Schizophrenia
Schizophrenia - Summary
Schizophrenia is a psychiatric disorder that typically first presents in adolescence and young adulthood.
It is characterized by psychotic symptoms (e.g. hallucinations, delusions, and thought disorders), negative symptoms, and a lack of insight by the person into their condition.
Schizophrenia is thought to occur due to a combination of genetic and environmental factors (such as migration, cannabis use, and stress).
Schizophrenia is usually, but not always, preceded by a prodromal period that may last months or years before psychotic symptoms develop.
With treatment, psychotic symptoms may resolve fully, recur intermittently with periods of remission between, or persist.
Complications include:
An increased risk of premature death due to an increased risk of suicide, cardiovascular disease, and Type 2 diabetes.
Social disability.
Substance misuse.
The availability of mental health services varies. Carers and primary care providers should ensure that they understand the local provision by seeking local advice. Available services include:
Community mental health services (CMHS).
Early intervention services.
Crisis resolution/home treatment teams.
For people with suspected schizophrenia, the decision to refer for same-day specialist assessment or urgent specialist assessment within a few days is determined by the risk of harm to themselves and to other people:
For people judged to be at high risk of harm to themselves or others, same-day specialist assessment should be arranged.
For people judged not to be at immediate risk of harm to themselves or others, urgent referral for a specialist assessment by the the early intervention service, if available, or the CMHS should be arranged.
Antipsychotic treatment should not be started while awaiting referral unless the clinician is experience in treating and managing schizophrenia.
For people with anxiety problems or insomnia who are awaiting referral, short-term treatment with an anxiolytic or hypnotic should be considered.
In secondary care, people with newly diagnosed schizophrenia will be offered an oral antipsychotic drug as well as psychological and psychosocial interventions. A care plan will be written and a copy sent to the referring primary healthcare professional.
For people with an established diagnosis of schizophrenia who relapse, a risk assessment should be done:
If they already have a treatment care plan, they should be managed according to the plan.
If they do not have a care plan and are judged to be at immediate risk of harm to themselves or others, same-day specialist assessment should be arranged.
If they do not have a care plan and are judged not to be at immediate risk of harm to themselves or others, urgent referral for a specialist assessment by the the early intervention service, if available, or the CMHS should be arranged.
Most people with schizophrenia will be under specialist mental health supervision, usually with a Care Programme Approach.
Have I got the right topic?
This CKS topic is based on guidance issued by the National Institute for Health and Clinical Excellence, Schizophrenia: core interventions in the treatment and management of schizophrenia in adults in primary and secondary care [NICE, 2009].
This CKS topic covers the recognition and management, in primary care, of people with schizophrenia.
This CKS topic does not cover the management of schizophrenia in secondary care, or unipolar depression.
There are separate CKS topics on Alcohol - problem drinking, Bipolar disorder, Depression, Depression - antenatal and postnatal, Depression in children, and Poisoning or overdose.
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
March 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic [BMA and NHS Employers, 2012]. Issued in April 2012.
February 2012 — minor update. New information about the rare association of quetiapine with diabetic ketoacidosis has been added [ABPI Medicines Compendium, 2011a]. Issued in February 2012.
January 2012 — minor update. Relevant information from the Medicines and Healthcare products Regulatory Agency (MHRA) safety alert about a risk of extra-pyramidal effects or withdrawal symptoms (or both) in newborns after maternal use of anti-psychotics during the third trimester of pregnancy has been added to this topic [MHRA, 2011b]. Issued in January 2012.
May 2011 — minor update. Relevant recommendations from the NICE guideline Psychosis with coexisting substance misuse have been incorporated into this topic. The 2011/2012 QOF indicators have also been added to this topic [BMA and NHS Employers, 2011]. Issued in June 2011.
March 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.
October 2009 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) has reminded prescribers that smoking induces metabolism of olanzapine and clozapine, so stopping smoking can increase levels of these drugs, possibly causing increased adverse effects [MHRA, 2009b]. Issued in October 2009.
July to October 2009 — 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 have been no major changes to the recommendations.
Previous changes
April 2009 — updated to include the indicators related to schizophrenia in the Quality and Outcomes Framework (QOF) of the General Medical Services (GMS) contract in the Goals and outcome measures section. Issued in May 2009.
March 2009 — text updated to include new advice from the Medicines and Healthcare products Regulatory Agency (MHRA) on the increased risk of stroke with atypical antipsychotics in the elderly. Risperidone has been reclassified as a black triangle drug by the Medicines and Healthcare products Regulatory Agency (MHRA) after the granting of a new narrow indication for short-term use for the treatment of dementia-related behavioural disturbances. Issued in April 2009.
September 2008 — minor correction to the Changes section. Issued in September 2008.
July to September 2006 — reviewed. Validated in December 2006 and issued in January 2007.
October 2005 — minor technical update. Issued in November 2005.
July 2005 — minor update. Quetiapine starter packs have been discontinued and the prescriptions have accordingly been updated. Issued in July 2005.
April 2004 — updated to include recent advice from the Committee on Safety of Medicines that risperidone and olanzapine should, where possible, be avoided in patients with a history of stroke or transient ischaemic attacks. Issued in July 2004.
March 2003 — written. Validated in June 2003 and issued in July 2003.
Update
New evidence
Evidence-based guidelines
Guidelines published since the last revision of this topic:
Kane, J.M. and Garcia-Ribera, C. (2009) Clinical guidelines recommendations for antipsychotic long-acting injections. British Journal of Psychiatry 195(52), S63-S67. [Abstract]
SIGN (2013) Management of schizophrenia. A national clinical guideline. Scottish Intercollegiate Guidelines Network. www.sign.ac.uk [Free Full-text]
NICE have produced an evidence summary on new medicine for schizophrenia:
NICE (2013) ESNM15: schizophrenia: lurasidone. National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]
HTAs (Health Technology Assessments)
HTAs published since the last revision of this topic:
NICE (2011) Aripiprazole for the treatment of schizophrenia in people aged 15 to 17 years. NICE technology appraisal guidance 213. National Institute for Health and Clinical Excellence www.nice.org.uk [Free full-text]
Economic appraisals
No new economic appraisals relevant to England since 1 May 2009.
