]

Role and responsibilities of key workers

What is the role and responsibilities of the key worker?

Although the key worker may be the GP, more commonly in primary care the key worker will be a drugs worker supporting the GP as part of a shared care agreement [NTA, 2006b; DH and Devolved Administrations, 2007].

The key worker is responsible for [NTA, 2006b]:

Supporting the drug misuser during engagement and delivery of treatment including long-term treatment. If the person wishes to become drug free the key worker should support them through detoxification and abstinence.

Drawing up the care plan with the drug user.

Coordinating the delivery of the plan, ensuring that all components of the community prescribing treatment programme work together to help drug users achieve the goals set out in their care plan.

As a minimum, the following should be covered during a session between the key worker and the drug user [NTA, 2006b; DH and Devolved Administrations, 2007]:

Developing and agreeing the care plan with the person, implementing the care plan, and checking progress against milestones in the care plan.

Giving information and advice on drug and alcohol misuse.

Harm-reduction work and motivational interventions.

Interventions to prevent relapse.

Helping to address social needs (e.g. access to welfare benefits).

For drug-misusing parents: monitoring the family situation; supporting parenting; helping the user to access resources; managing the interface with social services, antenatal services, and other relevant professionals; and formally monitoring child protection risk.

Other psychosocial and medical interventions may also be delivered during key-worker sessions, depending on the competency of the key worker.

Care plans

What is a care plan?

A care plan is an agreed plan of action between the drug misuser and service provider.

A care plan should document and enable routine review of the person's needs, subsequent goals, and progress across four key areas:

Drug and alcohol misuse.

Health (physical and psychological).

Offending.

Social functioning (including housing, employment, and relationships).

The care plan should explicitly identify the roles of specific individuals including the GP and support services, and the drug misuser, in the delivery of the care plan. Shared responsibilities will include monitoring compliance, and continuity of care. The GP is likely to lead on prescribing interventions and the shared care worker on monitoring progress against treatment goals and ensuring multidisciplinary discussion when appropriate.

It is important that the care plan is:

Drawn up as a shared exercise with the drug misuser.

Readily understood by all parties.

Brief.

A paper document which is available to the person and kept on their file.

Reviewed both routinely and opportunistically when a change in circumstances makes it necessary.

[NTA, 2006b; DH and Devolved Administrations, 2007]

Community pharmacists

What is the role of a community pharmacist?

Community pharmacists provide treatment to drug misusers in the context of a shared-care scheme and provide supervised consumption:

Buprenorphine supervision in the pharmacy may be difficult, as a sublingual tablet will usually take 5–10 minutes to dissolve [RCGP, 2004a; RPSGB, 2005a], but may take as little as 2–3 minutes. Supervision is most important in the first 2–3 minutes, during which time the tablets will have started to dissolve, and their value for diversion (i.e. their street price) will decrease:

Crushing the tablets before administration may reduce the supervision time. However, crushing the sublingual tablet of buprenorphine will render the product unlicensed, as it is outside the manufacturer's marketing authorization, and there is the potential for the product's bioavailability to be distorted.

Pharmacists may assume some liability for the supply of a product outside licensed indications and should ensure that their indemnity insurance covers such activity.

Some pharmacists may be prepared to crush the tablets as long as they are satisfied that it is in the person's best interests and that it has been previously agreed by the doctor and the drug misuser. The pharmacist requires written authorization from the prescriber to do this, and therefore it may be easiest to write this request on the prescription.

The Royal College of General Practitioners recommends that prescribers or pharmacists should contact their local Primary Care Trust or Mental Health Trust to determine the local policy, and confirm with their insurer that they have the necessary professional indemnity cover.

Pharmacists also have an important role in monitoring missed doses and how subsequent doses are dispensed.

Pharmacists are encouraged by the Royal Pharmaceutical Society of Great Britain to provide such services only as part of a locally agreed scheme to ensure consistent standards and integrated care [NTA and RPSGB, 2006].

Community pharmacists with an interest in drug misuse will usually provide needle and syringe programmes and dispensing services for drug users.

Community pharmacies will not (or should not) share information about clients who are on a substitute prescription and who also use the needle and syringe programme.

However, there are many more areas where pharmacists can, and do, contribute to the wider field of substance misuse work in prevention, harm minimization, and treatment, as well as helping to retain people in treatment [NTA and RPSGB, 2006]. These may not necessarily be in the community pharmacy setting, and include:

Providing smoking cessation services.

Signposting to other services.

Health promotion and health education.

Advising and treating self-limiting conditions.

Monitoring prescriptions.

Care management.

Drug testing.

Treating overdose.

Detecting and managing solvent misuse.

Advising on over-the-counter medicines.

Providing brief alcohol interventions.

Providing emergency hormonal contraception.

Advising about and testing for sexually transmitted infections (e.g. chlamydia).

Providing hepatitis A and B immunization (e.g. under a patient-group direction).

Providing and advising on wound care.

Checking injection sites.

For further information see the Best practice guidance for commissioners and providers of pharmaceutical services for drug users (pdf) [NTA and RPSGB, 2006] and the National Treatment Agency for Substance Misuse website (www.nta.nhs.uk).

Building relationships with patients

Building relationships with patients

When working with people with substance misuse:

Take time to engage the person from the start, and build a respectful, trusting, non–judgemental relationship in an atmosphere of hope and optimism.

Be direct in your communications, and use a flexible and motivational approach, and take into account that:

Stigma and discrimination are associated with substance misuse.

Some people will try to conceal some or all of their condition.

Many people with coexisting substance misuse, with or without psychosis, fear being detained or imprisoned, being given psychiatric medication forcibly, or having their children taken into care.

[NICE, 2011]

Needle and syringe programmes

Needle and syringe programmes

Most needle and syringe programmes are run by community pharmacies or drug action teams. Their principle aim is to reduce the transmission of infections such as HIV, hepatitis B, and hepatitis C that are caused by sharing injecting equipment.

Services may be provided on the following levels:

Level one

Supply of injecting equipment.

Provision of written information on harm reduction, such as advice about how to inject safely and how to avoid an overdose.

Provision of sharps bins with advice about how to dispose of needles and syringes safely.

Level two. As level one but in addition:

Supply of a selection of injecting equipment such as needles, syringes, filters, sterile water, and mixing containers.

Provision of verbal health promotion advice (including harm reduction).

Level three. As level two but in addition offering or helping people to access:

Counselling and testing for blood borne viral infections such as hepatitis B, hepatitis C, and HIV.

Vaccinations including hepatitis A, hepatitis B, and tetanus.

Drug treatment such as opioid substitution therapy.

Treatment of injection-site infections.

Encouragement to switch to non-injecting methods of drug taking.

Sexual health services including provision of condoms.

Psychosocial interventions.

Dental care.

Secondary care services such as treatment for hepatitis C and HIV.

Welfare and advocacy services such as housing and legal issues.

[NICE, 2009]

Diagnosis

Diagnosis of opioid dependence

Presentation of opioid dependency

When should I suspect a person has a problem with opioid dependency?

People may present in a variety of ways:

Asking for help:

With an active request for help with drug dependency (e.g. the user has realized that there are problems associated with taking drugs, or the user has become motivated to change behaviour, or a crisis has developed; perhaps as a result of an impending court case, health or relationship problems).

With an active request for help with alcohol dependency. Always ask about drug misuse.

Presenting with a complication of drug misuse:

Medical history: complications of drug use (e.g. abscess; thrombophlebitis; recurrent chest infections; hepatitis A, B, or C infection; HIV infection).

With clinical features of opioid intoxication or withdrawal. See Recognizing acute withdrawal syndrome.

Suspected by certain features in the presentation:

Psychiatric history: overdoses, depression, psychosis (not specifically an indicator of opioid misuse but may be linked to polydrug use).

Forensic history: past custodial sentences, probation, community service.

Social history: family problems, unemployment, accommodation issues, financial problems.

By disclosure of drug misuse while consulting with another medical problem.

On physical examination, there may be evidence of poor nutrition, dental caries, other signs of neglect, needle tracks, skin abscess, signs of drug intoxication or withdrawal. See Recognizing acute withdrawal syndrome.

On mental health assessment, there may be indications of abnormal general behaviour, disorders of mood (particularly anxiety or low mood), delusions or hallucinations, confusion.

Basis for recommendation

Basis for recommendation

This information is in line with expert advice from the Royal College of General Practitioners [RCGP, 2005a].

Initial investigations

What investigations should I consider initially?

Analysis of urine for drug screen:

Different opioids persist in the urine for different lengths of time (e.g. up to 48 hours for heroin, up to 7–9 days for methadone metabolite).

Detection depends on dose and whether the person is on a maintenance or detoxification programme.

Buprenorphine is detectable in urine and there are now a number of tests available.

Mouth swab tests (saliva and oral mucosal transudate) provide information about recent drug use, but there is a shorter detection window (e.g. heroin can be detected only up to 24–48 hours later with mouth swabs).

Be aware that false-positive and false-negative results can occur. See Confirming opioid use.

Basis for recommendation

Basis for recommendation

These recommendations are in line with expert advice from the Royal College of General Practitioners [RCGP, 2005a].

Management

Management

Scenario: New presentation : covers the initial assessment of a drug user that is required before treatment can be started and covers harm reduction, child protection issues, advice about driving and follow-up. There is also a summary about the support services which may be involved.

Scenario: Substitution therapy : covers how to determine a person's suitability for substitution therapy and how to help a person decide between maintenance and detoxification.

Scenario: Starting and stabilizing on maintenance therapy : covers how to choose between methadone and buprenorphine, and the initiation and dose titration of methadone or buprenorphine.

Scenario: Continuing maintenance therapy : covers the long-term use of methadone and buprenorphine for those who are unable to achieve abstinence. It also covers the management of people who continue to take illicit drugs, and how to switch from one substitute drug to another if this is required.

Scenario: Detoxification - from maintenance therapy : covers the management of a person who wishes to undergo detoxification from methadone or buprenorphine, and the management of relapse.

Scenario: Detoxification - not on maintenance therapy : covers the management of someone who does not wish to be stabilized on substitution therapy before undergoing detoxification.

Scenario: Missed or vomited doses : covers the management of people who have missed or vomited doses of substitution therapy.

Scenario: Acute withdrawal syndrome : covers the symptomatic management of acute withdrawal syndrome using non-opioid treatments.

Scenario: Collapse due to opioid overdose : covers the emergency management of opioid overdose.

Scenario: Travelling abroad : covers the management of people who wish to travel abroad and take controlled drugs with them.

Scenario: Pregnancy and breastfeeding : covers the management of opioid dependence in pregnancy and breastfeeding.

Scenario: Unknown patient : covers the management of a temporary resident/unknown patient.

Scenario: New presentation

Scenario: New presentation - not on substitution therapy

192months3060months
Both

Initial assessment

How should I assess the person initially to decide on future management?

The purpose of the initial assessment is to:

Determine why the person has presented and what their expectations are.

Gather information on the person's drug use and the impact this is having on their life.

Find out how motivated the person is to change and whether substitution therapy (maintenance or detoxification) should be considered.

Assess whether involving other services, such as the local specialist drug team, is appropriate.

Establish parental status and any immediate risk to children.

It may not be possible to cover all these areas adequately during a single consultation. It may be appropriate for concerned relatives or professionals already involved to attend.

When taking a history, in particular assess:

The degree of dependency.

The risk of harm. Ask about their supply of needles and syringes; sharing habits; knowledge of how to inject safely; correct disposal of used equipment; cleaning of equipment; knowledge of HIV and hepatitis A, B, and C; issues of transmission and safer sex.

Current or past complications.

Whether they use any other substances.

Motivation to stop or change their pattern of drug misuse.

Assess the person's interest in referral to other service providers for support to do this. Where appropriate discuss their attitude towards maintenance therapy or detoxification. If substitution therapy is being considered, see Suitability for substitution therapy.

Examine the person in order to:

Confirm evidence of drug misuse (e.g. needle tracks, signs of drug intoxication or withdrawal).

Check for the presence of complications (e.g. poor nutrition, signs of anaemia, skin abscess, thrombophlebitis, viral hepatitis, HIV, chest infection, tuberculosis).

Assess their mental health (e.g. general behaviour, depression, risk of self harm, delusions or hallucinations, confusional states).

Consider investigations to exclude complications.

Choice of investigations is guided by clinical judgement, but would usually include:

Full blood count (to exclude anaemia, signs of infection).

Liver function tests to look for liver damage (hepatitis, alcohol misuse). See Liver function tests.

Tests for blood-borne viral infection — hepatitis A, B, and C, and HIV (with informed consent). Pre-testing should never act as a barrier or delay to vaccination, and drug users should have access to Hepatitis and B vaccination without testing if desired.

If substitution therapy is being considered, opioid use will need to be confirmed by testing for the presence of opioids in oral fluids or urine. See Confirming opioid use.

Key features of history

Key features of history

The key features that should be covered in the taking of a history with a person with opioid dependence are shown in Table 1.

Table 1 . Key features of the history to cover in a person with opioid dependence:
History Specific information
Degree of dependence: past and current Age of starting; types of drugs used, frequency, route, and amount spent on drugs; overdoses; periods of abstinence; symptoms when unable to obtain the drug. Daily use is a strong indicator of dependence.
Motivation To stop or change pattern of drug misuse; attitude towards maintenance therapy.
At-risk behaviour Supply of needles and syringes; sharing habits; knowledge of how to inject safely; correct disposal of used equipment; cleaning of equipment; knowledge of HIV and hepatitis A, B, and C; issues of transmission and safer sex.
Medical history Complications of drug use (e.g. abscess; thrombosis; chest infections; hepatitis A, B, and C; HIV status if known), last menstrual period (in order to consider pregnancy), last cervical smear.
Psychiatric history Psychiatric admissions or outpatient attendance, overdoses (accidental and deliberate), depression, or psychosis.
Forensic history Past custodial sentences, probation, community service, outstanding charges.
Social history Family (especially children), domestic violence, employment, accommodation, financial situation; drug and alcohol use in partner and other family members; impact of drug misuse on other aspects of the person's life; social supports available. How drug use is funded (e.g. sex working, diversion of family income).
Assessment of drug misusing parents Effects of drug misuse on functioning, effect of drug-seeking behaviour (e.g. leaving children unsupervised, contact with unsuitable characters), impact of parent's physical and mental health on parenting, emotional availability to children, effect on family routines (e.g. getting children to school on time). Storage of illlicit drugs, prescribed medication and drug using paraphernalia. Other support networks.
Past contact with treatment services Previous efforts to reduce or stop taking drugs; past contact with treatment and rehabilitation, social, medical, and community services.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007], the National Institute for Health and Care Excellence [NICE, 2007d; NICE, 2011], and the Royal College of General Practitioners [RCGP, 2005a].

Reducing the risk of hepatitis, HIV and tetanus

How can the risk of acquiring hepatitis, HIV and tetanus be reduced?

Offer information and advice on safer sex, the dangers of sharing needles and other equipment, and the risks of acquiring blood-borne viruses.

Ensure that the person has access to clean needles and syringes.

Ensure that the person is immunized against tetanus, as intravenous drug misusers are at increased risk of tetanus. Give booster doses if there is any doubt about the person's immunization status.

Encourage hepatitis A and B vaccination. Pre-testing should never act as a barrier or delay to vaccination:

Vaccinate all drug users against hepatitis A and hepatitis B. Single-component vaccines are preferred to the combined hepatitis A and B vaccine, as one dose of the single-component hepatitis A vaccine confers more protection against hepatitis A than one dose of the combined vaccine. This is particularly important if there is a risk that the drug user will not return to complete the course.

Use the accelerated schedule for hepatitis B (given on days 0, 7, and 21) ideally with a booster at 12 months.

Warn the drug user that their partners and children are also at risk of hepatitis B infection. Advise that partners and children should be vaccinated against hepatitis B.

Consider the use of human tetanus immunoglobulin in people with injection site infections.

Explain that there is no vaccine available for prevention of hepatitis C.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion from the Department of Health, the Royal College of General Practitioners, and the Health Protection Agency [RCGP, 2005a; DH, 2006b; HPA, 2006a; DH and Devolved Administrations, 2007; RCGP, 2007]:

Around 90% of hepatitis C infections are related to current or previous injecting drug use, and prevention focuses on [RCGP, 2007; HPA, 2009]:

Reducing initiation of injecting drug use.

Helping people to stop injecting.

Promoting safer injecting practices.

Promoting safer sex (although transmission of hepatitis C by this route is uncommon).

Child protection issues

What child protection issues should I consider if the drug user has children?

Where appropriate, record the following information: name of child, age and if possible date of birth, where the child lives, the main carer for the child, any concerns about the child, current or previous social worker, whether the child had been on the child protection register.

Be vigilant regarding the welfare of any children:

There should be a low threshold for involving other professionals.

Although it is important not to miss a child at risk, drug misuse in a parent should not in itself automatically lead to child protection inquiries or other forms of compulsory intervention.

Where appropriate, and after discussion with the drug misuser, consider referral to other professionals (e.g. social worker, health visitor, welfare benefits officer) to enable the parents to provide adequate care for their children at home. Explain to the parents that the aim of referral is so that they can receive practical help.

Ensure that parents understand the necessity of safe storage of methadone and buprenorphine, which should be kept in a locked box or cabinet.

Basis for recommendation

Basis for recommendation

The basis of these recommendations is expert opinion in the report Hidden harm: responding to the needs of children of problem drug users, written by the Advisory Council on the Misuse of Drugs, and national guidance from the Royal College of General Practitioners [RCGP, 2005c; AMCD, 2006]:

Effective treatment of the parent can have major benefits for the child.

It is estimated that there are between 200,000 and 300,000 children in England and Wales where one or both parents have serious drug problems (i.e. about 2–3% of all children under 16 years of age). In Scotland it is estimated that there are between 41,000 and 59,000 children of problem drug users (i.e. about 4–6% of all children under 16 years of age).

Of people with serious drug problems, only 37% of fathers and 64% of mothers live with their children. Most children not living with their natural parents live with relatives, and about 5% of children are in care.

Problem drug use in the parent(s) can and does cause serious harm to children at every age, from conception to adulthood:

Maternal drug use during pregnancy may affect fetal growth, and there may be a risk of transmission of viral hepatitis and HIV.

Newborn babies may suffer from neonatal withdrawal syndrome.

The child may be exposed to poverty, physical and emotional abuse or neglect, dangerously inadequate supervision, inappropriate parenting practices, intermittent or permanent separation, inadequate accommodation and frequent changes in residence, exposure to toxic substances in the home, and interrupted or otherwise inadequate education and socialization. The child may observe adults using drugs and being intoxicated with them, and may be expected to carry out criminal or other inappropriate adult behaviour.

The effect on children can be cumulative and multiple, and include failure to thrive, acquisition of blood-borne viral infections, inadequate health care, and a wide range of emotional, cognitive, behavioural, and other psychological problems, early substance misuse, and offending behaviour and poor educational attainment.

Support services

What support services should I consider?

It is important to adopt a multidisciplinary approach to the management of people with opioid dependence. Drug users have multiple needs and it is important that GPs work with others to help deliver effective care to them. The level of expertise required to manage the person may alter over time.

Offer referral to a local shared care service, where the drug misuser will be assigned to a key worker taking into account the drug users wishes and expectations. See Role and responsibilities of key workers.

Direct referral to or advice about the following may be appropriate, although they will usually be accessed by the key worker. See Drug treatment interventions available locally.

A worker who will provide brief interventions (e.g. to increase access to and motivation for structured treatment, to reduce drug-related harm). Some of these interventions may be provided by members of the primary health care team.

Harm-reduction interventions, where appropriate (such as needle and syringe programmes).

Self-help groups (e.g. Narcotics Anonymous).

Structured psychosocial interventions, although in many cases this will be provided by the shared-care service and coordinated by the key worker.

Social services for social or housing problems.

Citizens Advice Bureau for financial problems.

If substitution treatment is being considered, arrange supervision services with a local community pharmacy.

Where appropriate, discuss whether or not family members/carers should be involved in their assessment and treatment plans.

Be aware that there may be child protection issues with some drug misusers (see Child protection issues).

Additional information

Additional information

Drug users have multiple needs and it is important that GPs work with others to help deliver effective care to them. Becoming stabilized on a substitute drug offers the opportunity to discover and address those issues that have led to drug misuse. Therefore, liaison with other professionals who will be able to help with factors contributing to an individual's drug misuse is very important. However, some people will be stable and will simply need regular prescriptions and routine follow up by their GP.

Brief interventions can be offered opportunistically and include:

Advice on harm reduction.

Exploring ambivalence about drug use and possible treatment, with the aim of increasing motivation to change behaviour.

The amount and type of psychosocial input required depends on individual need, and may include:

Contingency management that involves offering incentives for positive behaviours, such as abstinence or a reduction in illicit drug use and participating in health-promoting interventions.

Behavioural couples therapy which should be considered for people who are in close contact with a non–drug misusing partner, and who present for treatment of stimulant or opioid misuse.

Counsellor/key-worker skills and attributes can have as big an impact on outcomes as the intervention itself.

Voluntary counselling services may be available in some areas, and can be particularly useful while people are waiting for assessment by local specialist services.

Information about self help groups should be provided. These should normally be based on 12-step principles, such as Narcotics Anonymous.

Involving significant others and family members, who are not drug misusers in treatment (e.g. family therapy) can lead to improved outcomes. However, as well as being an important resource, family members are often in need of support themselves. Depending upon the relationships between drug misusers and their carers, and respecting confidentiality as far as possible and practicable, information should be exchanged both ways between clinicians and carers, and carers should be active partners in drug misuse treatment:

Carers should be offered specific information and advice on:

The risks from blood-borne viruses and overdose and, if appropriate, should be offered vaccination.

Safe storage of medicines.

The impact of drug misuse, and about treatment and the settings in which it may take place.

Self-help, group, and individual support for families and carers.

Basis for recommendation

Basis for recommendation

The basis for these recommendations is expert advice from the National Treatment Agency for substance misuse [NTA, 2006b] and the Department of Health [DH and Devolved Administrations, 2007].

Brief interventions: there is some evidence to suggest that people who misuse opioids who are not in formal drug treatment programmes may also benefit from brief interventions. In contrast, for people already receiving formal drug treatment, an additional brief intervention did not appear to have much effect on abstinence or drug use in most studies [National Collaborating Centre for Mental Health, 2007b].

A range of psychosocial interventions are effective in the treatment of drug misuse [NICE, 2007c]:

There is evidence that contingency management may be effective in reducing continued drug misuse amongst people taking methadone, encouraging people to attend counselling sessions, and helping unmotivated people to give up drugs [NTA, 2006a].

Psychotherapies, particularly cognitive behavioural therapies (CBT), have a positive evidence base for those with more specific needs (for instance, in people who are taking opiates or cocaine on top of maintenance therapy) and those with severe problems and social anxiety. CBT also improves communication between the person misusing drugs and the healthcare provider, leading to improved engagement and treatment outcomes.

Family- or couple-based interventions: for individuals who have contact with a family member or carer and who are in receipt of methadone maintenance treatment, the addition of behavioural couples therapy can lead to reduction in the use of illicit opioids or cocaine [National Collaborating Centre for Mental Health, 2007b].