Systematic reviews and meta-analyses
Systematic reviews published since the last revision of this topic:
Achilla, E. and McCrone (2013) The cost effectiveness of long-acting/extended-release antipsychotics for the treatment of schizophrenia: a systematic review of economic evaluations. Applied Health Economics and Health Policy 11(2), 95-106. [Abstract]
Ahmed, U., Jones, H., and Adams, C.E. (2010) Chlorpromazine for psychosis induced aggression or agitation (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Alvarez-Jimenez, M., Parker, A.G., Hetrick, S.E., et al. (2009) Preventing the second episode: a systematic review and meta-analysis of psychosocial and pharmacological trials in first-episode psychosis. Schizophrenia Bulletin 37(3), 619-630. [Abstract] [Free Full-text]
Ardizzone, I., Nardecchia, F., Marconi, A., et al. (2010) Antipsychotic medication in adolescents suffering from schizophrenia: a meta-analysis of randomized controlled trials. Psychopharmachology Bulletin 43(2), 45-66. [Abstract]
Asenjo Lobos, C., Komossa, K., Rummel-Kluge, C., et al. (2010) Clozapine versus other atypical antipsychotics for schizophrenia (Cochrane Review). The Cochrane Library. Issue 11. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Belgamwar, R.B., and El-Sayeh, H.G. (2011)Aripiprazole versus placebo for schizophrenia (Cochrane Review). The Cochrane Library. Issue 8. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Bola, J., Kao, D., and Soydan, H. (2011) Antipsychotic medication for early episode schizophrenia (Cochrane Review). The Cochrane Library. Issue 6. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Bundy, H., Stahl, D. and Maccabe, J.H. (2011) A systematic review and meta-analysis of the fertility of patients with schizophrenia and their unaffected relatives. Acta Psychiatrica Scandinavica 123(2), 98-106. [Abstract]
Chamberlain, I.J. and Sampson, S. (2013) Nidotherapy for people with schizophrenia (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Cohen, A.S., Brown, L.A., and Minor, K.S. (2010) The psychiatric symptomatology of deficit schizophrenia: a meta-analysis. Schizophrenia Research 118(1-3), 122-127. [Abstract]
Cohen, D., Bonnot, O., Bodeau, N., et al. (2012) Adverse effects of second-generation antipsychotics in children and adolescents: a Bayesian meta-analysis. Journal of Clinical Psychopharmacology 32(3), 309-316. [Abstract]
Cramer, H., Lauche, R., Klose, P., et al. (2013) Yoga for schizophrenia: a systematic review and meta-analysis. BMC Psychiatry 13(1), 32. [Abstract] [Free Full-text]
De Hert, M., Yu, W., Detraux, J., et al. (2012) Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs 26(9), 733-759. [Abstract]
Dipasquale, S., Pariante, C.M., Dazzan, P., et al. (2013) The dietary pattern of patients with schizophrenia: a systematic review. Journal of Psychiatric Research 47(2), 197-207. [Abstract]
Douglas, K.S., Guy, L.S., and Hart, S.D. (2009) Psychosis as a risk factor for violence to others: a meta-analysis. Psychological Bulletin 135(5), 679-706. [Abstract]
Duncan, E., Best, C., and Hagen, S. (2010) Shared decision making interventions for people with mental health conditions (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Edwards, S.J. and Smith, C.J. (2009) Tolerability of atypical antipsychotics in the treatment of adults with schizophrenia or bipolar disorder: a mixed treatment comparison of randomized controlled trials. Clinical Therapeutics 31(1), 1345-1359. [Abstract]
Fazel, S., Gulati, G., Linsell, L., et al. (2009) Schizophrenia and violence: systematic review and meta-analysis. PLoS Medicine 6(8), e1000120. [Abstract] [Free Full-text]
Foley, D.L. and Morley, K.I. (2011) Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Archives of General Psychiatry 68(6), 609-616. [Abstract]
Fleischhaker, W.W. (2009) Second-generation antipsychotic long-acting injections: systematic review. British Journal of Psychiatry 195(52), S29-S36. [Abstract]
Fusar-Poli, P. and Berger, G. (2012) Eicosapentaenoic acid interventions in schizophrenia: a meta-analysis of randomized, placebo-controlled studies. Journal of Clinical Psychopharmacology 32(2), 179-185. [Abstract]
Fusar-Poli, P., Kempton, M.J., and Rosenheck, R.A. (2013) Efficacy and safety of second-generation long-acting injections in schizophrenia: a meta-analysis of randomized-controlled trials. International Clinical Psychopharmacology 28(2), 57-66. [Abstract]
Gorczynski, P., and Faulkner, G. (2010) Exercise therapy for schizophrenia (Cochrane Review). The Cochrane Library. Issue 5. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Haddad, P.M., Taylor, M. and Niaz, O.S. (2009) First-generation antipsychotic long-acting injections v. oral antipsychotics in schizophrenia: systematic review of randomised controlled trials and observational studies. British Journal of Psychiatry 195(52), S20-S28. [Abstract]
Hartling, L., Abou-Setta, A.M., Dursun, S., et al. (2012) Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications: a systematic review and meta-analysis. Annals of Internal Medicine 157(7), 498-511. [Abstract] [Free Full-text]
Holley, H., Crone, D., Tyson, P. and Lovell, G. (2011) The effects of physical activity on psychological well-being for those with schizophrenia: a systematic review. British Journal of Clinical Psychology 50(1), 84-105. [Abstract]
Jaaskelainen, E., Juola, P., Hirvonen, N., et al. (2012) A systematic review and meta-analysis of recovery in schizophrenia. Schizophrenia Bulletin epub ahead of print. [Abstract]
Jones, C., Hacker, D., Cormac, I., et al. (2012) Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Kishi, T., Matsuda, Y., Nakamura, H., and Iwata, N. (2013) Blonanserin for schizophrenia: systematic review and meta-analysis of double-blind, randomized, controlled trials. Journal of Psychiatric Research 47(2), 149-154. [Abstract]
Kishi, T., Hirota, T., and Iwata, N. (2013) Add-on fluvoxamine treatment for schizophrenia: an updated meta-analysis of randomized controlled trials. European Archives of Psychiatry and Clinical Neuroscience epub ahead of print. [Abstract]
Kishimoto, T., Robenzadeh, A., Leucht, C., et al. (2013) Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophrenia Bulletin epub ahead of print. [Abstract]
Komossa, K., Rummel-Kluge, C., Hunger, H., et al. (2010) Amisulpride versus other atypical antipsychotics for schizophrenia (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Komossa, K., Rummel-Kluge, C., Hunger, H., et al. (2010) Zotepine versus other atypical antipsychotics for schizophrenia (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Komossa, K., Rummel-Kluge, C., Hunger, H., et al. (2010) Olanzapine versus other atypical antipsychotics for schizophrenia (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Komossa, K., Rummel-Kluge, C., Hunger, H., et al. (2009) Ziprasidone versus other atypical antipsychotics for schizophrenia (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Komossa, K., Rummel-Kluge, C., Schmid, F., et al. (2010) Quetiapine versus other atypical antipsychotics for schizophrenia (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Komossa, K., Rummel-Kluge, C., Schmid, F., et al. (2009) Aripiprazole versus other atypical antipsychotics for schizophrenia (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Komossa, K., Rummel-Kluge, C., Schwartz, S., et al. (2011) Risperidone versus other atypical antipsychotics for schizophrenia (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Lee, M.S., Shin, B.C., Ronan, P., and Ernst, E. (2009) Acupuncture for schizophrenia: a systematic review and meta-analysis. International Journal of Clinical Practice 63(11), 1622-1633. [Abstract] [Free Full-text]
Lee, Y.J. and Jeong, J.H. (2011) A systematic review of metformin to limit weight-gain with atypical antipsychotics. Journal of Clinical Pharmacy and Therapeutics 36(5), 537-545. [Abstract] [Free Full-text]
Leucht, C., Heres, S., Kane, J.M., et al. (2011) Oral versus depot antipsychotic drugs for schizophrenia-a critical systematic review and meta-analysis of randomised long-term trials. Schizophrenia Research 127(1-3), 83-92. [Abstract]
Leucht, S., Tardy, M., Komossa, K., et al. (2012) Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 379(9831), 2063-2071. [Abstract]
Leucht, S., Tardy, M., Komossa, K., et al. (2012) Maintenance treatment with antipsychotic drugs for schizophrenia (Cochrane Review). The Cochrane Library. Issue 5. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Li, C., Xia, J., and Wang, J. (2009) Risperidone dose for schizophrenia (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Matheson, S.L., Shepherd, A.M., Pinchbeck, R.M., et al. (2013) Childhood adversity in schizophrenia: a systematic meta-analysis. Psychological Medicine 43(2), 225-238. [Abstract]
Michalczuk, R., and Mitchell, A. (2009) Monetary incentives for schizophrenia (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Miller, B., Messias, E., Miettunen, J., et al. (2010) Meta-analysis of paternal age and schizophrenia risk in male versus female offspring. Schizophrenia Bulletin 37(5), 1039-1047. [Abstract] [Free Full-text]
Morriss, R., Vinjamuri, I., Faizal, M.A., et al. (2013) Training to recognise the early signs of recurrence in schizophrenia (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Moteshafi, H. and Stip, E. (2012) Comparing tolerability profile of quetiapine, risperidone, arpiprazole and ziprasidone in schizophrenia and affective disorders: a meta-analysis. Expert Opinion on Drug Safety 11(5), 713-732. [Abstract]
Mukundan, A., Faulkner, G., Cohn, T., and Remington, G. (2010)Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems (Cochrane Review). The Cochrane Library. Issue 12. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Newton-Howes, G. and Wood, R. (2013) Cognitive behavioural therapy and the psychopathology of schizophrenia: systematic review and meta-analysis. Psychology and Psychotherapy 86(2), 127-138. [Abstract]
Nussbaum, A.M., and Stroup, T.S. (2012) Paliperidone palmitate for schizophrenia (Cochrane Review). The Cochrane Library. Issue 6. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Ozbilen, M., Adams, C.E., and Marley, J. (2012) Anticholinergic effects of oral antipsychotic drugs of typical versus atypical over medium- and long-term: systematic review and meta-analysis. Current Medicinal Chemistry 19(30), 5214-5218. [Abstract]
Rajji, T.K., Ismail, Z., and Mulsant, B.H. (2009) Age at onset and cognition in schizophrenia: meta-analysis. British Journal of Psychiatry 195(4), 286-293. [Abstract] [Free Full-text]
Rattehalli, R.D., Jayaram, M.B., and Smith, M. (2010) Risperidone versus placebo for schizophrenia (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Rosenheck, R.A., Krystal, J.H., Lew, R., et al. (2011) Long-acting risperidone and oral antipsychotics in unstable schizophrenia. New England Journal of Medicine 364(9), 842-851. [Abstract] [Free Full-text]
Rossi, G., Frediani, S., Rossi, R., and Rossi, A. (2012) Long-acting antipsychotic drugs for the treatment of schizophrenia: use in daily practice from naturalistic observations. BMC Psychiatry 12, 122. [Abstract] [Free Full-text]
Rummel-Kluge, C., Komossa, K., Schwarz, S., et al. (2010) Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophrenia Research 123(2-3), 225-233. [Abstract] [Free Full-text]
Seida, J.C., Schouten, J.R., Boylan, K., et al. (2012) Antipsychotics for children and young adults: a comparative effectiveness review. Pediatrics 129(3), e771-e784. [Abstract]
Shen, X., Xia, J., and Adams, C.E. (2012) Flupenthixol versus placebo for schizophrenia (Cochrane review). The Cochrane Library. Issue 11. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Singh, J., Kour, K., and Jayaram, M.B. (2012) Acetylcholinesterase inhibitors for schizophrenia (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Singh, S.P., Singh, V., Kar, N. and Chan, K. (2010) Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. British Journal of Psychiatry 197(3), 174-179. [Abstract] [Free Full-text]
Sivaraman, P., Rattehalli, R.D., and Jayaram, M.B. (2010)Levomepromazine for schizophrenia (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Soares-Weiser, K., Bechard-Evans, L., Howard Lawson, A., et al. (2013) Time to all-cause discontinuation of olanzapine compared to other antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. European Neuropsychopharmacology 23(2), 118-125. [Abstract]
Subramanian, S., Rummel-Kluge, C., Hunger, H., et al. (2010) Zotepine versus other atypical antipsychotics for schizophrenia (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Tarricone, I., Ferrari Gozzi, B., Serretti, A., et al. (2009) Weight gain in antipsychotic-naive patients: a review and meta-analysis. Psychological Medicine 6(1), 1-14. [Abstract]
Tenback, D.E., van Harten, P.N., and van Os, J. (2009) Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: a meta-analysis. Movement Disorders 24(16), 2309-2315. [Abstract]
Topiwala, A. and Seena, S. (2011) The pharmacological management of violence in schizophrenia: a structured review. Expert Review of Neurotherapeutics 11(1), 53-63. [Abstract]
Tosh, G., Clifton, A., and Bachner, M. (2011) General physical health advice for people with serious mental illness (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Tsoi, D.T., Porwal, M. and Webster, A.C. (2010) Efficacy and safety of bupropion for smoking cessation and reduction in schizophrenia: systematic review and meta-analysis. British Journal of Psychiatry 196(5), 346-353. [Abstract] [Free Full-text]