There is limited evidence to suggest that 12-step programmes may be effective in their own right, but they may also be used to supplement other forms of treatment to maximize the benefit to people who are misusing drugs [NTA, 2006a].

People may be encouraged to engage in treatment by strong external influences (e.g. family, employment, or the criminal justice system), which can help to improve outcomes [Leshner, 1999]. It is important to discuss whether or not family members and carers should be involved in their assessment and treatment plans [National Collaborating Centre for Mental Health, 2007a].

There may be child protection issues with some drug misusers. See Child protection issues.

Advice about driving

How should I advise someone who wishes to drive?

Inform anyone who is opioid dependent or who is persistently using opioids that they need to inform the Driver and Vehicle Licensing Agency (DVLA). Some individuals may refuse to do this, and in certain circumstances confidentiality may need to be overridden. Whether the GP should breach confidence and inform the DVLA without the person's consent is a complex ethical issue. GPs may need to consult their defence union.

Explain that persistent use of or dependence on heroin, morphine, buprenorphine, or methadone will lead to refusal or revocation of a driving licence. A licence will be considered only if the person has been free of drug use for at least 1 year for Group 1 entitlement, and at least 3 years for Group 2 entitlement.

An exception may be made for an individual complying fully with a consultant-supervised methadone maintenance programme.

For more information, see the Driver and Vehicle Licensing Agency (DVLA) Guide to the Current Medical Standards of Fitness to Drive.

Methadone maintenance programme

Methadone maintenance programme

An exception may be made for an individual complying fully with a consultant-supervised methadone maintenance programme:

Group 1 entitlement may be granted subject to annual medical review, urine screen, and favourable assessment. People on an oral buprenorphine programme may also be considered, applying the same criteria. Those who are permitted to drive on methadone or buprenorphine will have their licence revoked if they use any illicit drugs, including cannabis.

Group 2 entitlement may be granted once a minimum 3-year period of stability on the maintenance programme has been established. People on an oral buprenorphine maintenance programme that is supervised by a consultant may be considered, applying the same criteria.

For more information, see the Driver and Vehicle Licensing Agency (DVLA) website.

Advise people who continue to drive that they should not:

Drive for 4–5 days after beginning an opioid treatment or after a dose increase.

Drive if they ever feel sedated and should report sedation, unsteadiness or cognitive decline immediately so that the dose can be reduced.

Use alcohol or other drugs that impair performance, such as cannabis and antihistamines, and drive.

Make any changes in their medication regimens without consulting a clinician.

Basis for recommendation

Basis for recommendation

These recommendations are from the Driver and Vehicle Licensing Agency (DVLA) Guide to the Current Medical Standards of Fitness to Drive [DVLA, 2010].

The General Medical Council's position on reporting relevant medical conditions to the DVLA is as follows: 'The doctor should explain to the patient that they have a legal duty to inform the DVLA. If the patient refuses to accept the diagnosis of the effect of the condition, you can suggest that the patient seeks a second opinion. You should advise the patient not to drive until the second opinion has been obtained. If the patient continues to drive, you should make every reasonable effort to persuade them to stop. This may involve telling their next of kin. If you do not manage to persuade a patient to stop driving, or you are given or find evidence that a patient is continuing to drive contrary to advice, you should disclose relevant medical information immediately in confidence to the medical adviser at the DVLA. Before giving information to the DVLA you should inform the patient of your decision to do so. Once the DVLA has been informed, you should also write to the patient to confirm that a disclosure had been made' [General Medical Council, 2004; DH and Devolved Administrations, 2007].

Reporting drug misuse

When should I report drug misuse?

Seek the patient’s consent to submitting their details to the National Drug Treatment Monitoring System (NDTMS) if in England, and to the national centre if in Scotland or Wales, when they start treatment.

Emphasize that the national monitoring systems do not collect fully identifiable data and are confidential. Their role is simply to note how many people are in treatment and monitor drug treatment trends.

Contact details for the regional centres of the NDTMS are available in the British National Formulary, in the section Guidance on prescribing: controlled drugs and drug dependence (www.bnf.org).

National Drug Treatment Monitoring System

National Drug Treatment Monitoring System

A report should be made when a person first starts treatment for drug misuse. Report all types of problem drug misuse (e.g. opioids, benzodiazepines, central nervous system stimulants).

The National Drug Treatment Monitoring System (NDTMS) only records structured treatment that has been care planned:

Inpatient detoxification.

Specialist prescribing.

GP prescribing.

Structured psychosocial interventions.

Structured day programmes.

Residential rehabilitation.

Other structured interventions.

Basis for recommendation

Basis for recommendation

The basis for recommendation is expert advice from the British National Formulary (www.bnf.org).

Follow up

What follow up should I arrange?

Arrange an appointment within a few days to establish:

How the person is coping.

Review how the person feels about the decisions made at this consultation and their goals.

Discuss the results of any investigations.

Find out if they have received an appointment or contact from any services that you have referred them to.

Basis for recommendation

Basis for recommendation

The basis for these recommendations is pragmatic advice.

Scenario: Substitution therapy

Scenario: Considering substitution therapy - maintenance or detoxification

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Suitability for substitution therapy

How should I assess suitability for substitution therapy?

Before proceeding with the assessment, determine whether the key considerations for substitution are fulfilled.

Confirm there is ongoing opioid use and that the person is dependent on opioids.

Perform liver function tests.

Report the person's details to the National Drug Treatment Monitoring System.

Key considerations

What key areas do I need to consider?

The key areas to cover when deciding whether a person is suitable for substitution therapy (maintenance or detoxification) are:

Is the person currently taking opioids and dependent on these? (Confirmation of opioid use does not mean that the person is dependent, or tolerant of opioids.)

Is the person suitably motivated to change their drug taking behaviour and participate in a detoxification or maintenance therapy programme?

Is it safe for the person to have substitution therapy?

Basis for recommendation

Basis for recommendation

These recommendations are based on recognized clinical practice in national guidance [DH and Devolved Administrations, 2007].

Confirming opioid use

How should I confirm opioid use?

Where possible, screen for opioid use with a point of care urine or oral fluid drug test.

Confirm positive results by sending the sample to the laboratory.

Consider repeating a negative test within a few days.

If point of care testing is not available, confirm opioid use with a laboratory test.

Try to ensure that the urine belongs to the person in question (e.g. a fresh sample should be warm).

Ask when drugs were last taken:

Opioids persist in the urine for different lengths of time (e.g. 48 hours for heroin, up to 7–9 days if on methadone maintenance treatment).

Oral fluid tests provide information only about recent drug use as there is a shorter detection window of 24–48 hours for most drugs.

Explain that there will be a delay before receiving the result from the laboratory.

Interpret unexpected or inconsistent results (point of care or laboratory) in the light of clinical findings, as false negatives and false positives can occur.

Additional information

Additional information

Interpret results in the light of clinical findings, as false positives and negatives may occur:

False positives can be caused by the use of loperamide or quinolones. Note that many over-the-counter medicines contain opioids (e.g. codeine).

Negative results can occur in people on low doses of methadone and in pregnancy. Although buprenorphine is not detectable in standard routine urine tests for opioids, there is a specific urine test for buprenorphine now available.

A negative result brings into doubt whether the person is currently dependent on drugs.

Consider repeating the test, as false negatives can occur, or the person may have abstained from drug misuse before the test was collected.

Check for objective signs of opioid dependence, including dilated pupils if the person is suffering from withdrawal symptoms and fresh injecting sites if the person is injecting. A limited number of prescribers may be experienced enough to be certain that a person is suffering from opioid withdrawal symptoms and be confident enough to prescribe despite a negative urine result.

Mouth swab tests:

May be more acceptable for those involved and produce quicker results.

Oral fluid tests are easier to collect and harder to adulterate.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from national guidance [RCGP, 2005c; DH and Devolved Administrations, 2007].

As oral fluid testing is a relatively new method of testing, there is less evidence for its use to confirm opioid dependence than for urine testing [DH and Devolved Administrations, 2007].

Quinolones have been shown to give false-positive results in common opiate screening assays [Baden et al, 2001].

Deciding whether a person is dependent

How do I decide whether the person is dependent on opioids?

Confirmation that the person has recently taken opioids is not in itself proof that the person is dependent on opioids.

Dependence may be diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders when three or more of the following are present in a 12-month period:

Is there evidence of tolerance (increased doses of the drug are required to produce the same effect)?

Does the person get withdrawal symptoms?

Is drug use increasing over time?

Is there a history of persistent or unsuccessful attempts to reduce drug use?

Is the person preoccupied with or spending excessive time on drug use or on recovering from the effects of drug use?

Is drug use having a negative impact on social, occupational, or recreational activity?

Is drug use continuing despite evidence it is causing psychological or physical problems?

Basis for recommendation

Basis for recommendation

The degree of dependence is based on diagnostic criteria according to the Diagnostic and Statistical Manual of Mental Disorders [American Psychiatric Association, 1994; National Collaborating Centre for Mental Health, 2007a].

Liver function tests

What is the value of liver function tests?

Ideally, check liver function tests (LFTs) at initial assessment.

If the person is known not to have liver disease (including hepatitis C), it is reasonable to start methadone or buprenorphine while waiting for the results.

If LFTs come back mildly abnormal, it is considered safe to start or continue substitution therapy.

For more significant abnormalities in LFTs or people with symptomatic liver disease, seek specialist advice.

Basis for recommendation

Basis for recommendation

Both methadone and buprenorphine are metabolized by the liver, and their activity may be extended in people with impaired hepatic function [RCGP, 2004a; RCGP, 2005c].

Reporting drug misuse

When should I report drug misuse?

Seek the patient’s consent to submitting their details to the National Drug Treatment Monitoring System (NDTMS) if in England, and to the national centre if in Scotland or Wales, when they start treatment.

Emphasize that the national monitoring systems do not collect fully identifiable data and are confidential. Their role is simply to note how many people are in treatment and monitor drug treatment trends.

Contact details for the regional centres of the NDTMS are available in the British National Formulary, in the section Guidance on prescribing: controlled drugs and drug dependence (www.bnf.org).

National Drug Treatment Monitoring System

National Drug Treatment Monitoring System

A report should be made when a person first starts treatment for drug misuse. Report all types of problem drug misuse (e.g. opioids, benzodiazepines, central nervous system stimulants).

The National Drug Treatment Monitoring System (NDTMS) only records structured treatment that has been care planned:

Inpatient detoxification.

Specialist prescribing.

GP prescribing.

Structured psychosocial interventions.

Structured day programmes.

Residential rehabilitation.

Other structured interventions.

Basis for recommendation

Basis for recommendation

The basis for recommendation is expert advice from the British National Formulary (www.bnf.org).

Refusing substitution treatment

Can I refuse to prescribe substitution treatment?

The prescribing of substitution in primary care has increased recently, but there is local variation regarding the degree to which GPs are involved in prescribing for drug misusers.

Under the terms of the GP contract, all GPs must ensure provision of general medical services and this includes screening drug misusers and referring them on to other service providers. GPs who do not wish to prescribe still remain the person's advocate, and should refer to local drug services and ask their local Primary Care Trust about local commissioning arrangements.

GPs should not prescribe beyond their experience. If they have not had suitable experience, they must seek the necessary expertise or ensure that they refer to local drug services for advice.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion [RCGP, 2005c; Cassidy, Personal Communication, 2006; NTA, 2006b].

Deciding between maintenance therapy or detoxification

How should I help a person decide between maintenance therapy or detoxification?

After confirming the person's suitability and motives for substitution therapy, a decision will need to made whether to opt for maintenance therapy or detoxification.

Discuss the goals and benefits of maintenance treatment, covering the following areas:

The goal is harm reduction and stabilization of lifestyle.

Specific benefits include reduction in use of illicit opioids, reduced risk of death and disease, reduced involvement in crime, and an improvement in well-being.

It is suitable for people who wish to stop using illicit opioids but do not feel able to abstain from all opioids, who wish to reduce their consumption of illicit opioids, or who currently have adverse circumstances (e.g. are homeless or waiting to go to court).

At least initially, it is likely to be a better option than detoxification for most people, particularly those who have been addicted for longer periods of time, who often inject, or who have high levels of drug use.

Discuss detoxification treatment covering the following areas:

The goal is to come off opioids altogether.

It is suitable for people who are highly motivated and wish to detoxify from all opioids and whose circumstances are stable and conducive to maintaining abstinence.

Some people may choose detoxification without entering maintenance therapy. This choice is more suitable for a young user, or people with a low level of drug use, or those who have used opioids for a short time or who rarely inject.

Motives for detoxification

Motives for detoxification

Take into account that people who request detoxification may do so for a number of reasons. They may have made a perfectly sensible and rational decision that they are ready for the next step in their recovery journey. On the other hand, some people may request detoxification because:

That it is what they believe the doctor wishes to hear.

There is no alternative (e.g. the person needs an HGV licence).

They have reached a point when they think the advantages of stopping the drug outweigh the advantages of continuing, and see stopping opioids as the only possibility.

They do not understand the value of maintenance treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion in national guidance from the Royal College of General Practitioners [RCGP, 2004a; RCGP, 2005b; RCGP, 2005c] and review articles [Marsch, 1998; Ward et al, 1999; Bell and Zador, 2000].

The choice between maintenance and detoxification is considered at many points during treatment. The first time it is considered is at the initial assessment, and then at various times as appropriate [RCGP, 2005c].

Maintenance treatment offers substantial benefits over no treatment (see evidence regarding methadone and buprenorphine). Research suggests a linear relationship between time spent on methadone maintenance, and reductions in heroin use and crime in the long term. People who leave treatment prematurely are at high risk of relapsing to heroin use [Ward et al, 1999].

The National Treatment Outcome Research Study suggests that people tend to do better on methadone maintenance treatment rather than detoxification [Gossop et al, 2001]. However, it is important that the option of detoxification is actively explored, particularly in those with a shorter duration of dependence.

Scenario: Starting and stabilizing on maintenance therapy

Scenario: Starting and stabilizing on maintenance therapy

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General points to consider

What general points should I consider before prescribing substitution therapy?

If prescribing substitution therapy, these are the issues that should be considered:

As with the rest of clinical practice, it is important that practitioners should only treat and prescribe within their level of competence. Usually there will be a shared care arrangement with the local drug team.

Confirm the person's wish to choose detoxification or maintenance and their commitment to change.

Discuss the importance of shared care.

Advise the person that all people entering treatment for drug misuse must be reported to the regional National Drug Treatment Monitoring System (NDTMS) if in England, and to the national centre if in Scotland or Wales, when they start treatment.

Never prescribe substitution therapy until opioid dependence has been confirmed by history, examination, and drug screen. See Suitability for substitution therapy. Before initiating substitution therapy, it is usually best to ensure that at least one positive test (and preferably two) for opioids has been obtained (although this may run the risk of losing the person before they have started treatment). See Confirming opioid use.

This means that it is usually not possible to start the person on methadone at first presentation.

Starting methadone is rarely an emergency, and starting methadone without evidence of opioid dependency can be very dangerous and should never be done. The same applies to buprenorphine. Occasionally it may be necessary to start substitution therapy urgently (e.g. a pregnant woman withdrawing or where there is a significant risk of self harm).

Warn the person that the risk of death is highest during titration (and also if drug misuse occurs after detoxification or a period of abstinence):

Emphasize that risk is increased by the use of other drugs, especially alcohol, sedatives, particularly benzodiazepines or short-acting opioids (e.g. heroin, morphine, dihydrocodeine, oxycodone).

If alcohol intake is very high, it may not be appropriate to start methadone.

Be particularly cautious in people who are pregnant or who have liver disease.

Reduce the delay before starting treatment as much as possible.

A verbal discussion may be very useful, stating responsibilities regarding prescriptions. Ensure that the person understands that replacement prescriptions can only be given under exceptional circumstances and will normally be refused.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion from the Royal College of General Practitioners [RCGP, 2004a; RCGP, 2004b; RCGP, 2005c]:

It is important to reduce the delay before starting treatment as much as possible:

A study of 182 people found that reducing the length of time people had to wait to start methadone resulted in a higher proportion starting treatment, although this did not influence the number of people retained in treatment [Strang et al, 2004].

In the past, entry to maintenance treatment has been made difficult because of practitioner's fears of either creating iatrogenic dependence or unnecessarily prolonging dependence [Bell et al, 1994].

Written contracts with the drug misuser are no longer widely used, but written agreements are common, as these act as agreements to share information. Pharmacists, for example, are bound by confidentiality regarding sharing information (e.g. people not turning up, missing doses) unless they have a formal agreement with the person, the prescriber, and the key worker. The agreement usually stipulates what sort of information will be shared. It is helpful to have a standardized agreement, as pharmacists, for example, will deal with prescriptions from several doctors at a time, so it can be very difficult if each prescriber has a different requirement (e.g. 'inform prescriber if the person misses 1 day', '2 days', or '3 days'). Modern agreements tend to be more balanced and will state the responsibilities of each of the partners involved (e.g. including what the GP agrees to do). Modern agreements are also less punitive to the drug misuser [Roberts, Personal Communication, 2006].

Methadone or buprenorphine?

Should I prescribe methadone or buprenorphine for maintenance treatment?

If methadone or buprenorphine are equally suitable, methadone should be prescribed as the first choice.

Buprenorphine may be the preferred option in people who:

Have experienced unwanted effects or difficulties with methadone currently or in the past.

Prefer the 'clear head' response often reported with buprenorphine, in contrast to the 'clouding' sometimes associated with methadone or heroin use.

Have previously had problems with using heroin 'on top' of maintenance methadone treatment and who wish to stop using heroin completely. The blockade effect of even moderate-dose buprenorphine interferes with the subjective effects of heroin use and discourages its use.

Are likely to be in maintenance for a relatively short time, and are likely to proceed to detoxification soon.

Are on long-term treatment with drugs that either induce or inhibit liver enzymes (such as anticonvulsants, rifampicin, ribavirin), as it is less affected by these liver enzymes than methadone. For further information regarding possible drug interactions, see Interactions.

Dihydrocodeine, slow-release oral morphine and injectable opioid treatments are not recommended for maintenance therapy.

For further information on prescribing methadone or buprenorphine, including information on drug interactions, see Prescribing information.

Basis for recommendation

Basis for recommendation

Methadone as first-line choice

If methadone or buprenorphine are equally suitable, methadone should be prescribed as the first choice [NICE, 2007b].

There is evidence from a National Institute for Health and Care Excellence Health Technology Assessment [Connock et al, 2007] that methadone is more effective than buprenorphine in retaining people in treatment, and from a Cochrane review that, although buprenorphine is an effective intervention, it is not as effective as methadone at adequate dosage in reducing the use of heroin [Mattick et al, 2003a].

Methadone substitution, at appropriate doses, is cost effective in reducing injecting behaviour, illicit opioid use, and criminal activity [NICE, 2007b].

Methadone is much cheaper than the equivalent dose of buprenorphine.

Methadone is easy to titrate and supervise.

Effectiveness of buprenorphine compared with methadone requires further investigation [Ling et al, 1996; Strain et al, 1996; Gowing et al, 2006b].

Buprenorphine as alternative choice

Buprenorphine is safer in overdose, but only when used alone. Gastrointestinal bioavailability of buprenorphine is poor, and swallowing the tablets will result in a milder effect compared with sublingual administration. It also has a ceiling effect, which adds to its safety in accidental or intentional overdose [Center for Substance Abuse Treatment, 2004; RCGP, 2004a].

The recommendation that buprenorphine may be the preferred choice in people who are likely to be in maintenance for a relatively short time, and are likely to proceed to detoxification soon is based on expert opinion [Law, Personal Communication, 2006]. This is because buprenorphine is much easier and simpler to withdraw from quickly, typically causing less suffering for the drug misuser than that experienced during methadone or heroin withdrawal [Law et al, 2004].

The disadvantages of buprenorphine include the following:

It can be injected, and so is liable to abuse.

It can precipitate withdrawal symptoms in those who have recently used heroin (within 8 hours) or methadone (within 24 hours). It typically occurs 1–3 hours after the first buprenorphine dose and peaks over the first 3–6 hours before subsiding [RCGP, 2004a].

Emotions and unpleasant feelings that may have been blocked by full agonists (e.g. methadone or heroin) may become more apparent. Some people welcome this, but others may take opioids to blunt painful feelings and are unprepared for this effect [Verster and Buning, 2005].

Buprenorphine supervision in the pharmacy may be difficult, as a sublingual tablet will usually take 5–10 minutes to dissolve [RCGP, 2004a; RPSGB, 2005a], but may take as little as 2–3 minutes. Supervision is most important in the first 2–3 minutes, during which time the tablets will have started to dissolve, and their value for diversion (i.e. their street price) will decrease:

Crushing the tablets before administration may reduce the supervision time. However, crushing the sublingual tablet of buprenorphine will render the product unlicensed, as it is outside the manufacturer's marketing authorization, and there is the potential for the product's bioavailability to be distorted.

Pharmacists may assume some liability for the supply of a product outside licensed indications and should ensure that their indemnity insurance covers such activity.

Some pharmacists may be prepared to crush the tablets as long as they are satisfied that it is in the person's best interests and that this has been previously agreed by the doctor and the person. To do this, the pharmacist requires written authorization from the prescriber, so it may be easiest to write this request on the prescription.

The Royal College of General Practitioners recommend that prescribers and/or pharmacists should contact their local Primary Care Trust or Mental Health Trust to determine the local policy and confirm with their insurer that they have the necessary professional indemnity cover.

Buprenorphine is more expensive than methadone, and the cost of a year's maintenance treatment at equivalent dosage is currently over five times the cost of methadone.

Drugs not recommended

Dihydrocodeine is not recommended for use in maintenance therapy. Although there is limited evidence that it is effective, studies have been conducted in specialist settings, and cannot be reasonably extrapolated to primary care. Dihydrocodeine may be considered by a specialist if [DH and Devolved Administrations, 2007]:

The person is unable or unwilling to consider treatment with methadone or buprenorphine, or is unable to tolerate these drugs.

There are unusual circumstances, for instance the person is in police custody.

Slow-release oral morphine may be a useful alternative to methadone in people who are unable to tolerate methadone, but given the current lack of evidence and high diversion risk of this medication it should only be prescribed by a specialist [DH and Devolved Administrations, 2007].

Injectable opioid treatment requires extensive supervision and time commitments from the treating physician and should only be used in specialist centres [DH and Devolved Administrations, 2007].

Using supervised consumption

When should supervised consumption be used?

Explain that it is accepted practice to take methadone or buprenorphine under daily supervised consumption in the following circumstances:

For at least 3 months after starting substitute medication subject to assessment of compliance and individual circumstances.

If substitute medication is restarted after a break.

If there is a considerable increase in the dose.

If when on non-supervised consumption they use opioids on top of the prescribed drugs, or use other drugs that increase the risk of overdose (such as alcohol or benzodiazepines).

Reassure the person that non-supervised consumption will be started as soon as stability of drug use has been achieved, and that their circumstances (e.g. employment/child care responsibilities) will be taken into account.

Non-supervised consumption

Non-supervised consumption

Always assess a person's circumstances [DH and Devolved Administrations, 2007]:

Highly compliant people may only need supervised consumption for a couple of weeks.

People who fail to respond to conventional treatment may require supervised consumption for much longer than 3 months.