Uchida, H., Suzuki, T., Takeuchi, H., et al. (2009) Low dose vs standard dose of antipsychotics for relapse prevention in schizophrenia: meta-analysis. Schizophrenia Bulletin 37(4), 788-799. [Abstract] [Free Full-text]
Valimaki, M., Hatonen, H., Lahti, M., et al. (2012) Information and communication technology in patient education and support for people with schizophrenia (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Vancampfort, D., Vensteelandt, K., Scheewe, T., et al. (2012) Yoga in schizophrenia: a systematic review of randomised controlled trials. Acta Psychiatrica Scandinavica 126(1), 12-20. [Abstract]
Wang, J., Omori, I.M., Fenton, M. and Soares, B. (2010) Sulpiride augmentation for schizophrenia (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Zou, H., Li, Z,. Nolan, M.T., et al. (2013) Self-management education interventions for persons with schizophrenia: a meta-analysis. International Journal of Mental Health Nursing 22(3), 256-271. [Abstract]
Primary evidence
A study which assessed clinical and economic ramifications of switching antipsychotics has been published since the last revision of this topic:
Faries, D.E., Ascher-Svanum, H., Nyhuis, A.W., et al. (2009) Clinical and economic ramifications of switching antipsychotics in the treatment of schizophrenia. BMC Psychiatry 9, 54. [Abstract] [Free Full-text]
Randomized controlled trials published since the last revision of this topic:
Addington, D.E., Mohamed, S., Rosenheck, R.A., et al. (2010) Impact of second-generation antipsychotics and perphenazine on depressive symptoms in a randomized trial of treatment for chronic schizophrenia. Journal of Clinical Psychiatry 72(1), 75-80. [Abstract]
Chen, E.Y., Hui, C.L., Lam, M.M., et al. (2010) Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial. BMJ 341, c4024. [Abstract] [Free Full-text]
Girgis, R.R., Phillips, M.R., Li, X., et al. (2011) Clozapine v. chlorpromazine in treatment-naive, first-episode schizophrenia: 9-year outcomes of a randomised clinical trial. British Journal of Psychiatry 199(4), 281-288. [Abstract] [Free Full-text]
Guo, X., Zhai, J., Liu, Z., et al. (2010) Effect of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia: a randomized, 1-year study. Archives of General Psychiatry 67(9), 895-904. [Abstract] [Free Full-text]
Roffman, J.L., Lamberti, J.S., Achtyes, E., et al. (2013) Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. JAMA Psychiatry 70(5), 481-489. [Abstract]
Observational studies published since the last revision of this topic:
Boden, R., Lundgren, M., Brandt, L., et al. (2012) Antipsychotics during pregnancy. Relation to maternal metabolic effects. Archives of General Psychiatry 69(7), 715-721. [Abstract]
Correll, C.U., Manu, P., Olshanskiy, V., et al., (2009) Cardiometabolic risk of second-generation antipsychotic medications first-time use in children and adolescents. JAMA 302(16), 1765-1773. [Abstract] [Free Full-text]
Glick, I.D., Correll, C.U., Altamura, A.C., et al. (2011) Mid-term and long-term efficacy and effectiveness of antipsychotic medications for schizophrenia: a data-driven, personalized clinical approach. Journal of Clinical Psychiatry 72(12), 1616-1627. [Abstract]
Hoang, U., Stewart, R., and Goldacre, M.J. (2011) Mortality after hospital discharge for people with schizophrenia or bipolar disorder: retrospective study of linked English hospital episode statistics, 1999-2006. BMJ 343, d5422. [Abstract] [Free Full-text]
Kessing, L.V., Thomsen, A.F., Mogensen, U.B., and Andersen, P.K. (2010) Treatment with antipsychotics and the risk of diabetes in clinical practice. British Journal of Psychiatry 197(4), 266-271. [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]
Parker, C., Coupland, C. and Hippisley-Cox, J. (2010) Antipsychotic drugs and risk of venous thromboembolism: nested case-control study. BMJ 341, c4245. [Abstract] [Free Full-text]
Trifirò, G., Gambassi, G., Sen, E.F., et al. (2010) Association of community-acquired pneumonia with antipsychotic drug use in elderly patients: a nested case-control study. Annals of Internal Medicine 152(7), 418-425. [Abstract]
New policies
The Government has published its Mental Health Strategy:
No health without mental health: a cross-Government mental health outcomes strategy for people of all ages.
Reference: HM Government (2011) No health without mental health: a cross government mental health outcomes strategy for people of all ages. Department of Health. www.dh.gov.uk [Free Full-text]
New safety alerts
September 2011: The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a safety alert following a recent Europe-wide review that concluded that there is a risk of extra-pyramidal effects or withdrawal symptoms (or both) in newborns after maternal use of anti-psychotics during the third trimester of pregnancy. This conclusion was based on worldwide post-marketing case reports and information provided by the US Food and Drugs Administration.
There are insufficient data to determine the size of the risk or any difference in risk between classes of antipsychotics or between individual antipsychotics.
The MHRA has issued the following advice to healthcare professionals:
Following maternal use of antipsychotics in the third trimester, examine newborns for symptoms which may include: agitation, hypertonia, hypotonia, tremor, somnolence, feeding problems, and respiratory distress.
Symptoms may vary in severity and duration, and they should be monitored and treated (if necessary) on an individual basis.
Expectant mothers should be counselled about the benefits and risks of antipsychotic treatment during pregnancy.
Reference: MHRA (2011) Antipsychotics: use during third trimester of pregnancy and extrapyramidal effects or withdrawal symptoms in newborns. Drug Safety Update 5(2), A2. [Free Full-text]
April 2011: The MHRA has reminded prescribers to monitor and manage weight, blood glucose, and lipid levels in people taking atypical (second–generation) antipsychotics.
Reference: MHRA (2011) Atypical (second-generation) antipsychotics: reminder to monitor and manage weight, glucose and lipid levels. Drug Safety Update 4(9), H1. [Free Full-text (pdf)]
October 2009: The MHRA has reminded prescribers that smoking induces metabolism of olanzapine and clozapine, so stopping smoking can increase levels of these drugs, possibly causing increased adverse effects.
Reference: MHRA (2009) Smoking and smoking cessation: clinically significant interactions with commonly used medicines. Drug Safety Update 3(3), 9-10 [Free Full-text]
Changes in product availability
No changes in product availability since 1 May 2009.
Goals and outcome measures
Goals
To ensure accurate diagnosis by referring all people with suspected schizophrenia for specialist confirmation of the diagnosis
To ensure optimal control of psychotic symptoms by:
Referring all people with suspected schizophrenia for specialist management
Referring all people experiencing a relapse of schizophrenia for specialist management
To manage cardiovascular disease risk by:
Annual assessment of cardiovascular disease risk
Managing cardiovascular disease risk factors in people at increased risk
To ensure that all people with schizophrenia and their carers are well informed about the support available; to help them back into work or education, their housing options, entitlement to benefits, and entitlement to drive
QOF indicators
| Indicator | Points | Payment stages |
|---|---|---|
| Mental health | ||
| MH 8The practice can produce a register of people with schizophrenia, bipolar disorder and other psychoses. | 4 | — |
| MH 11The percentage of patients with schizophrenia, bipolar affective disorder and other psychoses who have a record of alcohol consumption in the preceding 15 months. | 4 | 50–90% |
| MH 12The percentage of patients with schizophrenia, bipolar affective disorder and other psychoses who have a record of BMI in the preceding 15 months. | 4 | 50–90% |
| MH 13The percentage of patients with schizophrenia, bipolar affective disorder and other psychoses who have a record of blood pressure in the preceding 15 months. | 4 | 50–90% |
| MH 19The percentage of patients aged 40 years and over with schizophrenia, bipolar affective disorder and other psychoses who have a record of total cholesterol:HDL ratio in the preceding 15 months. | 5 | 45–80% |
| MH 20The percentage of patients aged 40 years and over with schizophrenia, bipolar affective disorder and other psychoses who have a record of blood glucose or HbA1c in the preceding 15 months. | 5 | 45–80% |
| MH 16The percentage of women (aged from 25 to 64 in England and Northern Ireland, from 20 to 60 in Scholand, and from 20 to 64 in Wales) with schizophrenia, bipolar affective disorder and other psychoses whose notes record that a cervical screening test has been performed in the preceding 5 years. | 5 | 45–80% |
| MH 10The percentage of patients on the register who have a comprehensive care plan documented in the records agreed between individuals, their family and/or carers as appropriate. | 6 | 30–55% |
| Smoking | ||
| SMOKING 5The percentage of patients with any or any combination of the following conditions: CHD, PAD, stroke or TIA, hypertension, diabetes, COPD, CKD, asthma, schizophrenia, bipolar affective disorder or other psychoses who smoke, whose notes record smoking status in the preceding 15 months. | 25 | 50–90% |
| SMOKING 6The percentage of patients with any or any combination of the following conditions: CHD, PAD, stroke or TIA, hypertension, diabetes, COPD, CKD, asthma, schizophrenia, bipolar affective disorder or other psychoses who smoke, whose notes contain a record of an offer of support and treatment within the preceding 15 months. | 25 | 50–90% |
Background information
Definition
What is it?
Schizophrenia is a psychiatric disorder that typically first presents in adolescence and young adulthood. It is characterized by:
Psychotic symptoms (also known as positive symptoms) comprising:
Hallucinations.
Delusions.
Thought disorder.
Negative symptoms, including emotional blunting, paucity of speech, loss of motivation, self neglect, and social withdrawal.
A lack of insight by the person into their condition.
Hallucinations are perceptions, indistinguishable from reality, occurring in the absence of an external stimulus.
Auditory hallucinations, in which voices are heard, are the most common. Voices may provide a running commentary on their actions, argue about the person, or echo the person's thoughts (thought echo).
Visual, smell, taste, or tactile hallucinations occur less commonly. Visual hallucinations occur in about 10% of people with schizophrenia, but organic disorders should be excluded.
Delusions are false personal beliefs that are held with conviction despite evidence to the contrary. They include:
Delusions of reference, in which the person believes that ordinary events, objects, or the behaviour of others has a particular and unusual meaning specifically for them. For example a delusional belief that people on the radio are talking about, or directly to, the person.
Delusions of control, in which the person believes that their thoughts, feelings, or behaviour are being controlled by other people. They include:
Thought insertion — the delusional belief that thoughts are being inserted into the person's mind by an outside agency.
Thought withdrawal — the delusional belief that thoughts are being removed from the person's mind by an outside agency.
Thought broadcasting — the delusional belief that the person's thoughts are being read or heard by others.
Delusions of persecution, in which the person believes that other people are plotting against them.
Thought disorder is an impairment of the ability to form thoughts from logically connected ideas. It is apparent in the person's speech. It may be mild, when occasional logical disruptions may make their conversation hard to follow, to severe, when logical connections between ideas are so greatly affected that speech becomes incoherent.
A prodromal period, typically (although not invariably) lasting months or years, precedes the development of psychotic symptoms. This period is characterized by:
Emotional and behavioural problems leading to a deterioration in personal functioning and social withdrawal.
Attenuated psychotic symptoms in some people. These are symptoms that are insufficiently unusual to be considered hallucinations, delusions, or thought disorders — for example subtle perceptual abnormalities that are insufficiently abnormal to be considered hallucinations, or peculiar ideas that are insufficiently abnormal to be considered delusions.
[Picchioni and Murray, 2007; National Collaborating Centre for Mental Health, 2009]
Causes/risk factors
What causes it?
Schizophrenia is thought to occur due to a combination of genetic and environmental factors [National Collaborating Centre for Mental Health, 2009]. The stress vulnerability model proposes that:
The degree of vulnerability to schizophrenia of an individual is genetically determined.
Schizophrenia is triggered by environmental stress.
If vulnerability is high, only low levels of environmental stress are needed to trigger schizophrenia.
Conversely, if vulnerability is lower, a high level of environmental stress can be experienced before schizophrenia is triggered.
The role of genetic factors in the development of schizophrenia is supported by the increased risk of schizophrenia in people with an affected relative [Stefan et al, 2002].
Lifetime risk in the child of one affected parent: 13%.
Lifetime risk in a child with two affected parents: 46%.
Lifetime risk in a sibling or a dizygotic twin: about 10%.
Lifetime risk in an identical twin: 48%.
Important environmental factors known to increase the risk of schizophrenia include:
Migration. Immigrants are 4.6 times more likely than a native population to be diagnosed with schizophrenia [McGrath et al, 2008].
Urban living. People living in an urban setting are almost twice as likely as people from a mixed urban-rural setting to develop schizophrenia [McGrath et al, 2008].
Cannabis use. Cannabis users as a group are 40% more likely than non-users to develop a psychotic illness [Moore et al, 2007]. This risk increases with heavier use, especially if daily use starts in adolescence.
Stress and traumatic life experiences are associated with the onset of schizophrenia. However, it is unclear whether they are the cause or the effect of the onset of schizophrenia [RCGP, 2007].
Prevalence
How common is it?
A systematic review of the incidence and prevalence of schizophrenia found [McGrath et al, 2008]:
On average, 15 per 100,000 people will be newly diagnosed with schizophrenia each year.
The incidence of schizophrenia is higher in immigrants and urban populations, and possibly also in men.
Immigrants are 4.6 times more likely than a native population to be diagnosed with schizophrenia.
People living in an urban setting are almost twice as likely as people from a mixed urban-rural setting to develop schizophrenia.
On average, 4 per 1000 people will have a diagnosis of schizophrenia.
Course and prognosis of schizophrenia
What is the course and prognosis of schizophrenia?
Schizophrenia is usually, but not always, preceded by a prodromal period that may last months or years before psychotic symptoms develop [National Collaborating Centre for Mental Health, 2009].
The diagnosis of schizophrenia is commonly delayed by several years after psychotic symptoms develop [RCGP, 2007]. This may be due to a lack of reporting of psychotic symptoms by the person experiencing them and a lack of enquiry about them by clinicians.