Take-home doses should not normally be considered if the person [DH and Devolved Administrations, 2007]:

Has not reached a stable dose.

Shows a continued and unstable pattern of drug misuse, including a significant increase in alcohol intake, the use of illicit drugs, benzodiazepines, or other tranquillizers.

Has a psychiatric illness or is threatening self harm.

Is suspected of diverting their substitution treatment or using it inappropriately.

Has children and there are concerns about the safety of medicines stored in the home.

Basis for recommendation

Basis for recommendation

These recommendations are based on guidance from the Department of Health, National Treatment Agency and the National Institute for Health and Care Excellence [DH and Devolved Administrations, 2007; NICE, 2007b]:

Supervised consumption is particularly useful for the first 3–6 months and can be reintroduced periodically, or when there is concern about a change in the person.

These arrangements should only be relaxed when the prescriber can be satisfied that compliance will be maintained. Such relaxation can be seen as an important component of rehabilitation and the re-establishment of acceptable, responsible behaviour.

Non-supervised consumption should be considered when stability of drug use has been achieved. In general, people starting substitute medication should be required to take their daily dose under direct supervision of a professional (usually a community pharmacist) for at least 3 months, and any change should be made after discussing the advantages and disadvantages. However social factors should be taken into account (e.g. whether the person has a job or childcare responsibilities) [NICE, 2007b].

Entering employment often leads to the biggest psychosocial improvement in a person's life and for some people is a good time to switch to non-supervised consumption. Practically, most working people can manage to attend the pharmacy for at least 1 day of supervised consumption, and therefore many consume their first dose under supervision at the pharmacy and then take out enough treatment for 6 days [Cassidy, Personal Communication, 2006].

Starting maintenance treatment with methadone

How should I start maintenance treatment with methadone?

When starting methadone, 'start low, go slow' and explain to the person why it is important to be cautious during dose induction (for example to avoid overdose). Remember that the reported use of street drugs may be inaccurate.

When starting methadone:

The usual recommended initial dose is 10–30 mg/day.

However, start methadone at no more than 20 mg/day if:

Tolerance is low or uncertain.

The person is taking other sedative drugs, including alcohol and benzodiazepines.

If there are concerns, observe the person for 1 hour after the first dose if this is feasible.

Determine the necessary maintenance dose of methadone by titration:

Titrate against withdrawal symptoms (warn the person about the possibility of these occurring).

It is advisable for the person to attend daily during the first few days.

Increase the dose cautiously, but not too slowly, until signs of withdrawal have disappeared:

Over the first week, the incremental increase for any one day should be no more than 10 mg. The total weekly increase over the first week should be no more than 30 mg above the starting dose.

Over subsequent weeks, the dose increases should not exceed 10 mg per day to a maximum of 30 mg per week, until a usual maintenance dose of between 60 mg/day and 120 mg/day is reached.

Larger doses (above 120 mg/day) are sometimes needed, but should be given only after consultation with a specialist.

Explain that it may take several weeks to reach the correct maintenance dose.

Additional information

Additional information

Methadone should be prescribed as 1 mg per 1 mL oral solution. Methadone tablets should not be prescribed as they are not licensed for treating drug dependence and have the potential for diversion.

When titrating the dose take into account the difficulties in prescribing for opiate-dependent drug misusers: there are three competing pressures:

To prescribe an effective and appropriate dose.

To minimize the risks of overdose during induction.

To rapidly respond to the person's needs for appropriate treatment in order to retain them in treatment and prevent harm from illicit drug misuse.

Take account of the risk factors for overdose during methadone induction which are:

Low opioid tolerance.

Use of central nervous system depressant drugs.

Too high an initial dose.

Increasing the dose too rapidly.

Slow methadone clearance.

A supplementary dose on the same day may be considered when there is evidence of persistent opioid withdrawal provided that the person has been fully assessed by a clinician with appropriate skills and experience.

It is extremely important to provide adequate information to carers (after obtaining consent from the drug misuser) about how to recognize and manage methadone toxicity. Note that the steady state concentration of methadone takes about 3–10 days to become established. During this time blood levels rise progressively even if the person remains on the same dose. This means that a dose tolerated on day one may become a toxic dose on day three.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice in national guidance from the Royal College of General Practitioners and the Department of Health and the National Treatment Agency [RCGP, 2005c; DH and Devolved Administrations, 2007]:

Self-reported habits may be misleading, because the purity of street heroin may vary and many people may be unaware of how much they have been taking.

Careful induction is necessary, as the first 2-week period of treatment is associated with a greater risk of overdose mortality. Not giving enough can also cause problems.

Commencing a dose of methadone that is too high may result in toxicity and death [Humeniuk et al, 2000].

Commencing a dose that is too low may cause withdrawal symptoms, prompting people to seek relief from use of illicit drugs (e.g. heroin and benzodiazepines), which will also increase the risk of toxicity and death [Humeniuk et al, 2000].

Deaths have occurred following commencement of a daily dose of 40 mg [RCGP, 2004b] and at 20 mg when using other drugs concurrently [Humeniuk et al, 2000].

Stabilization means finding a suitable dose that keeps the person engaged in treatment without the need to supplement with heroin and other drugs. Once stabilized, the person should feel comfortable, with no subjective or objective withdrawal and no sedation or euphoria after doses [RCGP, 2005c].

Starting maintenance treatment with buprenorphine

How should I start maintenance treatment with buprenorphine?

Explain that withdrawal syndromes:

May be precipitated by the partial agonist properties of buprenorphine, including restlessness, insomnia, headache, and diarrhoea.

Typically occur 1–3 hours after the initial dose of buprenorphine, peaking in severity over the first 3–6 hours, and generally subsiding thereafter.

When switching from heroin:

Reduce the risk of withdrawal symptoms occurring by delaying the first dose of buprenorphine until at least 6–12 hours after the last dose of heroin, and ask the person to wait as long as possible until they are experiencing features of opioid withdrawal.

'Start low and titrate rapidly' when starting buprenorphine:

Starting doses of 4 mg to 8 mg can be used, and are generally safe provided there are no circumstances needing caution, e.g. current use of alcohol, other opioids (for chronic pain), sedating drugs, or medical conditions (severe respiratory, renal, or hepatic disease).

Rapidly titrate dose by 2 mg to 8 mg daily (usually 4 mg) according to clinical response over the next few days, up to a maximum daily dose of 32 mg. The most commonly effective maintenance daily dose is 12 mg to 24 mg.

A cautious approach is to initiate treatment with 4 mg on day one, then 8–16 mg on day two. An experienced and competent clinician may increase the starting dose to 8 mg on day one and 16 mg on day two and thereafter increase the dose more slowly if necessary. Dividing the daily dose may be useful.

During dose titration, the person should be reviewed frequently.

When switching from methadone:

Reduce the risk of withdrawal occurring by:

Reducing the dose of methadone to 30 mg/day or less (see Table 1). This can be done by reducing the dose by 5 mg every 1–2 weeks until this goal is reached.

Delay the first dose of buprenorphine until the person is experiencing symptoms of opioid withdrawal (this typically means at least 24–36 hours after the last methadone dose).

The recommended starting and titrating doses of buprenorphine are outlined in Table 1.

If the person experiences severe precipitated withdrawal symptoms on switching to buprenorphine:

Symptomatic treatment such as lofexidine (400 micrograms four times a day for 1–2 days) can be given.

Alternatively, 10–20 mg diazepam may be given, but only to people who are not known to abuse it. Expert opinion differs on whether or not to use diazepam. It should only be prescribed as part of an agreed schedule.

Further increases in buprenorphine dose are not advisable.

Advise the person that 'on top' use of heroin will not help with withdrawal symptoms and may increase the risk of precipitated withdrawal because of the partial agonist properties of buprenorphine.

Table 1 . Buprenorphine doses when switching from methadone.
Last methadone dose Buprenorphine day 1 Buprenorphine day 2 Buprenorphine day 3 onwards
> 30 mg Not recommended in general practice unless GP is experienced
20–30 mg 4 mg 6–8 mg Daily increases of 4 mg a day are possible up to a maximum daily dose of 32 mg
10–20 mg 4 mg 4–6 mg
< 10 mg 2 mg 2–6 mg
Taken from: [RCGP, 2004a]

Additional information

Additional information

When titrating the dose, take into account the difficulties in prescribing for opiate-dependent drug misusers: there are three competing pressures [DH and Devolved Administrations, 2007]:

To prescribe an effective and appropriate dose.

To minimize the risks of overdose or precipitated withdrawal during induction.

To rapidly respond to the person's needs for appropriate treatment in order to retain them in treatment and prevent harm from illicit drug misuse.

Take account of the risk factors for overdose during induction with buprenorphine, which are [DH and Devolved Administrations, 2007]:

Low opioid tolerance.

Use of central nervous system depressant drugs, including alcohol.

There is also a risk of precipitating withdrawal which is increased if there is insufficient time before administering buprenorphine in people who have [DH and Devolved Administrations, 2007]:

Recently used heroin, particularly at higher doses.

Recently consumed long-acting opioids, such as methadone.

Rapid titration is essential to prevent drop out: people can usually be stabilized over 1–2 weeks.

When prescribing buprenorphine, sub-lingual tablets (400 microgram, 2 mg or 8 mg) should be specified. Temgesic® is another buprenorphine product used for analgesia, and is not licensed for opioid maintenance.

Prescribe buprenorphine initially for daily use — alternate-day dosing should not be considered until the person has been stable for at least 3 months. The effectiveness of alternate-day dosing remains unclear, and buprenorphine is not licensed for this.

The maximum licensed starting dose recommended by the manufacturer is buprenorphine 4 mg [ABPI Medicines Compendium, 2006].

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Royal College of General Practitioners [RCGP, 2004a], the National Institute for Health and Care Excellence [NICE, 2007b], and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007].

Monitoring a person starting substitution therapy

How should I monitor a person who is starting substitution therapy?

Arrange for the person to have supervised consumption for at least the first 3 months.

Dose increases in this early stage should be done following clinical assessment:

The ideal is for the person to be seen daily for the first few days while titration is being undertaken.

If this is not practicable, the person should be seen every few days and the dose only increased then.

During the titration, ask about what other drugs are being used 'on top', including opioids, alcohol, and benzodiazepines, and respond accordingly by cautious gradual dose increases.

Look for signs of withdrawal that would suggest that the dose is not sufficient. Continued illegal drug misuse may occur if the dose of the substitute drug is too low. Unless there are signs of intoxication, consider increasing the dose by small increments until the signs of withdrawal have disappeared and misuse of illegal drugs reduces or ceases.

Encourage feedback from the community pharmacist and other professionals who may be seeing the drug misuser more frequently. This needs to be carefully balanced with issues of confidentiality and should be discussed with the person to ensure consent.

Urine tests may be used:

To confirm treatment compliance.

To monitor illicit drug use including as a drug-specific treatment goal (e.g. as part of a psychosocial intervention such as contingency management).

Check that harm reduction issues have been covered. See Reducing the risk of hepatitis, HIV and tetanus.

Experienced clinicians recommend carrying out baseline liver function tests (LFTs) and regular LFTs at least twice a year. However, taking blood from drug users may not be easy and this advice should be considered against the reality of the clinical situation presented.

If there are mild alterations in LFTs then ideally monitor at least every 6 months and monitor alcohol intake.

If there is symptomatic liver disease, seek specialist advice as LFTs will need to be checked regularly, usually a minimum of every 2–3 months.

At any stage, if there is evidence of a marked deterioration in LFTs, seek specialist advice.

Urine tests

Urine tests

Urine tests can also be used [RCGP, 2005c]:

To gain more information about other drug use and to monitor this.

To confirm a person's suitability to finish supervised treatment or to return to it.

To inform a planned discussion about a person's progress in treatment.

At the request of the person, to create a usage history.

As part of comprehensive record keeping.

To confirm a parent's drug use in child protection cases.

For court reports (after discussion with the person about this).

Basis for recommendation

Basis for recommendation

The basis for these recommendations is expert advice in national guidance from the Royal College of General Practitioners [RCGP, 2004a; RCGP, 2005c] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007].

Referral

When should I refer?

Always adopt a multidisciplinary approach and refer to other service providers where appropriate. In many cases this will involve a shared care arrangement with the local drug team. Drug users have multiple needs and it is important that GPs work with others to help deliver effective care to them. However, some people will be stable and will simply need regular prescriptions and routine follow-up by their GP.

If there is evidence of liver disease or a marked deterioration in liver function test results, refer to or seek advice from a liver specialist.

Basis for recommendation

Basis for recommendation

These recommendations are pragmatic advice based on accepted clinical practice.

Scenario: Continuing maintenance therapy

Scenario: Continuing maintenance therapy

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Continuing maintenance therapy

How should I continue maintenance therapy?

After maintenance treatment has been started and stabilized, maintain the person on the recommended dosage of methadone and buprenorphine.

Arrange follow-up appointments according to the person's clinical needs.

Dose of methadone for maintenance treatment

What dose of methadone is used for maintenance treatment?

The usual maintenance dose is in the range 60 mg to 120 mg per day although lower or higher doses may be used.

Seek specialist advice if people need doses above 120 mg/day. Specialist assessment or advice is recommended if high doses are prescribed.

If the person is continuing to use illicit opioids and there is evidence of motivation to stop this illicit use, there should be a low threshold for increasing the dose of methadone.

Do not increase the dose by more than 10 mg per day, or 30 mg per week, for any one week.

Basis for recommendation

Basis for recommendation

The basis for these recommendations is expert opinion from the Royal College of General Practitioners and the National Institute for Health and Care Excellence [RCGP, 2005c; NICE, 2007b].

People maintained on doses of 60 mg to 120 mg are more likely to remain in a treatment programme and avoid use of illicit opioids. Lower or higher doses may be appropriate in some individuals, but methadone doses less than 60 mg/day are generally associated with poorer outcomes in terms of continued heroin use and retention in treatment [Strain et al, 1993; Strain et al, 1999; Johnson et al, 2000; Faggiano et al, 2003].

Buprenorphine for maintenance treatment

What dose of buprenorphine is used for maintenance treatment?

The daily dose of buprenorphine can be in the range 8 mg to 32 mg; the usual dose range is 12 mg to 24 mg, but lower doses may be adequate for some people.

Normally prescribe buprenorphine daily.

Carry out regular reviews of treatment at least 3-monthly, to review care plans and goals, and to check for injecting sites.

Consider a reduction in the frequency of dosing for people who have been stable on buprenorphine for 3 months, who have no high-risk drug use (e.g. ongoing use of heroin, other injecting drug use, alcohol or benzodiazepines, frequent intoxicated presentations, recent history of overdose) and who wish to do so.

The effectiveness of alternate-day dosing is unclear and should only be considered after consultation with an experienced prescriber.

If the person is continuing to use illicit opioids and there is evidence of motivation to stop this illicit use, there should be a low threshold for increasing the dose of buprenorphine.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Royal College of General Practitioners [RCGP, 2004a]:

Alternate-day dosing may be an advantage where consumption is supervised, as daily attendance at the pharmacy will not be necessary. The dose should be titrated to clinical need, and the following is a guide only:

Two-day dispensing regimen: twice the daily dose on alternate days, up to a maximum of 32 mg.

Three-day dispensing regimen: three times the daily dose every third day, up to a maximum of 32 mg.

Alternate-day dosing may be a disadvantage, as some people will not tolerate taking buprenorphine every second or third day, and may experience increased cravings or features of withdrawal on non-dosing days.

Follow-up for people on maintenance treatment

What follow-up is recommended for people on maintenance treatment?

Tailor regular reviews to the individual needs of the person. It is good practice to review care plans and goals about every 3 months. Review at regular intervals, initially fortnightly and then, if stable, at least monthly. A thorough review should be done at least every 3 months and should include achievements and goal setting. Discuss management and treatment options with the person and involve them in decision making.

Arrange regular urine or oral fluid testing for a drug screen:

The frequency of urine or oral fluid testing, both to confirm the use of methadone and to assess other drug use (e.g. heroin, benzodiazepines, cocaine), depends on the progress of the person. Drug testing to confirm drug use when the person has admitted to it is rarely useful.

It should be clearly understood between the person and the doctor that urine testing will be used to inform mutually agreed decisions about the person's future treatment. Reassurance should be given that the person will not be punished (e.g. by reduction in dose) if the results show use of non-prescribed drugs. The positive results can be used as a target in relapse-prevention work.

Mouth swab tests may be used to provide information about recent drug use. They may be more acceptable for those involved. However, they can be more time-consuming to perform.

Experienced clinicians recommend carrying out baseline liver function tests (LFTs) and regular LFTs at least twice a year. However, taking blood from drug users may not be easy and this advice should be considered against the reality of the clinical situation presented.

If there are mild alterations in LFTs then ideally monitor at least every 6 months and monitor alcohol intake.

If there is symptomatic liver disease, seek specialist advice as LFTs will need to be checked regularly, usually a minimum of every 2–3 months.

At any stage, if there is evidence of a marked deterioration in LFTs, seek specialist advice.

Follow-up review

Follow-up review

A review might include:

Reviewing drug use:

Current illicit drug use, including benzodiazepines and cannabis.

Alcohol intake on a typical day.

Any other prescribed drug use.

Updating hepatitis and HIV status, and completing any outstanding screening or vaccination requirements (including tetanus).

Checking for injection sites.

Testing urine.

Discussing harm reduction.

Discussing any lifestyle changes that the person would like to make, and what support they would need to make them.

Ensuring that the person is aware of local services (e.g. social services, counselling services) and that they know how to access them.

Reviewing general health, including blood pressure checks, cervical smears, contraception, smoking interventions.

Reviewing partner and family matters, especially regarding children.

Reviewing goals and progress made, and updating the care plan.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion from the Royal College of General Practitioners [RCGP, 2004a; RCGP, 2005c] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007]:

Urine testing is an important part of monitoring a person on maintenance therapy, as it may encourage compliance, particularly in people who have been entrusted with non-supervised consumption.

Associated alcohol or illicit drug misuse

How should I manage a person who is also taking other alcohol or illicit drugs?

Determine if the person is using illicit drugs (including heroin) and/or dangerous quantities of alcohol.

Expect some illicit use of drugs. People may not cease all illicit drug use on entering treatment: eliminating all alcohol misuse and illicit drug misuse may take months or years.

Do not stop substitution therapy if the person is taking street heroin unless there are exceptional circumstances.

Address hazardous or harmful consumption of alcohol and consider referral if the person is dependent on alcohol.

Consider referral for a person who is using benzodiazepines concomitantly with substitution therapy. It is rarely appropriate to prescribe ongoing benzodiazepines to a person who is opioid dependent.

Offer referral to a person who is using cocaine/crack and is opioid dependent, and warn of the dangers of overdose.

Determining whether the person is taking illicit drugs

How do I know if a person is taking illicit drugs in addition to maintenance treatment?

Look for evidence of continued drug use:

Drug-positive urine screens.

Heavy alcohol use.

Frequently intoxicated presentations.

Overdoses and presentations to Accident and Emergency departments.

Frequently missed doses.

Physical evidence (e.g. fresh track marks).

Mental deterioration.

Missed appointments.

Basis for recommendation

Basis for recommendation

This information is from the Royal College of General Practitioners [RCGP, 2005c; DH and Devolved Administrations, 2007].

Managing people continuing to take heroin

How should I manage people continuing to take heroin?

Many people fear that their treatment will be reduced or stopped as 'punishment' if they use other drugs. This approach is not effective or appropriate. In fact, an increase in both the dose of substitution therapy and frequency of psychological therapy may be needed if illicit drug use is occurring as a result of 'breakthrough' withdrawal symptoms.

Consider increasing rather than decreasing the intensity of the treatment programme if the person is failing to benefit from treatment.

Much of the management will be organized by the key worker but in some cases may be organized by the GP and may include:

Review of treatment, which may require dose-level adjustments, change of treatment, and renegotiation of short-term treatment goals.

Review of the care plan and its objectives and increased support from a drug worker/team.

Alteration to the dispensing regimen.

Psychosocial interventions.

Harm-reduction advice about alcohol and other drug use (e.g. cocaine, benzodiazepines).

A change of substitution therapy (e.g. to buprenorphine).

Referral to a more specialized service.

Identification of previously unrecognized mental health problems.

Methadone should only have to be withdrawn in exceptional circumstances (e.g. if there is evidence through clinical observation that there is no benefit, or that the person is unlikely to benefit if continued, or it would be detrimental to continue).

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion from the Royal College of General Practitioners [RCGP, 2005c] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007].

Managing people also taking alcohol

How should I manage people who are also taking alcohol?

Assess alcohol use.

If the person is not alcohol dependent then attempt to address their alcohol misuse.

If the person is alcohol dependent offer help with withdrawal. Discuss involving a specialist team.

Explain that alcohol may delay the metabolism of methadone, and lead to such complications as central nervous system depression and result in serious respiratory depression and hypotension:

Binge drinking and high-level alcohol use are particularly dangerous.

Impaired liver function also delays the metabolism of methadone.

For detailed information on the management of problem drinking, see the CKS topic on Alcohol - problem drinking.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion from the Royal College of General Practitioners [RCGP, 2005c] and the National Institute for Health and Care Excellence [NICE, 2007d].

Managing people also taking benzodiazepines

How should I manage people who are also taking benzodiazepines?

Consider referring for expert advice anyone taking benzodiazepines as well as opioids.

Only consider prescribing benzodiazepines after a full assessment, after at least two urine tests confirming benzodiazepine use, and after the identification of clear goals:

Long-term (maintenance) prescribing of benzodiazepines has not been shown to have any definite medical value and is rarely justified.

In some drug misusers, short-term prescribing (for less than 6 months) of 30 mg or less of diazepam may offer some benefit in supporting them to control their intake, and stabilize their lives.

However, there may be problems for the prescriber and the drug misuser:

Tablets can be crushed and injected, causing tissue damage and death in some cases.

Adverse effects and long-term problems may result from benzodiazepine use, and these should be explained to the person.

Diazepam is not licensed for maintenance or detoxification and should not be used for longer than 6 months.

Regular therapeutic doses of benzodiazepines may result in anterograde amnesia (impaired delayed recall) for a few hours after a dose.

Basis for recommendation

Basis for recommendation

These recommendations are based on those from the Substance Misuse Management in General Practice [Ford et al, 2005]:

There is a high prevalence of benzodiazepine use among drug misusers:

Up to 90% of people attending drug treatment centres reported benzodiazepine use in a 1-year period [Perera et al, 1987].

A survey of UK drug clinics in 1992 found that, of the 208 people surveyed, 186 had used benzodiazepines and 103 had injected them [Strang et al, 1994].

Benzodiazepines are taken because of their own effects of intoxication, to enhance the effect of another drug (especially opiates), or to counter early withdrawal symptoms from other drugs [Ford et al, 2005]. Illicit benzodiazepine use is a problem in many drug misusers [Ford et al, 2005]:

Taking benzodiazepines with methadone, buprenorphine, or alcohol can cause death.

People on methadone maintenance who use non-prescribed benzodiazepines have been found to exhibit more HIV/hepatitis C risk-taking behaviour, have greater polydrug use, and have higher levels of psychopathology and social dysfunction.

Physical dependence on benzodiazepines occurred in 26 (43%) of 61 people in one study of people who were also taking benzodiazepines and were admitted to hospital for treatment for opioid dependence [Williams et al, 1996].

Withdrawal symptoms may be severe, and in one study more than half of those who used opiates described benzodiazepine withdrawal as a worse experience than opioid withdrawal. Greater severity of withdrawal symptoms has been associated with use of high dosages, use of multiple benzodiazepines, and oral rather than injected use [Seivewright and Dougal, 1993].

There is no evidence for the value of substitute prescribing of benzodiazepines in people on methadone or buprenorphine maintenance treatment [Ford et al, 2005]. Most research on benzodiazepines has been done on psychiatric patients and should be interpreted with caution:

Short-term prescribing (less than 6 months) of 30 mg or less of diazepam may have some benefit in supporting drug misusers to control their intake.

Long-term prescribing of benzodiazepines is of uncertain benefit and may be harmful.

Regular therapeutic doses of benzodiazepines may result in anterograde amnesia [Maczaj, 1993].

Many drug services in both primary and secondary care refuse to prescribe benzodiazepine, but ignoring the problem does not make it go away [Ford et al, 2005]. However, as there is no evidence for benefit and there is concern about potential harm from long-term use, it is important that great care should be taken before starting a prescription for benzodiazepines.

Managing people also taking cocaine/crack

How should I manage people who are also taking cocaine/crack?

Offer referral to a professional with expertise in the management of people using cocaine/crack.

Offer harm-reduction advice and support. Warn that taking cocaine/crack can cause severe medical problems and is especially dangerous if taken with other drugs. Methadone and buprenorphine users are at particular risk of overdose if they use crack on top.

See Cocaine and crack for more information on assessment and management.

Cocaine and crack

Cocaine and crack

Cocaine/crack comes from the leaves of the coca plant and is taken in three main forms:

Cocaine hydrochloride — the leaves are processed to make cocaine hydrochloride powder, which is usually snorted but can also be injected or rubbed onto the gums.

Crack — cocaine hydrochloride powder can be heated in a microwave with bicarbonate of soda and water to make crack, which is usually smoked but can also be injected (by adding an acid).

Freebase cocaine — cocaine hydrochloride is heated with ammonia and water. Freebase cocaine is extracted with ether and is mainly smoked.

The following user categories are very generalized and may overlap:

Recreational users take small amounts infrequently on social occasions.

Binge or problematic users take large quantities in isolation, which is potentially life-threatening.

Chronic high-dose-dependent users consume as much as possible, with potential life-threatening consequences.

The effects of cocaine/crack are as follows:

Cocaine is a stimulant drug and users feel more alert, energetic, confident, and physically strong. The after-effects of crack use may include fatigue, depression, paranoid ideation, and depersonalization as the person 'comes down' from the high. People who have a severe come-down, with anxiety and paranoia, may need to use heroin to cope with the come-down from the crack.

Excessive doses can cause severe medical problems (e.g. pulmonary oedema, heart failure, myocardial infarction, cerebral haemorrhage, stroke, hyperthermia, and death).

Chronic high-dose users, particularly of crack, are likely to need treatment for a large range of physical and psychological problems. Some physical and marked psychological dependence can occur.

There may be a link with stillbirths, miscarriages, premature labour, low birthweight, and small-for-dates babies. The baby may suffer agitation and apnoea at birth.

Cocaine/crack can be very dangerous when taken with other drugs:

Methadone and buprenorphine users are at particular risk of overdose if they use crack on top. Methadone and buprenorphine act as suppressants, whereas crack is a stimulant. Taking both together does not achieve the anticipated 'high', and the person may be tempted to increase the amount of crack taken and therefore may be at risk of overdose.

Injecting heroin and cocaine together (speedballing) increases the risk of overdose, as it is difficult to assess the effect of each drug individually.

Alcohol and cocaine taken together produce cocaethylene, which increases the risk of liver and heart disease, stroke, and epilepsy.

Heavy cannabis use with crack may increase the risk of paranoid ideation.

Ketamine and sildenafil can complicate the effects of crack on the cardiovascular and central nervous systems.

The person may present:

As an acute crisis due to the effects of an overdose, with agitation, confusion, and visual or auditory hallucinations.

With paranoia, depression, or after a suicide threat or attempt.

With specific symptoms such as chest pains, breathing difficulties, and weight loss.

While already attending for opioid dependence, and where cocaine/crack use is a new problem.

Principles of management for a professional with expertise in the management of people taking cocaine/crack:

Assess fully and develop a treatment plan.

Involve local integrated shared-care pathways.

Provide harm-reduction advice, particularly in order to reduce crack-related harm.

Only use prescribed medication as part of a package of care:

Benzodiazepines may be useful to help the come-down from the agitated state that can result from a binge, to relax and help sleep. They should not be prescribed for more than 2 weeks.

Antidepressants should only be initiated once cocaine use has ceased, if underlying depression is confirmed.

Propanolol may reduce anxiety and relapse rate. It can be used during withdrawal.

In people who use both heroin and crack, and who need heroin to cope with the severe come-down from crack, naltrexone may be more beneficial in preventing relapse to both drugs [Kosten et al, 1989].

Psychological interventions may be helpful.

Switching substitution treatment

When and how should I switch substitution treatment?

Consider switching from methadone to buprenorphine or buprenorphine to methadone if either drug has a clear advantage over the other.

Indications for changing maintenance drug

What are the indications for changing to a different maintenance treatment drug?

As with the rest of clinical practice it is important that practitioners should only treat and prescribe within their competence.

Drug users have multiple needs and it is important that GPs work with others to help deliver effective care to them.

Advise people who are doing well on methadone or buprenorphine maintenance treatment that they should remain on their medication.

Discuss with people that they may need to change from methadone to buprenorphine if:

They have a preference for the 'clear head' response often reported with buprenorphine in contrast to the 'clouding' sometimes associated with methadone.

They have previously had problems with using heroin 'on top' of maintenance methadone treatment and wish to stop using heroin completely. The blockade is dose-related and the effect of even moderate-dose buprenorphine interferes with the subjective effects of heroin use.

They experience unwanted effects (such as nausea, vomiting, constipation, and drowsiness) or difficulties (such as a 'clouding' effect in the mind, sore leg muscles) with methadone.

Discuss with people that they may need to transfer from buprenorphine to methadone if they:

Have an inadequate treatment response.

Experience intolerable adverse effects.

Need other opioids for pain control.

Are moving to an area where buprenorphine is not used.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion in national guidance by the Royal College of General Practitioners [RCGP, 2004a; RCGP, 2005c].

Switching from methadone to buprenorphine

How should I switch someone on methadone maintenance to buprenorphine maintenance?

For people on 30 mg or less of methadone daily, see Starting maintenance treatment with buprenorphine.

Changing people to buprenorphine from methadone doses in the range 30 mg to 60 mg should only be undertaken in intermediate or specialist service, or if the doctor has necessary experience. For people on 30 mg to 60 mg of methadone daily:

The methadone dose should be reduced as far as possible without the person becoming unstable or chaotic, and then abruptly stopped.

The first buprenorphine dose should be delayed until the person displays clear signs of withdrawal, which is generally longer than 24–36 hours, but may be as long as 48–96 hours after the last methadone dose. Symptomatic medication, such as lofexidine, may be useful to provide the person with some transitory relief. As with the rest of clinical practice it is important that practitioners should only treat and prescribe within their level of competence.

An initial dose of 4 mg of buprenorphine should be given, and the person should be reviewed 2–3 hours later.

If there has been no precipitation or worsening of withdrawal, an additional 2 mg to 4 mg of buprenorphine can be dispensed on the same day.

The person should be reviewed the following day, at which point the dose should be increased to 8–12 mg. Thereafter, titration should be effected as when starting buprenorphine in people who were taking street heroin — see Starting maintenance treatment with buprenorphine.

Refer people on more than 60 mg of methadone daily and wanting to change to buprenorphine to the local specialist drug service.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Royal College of General Practitioners [RCGP, 2004a].

Switching from buprenorphine to methadone

How should I switch someone on buprenorphine maintenance to methadone maintenance?

If a person is stable on buprenorphine, methadone can be commenced 24 hours after the last dose, at an initial daily dose of up to 40 mg. Always be aware of the risk of overdose if the higher starting doses are used especially if there is uncertainty about the reliability of the reported dose or if the drug user may be using 'on top'.

Methadone should be titrated according to the person's response, taking into account the long half-life and the residual partial antagonist action of buprenorphine, which may persist for several days. Proposed starting doses for switching from buprenorphine to methadone:

Buprenorphine dose > 8 mg, proposed starting dose of methadone 40 mg.

Buprenorphine dose 4 mg, proposed starting dose of methadone 20 mg.

Buprenorphine dose 2 mg, proposed starting dose of methadone 10 mg.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Royal College of General Practitioners [RCGP, 2004a].

Scenario: Detoxification - from maintenance therapy

Scenario: Detoxification - from maintenance therapy

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Considerations before starting detoxification

What points should I consider before starting detoxification?

For those suitably experienced, these are the issues that should be considered:

As with the rest of clinical practice it is important that practitioners should only treat and prescribe within their level of competence.

If detoxification is requested, discuss goals, a starting date, and aftercare plan, including the extra support needed (e.g. what sort of support will enable the person to get through the programme and prevent relapse). Detoxification should be seen as part of a package, which will include relapse prevention, counselling, rehabilitation, and ongoing support. Maintaining engagement with services after detoxification is important. Offer continued support and monitoring for at least 6 months after opioid detoxification.

It is important that there is a clear distinction between maintenance and detoxification so that the person does not slip between the two. In other words, it is important to avoid a situation whereby a lower level of substitute drug is reached and the person stays on this dose long-term, using illicit drugs 'on top' and deluding themselves that they are still in detoxification.

Detoxification should be planned and continued at a pace judged appropriate by the drug misuser, after clinical assessment and jointly agreed treatment goals have been set.

It is essential that the person is highly motivated to abstain from opioids and has circumstances that are conducive to maintaining abstinence. See Deciding between maintenance therapy or detoxification.

Ensure that the person is in a stable supportive social situation or is able to go into one following detoxification.

If the person decides to try detoxification, advise:

About the risks of overdose due to loss of tolerance and the ensuing increased risk of overdose and death from illicit drug use that may be potentiated by the use of alcohol or benzodiazepines.

About the importance of continued support, as well as psychosocial and appropriate pharmacological interventions, to maintain abstinence, treat comorbid mental health problems and reduce the risk of adverse outcomes (including death).

That maintenance treatment may be necessary, and should not be considered a failure.

Help the service user to identify situations or states when they would be vulnerable to drug misuse and explore alternative coping strategies with them.

Consider if supervised consumption would be helpful.

Routinely offer a community-based programme to all people considering opioid detoxification. Exceptions to this include service users who have not benefited from previous formal community-based detoxification, need medical or nursing care because of physical or mental health problems, require polydrug detoxification, or have social problems sufficient to limit the benefit of community-based detoxification.

Provide information about self-help groups (such as 12-step groups) and support groups (such as the Alliance). Consider facilitating engagement with such services.

If the person is currently misusing alcohol, then alcohol detoxification should be offered. This should be carried out before starting opioid detoxification in the community.

If the person is dependent on benzodiazepines, then benzodiazepine detoxification should be offered. Whether or not this is carried out at the same time as the opioid detoxification will depend on the person's preferences and the degree of dependence on both substances.

Do not reduce dosage without discussion and in most cases agreement with the person.

Do not routinely offer rapid or accelerated detoxification, and never offer ultra-rapid detoxification.

Consider contingency management (agreeing suitable incentives and targets in collaboration with the person) both during detoxification and for up to 3–6 months after completion of detoxification.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Royal College of General Practitioners [RCGP, 2005c], the National Institute for Health and Care Excellence [NICE, 2007d] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007].

Detoxification is likely to be successful only if both the person and the doctor agree that it is desirable. Little clinical improvement can be expected if it carried out against the person's wishes. If the person is unlikely to comply, it is best to continue with the existing stable regimen [RCGP, 2005b; RCGP, 2005c].

Most individuals are mildly anxious about the possibility of withdrawal symptoms. However, about a third of people on methadone maintenance treatment report a phobia-like fear of detoxification [Milby et al, 1986].

Slow reduction of methadone without consent is completely ineffective and should not be done. If a person does not wish to reduce, then continue at an optimal maintenance dose for as long as necessary [Ford, Personal Communication, 2003].

Many people will relapse, as heroin addiction is a chronic relapsing disorder [O'Brien and McLellan, 1996].

Studies on inpatient opiate detoxification and its outcomes are relatively rare. In general, they report higher rates of successful completion of treatment than outpatient-focused studies [Day, 2005]. However, studies have been small, with methodological problems. Residential or inpatient detoxification requires more resources than community detoxification, and research is needed on whether detoxification in such settings is clinically and cost effective and whether there are subgroups of opioid misusers who would benefit from detoxification in these settings [NICE, 2007d].

Evidence from five randomized controlled trials (n = 417, one trial quasi-randomized) suggested that people receiving contingency management were more likely to be abstinent at the end of treatment (31.1% vs. 16.6%; relative risk 1.86, 95% CI 1.18 to 2.16) and to complete treatment (61.5% vs. 38.3%; relative risk 1.60, 95% CI 1.18 to 2.16). This effect was found for short-term interventions (for example, 2 weeks) and those of longer duration (for example, 6 months) [National Collaborating Centre for Mental Health, 2007a].

Ultra-rapid detoxification under general anaesthesia or heavy sedation (where the airway needs to be supported) should never be offered because of the risk of serous adverse effects, including death [NICE, 2007d].

Rapid detoxification using precipitated withdrawal should not be offered routinely because of the complex adjunctive medication and the high level of nursing and medical supervision required [NICE, 2007d].

Accelerated detoxification using opioid antagonists at lower doses to shorten detoxification should not be offered routinely because of the increased severity of withdrawal symptoms and the risks associated with the increased use of adjunctive medications [NICE, 2007d].

Drugs recommended

What drugs are recommended for detoxification from maintenance therapy?

Offer methadone or buprenorphine as first-line treatment in opioid detoxification, taking into account:

The type of opioid that the person is currently taking for maintenance therapy (detoxification would normally be started with the same opioid).

The person's preference.

If buprenorphine is to be used for detoxification, the dose of methadone should first be reduced to 30 mg/day or less.

Naltrexone may be an option in some highly-motivated people if the primary healthcare professional has the necessary experience.

Suboxone, dihydrocodeine, and clonidine are not routinely recommended for detoxification from maintenance. See Drugs not routinely recommended.

Basis for recommendation

Basis for recommendation

The basis for these recommendations is expert opinion from the Royal College of General Practitioners [RCGP, 2004a; RCGP, 2005c], the National Institute for Health and Care Excellence [National Collaborating Centre for Mental Health, 2007a] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007].

Buprenorphine has mixed agonist and antagonist properties, which potentially makes it a good drug for the management of opioid withdrawal.

Although lofexidine may be used for the management of opioid withdrawal, we do not recommend its use in people on maintenance therapy because:

The evidence for its effectiveness is poor, especially when used alone [DH and Devolved Administrations, 2007].

It is probably only effective in people who are using small amounts of opioids and are keen to achieve abstinence [DH and Devolved Administrations, 2007].

It is not commonly used in primary care.

Buprenorphine and methadone both have the advantage over lofexidine of also being suitable for maintenance treatment if the person is unable to complete detoxification, and needs to return to maintenance treatment.

Detoxification from methadone maintenance

How does a person undergo detoxification from methadone maintenance?

Ensure that a full assessment has been carried out and a discussion of general considerations.

Explain that the duration of detoxification regimens using methadone are usually weeks or months in primary care.

Suggest a dose reduction of about 5 mg methadone every week or two.

Adjust the rate depending on the severity of the withdrawal symptoms. As the daily dose of methadone decreases, smaller reductions in dosage should be made, to reduce the severity of withdrawal and risk of relapse. It may be necessary to hold the stage of detoxification steady at a given dose over a few weeks (or, more rarely, a few days) to allow the withdrawal symptoms to subside and to allow the person's body to adapt to the reduced dose, anxiety to decrease, and sense of control to increase.

It is important that there is a clear distinction between maintenance and detoxification so that the person does not slip between the two. This may occur if the reduction rate is too slow and the person becomes unstable on the reduced dose. It is important to avoid a situation whereby a lower level of substitute drug is reached and the user stays on this dose long-term using illicit drugs 'on top' and therefore failing to achieve their detoxification goals. In this situation, increase the dose of methadone until illicit drug use has stopped, and then restart a slow reduction in methadone dose.

At the later stages of detoxification, symptomatic treatments, such as anti-diarrhoeal medication, nonsteroidal anti-inflammatory drugs, hypnotics, or anxiolytics, may be helpful. Advise that the person may feel withdrawal symptoms 2–3 days after stopping the final dose (due to the long half-life of methadone).

Detoxification with buprenorphine for the final stages may be preferred. Switch to buprenorphine when a daily dose of 30 mg methadone has been reached and the person is stabilized (see Starting maintenance treatment with buprenorphine). Once stable on buprenorphine, the person should remain on that dose for 2–3 days and then the dose of buprenorphine may be reduced by 2 mg per day over 5–10 days. A more rapid detoxification regimen should only be attempted after specialist advice.

Dose reductions

Dose reductions

Reductions of about 5 mg methadone every week or two are recommended, but these are dependent on the person and will vary.

Methadone doses can be reduced at any time interval (e.g. daily, alternate days, weekly), with the rate depending on the severity of the withdrawal symptoms.

Most people find gradual dose reduction down to 20 mg to 30 mg methadone relatively easy, but coming off the last bit more difficult because of chronic mild withdrawal symptoms following every dose reduction. If problematic withdrawal symptoms occur at lower doses, consider switching to a more rapid detoxification with buprenorphine or lofexidine (see Switching from methadone to buprenorphine).

Basis for recommendation

Basis for recommendation

The basis for these recommendations is expert advice from the Royal College of General Practitioners [RCGP, 2005c] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007], and advice from experts in the field [Ford, Personal Communication, 2006; Law, Personal Communication, 2006].

There is no evidence from three randomized controlled trials to suggest that a long methadone taper (up to 70 days) is any better than a shorter programme (of 14 or 21 days). However, the duration of detoxification is usually up to 12 weeks in a community setting [National Collaborating Centre for Mental Health, 2007a].

People often prefer a faster reduction at the beginning, although there is no research evidence to indicate the superiority of a linear or exponential dose reduction [DH and Devolved Administrations, 2007].

Detoxification from buprenorphine maintenance

How does a person undergo detoxification from buprenorphine maintenance?

For a gradual dose-reduction schedule of buprenorphine during detoxification, see Table 1.

Many people do not experience significant withdrawal discomfort until they have reduced to low doses of buprenorphine or until after it has been stopped. Withdrawal symptoms are worse after buprenorphine maintenance treatment of 6 months or longer.

Table 1 . Proposed schedule for detoxification using buprenorphine.
Daily buprenorphine dose Reduction rate
Above 16 mg 4 mg every 1–2 weeks
8 mg to 16 mg 2 mg to 4 mg every 1–2 weeks
2 mg to 8 mg 2 mg every 1–2 weeks
Below 2 mg 0.4 mg to 0.8 mg every 1–2 weeks

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Royal College of General Practitioners [RCGP, 2004a].

The role of naltrexone in detoxification

What is the role of naltrexone in detoxification?

As with the rest of clinical practice, it is important that practitioners should only treat and prescribe within their level of competence and seek advice when necessary.

Consider using naltrexone in highly motivated people who wish to remain opioid-free.

Check liver function tests before starting naltrexone and during treatment.

Start naltrexone only if the person has been opioid-free for at least 7–10 days (7–14 days for methadone).

If there is uncertainty about whether the person is opioid free then make arrangements for a naloxone challenge test to be done.

Where appropriate involve carers to ensure compliance with treatment.

For more information, see Additional information.

Additional information

Additional information

Naltrexone is an opioid antagonist which, when taken regularly, blocks a former opiate user from experiencing the effects of opiates. It can be helpful following detoxification in enabling a patient to maintain abstinence. It is recommended as a treatment option in people who have successfully completed detoxification (i.e. formerly opioid-dependent people). It should only be started as part of a programme of supportive care:

Naltrexone is suitable for highly motivated people who wish to remain abstinent.

Naltrexone should only be administered under adequate supervision to people who have been fully informed of the potential adverse effects of treatment. Warn that it is dangerous to attempt to overcome the antagonistic effect of the drug by using large doses of an opioid agonist, such as heroin (coma and death can occur as the effect of naltrexone decreases).

The effectiveness of naltrexone should be reviewed regularly. If it is not proving to be effective, or if there is evidence of further drug misuse, discontinuation should be considered.

If there is uncertainty about whether the person has used opioids recently, then it may be necessary to conduct a naloxone dose challenge before giving naltrexone. A withdrawal syndrome precipitated by naloxone will be of shorter duration than one precipitated by naltrexone.

If the person needs supervision it may not be practical to carry out a challenge test in primary care.

Naloxone challenge test:

Check that a recent urine test or oral fluid test is negative for opioids.

Check that the person is not experiencing any withdrawal symptoms or signs.

Give naloxone 200 micrograms intravenously.

If after 30 seconds no adverse reactions occur a further intravenous dose of 600 micrograms of naloxone may be given.

Observe the person continuously for 30 minutes for withdrawal symptoms.

If symptoms of withdrawal occur then naltrexone must not be given.

If any doubt exists that the person is opioid free then the naloxone challenge may be repeated with a dosage of 1.6 mg.

If the person does not experience any withdrawal symptoms after a few hours, give naltrexone at a starting dose of 25 mg.

If there are no symptoms of withdrawal then the usual maintenance dose is 50 mg per day may be started the next day.

Naloxone may also be given as a challenge at a dose of 400 micrograms of naloxone intramuscularly or subcutaneously.

Some experts recommend a challenge using 25 mg of naltrexone instead of naloxone with supervision for 2 hours afterwards.

Basis for recommendation

Basis for recommendation

These recommendations are based expert opinion in a technology appraisal guidance [NICE, 2007a], national guidance from the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007], a Health Technology Assessment [Adi et al, 2007] and information from UK manufacturers of naltrexone [ABPI Medicines Compendium, 2005; ABPI Medicines Compendium, 2007].

Naltrexone is an opioid antagonist, and competitively inhibits opioid agonists, such as diamorphine and methadone. It blocks the euphoric effect of these drugs, thereby minimizing the reward associated with them.

The effectiveness of naltrexone in maintaining abstinence from opioids has been investigated by the National Institute for Health and Care Excellence, who identified 17 relevant studies: a Cochrane review, 13 randomized controlled trials, and 3 non-randomized comparative studies. Overall the quality of these studies was found to be poor, with conflicting results. However, when results were pooled in a meta-analysis, naltrexone was found to be significantly associated with a reduction in relapse.

The NICE Technology appraisal states: In summary, the Committee was convinced of the clinical effectiveness of naltrexone treatment in a selected, highly motivated group of people. The committee concluded that for people who preferred an abstinence programme, who were fully informed of the potential adverse effects and benefits of treatment, and who were highly motivated to remain on treatment, naltrexone treatment would fall within acceptable cost-effectiveness limits [NICE, 2007a].