A longer duration of untreated psychosis is associated with poorer long-term outcomes, with a poorer response to treatment, and more pronounced negative and psychotic symptoms and lower global functioning [Bottlender et al, 2003].
With treatment, psychotic symptoms may [Mason et al, 1996]:
Resolve fully and not recur. About 20% of people who are admitted to hospital for their first episode of schizophrenia do not have another acute episode.
Recur intermittently with periods of remission between. About 50% of people with schizophrenia treated in standard services will relapse and require readmission within the first 2 years of their illness.
Persist. Around 30% of people have a more continuous illness, in which they are never free of symptoms, although the severity of symptoms changes over time.
Factors associated with a poor prognosis include [Barnes and Pant, 2002; Stefan et al, 2002]:
A longer duration of untreated psychosis.
Early or insidious onset of schizophrenia.
Male sex.
Negative symptoms.
Family history of schizophrenia.
Low level of intelligence, low social class, or social isolation.
Significant psychiatric history.
Continued substance abuse.
Complications
What are the complications?
Schizophrenia is associated with an increased risk of premature death. On average, people with schizophrenia die 10 years earlier than the general population [RCGP, 2007]. This is due to an increased risk of:
Suicide. About 1 in 10 people with schizophrenia commit suicide [RCGP, 2007]. The risk of suicide is highest in people who:
Have recently been diagnosed with schizophrenia.
Are socially isolated, depressed, or unemployed.
Cardiovascular disease. This is probably because smoking, obesity, and a poor diet are more common among people with schizophrenia [National Collaborating Centre for Mental Health, 2009].
Type 2 diabetes. This is thought to be caused by a combination of lifestyle factors, such as poor diet and lack of exercise, and treatment with antipsychotic drugs [National Collaborating Centre for Mental Health, 2009]. Both first-generation and second-generation antipsychotic drugs have been associated with an increased risk of diabetes. Weight gain, which is more common with the second-generation antipsychotics, is probably a contributory factor.
Social disability — negative symptoms, such as emotional blunting, paucity of speech, loss of motivation, self neglect, and social withdrawal, are often the major cause of social disability for people with schizophrenia by impairing the person's ability to learn, work, and maintain relationships [RCGP, 2007].
Substance misuse — 9–35% of people in the UK with schizophrenia misuse alcohol or drugs [Stefan et al, 2002].
Mental health services
Which mental health services are available (depending on locality), and what is their role?
The availability of mental health services varies. Carers and primary care providers should ensure they understand the local provision by seeking local advice. These services include:
Community mental health services (CMHS) provide the core of local specialist mental health services and offer assessment, treatment, and social care to adults with mental health problems in the community. They typically operate from mental health resource centres based away from the main psychiatric hospital site. In many areas, the CMHS is the gateway to the more specialized teams (such as assertive outreach teams) [DH, 2002]. People are referred to the CMHS for an initial assessment and are then placed with the team that best suits their needs.
Early intervention services provide care for people during a first episode of psychosis [National Collaborating Centre for Mental Health, 2009]. In general, they are restricted to providing care to people 14–35 years of age, but different age criteria may be used in some areas. Early intervention teams (where they exist) can be accessed directly by the GP. Some areas have direct access to all their specialist mental health teams. The service may be provided by a team, or a specialized element of a team, which has designated responsibility for at least two of the following functions:
Early identification and therapeutic engagement of people in the prodromal phase.
Provision of specialized pharmacological and psychosocial interventions during, or immediately after, a first episode of psychosis.
Education of the wider community to reduce obstacles to early engagement in treatment.
Assertive outreach teams (also known as assertive community treatment) deliver intensive treatment and rehabilitation in community settings for severely mentally ill people. They provide rapid help in crises. Staff will visit people at home, act as an advocate, and liaise with other services, such as the GP or social services. People using this service often need help to find housing, secure an adequate income, and sustain basic daily living (for example shopping, cooking, and washing) [DH, 1999]. They aim to keep people with serious mental health problems, who have difficulty engaging with services and managing their illness, more independently in-touch with services, to reduce the number and frequency of hospital admissions, and to improve outcomes [National Collaborating Centre for Mental Health, 2009]. They should provide care for homeless people with schizophrenia.
Crisis resolution/home treatment teams enable people to be treated at home (instead of as inpatients) during a relapse of their illness [National Collaborating Centre for Mental Health, 2009]. They are the only specialist mental health team that is available to help with crises that occur outside normal office hours (although crisis numbers and lines are often available). However, these teams may not accept people who are not already known to the mental health services.
Inpatient care is the most widely available option for people who need rapid assessment and stabilization during an acute episode. This includes people who need compulsory care under the Mental Health Act because they are so severely ill that they cannot make a decision about treatment, or because they decline any type of treatment.
Acute day hospital is another alternative to inpatient care. It also facilitates early discharge from inpatient care [National Collaborating Centre for Mental Health, 2009].
Building relationships with patients
Building relationships with patients
When working with people with known or suspected psychosis, with or without coexisting 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 both psychosis and substance misuse.
Some people will try to conceal some or both of their conditions.
Many people with psychosis and coexisting substance misuse fear being detained or imprisoned, being given psychiatric medication forcibly, or having their children taken into care.
Diagnosis
Diagnosis of schizophrenia
Screening
When should I screen and assess a person for schizophrenia?
Assess for schizophrenia in people presenting with:
Psychotic symptoms (hallucinations, delusions, and thought disorders manifest by incoherent or illogical speech).
Attenuated psychotic symptoms, when symptoms are insufficiently abnormal to be considered hallucinations, delusions, or thought disorders.
Screen for psychotic symptoms in young people with emotional or behavioural problems, including:
Anxiety or depression, or
Difficulties concentrating, or
Deterioration in personal functioning, such as a deterioration in academic achievement, work, or social interaction.
Screen for psychotic symptoms by asking:
Have you ever had the experience of hearing noises or voices when there is nobody around and nothing else to explain it?
Has it ever seemed to you that people are talking or gossiping about you, maybe even plotting against you?
Has it ever seemed to you that people can pick up on what you are thinking or can manipulate what you are thinking?
Young people with emotional or behavioural problems who do not have psychotic symptoms but do have a family history of schizophrenia are at increased risk of schizophrenia. These people should be monitored regularly for psychotic symptoms while emotional or behavioural problems continue.
Basis for recommendation
Basis for recommendation
Recommendations on who to screen and assess for schizophrenia are based on expert opinion from International clinical practice guidelines for early psychosis, published by the International Early Psychosis Association Writing Group [International Early Psychosis Association, 2005] and a review article [Picchioni and Murray, 2007].
Assessment
How should I assess a person for possible schizophrenia??