Naltrexone is associated with opioid withdrawal symptoms if people are opioid dependent. Severe and prolonged withdrawal symptoms will occur if the person has taken opioids and naltrexone is administered. A challenge test with naloxone hydrochloride (a shorter-acting injectable opioid antagonist) should be done to screen for the presence of opioids if it is not certain whether the person is detoxified.

Some experts recommend using naltrexone in a dose of 25 mg as a challenge instead of naloxone [DH and Devolved Administrations, 2007; Gallagher, Personal Communication, 2008].

People may be at risk of a fatal overdose caused by respiratory depression if they relapse while taking naltrexone. This can happen if the person tries a larger dose of diamorphine to achieve euphoria, or if they return to diamorphine use after naltrexone treatment, because of loss of tolerance to diamorphine [Adi et al, 2007].

Drugs not routinely recommended

What drugs are not routinely recommended for detoxification?

Naltrexone is not licensed for detoxification, but is licensed as an adjunct to prevent relapse in detoxified formerly opioid-dependent people.

However, some services, particularly in the private sector, may induct people onto naltrexone treatment using rapid assisted withdrawal techniques (using heavy sedation or anaesthesia).

In these cases the people or services involved may request, at short notice, ongoing maintenance prescribing of naltrexone.

The value of naltrexone in ultra-rapid detoxification procedures remains controversial.

Dihydrocodeine is not licensed for the treatment of drug dependence, and is not recommended for use in primary care. It is associated with problems of abuse on the street.

Dihydrocodeine may occasionally be prescribed for people unable or unwilling to consider or tolerate methadone or buprenorphine. However, it should only be prescribed by clinicians with appropriate specialist competencies.

Clonidine is not licensed for detoxification and should not be used routinely in opioid detoxification.

Suboxone® is a combination of buprenorphine and naloxone. Clinical experience with suboxone is extremely limited in the UK, and it is not possible to make recommendations regarding its use at present.

Basis for recommendation

Basis for recommendation

Information on drugs that are not routinely recommended for detoxification in primary care is based on national guidelines [DH and Devolved Administrations, 2007; National Collaborating Centre for Mental Health, 2007b] and a review article [Gossop and Strang, 1997].

Dihydrocodeine

Although, in practice, dihydrocodeine is sometimes prescribed to aid withdrawal in people using illicit dihydrocodeine, it is not a recommended treatment.

The evidence that dihydrocodeine can be used effectively for maintenance is limited, and there is no evidence that it is superior to other opioid medicines. In addition, dihydrocodeine:

Is difficult to supervise.

Is short-acting (requiring frequent dosing).

Can be easily diverted.

Clonidine

The recommendation that clonidine should not be used routinely in opioid detoxification is from expert opinion [National Collaborating Centre for Mental Health, 2007a].

Suboxone

When taken sublingually as intended, the naloxone has very low bioavailability and does not diminish the therapeutic effect of the buprenorphine. However, if injected, the naloxone has high bioavailability and is liable to precipitate withdrawal in an opioid-dependent person.

Suboxone® is available for prescription using a FP10 MDA form [Prunty, 2007]. CKS recommends it should only be prescribed under the advice of people experienced with its use.

The 'Orange Book' states that 'clinical experience with this new combination product is, at the time of publication, extremely limited in the UK, and it is too early to indicate the relative positions of these two versions of buprenorphine' [DH and Devolved Administrations, 2007].

Suboxone® is a black-triangle drug and is significantly more expensive compared with standard buprenorphine.

Support during abstinence

What support should be given during abstinence?

Detoxification should be supported by aftercare because of the high risk of relapse, the loss of tolerance, and the risk of overdose and death.

Ensure that the aftercare plan includes measures that cover possible relapse and ensure a swift access back to treatment if required.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Royal College of General Practitioners [RCGP, 2005c] and the National Treatment Agency [NTA, 2006b]:

One study found that death is more common in people who have successfully completed detoxification than in those who failed to complete detoxification. Opioid detoxification in 137 people was followed up for an average of 9 months as part of an inpatient 28-day treatment programme [Strang et al, 2003]:

The majority of people (100) either failed to complete detoxification (43 people) or prematurely left the treatment programme (57 people).

Only 37 of 157 people successfully completed the inpatient detoxification and therefore lost their tolerance to opioids. The only deaths from overdose (3 people) were in this group.

Withdrawal and detoxification regimens have a high failure rate unless linked to long-term rehabilitation [DH, 1999]. Continuation of supportive counselling both during detoxification and after cessation of methadone reduces the risk of relapse [McAuliffe, 1990; Amato et al, 2005].

Opioid dependence is a chronic relapsing disorder, and cravings and relapses are common.

Follow up in detoxification

What follow up is recommended in a person undergoing detoxification?

Review at intervals, determined by the speed of withdrawal and the supportive care available from the shared-care team.

If lofexidine is used arrange for the person to be reviewed daily for blood pressure monitoring in the early stages of treatment as hypotension and bradycardia can be clinically significant.

Review, according to clinical judgement and the person's wishes, once a person is off opioids, to address any outstanding or new problems. A follow-up appointment at 3 months is advisable.

Advise that relapse is common and that it is in the person's own interests to seek help as soon as possible.

Basis for recommendation

Basis for recommendation

The basis for these recommendations is pragmatic advice.

Managing relapse

How should I help people who have relapsed?

Establish what precipitated the relapse, what prompted the person to consult, and their expectations and goals.

Consider restarting substitution therapy. This may be best carried out in consultation with the local drug dependency service. See Initial assessment, Starting and stabilizing on maintenance therapy, and Acute withdrawal syndrome.

Basis for recommendation

Basis for recommendation

These are pragmatic recommendations based on usual clinical practice.

It is important that the aftercare plan should include measures that cover possible relapse and ensure swift access back to treatment if required. The aftercare plan must be passed from the drug treatment agency to the agencies responsible for delivering the aftercare, and key staff in this agency should ensure that the plan is implemented and clients receive what is outlined in the aftercare plan [NTA, 2006b].

Scenario: Detoxification - not on maintenance therapy

Scenario: Detoxification - not on maintenance therapy

192months3060monthsBoth

Considerations before starting detoxification

What points should I consider before starting detoxification in a person taking street heroin?

For those suitably experienced, these are the issues that should be considered:

As with the rest of clinical practice it is important that practitioners should only treat and prescribe within their level of competence.

If detoxification is requested, discuss goals, a starting date, and aftercare plan, including the extra support needed (e.g. what sort of support will enable the person to get through the programme and prevent relapse). Detoxification should be seen as part of a package, which will include relapse prevention, counselling, rehabilitation, and ongoing support. Maintaining engagement with services after detoxification is important. Offer continued support and monitoring for at least 6 months after opioid detoxification.

It is essential that the person is highly motivated to abstain from opioids and has circumstances that are conducive to maintaining abstinence. see Deciding between maintenance therapy or detoxification.

Ensure that the person is in a stable supportive social situation or is able to go into one following detoxification.

If the person decides to try detoxification, advise:

About the risks of overdose due to loss of tolerance and the ensuing increased risk of overdose and death from illicit drug use that may be potentiated by the use of alcohol or benzodiazepines.

About the importance of continued support, as well as psychosocial and appropriate pharmacological interventions, to maintain abstinence, treat comorbid mental health problems and reduce the risk of adverse outcomes (including death).

That maintenance treatment may be necessary, and should not be considered a failure.

That all cases of drug misuse must be reported anonymously to the regional National Drug Treatment Monitoring System (NDTMS) if in England, and to the national centre if in Scotland or Wales, when they start treatment.

Help the service user to identify situations or states when they would be vulnerable to drug misuse and explore alternative coping strategies with them.

Consider if supervised consumption would be helpful.

Routinely offer a community-based programme to all people considering opioid detoxification. Exceptions to this include service users who have not benefited from previous formal community-based detoxification, need medical or nursing care because of physical or mental health problems, require polydrug detoxification, or have social problems sufficient to limit the benefit of community-based detoxification.

Provide information about self-help groups (such as 12-step groups) and support groups (such as the Alliance). Consider facilitating engagement with such services.

If the person is currently misusing alcohol, then alcohol detoxification should be offered. This should be carried out before starting opioid detoxification in the community.

If the person is dependent on benzodiazepines, then benzodiazepine detoxification should be offered. Whether or not this is carried out at the same time as the opioid detoxification will depend on the person's preferences and the degree of dependence on both substances.

Do not reduce dosage without discussion and in most cases agreement with the person.

Do not routinely offer rapid or accelerated detoxification, and never offer ultra-rapid detoxification.

Consider contingency management (agreeing suitable incentives and targets in collaboration with the person) both during detoxification and for up to 3–6 months after completion of detoxification.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Royal College of General Practitioners [RCGP, 2005c], the National Institute for Health and Care Excellence [NICE, 2007d] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007].

Detoxification is likely to be successful only if both the person and the doctor agree that it is desirable. Little clinical improvement can be expected if it carried out against the person's wishes. If the person is unlikely to comply, it is best to continue with the existing stable regimen [RCGP, 2005b; RCGP, 2005c].

Most individuals are mildly anxious about the possibility of withdrawal symptoms. However, about a third of people on methadone maintenance treatment report a phobia-like fear of detoxification [Milby et al, 1986].

Slow reduction of methadone without consent is completely ineffective and should not be done. If a person does not wish to reduce, then continue at an optimal maintenance dose for as long as necessary [Ford, Personal Communication, 2003].

Many people will relapse, as heroin addiction is a chronic relapsing disorder [O'Brien and McLellan, 1996].

Studies on inpatient opiate detoxification and its outcomes are relatively rare. In general, they report higher rates of successful completion of treatment than outpatient-focused studies [Day, 2005]. However, studies have been small, with methodological problems. Residential or inpatient detoxification requires more resources than community detoxification, and research is needed on whether detoxification in such settings is clinically and cost effective and whether there are subgroups of opioid misusers who would benefit from detoxification in these settings [NICE, 2007d].

Evidence from five randomized controlled trials (n = 417, one trial quasi-randomized) suggested that people receiving contingency management were more likely to be abstinent at the end of treatment (31.1% vs. 16.6%; relative risk 1.86, 95% CI 1.18 to 2.16) and to complete treatment (61.5% vs. 38.3%; relative risk 1.60, 95% CI 1.18 to 2.16). This effect was found for short-term interventions (for example, 2 weeks) and those of longer duration (for example, 6 months) [National Collaborating Centre for Mental Health, 2007a].

Ultra-rapid detoxification under general anaesthesia or heavy sedation (where the airway needs to be supported) should never be offered because of the risk of serous adverse effects, including death [NICE, 2007d].

Rapid detoxification using precipitated withdrawal should not be offered routinely because of the complex adjunctive medication and the high level of nursing and medical supervision required [NICE, 2007d].

Accelerated detoxification using opioid antagonists at lower doses to shorten detoxification should not be offered routinely because of the increased severity of withdrawal symptoms and the risks associated with the increased use of adjunctive medications [NICE, 2007d].

Drugs recommended for detoxification from street heroin

What drugs are recommended for detoxification from street heroin?

Some people may wish to undergo detoxification without first being stabilised on substitution therapy. In this situation there are two drugs that are preferred:

Buprenorphine is the drug of choice.

Lofexidine is sometimes used. Lofexidine therapy is most likely to be successful in people who have shorter drug and treatment histories, have made an informed and clinically appropriate decision not to use methadone or buprenorphine for substitution treatment or detoxification, wish to detoxify within a short time period, or have mild or uncertain dependence (including young people).

Methadone is not a good drug for detoxification from street heroin.

Basis for recommendation

Basis for recommendation

The basis for these recommendations is expert opinion from the Royal College of General Practitioners [RCGP, 2005c], the National Institute for Health and Care Excellence [National Collaborating Centre for Mental Health, 2007a] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007] and expert reviewers [Ford, Personal Communication, 2006; Law, Personal Communication, 2006].

Prescribing buprenorphine for detoxification from street heroin

How should I prescribe buprenorphine for someone on street heroin who wants to undergo detoxification?

Buprenorphine detoxification may be carried out at different rates according to the person's preference, drug use, and history, although expert opinion is that detoxification should happen very fast over a 10-day period (see Table 1) or more slowly (2 mg to 4 mg per week). The dose of buprenorphine determines the speed of reduction:

With higher doses, reduction can be fast.

With middle-range doses, the reduction is slower.

With lower doses, reduction may be faster, particularly when aided by lofexidine.

Table 1 . Proposed schedule for very fast detoxification from heroin using buprenorphine.
Day of detoxification 1 2 3 4 5 6 7 8 9 10 11
Buprenorphine dose (mg) in low/moderate-dose users (1 g heroin or less) 4 6 8 10 8 6 4 2 0.8 0.4 stop
Buprenorphine dose (mg) in high-dose users (more than 1 g heroin) 4 8 12 16 12 8 4 2 0.8 0.4 stop
Data from: [Law, Personal Communication, 2006]

Expert opinion differs on whether or not diazepam should be given. It should only be given as part of an agreed detoxification schedule in people who are not known to abuse it. Benzodiazepines do not reduce the severity of withdrawal symptoms, but help the person feel better. Diazepam may be appropriate in someone with acute withdrawal who is requesting detoxification with buprenorphine rather than maintenance treatment. When diazepam is prescribed as part of the management of illicit drug use, it should be issued on the FP10MDA-SS (blue) prescription form for daily pick-up from the pharmacy:

The person must be in withdrawal before buprenorphine can be commenced, and will often be agitated.

Diazepam (10 mg to 20 mg) can be taken the night before detoxification with buprenorphine is started.

A second dose (10 mg to 20 mg) may be taken the following night, but it is very rare that any further doses will be needed.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion [Ford, Personal Communication, 2006; Law, Personal Communication, 2006].

Prescribing lofexidine for detoxification

How should lofexidine be prescribed for detoxification?

Lofexidine needs to be monitored carefully. The blood pressure and pulse rate should be measured daily while the dose is increasing, so it may not be ideal for use in general practice. As with the rest of clinical practice it is important that practitioners should only treat and prescribe within their level of competence.

Treat for 7–10 days with doses starting at 800 micrograms daily and rising to a maximum of 2.4 mg daily in divided doses.

The dose is then reduced over subsequent days.

See the person daily in the early stages of treatment for blood pressure monitoring as hypotension and bradycardia can be clinically significant.

Prescribe additional short-term medication if needed to control symptoms of opioid withdrawal. See Treatments for symptoms of acute withdrawal.

Drowsiness and a dry mouth may occur. Sedation is made worse by alcohol.

Basis for recommendation

Basis for recommendation

This recommendation is based on expert advice from the National Institute for Health and Care Excellence [NICE, 2007d] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007].

Prescribing methadone for detoxification from street heroin

How should I prescribe methadone for detoxification from street heroin?

Methadone is not a good drug to use for detoxification from street heroin.

Some clinicians and their patients may choose to use methadone. This requires titration of the dose until symptoms and signs of withdrawal have disappeared (see Starting maintenance treatment with methadone) and then a reduction at a speed dependent on the individual person but usually reducing the dose by 5 mg weekly. It is also possible to reduce to a dose of methadone 30 mg/day or less and then switching to buprenorphine for the final reduction. See Starting maintenance treatment with buprenorphine.

Basis for recommendation

Basis for recommendation

Methadone is the standard treatment for people who are taking maintenance treatment but is less preferred for detoxification [RCGP, 2005b; Ford, Personal Communication, 2006].

Methadone is more commonly used for maintenance rather that detoxification. Our reviewers stressed that buprenorphine is the first choice drug for detoxification. Withdrawing from methadone is a reduction leading to abstinence rather than a detoxification. The suggested regime is based on feedback from expert reviewers.

Follow up in detoxification

What follow up is recommended in a person undergoing detoxification?

Review at intervals, determined by the speed of withdrawal and the supportive care available from the shared-care team.

Review according to clinical judgement and the person's wishes once a person is off opioids, to address any outstanding or new problems. A follow-up appointment at 3 months is advisable.

Consider the use of naltrexone after detoxification for highly motivated people who wish to remain abstinent.

Advise that relapse is common and that it is in the person's own interests to seek help as soon as possible.

Basis for recommendation

Basis for recommendation

The basis for these recommendations is pragmatic advice.

Support during abstinence

What support should be given during abstinence?

Detoxification should be supported by aftercare because of the high risk of relapse, the loss of tolerance, and the risk of overdose and death.

Ensure that the aftercare plan includes measures that cover possible relapse and a swift access back to treatment if required.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert advice from the Royal College of General Practitioners [RCGP, 2005c] and the National Treatment Agency [NTA, 2006b]:

One study found that death is more common in people who have successfully completed detoxification than in those who failed to complete detoxification. Opioid detoxification in 137 people was followed up for an average of 9 months as part of an inpatient 28-day treatment programme [Strang et al, 2003]:

The majority of people (100) either failed to complete detoxification (43 people) or prematurely left the treatment programme (57 people).

Only 37 of 157 people successfully completed the inpatient detoxification and therefore lost their tolerance to opioids. The only deaths from overdose (3 people) were in this group.

Withdrawal and detoxification regimens have a high failure rate unless linked to long-term rehabilitation [DH, 1999]. Continuation of supportive counselling both during detoxification and after cessation of methadone reduces the risk of relapse [McAuliffe, 1990; Amato et al, 2005].

Opioid dependence is a chronic relapsing disorder, and cravings and relapses are common.

The role of naltrexone in detoxification

What is the role of naltrexone in detoxification?

As with the rest of clinical practice, it is important that practitioners should only treat and prescribe within their level of competence and seek advice when necessary.

Consider using naltrexone in highly motivated people who wish to remain opioid-free.

Check liver function tests before starting naltrexone and during treatment.

Start naltrexone only if the person has been opioid-free for at least 7–10 days (7–14 days for methadone).

If there is uncertainty about whether the person is opioid free then make arrangements for a naloxone challenge test to be done.

Where appropriate involve carers to ensure compliance with treatment.

For more information, see Additional information.

Additional information

Additional information

Naltrexone is an opioid antagonist which, when taken regularly, blocks a former opiate user from experiencing the effects of opiates. It can be helpful following detoxification in enabling a patient to maintain abstinence. It is recommended as a treatment option in people who have successfully completed detoxification (i.e. formerly opioid-dependent people). It should only be started as part of a programme of supportive care:

Naltrexone is suitable for highly motivated people who wish to remain abstinent.

Naltrexone should only be administered under adequate supervision to people who have been fully informed of the potential adverse effects of treatment. Warn that it is dangerous to attempt to overcome the antagonistic effect of the drug by using large doses of an opioid agonist, such as heroin (coma and death can occur as the effect of naltrexone decreases).

The effectiveness of naltrexone should be reviewed regularly. If it is not proving to be effective, or if there is evidence of further drug misuse, discontinuation should be considered.

If there is uncertainty about whether the person has used opioids recently, then it may be necessary to conduct a naloxone dose challenge before giving naltrexone. A withdrawal syndrome precipitated by naloxone will be of shorter duration than one precipitated by naltrexone.

If the person needs supervision it may not be practical to carry out a challenge test in primary care.

Naloxone challenge test:

Check that a recent urine test or oral fluid test is negative for opioids.

Check that the person is not experiencing any withdrawal symptoms or signs.

Give naloxone 200 micrograms intravenously.

If after 30 seconds no adverse reactions occur a further intravenous dose of 600 micrograms of naloxone may be given.

Observe the person continuously for 30 minutes for withdrawal symptoms.

If symptoms of withdrawal occur then naltrexone must not be given.

If any doubt exists that the person is opioid free then the naloxone challenge may be repeated with a dosage of 1.6 mg.

If the person does not experience any withdrawal symptoms after a few hours, give naltrexone at a starting dose of 25 mg.

If there are no symptoms of withdrawal then the usual maintenance dose is 50 mg per day may be started the next day.

Naloxone may also be given as a challenge at a dose of 400 micrograms of naloxone intramuscularly or subcutaneously.

Some experts recommend a challenge using 25 mg of naltrexone instead of naloxone with supervision for 2 hours afterwards.

Basis for recommendation

Basis for recommendation

These recommendations are based expert opinion in a technology appraisal guidance [NICE, 2007a], national guidance from the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007], a Health Technology Assessment [Adi et al, 2007] and information from UK manufacturers of naltrexone [ABPI Medicines Compendium, 2005; ABPI Medicines Compendium, 2007].

Naltrexone is an opioid antagonist, and competitively inhibits opioid agonists, such as diamorphine and methadone. It blocks the euphoric effect of these drugs, thereby minimizing the reward associated with them.

The effectiveness of naltrexone in maintaining abstinence from opioids has been investigated by the National Institute for Health and Care Excellence, who identified 17 relevant studies: a Cochrane review, 13 randomized controlled trials, and 3 non-randomized comparative studies. Overall the quality of these studies was found to be poor, with conflicting results. However, when results were pooled in a meta-analysis, naltrexone was found to be significantly associated with a reduction in relapse.

The NICE Technology appraisal states: In summary, the Committee was convinced of the clinical effectiveness of naltrexone treatment in a selected, highly motivated group of people. The committee concluded that for people who preferred an abstinence programme, who were fully informed of the potential adverse effects and benefits of treatment, and who were highly motivated to remain on treatment, naltrexone treatment would fall within acceptable cost-effectiveness limits [NICE, 2007a].

Naltrexone is associated with opioid withdrawal symptoms if people are opioid dependent. Severe and prolonged withdrawal symptoms will occur if the person has taken opioids and naltrexone is administered. A challenge test with naloxone hydrochloride (a shorter-acting injectable opioid antagonist) should be done to screen for the presence of opioids if it is not certain whether the person is detoxified.

Some experts recommend using naltrexone in a dose of 25 mg as a challenge instead of naloxone [DH and Devolved Administrations, 2007; Gallagher, Personal Communication, 2008].

People may be at risk of a fatal overdose caused by respiratory depression if they relapse while taking naltrexone. This can happen if the person tries a larger dose of diamorphine to achieve euphoria, or if they return to diamorphine use after naltrexone treatment, because of loss of tolerance to diamorphine [Adi et al, 2007].

Scenario: Missed or vomited doses

Scenario: Missed or vomited doses

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Missed doses

What should I do if doses are missed?

Ask the person when they last took a dose of methadone or buprenorphine. If necessary, telephone the supervising pharmacist to clarify the situation.

If a person misses doses of methadone or buprenorphine:

Do not replace the missed doses (i.e. do not give a double dose the next day).

It may be appropriate to assess the person to find out why this occurred, especially if several doses have been missed.

Ensure they are not intoxicated before prescribing.

Assess for symptoms and signs of withdrawal.

Check that people on buprenorphine have not used heroin in the intervening period: if they have the dose must be re-titrated as outlined in the instructions regarding initiation from heroin (see Starting maintenance treatment with buprenorphine).

If a person misses a methadone or buprenorphine dose for:

1, 2, or 3 days: the usual dose may be given.

4 days: it may be appropriate to reduce the dose and titrate back up to the original dose as their tolerance may be reduced or lost. Often the drug misuser claims to have used street drugs, but this can never be verified or the purity known.

5 days or more: the dose should be retitrated to an appropriate maintenance dose (see Starting maintenance treatment with methadone and Starting maintenance treatment with buprenorphine).

It is possible to issue a written directive to the pharmacist for people who are picking up several days' methadone at a time and may miss a pick-up, enabling them to dispense medication on a subsequent day minus the doses for the days missed. As tolerance is lost after 3 days it is advisable to specify that the instalments should be supplied provided no more than 3 days have been missed. It is important to use the correct wording on the prescription:

Instalment prescriptions covering more than one day should be collected on the specified day. If this collection is missed, the remainder of the instalment (i.e. the total amount less the instalments for the days missed) may continue to be supplied in the specified instalments at the stated intervals, provided no more than 3 days are missed.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion from the Royal College of General Practitioners [RCGP, 2004a; RCGP, 2005c] and the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007].

Vomiting following a dose of methadone

What should I do if a person vomits following a dose of methadone?

Ask the person how long the interval was between ingestion of the methadone and vomiting:

If vomiting occurred more than 20 minutes after ingestion, the dose is likely to have been absorbed.

If vomiting occurred within 20 minutes of ingestion:

Review the person 4–6 hours after ingestion.

The presence of withdrawal symptoms and signs suggests inadequate absorption of methadone, as plasma levels of methadone usually peak 4–6 hours after ingestion.

If there is good evidence of opioid withdrawal, consider administering a supplementary dose of half the usual dose.

If you have doubts about the amount of methadone absorbed despite vomiting, it is better to be cautious and not administer additional methadone.

Ask the person to return for review the next day.

Basis for recommendation

Basis for recommendation

The basis for these recommendations is expert opinion in national guidance from Australia [State Government of Victoria, 2000]:

People may vomit after ingesting their methadone dose, creating uncertainty about whether they have absorbed it. Consider the interval between ingestion and vomiting. Methadone is fully absorbed within 20–30 minutes of ingestion. Therefore:

If vomiting occurs more than 20 minutes after ingestion, the methadone is likely to have been absorbed.

Vomiting soon after ingestion may prevent absorption of the methadone, although the person may not vomit all their stomach contents.

Plasma levels of methadone peak 4–6 hours after methadone has been ingested. Therefore, it is advisable to review the person at this time.

Scenario: Acute withdrawal syndrome

Scenario: Acute withdrawal syndrome

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Recognizing acute withdrawal syndrome

How do I recognize an acute withdrawal syndrome?

Diagnose opioid withdrawal by the symptoms and signs:

Symptoms and signs of acute withdrawal include:

Sweating, watering eyes, rhinorrhoea, yawning, feeling hot and cold, goose flesh (goosebumps), dilated pupils, cough.

Anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased bowel sounds.

Tremor, insomnia, restlessness, anxiety, irritability, tachycardia, hypertension.

Generalized aches and pains.

The resolution of acute symptoms is often followed by protracted fatigue, insomnia, and craving for opioids lasting 6 weeks to 6 months or longer.

Heroin withdrawal symptoms reach their peak 36–72 hours after the last dose of heroin. Symptoms will have subsided substantially after 5 days.

Methadone withdrawal symptoms typically reach their peak 2–4 days after the last dose of methadone (4–6 days after stopping high doses). Symptoms do not substantially subside for 10–12 days.

Buprenorphine withdrawal symptoms emerge within 3–5 days after the last dose of buprenorphine, and mild withdrawal features continue for up to several weeks.

Buprenorphine use may cause precipitated withdrawal in someone who has recently used heroin (less than 8 hours previously) or methadone (less than 24 hours previously). This typically occurs 1–3 hours after the first buprenorphine dose, peaking in severity over the first 3–6 hours.

Basis for recommendation

Basis for recommendation

This information is based on expert opinion in national guidance from the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007] and guidelines from Australia [State Government of Victoria, 2000].

Considerations when managing acute withdrawal syndrome

What important points should I consider when managing someone with an acute withdrawal syndrome?

Do not be pressurized into prescribing opioids in an unplanned manner in order to abolish withdrawal symptoms. Remember that it is considered good practice not to do so. Seek specialist advice if needed.

Offer referral to the local drug service for support and to discuss management options.

Use symptomatic treatments to relieve the symptoms.

Consider using lofexidine, which is licensed for the management of symptoms of opioid withdrawal. See Prescribing lofexidine for detoxification.

Check that the person has been fully informed about harm reduction, especially about the dangers of injecting and overdose.

Warn the person about the dangers of overdose if street drugs are used to alleviate symptoms, especially if injected. Explain that loss of tolerance may lead to an unintentional overdose and death.

Basis for recommendation

Basis for recommendation

These recommendations are based on pragmatic advice and expert opinion from the Royal College of General Practitioners [RCGP, 2004a; RCGP, 2005a; RCGP, 2005c].

Treatments for symptoms of acute withdrawal

What symptomatic treatments can I prescribe to help with the symptoms of acute withdrawal?

Consider prescribing symptomatic treatment to help with the symptoms of withdrawal:

Diarrhoea: loperamide or co-phenotrope used in standard doses may be used in the treatment of diarrhoea.

Nausea and or vomiting: metoclopramide (maximum duration of treatment is 5 days) or prochlorperazine.

Stomach cramps: metoclopramide (maximum duration of treatment is 5 days) or mebeverine.

General aches and pains (e.g. headache, muscular pains): paracetamol, ibuprofen or other nonsteroidal anti-inflammatory drugs, or topical rubefacients.

Anxiety, agitation, and sleeplessness: benzodiazepines can be useful if used short term, but care should be taken not to extend prescribing beyond a short period:

Diazepam (for maximum of 2–3 days only) may be appropriate in someone with acute withdrawal who is requesting detoxification with buprenorphine rather than maintenance treatment:

The person must be in withdrawal before buprenorphine can be commenced, and will often be agitated.

Diazepam (10 mg to 20 mg) can be taken the night before detoxification with buprenorphine is started.

A second dose (10 mg to 20 mg) may be taken the following night, but it is very rare that any further doses will be needed.

Warn of the increased risk of an overdose if benzodiazepines are taken with opioids or with alcohol.

Basis for recommendation

Basis for recommendation

These recommendations are based on usual clinical practice, national guidance from the Department of Health and the National Treatment Agency [DH and Devolved Administrations, 2007] and expert opinion [Ford, Personal Communication, 2003].

Duration of treatment of metoclopramide

Following a review by the European Medicines Agency (EMA) metoclopramide should not be taken for longer than 5 days [EMA, 2013]. The EMA review confirmed the well-known risks of neurological effects such as short-term extrapyramidal effects associated with metoclopramide. The risk of acute (short-term) neurological effects is higher in children, although tardive dyskinesia was reported more often in the elderly, and the risk is increased at high doses or with long-term treatment. The EMA states that the risks outweighed the benefits of metoclopramide in conditions requiring long-term treatment. There have also been very rare cases of serious effects on the heart or circulation, particularly after injection.

Scenario: Collapse due to opioid overdose

Scenario: Collapse due to opioid overdose

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Collapse due to opioid overdose

How do I manage someone who has collapsed due to opioid overdose?

Call an ambulance and check for any immediate risks (e.g. discarded used needles).

Start routine emergency lifesaving procedures (i.e. airway, breathing, and circulatory support).

Try to establish if an overdose of opioids is likely to be the cause of the collapse. People may inadvertently take an overdose because of:

Varying purity of illicit supplies.

Reduction in tolerance after a period of abstinence (e.g. release from prison, or discharge from rehabilitation or hospital; recently having stopped naltrexone use).

Mixing drugs (particularly injecting benzodiazepine or cocaine) and drinking alcohol.

Leakage from poorly wrapped drugs that have been ingested (body-stuffers and packers).

Accidentally taking other methadone-containing preparations (diversion of methadone linctus is related to an increasing number of deaths among drug misusers).

Be aware of other causes of coma or collapse (e.g. hypoglycaemia, head injury), particularly if there is no history available from a witness.

Administer naloxone (an opioid antidote):

The British National Formulary recommends naloxone 0.4 mg to 2 mg intravenously, repeated every 2–3 minutes up to a maximum of 10 mg. If respiratory depression does not improve, then question the diagnosis. In practice, most overdoses will respond to 400 micrograms to 800 micrograms naloxone (i.e. 1–2 ampoules). GPs should make a decision on how many ampoules to carry in their emergency bag, based on their local circumstances and ambulance services.

Intramuscular or subcutaneous administration may be necessary if dosing by the intravenous route is not accessible.

If respiratory function does not improve, question the diagnosis and consider other causes of collapse, such as other drug intoxication or other organic causes of loss of consciousness, including hypoglycaemia.

Naloxone is short-acting, and repeated injections or intravenous infusion may be needed if longer-acting opioids, such as dextropropoxyphene, or methadone have been taken.

Buprenorphine is not easily displaced by the opioid antagonist naloxone, and therefore 10–30 times the usual dose of naloxone may be needed to reverse the effects of buprenorphine.

Admit the person to hospital. Intoxication is not in itself sufficient grounds for compulsory admission under the Mental Health Act. If the person is conscious, explain that they should stay in hospital until medical staff judge that discharge is safe.

Explain that the person will need a follow-up appointment for either initial assessment or ongoing assessment as appropriate after discharge from hospital.

Basis for recommendation

Basis for recommendation

These recommendations based on expert advice from the British National Formulary [BNF 53, 2007] and expert opinion [Heyworth, Personal Communication, 2002].

The person should be admitted to hospital for observation because:

The effect of methadone overdose can persist for up to 72 hours.

Naloxone's duration of action is shorter than that of many opioids, and therefore close monitoring with repeated administration of naloxone may be necessary.

Scenario: Travelling abroad

Scenario: Travelling abroad whilst on substitution therapy

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Travelling abroad on substitution therapy

How do I advise someone who is travelling abroad?

Ask the person how long they will be travelling for. Explain that:

People travelling for 3 months or less do not need a personal import/export license to take the methadone or buprenorphine out of the UK and to bring any surplus back.

Only people carrying with them prescribed controlled drugs in schedules 2, 3, and 4 part 1, and travelling abroad for more than 3 months, require a personal import/export licence. See Travelling with controlled drugs.

If a person is staying outside the UK for a period exceeding 3 months, they are advised to register with a doctor in the country they are visiting for the purpose of receiving further prescriptions.

Advise all travellers to check with the relevant embassy/consulate that the country or countries to be visited will allow the drug user entry with controlled drugs for medical use. A list of the contact numbers for embassies and consulates (pdf) can be found on the Home Office website.

Advise that all travellers should note that controlled drugs should be carried:

With a letter from the prescribing doctor confirming the carriers name, destination, drug details, and amounts.

In their original packaging.

In hand luggage (BAA/airline regulations permitting). All travellers should check that the airline with whom they are travelling permits carriage of the controlled drug. Advise them to contact their airline or the BAA.

With a valid personal import/export licence if travelling for more than 3 months.

Advise that anyone applying for a Home Office import/export licence should allow a minimum of 2 weeks for issue. To obtain the import/export licence, the prescriber or patient must either post or fax an application form to the Home Office, Drug Licensing Section, 6th Floor, Peel Building, 2 Marsham Street, London, SW1P 4DF. Fax: 020 7035 6161. The following must be stated:

The name of the person travelling.

Their address.

The outward and return dates of their travel.

The country they are visiting.

The drugs that are being carried including dosages and total amounts.

To minimize the risk of breakage and spillage, it is advisable to ask the pharmacist to supply measured daily doses in plastic bottles.

If there are any queries, advise that the Home Office can be contacted by email on licensing_enquiry.aadu@homeoffice.gsi.gov.uk.

Import/export license

Import/export license

An import/export licence is required to take the drug out of the UK and bring any surplus back. It does not mean that the holder of the licence has the right to take the drug into the country to be visited. All people carrying controlled drugs including those travelling for 28 days or less must check with the relevant embassy or consulate before departure, to establish that the country or countries to be visited will allow the drug user entry with the controlled drugs for medical use.

For more information, please see the notes on 'Controlled drugs and drug dependence' within the 'Guidance on prescribing' section of the British National Formulary (www.bnf.org).

Basis for recommendation

Basis for recommendation

The basis for these recommendations is information on the website:https://www.gov.uk/travelling-controlled-drugs.

National guidance from the Royal College of General Practitioners suggests that to minimize the risk of breakage and spillage it is advisable to ask the pharmacist to supply measured daily doses in plastic bottles [RCGP, 2005c].

Scenario: Pregnancy and breastfeeding

Scenario: Pregnancy and breastfeeding

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Management in pregnancy

How should I manage a woman who is opioid dependent and is pregnant?

Remember that as well as having the same hopes and anxieties that other pregnant women have, the woman may have other concerns, such as fear of professional attitudes.

The aim of management is to stabilize the condition, prevent injecting, and minimize complications.

Refer all woman to an obstetrician and/or a midwife specializing in drug misuse (depending on local expertise) and to the local drug dependency service.

Testing for HIV and hepatitis B is now offered routinely to all pregnant women. The antenatal setting provides an opportunity for offering hepatitis C testing to injecting women who are at increased risk.

Methadone maintenance treatment is the preferred option for ensuring continuity of care during pregnancy and afterwards:

Methadone has been used safely for many years. Follow-up studies suggest that the long-term outcomes in women who enter methadone treatment programmes during pregnancy are better in terms of their pregnancy, childbirth, and infant development, irrespective of continuing drug use.

Pregnant women should be maintained on a dose of methadone that is sufficient to maintain stability and prevent injecting. Higher doses may be required if illicit opioid use persists or the woman relapses. It is important to choose the right dose so that the woman is happy and the unborn child is protected.

There is a possibility that higher doses may be needed in pregnancy, especially during the third trimester, due to slowed gastrointestinal absorption, expanded fluid load, and increased glomerular filtration rate (although there is little evidence to support this).

Split dosing may be more beneficial, as methadone clearance increases during pregnancy.

Detoxification or reduction should only be considered if this is appropriate for the woman's wishes, circumstances, and ability to cope. Many women request detoxification:

In the first trimester the woman should be stabilized as there is an increased risk of spontaneous abortion. As miscarriage is most likely to occur in the first trimester in all women it might be pragmatic not to detoxify a woman in the first trimester as the detoxification may be blamed for the miscarriage.

In the second trimester detoxification may be undertaken in small frequent reductions (e.g. 2–3 mg methadone every 3–5 days) as long as illicit opioid use is not continuing. There is no evidence for this and this advice is based on expert opinion in national guidance.

In the third trimester further detoxification should not usually be undertaken, as there is evidence that even mild maternal withdrawal is associated with fetal stress, fetal distress, and stillbirth. Rarely, slow careful reduction may be continued safely provided there are no obstetric complications or illicit drug use.

Buprenorphine is not licensed for use during pregnancy, but there is no evidence of adverse effects on pregnancy or neonatal outcomes. A pregnant woman can continue with buprenorphine treatment on specialist advice, and it is recommended that the woman gives her informed and documented consent.

Encourage the woman to use healthcare services:

In particular, emphasize and reinforce the importance of regular attendance for antenatal care.

It is important for all relevant healthcare and social care professionals to work together, as there may be child protection issues.

Try to involve the woman's partner where appropriate.

Morning sickness may lead to the vomiting of methadone soon after it is swallowed, and it is essential to ensure quick replacement of prescriptions and, if appropriate, the prescribing of a safe anti-emetic.

Basis for recommendation

Basis for recommendation

Recommendations for the management of pregnant women who are dependent on opioids are from national guidelines [RCGP, 2004a; RCGP, 2005c; DH and Devolved Administrations, 2007], review articles [Finnegan, 1991; Scimeca et al, 2000], and expert opinion [Moran, Personal Communication, 2002; Ford, Personal Communication, 2006].

Complications

What are the specific complications of using opioids in pregnancy?

Mothers of babies with severe withdrawal symptoms may feel guilt and need help in addressing these feelings. Caring for a neonate with withdrawal symptoms can be demanding, and additional parenting support may be needed.

During pregnancy, opioid dependency decreases fetal growth.

An increased incidence of intrauterine growth retardation and preterm delivery contributes to an increased rate of low birthweight and perinatal mortality in women using illicit drugs. These data must be interpreted with caution, as the outcomes are also affected by such factors as socioeconomic deprivation and smoking.

Heroin seems to have an effect on fetal growth, with a higher rate of small-for-dates babies and pre-term delivery even when allowing for confounding factors.

After birth, there may be problems with neonatal withdrawal.

Severity and likelihood of neonatal withdrawal symptoms increase with higher doses of maternal opioid use.

Symptoms typically develop within 48 hours of birth for heroin-dependent neonates, and within 7 days for methadone-dependent neonates.

Occasionally, methadone withdrawal may take 7–10 days or more to manifest.

All doses of methadone pose a risk of neonatal abstinence syndrome. This is a generalized disorder presenting as central nervous system hyper-irritability, high-pitched cry, rapid breathing, gastrointestinal dysfunction, respiratory distress, hungry but ineffective sucking, and excessive wakefulness.

Compared with methadone, there is a similar incidence of neonatal abstinence syndrome in people who have taken buprenorphine, but this tends to be less severe.

However, not all babies suspected of being drug dependent require pharmacological treatment.

Basis for recommendation

Basis for recommendation

Recommendations for the management of pregnant women who are dependent on opioids are from national guidelines [RCGP, 2005c; DH and Devolved Administrations, 2007] review articles [Wills, 2000; Schindler et al, 2003].

Data from the Northern and Yorkshire region recorded that 139 babies from 365 live births received treatment for withdrawal symptoms [North East Public Health Observatory, 2002].

Management in breastfeeding

How should manage a woman who is opioid dependent and is breastfeeding?

Breastfeeding should be encouraged in most women, even if the mother continues to use substitution therapy. Exceptions include women who are:

Using high-dose benzodiazepines.

Using cocaine/crack.

It is recommended that mothers should breastfeed immediately before an opioid dose is taken (to avoid peak concentrations of opioid in breast milk).

Seek specialist advice if the woman is HIV positive or hepatitis C positive.

Basis for recommendation

Basis for recommendation

These recommendations are in line with national guidelines [DH and Devolved Administrations, 2007].

Some methadone is excreted in breast milk, and this may reduce the severity of any withdrawals the infant might experience [RCGP, 2005c]. When methadone substitution is continued, a fully breastfed infant who has already been exposed in utero to opioids or methadone is likely to develop fewer withdrawal symptoms after birth than one who is not breastfed [Schaefer, 2001].

Buprenorphine is also excreted in breast milk, and research has shown that it is poorly absorbed by infants via the oral route [Center for Substance Abuse Treatment, 2005]. Although breastfeeding should be encouraged in women maintained on buprenorphine because of the benefits to infants and mother-child interaction, the potential risks to the infant should also be borne in mind.

However, neither methadone nor buprenorphine is recommended during breastfeeding by the manufacturers [ABPI Medicines Compendium, 2006; ABPI Medicines Compendium, 2008].

Scenario: Unknown patient

Scenario: Unknown patient - temporary resident/out of hours

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Temporary residents requesting opioids

How should I manage a temporary resident who is requesting opioids?

Be polite and non judgmental. Find out what the patient wants and work out a treatment plan dependent on their needs and your expertise, which is in line with good medical practice.

Do not prescribe opioids unless the person's continued consumption of substitute medication can be confirmed (e.g. consumption is supervised regularly with no missed doses). Potential sources of information include:

Past or current GP.

Current pharmacist, who may be able to confirm when the last dose was taken and advise on the suitability of prescribing further substitution therapy.

Prison medical officer, if the person has recently been released from prison.

Previous prescribers/drug service.

Advise a temporary resident (who will be returning home within a short time) who is requesting a prescription for substitution therapy that it would be more appropriate for them to see their own GP. Loss of a prescription is the person's own responsibility.

Fully assess a temporary resident who is staying for several weeks before deciding on the appropriateness of prescribing substitution therapy. Discuss with their usual prescriber.

If there are acute withdrawal symptoms, symptomatic treatment with non-opioid drugs is generally the appropriate action. See Treatments for symptoms of acute withdrawal.

Check that the person has been fully informed about harm reduction, including:

Safer sex.

Access to sterile needles and syringes.

The importance of being fully vaccinated against hepatitis A and B, and tetanus.

If you decide to prescribe opioids it is important to liaise with the local pharmacist in order to agree arrangements for the supervision of substitution treatment.

Refer pregnant women urgently to a specialist in obstetrics and drug misuse.

Basis for recommendation

Basis for recommendation

These are pragmatic recommendations based on usual clinical practice.

Unknown patients requesting opioids out of hours

How should I manage an unknown patient who is requesting opioids out of hours?

Do not prescribe methadone or buprenorphine in emergency situations.

Prescribing is the responsibility of the person signing the prescription and this responsibility cannot be delegated. Therefore it is important that this person works within their level of competence and seeks help if necessary.

Explain that the person's own GP is responsible for prescribing, and that there will be an agreement in place with that GP regarding prescriptions. Loss of a prescription is the person's own responsibility. Advise the person to contact their own GP if appropriate.

Empathise with their situation. Explain that withdrawal is unpleasant but there are more risks in prescribing for them. Consider symptomatic treatment with non-opioid drugs for withdrawal symptoms (see Treatments for symptoms of acute withdrawal).

Basis for recommendation

Basis for recommendation

These are pragmatic recommendations based on usual clinical practice.

If methadone or buprenorphine is prescribed, this may make it difficult to manage further out-of-hours contacts. Many cooperatives or groups of GPs who share an on-call rota have a policy of no prescriptions of opioids [DH, 1999].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

Writing prescriptions for substitution therapy

How should I write a prescription for substitution therapy (methadone or buprenorphine)?

Following the amendments to the Misuse of Drugs Regulation 2001 in November 2005, prescribers no longer need to have a handwriting exemption.

Prescriptions must still be written so as to be indelible, and other requirements still apply (see Table 1).

Only the signature now needs to be handwritten by the person authorizing the prescription.

All other details on Controlled Drugs prescriptions, including the date, can be computer generated.

This change also permits the use of stamps (such as date or address stamps) and allows other people to write the body of the prescription.

From 1 January 2007, the 'open general licence' which applies to all methadone prescriptions under 500 mg was extended to cover all scripts lasting less than 1 month. Licences will only have to be applied for regarding scripts lasting more than 1 month. This only applies to export from the UK [SMMGP, 2006].

It is essential that the correct wording is used when writing the prescription. For further information on writing prescriptions, including the required wording with examples, see Annex 3 of the 'Orange Book' [DH and Devolved Administrations, 2007], which can be found at www.nta.nhs.uk (pdf). Selected wording which may be of use is given in Table 2.