For people with any psychotic or attenuated psychotic symptoms:
Conduct a medical assessment to look for an underlying cause for symptoms, such as:
Prescribed drugs that can cause psychosis, such as anticonvulsants, high-dose corticosteroids, levodopa and dopamine agonists, or opioids.
Temporal lobe epilepsy.
Cerebrovascular disease.
Conduct a psychiatric assessment to assess for:
Abnormalities of mood, including anxiety or depressed or elevated mood.
Deterioration in personal functioning.
Illicit drug use that can cause psychosis, such as amphetamines or cocaine.
A family history of schizophrenia.
Psychotic symptoms in detail.
A detailed assessment of psychotic symptoms should include questions about:
Hallucinations — 'Have you ever had the experience of hearing noises or voices when there is nobody around and nothing else to explain it?', and 'Have you ever experienced hearing your own thoughts?'
Delusions, including:
Delusions of reference — 'Have you ever felt that strangers are talking about you behind your back?', and 'Have you ever felt that people on the TV or radio are talking about, or directly to, you?'
Thought insertion and withdrawal — 'Has it ever seemed to you that thoughts are being put into, or taken out of, your mind?'
Thought broadcasting — 'Has it ever seemed to you that other people are aware of your thoughts?'
Delusions of control — 'Have you ever felt under the control of an outside force?'
Delusions of persecution — 'Has it ever seemed to you that there is a conspiracy against you?'
Thought disorders — manifest by incoherent or illogical speech.
If the person has used substances, ask them about all of the following:
Particular substance(s) used.
Quantity, frequency, and pattern of use.
Route of administration.
Duration of current level of use.
Basis for recommendation
Basis for recommendation
Recommendation on how to assess a person with suspected schizophrenia are based on expert opinion from review articles [Blashki et al, 2004; Keks and Blashki, 2006].
The recommendation regarding questions to ask if the person has used substances is based on the NICE guideline Psychosis with coexisting substance misuse [NICE, 2011].
Diagnosis
How is schizophrenia diagnosed?
Refer people with psychotic or attenuated psychotic symptoms to specialist mental health services to establish the diagnosis.
The International Classification of Diseases-10 criteria for the diagnosis of schizophrenia require symptoms to be present most of the time for 1 month or more, including:
One or more of the following features if they are clear-cut, or two or more of the following features if they are not clear-cut:
Hallucinatory voices giving a running commentary on the person's behaviour, or discussing the person among themselves, or other types of hallucinatory voices coming from some part of the body.
Thought echo, thought insertion or withdrawal, and thought broadcasting.
Delusions of control, influence, or passivity, clearly referred to body or limb movements or specific thoughts, actions, or sensations.
Any two of the following criteria:
Persistent hallucinations in any form, when accompanied by fleeting or half-formed delusions without clear affective content, or by persistent over-valued ideas (similar to preoccupations), or when occurring every day for weeks or months on end.
Persistent delusions of other kinds that are culturally inappropriate and completely impossible, such as religious or political identity, or superhuman powers and abilities (for example being able to control the weather, or being in communication with aliens from another world).
Breaks or interpolations in the train of thought, resulting in incoherence or irrelevant speech, or neologisms (invented words).
Catatonic behaviour, such as: excitement, posturing, or waxy flexibility; negativism; mutism; and stupor.
Negative symptoms, such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses, usually resulting in social withdrawal and lowering of social performance; it must be clear that these are not due to depression or to antipsychotic medication.
A significant and consistent change in the overall quality of some aspects of personal behaviour, manifest as loss of interest, aimlessness, idleness, a self-absorbed attitude, and social withdrawal.
People with attenuated or intermittent psychotic symptoms who do not meet the diagnostic criteria for schizophrenia are considered to be at a higher risk of schizophrenia when:
Brief, limited psychotic symptoms appear intermittently, but too briefly to meet the diagnostic criteria for schizophrenia.
Attenuated psychotic symptoms are insufficiently abnormal to be considered to be hallucinations, delusions, or thought disorders.
Basis for recommendation
Basis for recommendation
Information about diagnosing schizophrenia is from expert opinion in a review article [Drake and Lewis, 2005].
Differential diagnosis
What else might it be?
Severe affective (mood) disorders associated with psychotic symptoms, including severe depression and bipolar disorder.
These conditions are distinguished from schizophrenia by the predominance of affective symptoms that may at times trigger psychosis.
In contrast, schizophrenia is dominated by psychotic symptoms that may at times be associated with affective symptoms.
Drug-induced psychosis caused by corticosteroids and opioids or by drugs of abuse, such as cocaine or amphetamines.
An underlying medical condition, such as cerebrovascular disease, cerebral tumours, epilepsy, or sepsis.
Basis for recommendation
Basis for recommendation
Information on the differential diagnosis of schizophrenia is based on expert opinion from a review article [Schultz et al, 2007].
Management
Management
Scenario: New or suspected schizophrenia: covers the risk assessment and management of people with new or suspected schizophrenia.
Scenario: Managing relapse: covers the risk assessment and management of people with known schizophrenia who have relapsed.
Scenario: The routine schizophrenia review: covers the routine follow up in primary care of people with known schizophrenia.
Scenario: Women of childbearing age: covers the management of women with schizophrenia who are planning a pregnancy, who present with an unplanned pregnancy, or who are planning to breastfeed.
Scenario: New or suspected schizophrenia
Scenario: New or suspected schizophrenia
Initial management in primary care
How should I manage people with suspected schizophrenia?
For all people with psychotic symptoms or attenuated psychotic symptoms, undertake a risk assessment and:
For people judged to be at high risk of harm to themselves or others, arrange same-day specialist assessment. Depending on local service arrangements, this may be carried out at home by liaison with a crisis resolution or home treatment team or require hospital admission.
If the person needs to be admitted to hospital, every attempt should be made to persuade them to go voluntarily.
If admission is necessary but the person declines, compulsory admission may be arranged under sections 2, 3, or 4 of the Mental Health Act.
For people judged not to be at immediate risk of harm to themselves or others, urgently refer for a specialist assessment to:
The early intervention service if available, or
The community mental health service (CMHS) if an early intervention service is not available. In many areas, the CMHS is the gateway to the more specialized teams, including crisis resolution or home treatment teams (the only team available out of hours) and acute day hospital. See Mental health services for more information.
Do not start antipsychotic treatment while awaiting referral unless you have experience in treating and managing schizophrenia (for example GPs with a special interest).
For people with anxiety problems or insomnia who are awaiting referral, consider short-term treatment with an anxiolytic or hypnotic.
Mental Health Act
Mental Health Act
The Mental Health Act allows compulsory admission of people who:
Have a mental disorder of a nature and degree that warrants treatment in hospital, and
Need to be admitted in the interests of their own health or safety, or for the protection of other people.
Compulsory admission is arranged using the appropriate section of the Mental Health Act:
Section 2 allows compulsory admission for up to 28 days for assessment.