Table 1 . Writing of prescriptions for substitute prescribing of methadone and buprenorphine.
Issue Comments
Legal requirements for writing prescriptions All prescriptions must include the following: The patient's full name, address and, where appropriate, age The form and strength of the preparation The dose to be taken The total quantity of the preparation or the number of dose units in both words and figures The signature of the prescriber who has written the prescription The date of signing by the prescriber who has written the prescription
Other practical points when writing blue instalment prescriptions forms (FP10MDA-SS) Instalments can only be authorized for up to 14 days. State the intended date on which the first instalment should start. Specify the dispensing instructions (e.g. daily dispensing) and the amount to be dispensed on the instalment prescription form. If the prescriber wants supervised consumption in the pharmacy, specify 'supervised consumption' on the prescription if a local scheme is in place. If extra quantities need to be prescribed on any day because the pharmacy is closed on a Sunday or Bank Holiday, then the prescriber should specify the actual days and quantities to be supplied for those days. Once specified, the prescription cannot be dispensed on alternative days. The amount of a controlled drug that can be dispensed on a single prescription should be limited to a supply sufficient to last 28 days. A prescription for a controlled drug is valid for 28 days from the date stated thereon. The Home Office has expressed a view that a dose of 'as directed' or 'when required' is not acceptable, but 'one to be taken as directed/when required' is acceptable. Where possible, always issue a prescription directly to the drug misuser. A prescription that was posted to the pharmacy but has not arrived cannot be dispensed, even at the verbal request of the prescriber. Unsupervised collection of methadone or buprenorphine should usually be required to be undertaken by the person the prescription is for. If a third-party is collecting the prescription, the pharmacy will require a covering letter from the person the prescription is for, and the prescriber should add this instruction to the prescription. Other prescription items cannot be written on the same form. Diazepam, as well as buprenorphine and other Schedule 2 controlled drugs, can be issued by instalment prescription.
Table 2 . Wording requirements when writing blue instalment prescriptions forms (FP10MDA-SS).
Situation Examples of what to write on the prescription
If you want the buprenorphine tablets crushed (local policy or agreement must be in place). Please crush.
If you want patients who pick up their medicine less frequently than daily to be able to collect a part instalment as soon as possible after they miss a dose. If an instalment prescription covers more than one day and is not collected on the specified day, the total amount prescribed less the amount prescribed for the days missed may be supplied. OR Instalment prescriptions covering more than one day should be collected on the specified day; if this collection is missed the remainder of the instalment (i.e. the instalment less the amount prescribed for the days missed) may be supplied.
If you want the patient to be supervised consuming their dose on the days that they collect from the pharmacy but still want them to be able to obtain a part instalment of their medicine if they miss their prescribed collection day. Supervised consumption of daily dose on specified days; the remainder of the supply to take home. If an instalment prescription covers more than one day and is not collected on the specified day, the total amount prescribed less the amount prescribed for the days missed may be supplied.
If you want to ensure that the patient is not supplied with their dose if they have missed collecting for three days. Instalment prescriptions covering more than one day should be collected on the specified day. If this collection is missed, the remainder of the instalment (i.e. the total amount less the instalments for the days missed) may continue to be supplied in the specified instalments at the stated intervals, provided no more than three days are missed.
If you want the pharmacy to supply methadone in pre-measured amounts for days of multiple collection. Supply in daily dose containers.
For Bank Holidays when unsure which days the pharmacy is closed. Instalments due on days when the pharmacy is closed should be dispensed on the day immediately prior to closure.

[RPSGB, 2005b; DH, 2006a; NPC, 2006]

Methadone

Types of methadone available

What types of methadone are available?

Methadone oral solution (previously known as methadone mixture) is the recommended choice:

Methadone oral solution (1 mg/mL) is licensed for the treatment of opioid dependence in the UK. This is the preparation that should usually be prescribed.

Other strengths (e.g. 10 mg/mL or 20 mg/mL) may rarely be prescribed in specialist settings to people on high-dose methadone, but these should normally be on a supervised consumption basis because:

There is a greater risk of overdose, should it be diverted on to the illicit market.

It is easy to inject because, unlike the 1 mg/mL strength, it is not viscous.

Methadone linctus (2 mg/5 mL) is not licensed for the treatment of drug dependence. It is used in palliative care for the treatment of distressing cough.

Methadone tablets are not recommended:

Methadone tablets (5 mg) are not licensed for the treatment of opioid dependence.

They can be crushed and inappropriately injected, and should only be prescribed under specialist supervision.

Methadone injectable formulation is not advised except under specialist supervision. Under these circumstances it might occasionally be considered for a person with a long history of injecting heroin who has gained no benefit from using oral methadone.

[RCGP, 2005c]

Effective period

How long is methadone effective for?

Methadone pharmacokinetics vary widely between people who are dependent on opioids according to age, gender, ethnic background, prior drug history, past medical history, and body mass:

The time to peak concentration after oral administration is 4 hours (range 2–6 hours).

The time to peak clinical effect is 2–4 hours after the first dose.

An optimal dose will exert clinical effects for 24–36 hours, but low doses may exert clinical effects for only a few hours.

The half-life of methadone varies:

A single one-off dose has a half-life of 12–18 hours (mean 15 hours).

Regular daily dosing has a longer half-life of 13–112 hours (mean 37 hours), and there is a risk of drug accumulation:

Methadone binds to albumin and other proteins in the lungs, kidneys, liver, and spleen, and there is gradual equilibration between these tissues and the blood over the first 4–5 days of dosing. This reaches a steady state by 10 days. Once this level is reached, variation in blood concentration is small.

Repeated dosing leads to accumulation, and therefore methadone initiation should be done cautiously and gradually.

Once stabilized, the half-life is usually 20–37 hours, but may range up to 91 hours.

The relatively slow onset of action and long half-life mean that methadone overdose and toxic effects may become life threatening several hours after a dose is taken.

Tolerance develops at different rates in different individuals and differently for different effects (e.g. quickly for vomiting but not completely developed for respiratory depression).

[RCGP, 2005c; NICE, 2007b]

Potency

How potent is methadone?

Methadone is a long-acting synthetic opioid that acts as a full opioid agonist.

Direct equivalence is difficult to estimate, for example:

Street heroin differs in its purity; roughly, 1 g street heroin is equivalent to 50 mg to 80 mg (0.05 g to 0.08 g) methadone (approximately 20:1 ratio).

Injectable pharmaceutical diamorphine varies from a methadone:diamorphine ratio of 1:3 (but 1:1 for very low doses) to 1:5 for very high doses. For example, 120 mg methadone is equivalent to between 360 mg to 600 mg of injectable diamorphine.

Buprenorphine is a partial agonist and there is no linear dosage relationship between buprenorphine and methadone. For maintenance doses, 50 mg to 80 mg methadone is approximately equivalent to 12 mg to 16 mg buprenorphine in terms of effectiveness.

[RCGP, 2005c]

Splitting doses

Should I split the dose of methadone?

Some people are more comfortable taking split doses. If a person is entering withdrawal before their next dose is due, it might be more effective to split the dose rather than increase it. Seek specialist advice if unsure. Split dosing can cause problems with supervised consumption. The following may benefit from split dosing [RCGP, 2005c]:

People on low doses.

Women in the third trimester of pregnancy.

People on enzyme-inducing medication (e.g. anticonvulsants).

Contraindications

Who should avoid taking methadone?

Methadone should not be used in people who:

Are non-opioid dependent (that is, substitution therapy with either methadone or buprenorphine should not be given to people who are dependent on other drugs).

Have allergy or proven intolerance to either methadone or buprenorphine.

Have severe liver disease.

Are under 16 years of age, except on the advice of a specialist.

Have medical conditions, such as:

Recent head injury.

Acute abdominal condition.

Have severe mental illness with limited capacity to provide informed consent.

Certain drugs interact with methadone, which may necessitate stopping one of the drugs (i.e. methadone or the interacting drug), increasing or decreasing the dose, or monitoring plasma levels of the interacting drug. See Interactions.

Interactions

Which drugs interact with methadone?

Methadone is extensively metabolized by the liver via the cytochrome P450 system, and blood levels can be affected by the concurrent use of drugs that either inhibit or induce liver enzymes.

Drugs that may increase blood levels of methadone and buprenorphine include:

Selective serotonin re-uptake inhibitors (SSRIs) (e.g. sertraline, fluoxetine).

Serotonin and noradrenaline re-uptake inhibitors (e.g. duloxetine, nefazodone, venlafaxine).

Broad-spectrum antifungals and antibacterials (e.g. clotrimazole).

HIV treatments (e.g. zidovudine, ritonavir).

Hormones (e.g. progesterone, ethinylestradiol).

Calcium-channel blockers (e.g. nifedipine, verapamil).

Antibiotics (e.g. erythromycin).

Others (quinidine, midazolam, ciclosporin, vinblastine, bromocriptine, cimetidine).

Drugs that may decrease blood levels of methadone and buprenorphine include:

Antiepileptics (phenobarbital, phenytoin, primidone, carbamazepine).

Glucocorticoids.

Anti-tuberculosis medication (rifampicin, rifabutin).

Initiation of treatment with methadone presents a potential risk of respiratory depression, and interactions with other respiratory depressants, such as alcohol, benzodiazepines, newer hypnotics (z-drugs), other sedatives, or tricyclic antidepressants, should be considered before starting treatment [NICE, 2007b].

Any dose adjustments made for methadone because of concomitant medication, such as rifampicin, should be reassessed on stopping this medication.

[RCGP, 2004a; RCGP, 2005c; Micromedex, 2006]

Adverse effects

What are the adverse effects of methadone?

Adverse effects include the following [RCGP, 2005c]:

Many people report a 'clouding' effect in the mind. Some people value this effect, whilst others do not.

People commonly complain of sore leg muscles, particularly when starting treatment or if taking suboptimal maintenance doses, and this may be due to 'breakthrough' withdrawal effects.

Other effects are common to opioids (e.g. nausea, vomiting, drowsiness, and constipation). Dry mouth, sweating, headache, amenorrhoea, and decreased libido may also occur.

Methadone has been reported to cause QT-interval prolongation and torsades de pointes (particularly at high doses of more than 100 mg/day) [ABPI Medicines Compendium, 2008]. People at increased risk of QT-interval prolongation (e.g. those with heart or liver disease, electrolyte abnormalities, concomitant treatment with CYP 3A4 inhibitors or medicines with the potential to cause QT-interval prolongation) and people requiring more than 100 mg methadone per day should be closely monitored [CHM, 2006]. Buprenorphine may be a better alternative in these people.

Electrocardiography might be considered before induction on to methadone, before increasing the dose of methadone and subsequently after stabilization. at least with doses of over 100 mg per day and in those with substantial risk factors for QT prolongation [DH and Devolved Administrations, 2007].

Buprenorphine

Types of buprenorphine available

What types of buprenorphine are available?

The only product containing buprenorphine licensed for the management of drug dependence is buprenorphine sublingual tablets. It is available in 400 microgram, 2 mg, and 8 mg formulations.

Buprenorphine is inactivated by gastric acid and has a high first-pass metabolism. It is therefore available as sublingual tablets and transdermal patches (not used in treatment of drug dependence) [RCGP, 2004a].

Care should be taken that a product that is licensed for the treatment of opioid dependence is dispensed.

Temgesic® sublingual tablets and buprenorphine patches (Bu Trans®, Transtec®) are not licensed for the management of opioid dependence, do not contain the correct patient information leaflet, and should not be used for this purpose.

Effective period

How long is buprenorphine effective for?

The time to peak concentration is 90–150 minutes after sublingual administration.

The time to peak clinical effect is 1–4 hours after the dose.

Buprenorphine's duration of action is related to dose:

Low doses (e.g. 2 mg to 4 mg) exert clinical effects for up to 12 hours.

Higher doses (e.g. 16 mg to 32 mg) can exert clinical effects for up to 48–72 hours.

Precipitated withdrawal can occur in someone commencing buprenorphine who has used heroin (within 8 hours) or methadone (within 24 hours). It typically occurs 1–3 hours after the first buprenorphine dose and peaks over the first 3–6 hours before subsiding.

[RCGP, 2004a]

Potency

How potent is buprenorphine?

Buprenorphine is a semi-synthetic opioid with partial agonist properties, and also has antagonist properties.

High doses of buprenorphine produce a less sedating effect than high doses of heroin, methadone, or morphine, and less respiratory depression.

At doses of more than 8 mg, buprenorphine blocks the effects of additional opioid use by preventing occupation of opioid receptors.

It is difficult to estimate equivalence between methadone and buprenorphine because there is not a linear relationship. Buprenorphine 12 mg to 16 mg is approximately as effective as methadone 50 mg to 80 mg in reducing heroin use and maintaining people in treatment. It is difficult to compare doses above methadone 80 mg and above buprenorphine 16 mg because of their different effects [RCGP, 2004a].

Interactions

Which drugs interact with buprenorphine?

Buprenorphine is extensively metabolized by the liver via the cytochrome P450 system, and blood levels can be affected by the concurrent use of drugs that either inhibit or induce liver enzymes. However, buprenorphine is a weaker inhibitor of cytochrome 3A4 in contrast to methadone, which is a strong inhibitor, and so may be preferred to methadone in some instances.

Drugs that may increase blood levels of buprenorphine include:

Selective serotonin re-uptake inhibitors (e.g. sertraline, fluoxetine).

Serotonin and noradrenaline re-uptake inhibitors (e.g. duloxetine, nefazodone, venlafaxine).

Broad-spectrum antifungals and antibacterials (e.g. clotrimazole).

HIV treatments (e.g. zidovudine, ritonavir).

Hormones (e.g. progesterone, ethinylestradiol).

Calcium-channel blockers (e.g. nifedipine, verapamil).

Antibiotics (e.g. erythromycin).

Others (e.g. quinidine, midazolam, ciclosporin, vinblastine, bromocriptine, cimetidine).

Drugs that may decrease blood levels of buprenorphine include:

Antiepileptics (phenobarbital, phenytoin, primidone, carbamazepine).

Glucocorticoids.

Anti-tuberculosis medication (rifampicin, rifabutin).

Initiation of treatment with methadone presents a potential risk of respiratory depression, and interactions with other respiratory depressants such as alcohol, benzodiazepines, newer hypnotics (z-drugs), other sedatives, or tricyclic antidepressants should be considered before starting treatment [NICE, 2007b].

Any dose adjustments made for buprenorphine, because of concomitant medication such as rifampicin, should be reassessed on stopping this medication.

[RCGP, 2004a; RCGP, 2005c; Micromedex, 2006]

Contraindications

hWho should avoid taking buprenorphine?

Buprenorphine should not be used in people with the following conditions:

Non-opioid dependence (that is, substitution therapy with either methadone or buprenorphine should not be given to people who are dependent on other drugs).

Allergy or proven intolerance to either methadone or buprenorphine.

Severe liver disease.

Aged under 16 years, except on the advice of a specialist.

Medical conditions, such as:

Recent head injury.

Acute abdominal condition.

Severe mental illness with limited capacity to provide informed consent.

Severe respiratory insufficiency.

Acute alcoholism or delirium tremens.

Renal insufficiency — 20% of the administered dose is eliminated by the renal route, and thus renal elimination may be prolonged.

Respiratory disease, as there may be in increased risk of respiratory depression with buprenorphine (although less than with other opioids).

Breastfeeding: although the manufacturer of buprenorphine recommends avoiding its use during breastfeeding, the effect on the infant would be minimal and its use may be appropriate (see Management in breastfeeding).

[ABPI Medicines Compendium, 2006]

Adverse effects

What are the adverse effects of buprenorphine?

Adverse effects of buprenorphine include:

Many people report a clear-head response, which is different to the 'clouding' associated with heroin and methadone use. Some people prefer this, whilst others find it uncomfortable.

Adverse effects common to opioids include constipation, sleeplessness, sickness, sweating, bitter taste, and headaches.

[RCGP, 2004a]

Evidence

Evidence

Supporting evidence

A number of Cochrane reviews have reported on the best treatments for detoxification and maintenance in opioid dependence, optimal doses for detoxification, and comparisons of pharmacological treatments and psychosocial interventions. Overall the following have been concluded:

Methadone dosages ranging from 60 mg/day to 100 mg/day were more effective than lower dosages in retaining people and in reducing use of heroin and cocaine during treatment [Faggiano et al, 2003].

Slow tapering with long-acting opioids, accompanied by medical supervision and ancillary medications, can reduce withdrawal severity [Amato et al, 2005].

Buprenorphine was more effective than clonidine and of similar effectiveness to methadone for the management of opioid withdrawal [Gowing et al, 2006b].

Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages [Mattick et al, 2003a].

Four meta-analyses of randomized controlled trials (RCTs) found that fixed doses of methadone maintenance therapy had retention on treatment rates better than those of comparable fixed doses of buprenorphine maintenance therapy [NICE, 2007b].

Alpha-2 adrenergic agonists (lofexidine and clonidine) are as effective as reducing doses of methadone for the management of withdrawal from heroin or methadone [Gowing et al, 2004b].

Levomethadyl acetate hydrochloride (LAAM) appeared to be more effective than methadone at reducing heroin use, but there was insufficient evidence to draw any conclusions regarding safety [Clark et al, 2002]. However, LAAM has been discontinued in a number of countries, including the UK, due to the increased risk of fatal arrhythmias.

Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, results at follow up, and compliance [Amato et al, 2004b].

Adding any psychosocial support to standard methadone maintenance therapy significantly improves the non-use of heroin during treatment [Amato et al, 2004a].

There is insufficient evidence to suggest psychosocial treatments alone are an adequate treatment regimen for opioid dependence, or are superior to any other type of treatment [Mayet et al, 2004].

Opioid antagonists during heavy sedation or anaesthesia

Evidence on the use of opioid antagonists under heavy sedation or anaesthesia

There is good evidence to recommend that opioid withdrawal with opioid antagonists under heavy sedation should never be used:

A Cochrane review aimed to assess the effectiveness of interventions involving the administration of opioid antagonists to induce opioid withdrawal with concomitant heavy sedation or anaesthesia, in terms of withdrawal signs and symptoms, completion of treatment, and adverse effects [Gowing et al, 2006c]:

The authors searched the Drugs and Alcohol Group register (October 2003), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2004), Medline (January 1966 to January 2005), Embase (January 1985 to January 2005), PsycINFO (1967 to January 2005), and Cinahl (1982 to December 2004), and reference lists of studies.

Trials included in the review were controlled trials comparing antagonist-induced withdrawal under heavy sedation or anaesthesia with another form of treatment or a different regimen of anaesthesia-based antagonist-induced withdrawal. Six studies were included in the analysis (five randomized controlled trials) involving 834 participants.

The review found that:

Antagonist-induced withdrawal is more intense but less prolonged than withdrawal managed with reducing doses of methadone.

The dose of naltrexone sufficient for blockade of opioid effects can be established significantly more quickly with antagonist-induced withdrawal than withdrawal managed with clonidine and symptomatic medications.

The level of sedation does not affect the intensity and duration of withdrawal, although the duration of anaesthesia may influence the severity of withdrawal.

Adverse effects were significantly more common with heavy, than with light, sedation (RR 3.21, 95% CI 1.13 to 9.12, p = 0.03): these included respiratory depression, aspiration pneumonia, pulmonary oedema, and diabetic ketoacidosis.

The authors concluded that as adverse events are potentially life-threatening, antagonist-induced withdrawal under heavy sedation should not be used.

Treatment of opioid dependence in primary care

Can opioid dependence be treated effectively in primary care?

There is good evidence that opioid dependence can be treated effectively in primary care.

A prospective, multisite, follow-up study of treatment outcomes in 452 people addicted to opioids found that the treatment outcomes at 6 months for people treated in general practice were no different from those for people treated in a specialist drug clinic [Gossop et al, 1999].

A longitudinal cohort study of 96 people attending a primary care clinic for drug dependence in Sheffield in 1999 who were followed up for 1 year found that [Keen et al, 2003]:

The frequency of heroin use was reduced from a mean of 3.02 episodes a day to 0.22 episodes a day.

Convictions and cautions for crime fell by 62%.

HIV-risk-taking behaviour improved: 80% of the cohort had injected drugs in the previous month before attending the clinic. This fell to 36% after 1 year in treatment.

Social functioning improved: this was measured using a social functioning score comprising questions in three areas; employment, residential stability, and interpersonal conflict.

Risk-taking behaviour fell: 62% of the cohort reported that more than half of their associates were illicit drug users at intake, falling to 12% at 1 year.

Physical health showed a 46% improvement at 12 months, using the Opiate Treatment Index.

There were significant improvements in anxiety, depression, social dysfunction, and somatic symptoms as assessed by the General Health Questionnaire 28-item version (GHQ-28) subsections.

Although the number of people receiving methadone approximately doubled for the whole of Sheffield in the 2 years between April 1999 and March 2001 because a primary care clinic for drug dependence opened, there was no increase in the number of deaths from methadone [Keen et al, 2002].

Many people entering methadone treatment within a GP-centred scheme in Glasgow improved, supporting the view that methadone maintenance can be successfully provided by GPs supported by specialist services [Hutchinson et al, 2000].

A Cochrane review found that there is no good research to provide information about the outcomes or cost effectiveness of inpatient or outpatient approaches to opioid detoxification [Day, 2005].

Methadone

Methadone maintenance therapy

Methadone maintenance therapy is effective at retaining people in treatment than no drug treatment or placebo. A dose of 60 mg to 100 mg daily is more likely to keep people in treatment than a lower daily dose.

A Health Technology Assessment (HTA) examined the evidence for methadone maintenance therapy (MMT) versus no drug therapy or placebo. The results from the meta-analyses showed that fixed-dose MMT had superior levels of retention on treatment compared with placebo or no treatment [Connock et al, 2007; NICE, 2007b]:

A meta-analysis (n = 505) compared methadone 20 mg/day to 50 mg/day with no therapy: the relative risk (RR) of remaining on treatment was 3.05 (95% CI 1.75 to 5.35).

A systematic review (n = 348) pooled the results from trials that used daily doses of methadone of 20 mg to 97 mg: the RR of remaining on treatment was 3.91 (95% CI 1.17 to 13.2).

Fixed-dose MMT resulted in lower rates of illicit opioid use compared with placebo or no treatment. Higher doses of methadone were more effective than lower doses:

A systematic review (n = 246) compared 60 mg methadone daily with no therapy: the RR of illicit opioid use (self-reported) was 0.31 (95% CI 0.23 to 0.42).

A systematic review (n = 347) compared doses of 50 mg methadone with placebo: the RR of illicit opioid use was 0.82 (95% CI 0.69 to 0.98).

There were fewer self-reported adverse events with MMT compared with placebo or no therapy, but the difference did not reach statistical significance (RR 0.59, 95% CI 0.33 to 1.04).

A meta-analysis of observational studies on people in and out of methadone treatment found that people on methadone maintenance treatment were four times less likely to die than those not on treatment or discharged from treatment (RR 0.25, CI 0.19 to 1.33). Results from three randomized trials did not reach statistical significance.

A small number of systematic reviews have shown that, compared with placebo or no treatment, methadone maintenance treatment significantly improved HIV outcomes (HIV risk behaviour score, number of sex partners, frequency of unprotected sex, and rates of seroconversion).

The level of criminal activity appeared to be lower in those on methadone maintenance treatment compared with placebo or no treatment, but the difference was not statistically significant.

A Cochrane review (search date to 2001) concluded that methadone is an effective maintenance therapy intervention for the treatment of heroin dependence, as it retains people in treatment and decreases heroin use better than treatments that do not utilize opioid replacement therapy (i.e. detoxification, offer of drug-free rehabilitation, placebo medication, wait-list controls) [Mattick et al, 2003b]:

Retention in treatment was greater in the methadone treatment group compared with placebo medications and with the wait-list control (three studies; n = 505; RR 3.05, 95% CI 1.75 to 5.35).

A greater reduction in heroin use (heroin metabolites in urine) was noted in the methadone treatment group compared with detoxification and with the wait-list control (two studies; n = 409; RR –0.32, 95% CI –0.40 to –0.23).

A greater reduction in heroin use (self-reported data) was noted in the methadone treatment group compared with control (three studies; n = 230; RR 0.32, 95% CI 0.23 to 0.44).

Another Cochrane review (search date to 2001) concluded that methadone dosages ranging from 60 mg/day to 100 mg/day were more effective than lower dosages in retaining people and in reducing use of heroin and cocaine during treatment [Faggiano et al, 2003]:

Retention rates:

Higher doses (60 mg/day to 109 mg/day) showed better retention rates than low doses (1 mg/day to 39 mg/day), both in shorter follow ups (five studies; n = 496; RR 1.36, 95% CI 1.13 to 1.63) and longer follow ups (one study; n = 75; RR 1.62, 95% CI 0.95 to 2.77).

Higher doses compared with medium doses (40 mg/day to 59 mg/day) seemed to show no differences in effectiveness only for follow ups longer than 27 weeks (three studies; n = 560; RR 1.23, 95% CI 1.05 to 1.45), whereas for shorter follow up no differences were reported (two studies; n = 347).

Very high doses appeared to be more effective compared with medium doses (one study; n = 80; RR 1.67, 95% CI 1.05 to 2.66).

Heroin/cocaine use:

High dose compared with low dose reduces the use of heroin (three studies; n = 237; RR 1.59, 95% CI 1.16 to 2.18).

High dose increases the probability of staying abstinent from cocaine compared with low dose (two studies; n = 168; RR 1.81, 95% CI 1.15 to 2.85).

Tapering doses of methadone

Slow tapering of methadone accompanied by medical supervision and ancillary medications, can reduce withdrawal severity.

A Cochrane review (search date to December 2004) confirmed that slow tapering with long-acting opioids, accompanied by medical supervision and ancillary medications, can reduce withdrawal severity [Amato et al, 2005]. Data from the literature were not comparable and varied widely with regard to duration, design, and treatment objectives:

Completion of treatment:

Methadone was compared against adrenergic agonists, opioid agonists, and chlordiazepoxide.

No difference was found between tapered methadone and any other pharmacological treatment (11 studies; n = 748; RR 1.12, 95% CI 0.94 to 1.34).

However, methadone was significantly better than propoxyphene (one study; n = 72; RR 1.67, 95% CI 1.07 to 2.60).

Duration and symptom severity:

Withdrawal symptoms were generally higher in the methadone group compared with propoxyphene, and the finding was statistically significant.

No other statistically significant differences were found between methadone and other pharmacological treatments.

Effect on drug-related behaviours

Oral substitution therapy reduces drug-related behaviours that have a high risk of HIV transmission.

A Cochrane review (search date to July 2003) concluded that oral substitution therapy reduces drug-related behaviours with a high risk of HIV transmission, but has little effect on sex-related risk behaviours [Gowing et al, 2004a]:

The authors were unable to carry out a meta-analysis, as the included studies varied in a number of aspects, including;

The interval between baseline and follow-up interviews (1–24 months).

The proportion of participants who were injecting drug users at baseline (62–100%).

The reporting period for assessment of HIV risk behaviours (2 weeks to 6 months).

The main outcomes included:

A decrease in injecting behaviour (whether represented as a proportion of people or frequency of use).

Fewer multiple sex partners or exchanges of sex for drugs or money in the participants in substitution therapy.

Fewer participants reporting unprotected sex following substitution therapy.

Methadone maintenance therapy (MMT) versus buprenorphine maintenance therapy (BMT)

Methadone maintenance therapy is more effective than buprenorphine therapy at retaining people in treatment except at low doses.

A NICE Health Technology Assessment compared methadone maintenance therapy with buprenorphine maintenance therapy [Connock et al, 2007]:

Across comparable fixed doses methadone maintenance therapy was more effective in retaining people in treatment than buprenorphine maintenance therapy, except at low doses, when there appeared to be no difference between the two drugs.

Retention in treatment was superior for flexible-dose methadone compared with flexible-dose buprenorphine (pooled hazard ratio 1.40, 95% CI 1.15 to 1.69) for retention in treatment but there was no significant difference in opiate use (standardised mean difference 0.12, 95% CI –0.02 to +0.26).

A Cochrane review concluded that [Mattick et al, 2003a]:

Buprenorphine at flexible doses was less likely to retain people than methadone at flexible doses (six studies; n = 837; relative risk [RR] 0.82, 95% CI 0.69 to 0.96).

There was no statistically significant difference between:

Low-dose buprenorphine and low-dose methadone (two studies; n = 121; RR 0.74, 95% CI 0.52 to 1.06).

Low-dose buprenorphine and high-dose methadone (two studies; n = 120; RR 0.69, 95% CI 0.45 to 1.06).

High-dose buprenorphine and high-dose methadone (five studies; n = 449; RR 0.79, 95% CI 0.62 to 1.01).

Compared with placebo, low-dose (2 mg or 4 mg), high-dose (8 mg), and very high-dose (16 mg) buprenorphine showed significantly more people retained in therapy:

Low-dose: two studies; n = 487; RR 1.24, 95% CI 1.06 to 1.45.

High-dose: two studies; n = 463; RR 1.21, 95% CI 1.02 to 1.44.

Very high-dose: one study; n = 366; RR 1.52, 95% CI 1.23 to 1.88.

Buprenorphine

Compared with clonidine

Buprenorphine was more effective than clonidine, and of similar effectiveness to methadone, for the management of opioid withdrawal.

A Cochrane review (search date to August 2005) found that buprenorphine was more effective than clonidine and of similar effectiveness to methadone for the management of opioid withdrawal [Gowing et al, 2006b]:

Buprenorphine showed a greater intensity of withdrawal, compared with clonidine:

Data were presented differently across the studies; mean peak withdrawal score (three studies; n = 266; standardised mean difference [SMD] –0.61, 95% CI –0.86 to –0.36) and overall withdrawal score (two studies; n = 452; SMD –0.59, 95% CI –0.79 to –0.39) were lower for buprenorphine compared with clonidine.

More people were likely to complete withdrawal therapy when taking buprenorphine compared with clonidine:

Inpatient setting (three studies; n = 213; SMD 0.68, 95% CI –0.29 to 1.65)

Outpatient setting (two studies; n = 345; SMD 0.82, 95% CI 0.57 to 1.06)

The combined effect over both settings was also significant, favouring buprenorphine (SMD 0.75, 95% CI 0.31 to 1.19).

Compared with reducing doses of methadone

Buprenorphine is as effective as methadone for withdrawal therapy.

Buprenorphine and methadone had similar completion rates for withdrawal therapy [Gowing et al, 2006b]:

However, there was a trend towards an increased rate of completion associated with buprenorphine (three studies; n = 156; relative risk 1.30, 95% CI 0.97 to 1.73).

No significant differences in intensity or duration of withdrawal were found between buprenorphine and methadone.

Reducing doses of buprenorphine

People are more likely to remain drug free if buprenorphine is tapered gradually rather than rapidly.

Although people may achieve greater peak withdrawal following a rapid-taper regimen, fewer of them remain drug free, and they experience more adverse effects and use more adjunct medication [Gowing et al, 2006b]:

One study (n = 8) reported that self-reported withdrawal severity was significantly greater in the rapid-taper group. People were more likely to complete withdrawal in the gradual-taper group.

A second study (n = 23) reported greater adverse effects (muscle aches, lengthy insomnia) regardless of adjunct medication in people in the rapid-taper group. More people remained drug-free in the gradual-taper group (71%) compared with the rapid-taper group (37.5%).

The third study (n = 40) reported greater peak withdrawal in the more rapid-taper group, but they also used more adjunct medication.

Buprenorphine maintenance therapy

Buprenorphine maintenance therapy is more effective at retaining people in treatment than placebo or no therapy.

A NICE Health Technology Assessment looked at buprenorphine maintenance therapy (BMT) versus no drug therapy or placebo [Connock et al, 2007; NICE, 2007b]:

A systematic review of randomized controlled trials (RCTs) reported retention on treatment for various doses of buprenorphine compared with placebo or no therapy. All doses of buprenorphine were more effective than no treatment or placebo, but the higher doses were more effective:

Five RCTs (n = 1131) used doses of less than 5 mg buprenorphine: relative risk (RR) 1.50 (95% CI 1.19 to 1.88).

Four RCTs (n = 887) used a dose of 6 mg to 12 mg: RR 1.74 (95% CI 1.06 to 2.87).

Four RCTs (n = 728) used a dose of 18 mg: RR of 1.74 (95% CI 1.02 to 2.96).

A small RCT (n = 40), included in an unpublished systematic review reported a reduction in mortality in people on BMT (16 mg) compared with those on placebo and counselling treatment over a 12-month period (RR 0.05, 95% CI 0 to 0.79).

An unpublished review identified one RCT that demonstrated the capacity of buprenorphine maintenance treatment to reduce deaths compared with placebo or no treatment (0/20 deaths with BMT and 4/20 with placebo).

No studies comparing BMT with placebo or no treatment reported data on illicit opioid use, adverse events, HIV risk behaviour, or crime.

Alpha-2 adrenergic agonists

Alpha-2 adrenergic agonists (lofexidine and clonidine) are as effective as reducing doses of methadone for the management of withdrawal from heroin or methadone.

One Cochrane review (search date to September 2004) concluded that alpha-2 adrenergic agonists (lofexidine and clonidine) are as effective as reducing doses of methadone for the management of withdrawal from heroin or methadone [Gowing et al, 2004b]. The studies varied in who assessed withdrawal severity, the particular scale used to rate withdrawal severity, and the form in which results were reported. This diversity prevented quantitative analysis of all the withdrawal parameters:

Alpha-2 adrenergic agonists compared with reducing doses of methadone:

There was no significant difference in rates of completion of withdrawal for alpha-2 adrenergic agonists compared with reducing doses of methadone (nine studies; n = 612; relative risk 0.89, 95% CI 0.77 to 1.03).

There was a greater incidence of overall adverse effects with clonidine treatment (64–72%) compared with reducing doses of methadone (35–40%). Orthostatic hypotension was also more frequent (20–34% with clonidine compared with 0–27% for methadone).

There was no significant difference in mean blood pressure for lofexidine compared with reducing doses of methadone.

Lofexidine compared with clonidine:

There was no significant difference in any parameters for withdrawal management with lofexidine compared with clonidine.

There were significantly more cases of hypotension in the clonidine-treated group compared with the lofexidine-treated group.

Opioid antagonists

Opioid antagonists alone and in combination with psychosocial therapy

Evidence on opioid antagonists (naltrexone) alone and in combination with psychosocial therapy

There is very limited evidence about the effectiveness of naltrexone alone or associated with psychosocial therapy in limiting the use of heroin during treatment.

A Cochrane review (search date: to January 2005) reported that naltrexone maintenance therapy alone or associated with psychosocial therapy is more efficacious than placebo alone or associated with psychosocial therapy in limiting the use of heroin during the treatment [Minozzi et al, 2006]. However, the conclusions are limited owing to the heterogeneity of the trials, both in the interventions and in the assessment of outcomes:

There was no significant difference in retention in treatment rates for any of the comparisons:

Naltrexone vs. placebo (two studies; n = 88; relative risk [RR] 0.50, 95% CI 0.20 to 1.24).

Naltrexone plus psychosocial therapy vs. placebo plus psychosocial therapy (three studies; n = 115; RR 1.38, 95% CI 0.90 to 2.10).

Naltrexone plus psychosocial therapy vs. psychosocial therapy alone (one study; n = 51; RR 1.50, 95% CI 0.73 to 3.07).

Naltrexone alone vs. naltrexone plus psychosocial therapy (one study; n = 43; RR 0.94, 95% CI 0.59 to 1.48).

There was a trend in favour of naltrexone when assessing the use of primary substance of abuse:

Naltrexone vs. placebo (three studies; n = 134; RR 0.79, 95% CI 0.59 to 1.06).

Naltrexone plus psychosocial therapy vs. placebo plus psychosocial therapy (three studies; n = 115; RR 0.66, 95% CI 0.47 to 0.92).

Naltrexone vs. psychosocial therapy (one study; n = 19; RR 0.71, 95% CI 0.28 to 1.82).

There was no significant difference in results of follow up for any of the comparisons:

Naltrexone vs. placebo (one study; n = 50; RR 0.50, 95% CI 0.71 to 1.60).

Naltrexone plus psychosocial therapy vs. placebo plus psychosocial therapy (one study; n = 31; RR 0.75, 95% CI 0.39 to 1.45).

Naltrexone plus psychosocial therapy vs. psychosocial therapy alone (one study; n = 35; RR 1.50, 95% CI 0.55 to 4.06).

Naltrexone vs. psychosocial therapy (one study; n = 38; RR 0.65, 95% CI 0.19 to 2.22).

Naltrexone alone vs. naltrexone plus psychosocial therapy (one study; n = 43; RR 1.16, 95% CI 0.29 to 4.57).

Opioid antagonists alone and in combination with alpha-2 adrenergic agonists

Evidence on opioid antagonists (naltrexone, naloxone) alone and in combination with alpha-2 adrenergic agonists (lofexidine and clonidine)

There is evidence that naltrexone has limited benefit in helping former opioid addicts to remain abstinent, but this evidence is poor.

A NICE Health Technology Assessment aimed to assess the clinical effectiveness of naltrexone in relapse prevention in people who had been addicted to opioids but had been detoxified [Adi et al, 2007]. Twenty-six randomized controlled trials (RCTs) met the inclusion criteria, but the methodological quality was poor to moderate. The results suggested that:

Naltrexone maintenance therapy may be better than placebo at retaining people in treatment, but this was not statistically significant.

The risk of drug abuse in naltrexone versus placebo, with or without psychological support, gave a statistically significant difference in favour of naltrexone.

Three RCTs studied opioid relapse-free rates, and these were significantly different from placebo in favour of naltrexone; however, as this difference diminished over time, the clinical significance is doubtful.

The relative risk of re-imprisonment whilst on naltrexone therapy showed results in favour of naltrexone in the two combined studies of people on parole or people on probation, but the number of participants was small.

The adverse events data showed no significant difference between the naltrexone and placebo groups.

It was not possible to identify specific populations who may benefit.

The authors concluded that there is little evidence to support wider use of naltrexone in the UK.

An earlier Cochrane review (search date to August 2005) reported on the use of opioid antagonists (naltrexone, naloxone) combined with alpha-2 adrenergic agonists (lofexidine and clonidine) in the management of opioid withdrawal [Gowing et al, 2006a]:

The small number of studies (seven), variability in treatment regimen, and variability in the means of assessing and reporting withdrawal severity made it impossible to draw firm conclusions as to the nature and intensity of withdrawal induced by an opioid antagonist–adrenergic agonist combination compared with withdrawal managed primarily with alpha-2 adrenergic agonist.

The authors concluded that:

Adding alpha-2 adrenergic agonists to the treatment regimen to ameliorate the signs and symptoms of withdrawal was a feasible approach to the management of opioid withdrawal.

There was insufficient evidence to determine whether opioid antagonists in combination with adrenergic agonists:

Reduce the duration of withdrawal treatment.

Increase the likelihood of completion of treatment withdrawal.

Increase rates of transfer to maintenance treatment with an opioid antagonist.

Levomethadyl acetate hydrochloride

Although levomethadyl acetate hydrochloride (LAAM) appears to be more effective than methadone at reducing heron use, it should not be used because of the risk of life-threatening cardiac arrhythmias.

Following cases of life-threatening arrhythmias in association with QT prolongation, the European Agency for the Evaluation of Medicinal Products (EMEA) has recommended that marketing authorization be withdrawn in Europe; the US Food and Drug Administration has recommended that LAAM not be used as first-line therapy.

A Cochrane review (search date to August 2000) found that LAAM appeared to be more effective than methadone at reducing heroin use [Clark et al, 2002]. LAAM has an advantage over methadone in that it has a longer duration of action and can therefore be dispensed on alternate days or three times a week. However, there was insufficient evidence to comment on the safety of LAAM:

People were more likely to have ceased LAAM than to have ceased methadone by the end of the study period (ten studies; n = 1454; RR 1.36, 95% CI 1.07 to 1.73, p = 0.0004).

There were significantly lower rates of non-abstinence in people allocated to LAAM treatment (five studies; n = 983; RR 0.81, 95% CI 0.72 to 0.91, p = 0.0003).

The percentage of urine tests negative for opiates was greater in the LAAM group (one study; n = 110; weighted mean difference –10.0, 95% CI –11.0 to –8.5, p < 0.00001).

Dihydrocodeine

Dihydrocodeine may have a role in maintenance treatment but evidence is very limited.

An open-label randomized controlled study compared the efficacy of dihydrocodeine with methadone maintenance treatment in people with opioid dependence. Participants (n = 235) were randomized to receive either methadone (dose range 40 mg to 150 mg methadone daily) or an equivalent dose of dihydrocodeine. The authors stated that equivalent amounts of dihydrocodeine were used (30 mg of dihydrocodeine was taken to be roughly equivalent to 2.5 mg methadone). Follow up was for 42 months [Robertson et al, 2006]:

There were similar rates of retention in treatment in the two groups.

People taking dihydrocodeine were more likely to switch to methadone.

Although these results look promising, they may reflect a high quality of care provided, and it is not known if they can be generalized to other clinical settings [Hall and Mattick, 2007].

An open-label randomized controlled study of 60 participants compared buprenorphine with dihydrocodeine for opioid detoxification in primary care. Only 13 people completed the study, but more people on buprenorphine completed detoxification, provided a clean urine sample at the end of the study, and were abstinent at 3 months of follow up [Wright et al, 2007].

Psychosocial interventions

Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, results at follow up, and compliance.

For a full discussion of the evidence see NICE clinical guidelines on Drug misuse, psychosocial interventions, available at www.nice.org.uk [National Collaborating Centre for Mental Health, 2007b].

A Cochrane review (search date to April 2003) reported that psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, results at follow up, and compliance [Amato et al, 2004b]. The authors identified limitations of the review, notably the heterogeneity of the assessment of outcomes, and therefore no meta-analysis could be performed:

Completion of treatment:

People undergoing any psychosocial treatment plus any drug therapy had better treatment-completion rates compared with any drug therapy alone (five studies; n = 184; relative risk [RR] 1.86, 95% CI 1.11 to 2.55).

There were trends towards better treatment-completion rates for psychosocial interventions plus drug therapy compared with drug therapy alone:

Any psychosocial intervention plus methadone compared with methadone alone (four studies; n = 145; RR 1.48, 95% CI 0.93 to 2.35).

Contingency management approaches plus methadone compared with methadone alone (three studies; n = 95; RR 1.51, 95% CI 0.93 to 2.46).

Contingency management approaches plus buprenorphine compared with buprenorphine alone (one study; n = 39; RR 2.63, 95% CI 0.99 to 6.98).

Psychotherapeutic counselling plus methadone compared with methadone alone (one study; n = 50; RR 1.33, 95% CI 0.33 to 5.36).

Use of primary substance:

The authors found trends in favour of contingency-management approaches and psychotherapeutic counselling compared with pharmacological treatments alone:

Contingency-management approaches plus methadone compared with methadone alone (one study; n = 20; RR 0.50, 95% CI 0.27 to 0.93).

Psychotherapeutic counselling plus methadone compared with methadone alone (one study; n = 50; RR 083, 95% CI 0.44 to 1.56).

Contingency-management approaches plus buprenorphine compared with buprenorphine alone (one study; n = 39; RR 0.88, 95% CI 0.67 to 1.15).

No statistically significant differences were reported for other comparisons:

Any psychosocial intervention plus any pharmacological intervention compared with any pharmacological intervention alone (three studies; n = 109; RR 0.77, 95% CI 0.59 to 1.01).

Any psychosocial intervention plus methadone compared with methadone alone (two studies; n = 70; RR 0.68, 95% CI 0.43 to 1.07).

Compliance:

People taking any psychosocial treatment plus any drug therapy had better compliance (measured as clinic attendance) compared with any drug therapy alone:

Any psychosocial intervention plus methadone compared with methadone alone (three studies; n = 1138; RR 0.48, 95% CI 0.38 to 0.59).

Contingency-management approaches plus methadone compared with methadone alone (two studies; n = 66; RR 0.29, 95% CI 0.15 to 0.56).

Psychotherapeutic counselling plus methadone compared with methadone alone (one study; n = 50; RR 0.51, 95% CI 0.41 to 0.65).

A second Cochrane review (search date to April 2003) reported that adding any psychosocial support to standard methadone maintenance therapy (MMT) significantly improves the non-use of heroin during treatment [Amato et al, 2004a]. The authors did report on limitations of the review, notably the heterogeneity of the trials both in the interventions and the assessment of outcomes; the duration of the studies was also too short to analyse all relevant outcomes:

Retention in treatment:

No statistically significant difference was found between any psychosocial intervention plus MMT and standard MMT alone:

Any psychosocial intervention plus MMT compared with standard MMT alone (eight studies; n = 510; RR 0.94, 95% CI 0.85 to 1.02).

All behavioural interventions plus MMT compared with standard MMT alone (five studies; n = 298; RR 0.96, 95% CI 0.87 to 1.06).

Contingency-management approaches plus MMT compared with standard MMT alone (three studies; n = 247; RR 0.98, 95% CI 0.90 to 1.08).

Psychoanalytically oriented interventions plus MMT compared with standard MMT alone (two studies; n = 140; RR 0.97, 95% CI 0.82 to 1.14).

Short-term interpersonal therapy plus MMT compared with standard MMT alone (one study; n = 72; RR 0.51, 95% CI 0.20 to 1.31).

Use of primary substance:

Statistically significant differences were found in favour of psychosocial interventions associated with MMT compared with standard MMT alone, except for psychoanalytically-oriented interventions:

Any psychosocial intervention plus MMT compared with standard MMT alone (five studies; n = 388; RR 0.69, 95% CI 0.53 to 0.91).

Contingency management approaches plus MMT compared with standard MMT alone (two studies; n = 169; RR 0.71, 95% CI 0.54 to 0.94).

Psychoanalytically oriented interventions plus MMT compared with standard MMT alone (two studies; n = 127; RR 0.83, 95% CI 0.47 to 1.45).

Enhanced methadone services plus MMT compared with standard MMT alone (one study; n = 92; RR 0.43, 95% CI 0.23 to 0.80).

A third Cochrane review (search date to 2003) concluded that there is insufficient evidence to suggest that psychosocial treatments alone are an adequate treatment regimen for opioid dependence, or are superior to any other type of treatment [Mayet et al, 2004]:

Five trials were included in the review, but the results could not be pooled or summarized, due to heterogeneity.

The main findings were that both the 'Enhanced Outreach Counselling' and 'Brief Reinforcement Based Intensive Outpatient Therapy' coupled with 'Contingency Management' had significantly better outcomes than control (standard) therapy:

The Enhanced Outreach Counselling Program had a beneficial effect on re-enrolling people who failed on MMT back into drug treatments, as compared with control (one study; n = 41; RR 0.27, 95% CI 0.14 to 0.52).

Brief Reinforcement Based Intensive Outpatient Therapy was more likely to retain people in treatment (one study; n = 52; RR 0.47, 95% CI 0.29 to 0.77). They also reported more abstinence from opioids and other illicit substances and a higher chance of employment after the therapy had been finished.

Contingency Management (Voucher Reinforcement) and Cue Exposure therapies showed no advantage over control therapy.

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