Section 3 allows compulsory admission for up to 6 months for treatment.
Sections 2 and 3 require an application from an Approved Mental Health Professional (AMHP, formerly an Approved Social Worker), or, rarely, the person's nearest relative, and recommendations from two doctors; one of whom is section 12-approved (usually a psychiatrist) and one who has previous acquaintance with the individual (usually the person's GP if at all practicable).
Ideally, the person should be examined jointly by the two doctors with the AMHP also present. Where this is not possible, each doctor may carry out a separate examination. If the AMHP is not present, it is essential that at least one of the doctors discusses the person with the AMHP.
Section 4 is used in exceptional cases to permit compulsory admission for up to 72 hours if there is urgent necessity, and undesirable delay would occur while trying to arrange admission under section 2.
It requires an application from an AMHP (or, rarely, the person's nearest relative) and just one medical recommendation, preferably from a doctor with previous acquaintance (usually the GP).
Section 136 may be used by police to take people from a public place to a place of safety and enable examination by a registered medical practitioner and interview by an AMHP. The person's GP, where known, may be informed.
Details of guidance and forms for the most common sections of the Mental Health Act can be accessed from the Department of Health website, as well as details of amendments made in the Mental Health Act 2007.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidance issued by the National Institute for Health and Clinical Excellence (NICE), Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care [National Collaborating Centre for Mental Health, 2009].
Referral for early intervention
Evidence from observational studies strongly supports an association between a longer duration of untreated psychosis and poorer outcomes for people with schizophrenia [Bottlender et al, 2003; Harrigan et al, 2003]. Supported by evidence of this association, many experts believe that early intervention to reduce the duration of untreated psychosis is likely to improve outcomes as well as reduce the duration of distressing symptoms.
NICE found evidence from three randomized controlled trials with 741 participants that, compared with standard care, early intervention services produced clinically significant benefits for several outcomes, including relapse, rehospitalization, symptom severity, satisfaction, and quality of life at 18–24 months of follow up [National Collaborating Centre for Mental Health, 2009].
Risk assessment
How do I assess risks in people with suspected schizophrenia?
For people with suspected schizophrenia, the decision to refer for same-day specialist assessment or urgent specialist assessment within a few days is determined by the risk of harm to themselves and to other people.
Assess the risk of suicide by:
Identifying risk factors that increase the risk of suicide, including:
Previous suicide attempts.
Precipitants for suicide, such as problems at work or school, conflict or breakdown in relationships, bereavement, or risk of imprisonment.
Substance abuse.
Presence or history of depression.
Agitation and fear of mental disintegration.
Low self esteem, hopelessness, or impulsivity; poor coping strategies for dealing with difficulties.
Environmental factors, such as social isolation or unemployment.
Family history of mental illness.
Identifying factors that reduce the risk of suicide, including:
Good social support.
Responsibility for children.
Assessing for suicidal ideation:
Ask 'Do you ever think about suicide?' and 'Do you hear voices commanding you to harm yourself?'
If the answer is 'yes', assess for suicidal intent.
Assessing for suicidal intent by asking:
Have you made any plans for ending your life?
Do you have the means for doing this available to you?
What has kept you from acting on these thoughts?
Assess the person's risk of unintentional harm to themselves caused by disorganized behaviour or poor judgement of risk due to their absorption with psychotic experiences and beliefs. This may leave them vulnerable to traumatic injuries, accidents, assault, or exploitation.
Determine the risk of harm to others by assessing:
The risk of violence towards others by asking about:
A history of violence or threats of violence.
Emotions related to violence, such as anger, hostility, or suspiciousness.
Persecutory delusions or hallucinations commanding them to harm other people.
Access to people identified in their delusions.
The risk of neglect of people dependant on them for care.
Basis for recommendation
Basis for recommendation
Assessment of risk of suicide
These recommendations are based on evidence from a systematic review [Hawton et al, 2005], and expert opinion taken from Suicide risk: a guide for primary care and mental health staff [Newcastle North Tyneside and Northumberland Mental Health NHS Trust, 2001].
Assessment of risk of harm to others
These recommendations are taken from Assessment and clinical management of risk of harm to other people, produced by the Royal College of Psychiatrists, and are based on expert opinion [RCPsych, 1996].
Management in secondary care
What management may people receive in secondary care?
The following treatments should be offered to people with newly diagnosed schizophrenia:
An oral antipsychotic (first generation or second generation)
The decision regarding which antipsychotic to use is made in partnership with the person (and carer if appropriate), taking into account the adverse effect profile of each drug.
Oral antipsychotics are usually continued for at least 1–2 years after the person has recovered and remained stable.
Psychological and psychosocial interventions
Cognitive behavioural therapy, with at least 16 planned sessions.
Family intervention for the relatives of people with schizophrenia who live with, or who are in close contact with, the affected person. This consists of 10 planned sessions over 3 months to 1 year.
Arts therapies may be offered, particularly to help with negative symptoms.
A care plan should be written and a copy sent to the referring primary healthcare professional. The care plan should define the roles of primary and secondary healthcare and include:
A crisis plan.
An advance statement — a written statement, drawn up and signed when the person is well, which sets out how they would prefer to be treated (or not treated) if they were to become ill in the future.
Key clinical contacts in case of emergency or impending crisis.
Basis for recommendation
Basis for recommendation
This information is based on guidance issued by the National Institute for Health and Clinical Excellence (NICE), Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care [National Collaborating Centre for Mental Health, 2009].
Choice of antipsychotic
The previous NICE guidance (issued in 2002) recommended second-generation antipsychotics (for example olanzapine, risperidone, and quetiapine) in some situations as first-line treatment for schizophrenia based on a lower potential for extrapyramidal adverse effects. However, other adverse effects, such as metabolic disturbance, have assumed greater importance, and NICE now underlines that choosing the most appropriate drug and formulation for an individual is more important than the drug group [Leucht et al, 2009].
Considering the similarity of antipsychotics in terms of efficacy, and the uncertainty of health economic evidence, NICE could not make a recommendation for a preference of one antipsychotic over another. The exception is clozapine, for which there is robust evidence (given the necessary precautions to screen for neutropenia) supporting the recommendations for its use in people who do not respond adequately to other antipsychotics.
Length of treatment with an antipsychotic
People who are stabilized on an antipsychotic drug show high rates of relapse when their treatment is stopped or switched to placebo [Hogarty et al, 1976; Kane, 1990]. NICE looked at evidence from a Cochrane systematic review, which included 10 trials of chlorpromazine cessation in 1042 people with stable schizophrenia [Almerie et al, 2008]. This review found evidence that people stopping chlorpromazine had a relative risk of relapse in the short term (up to 8 weeks) of 6.76 (95% CI 3.37 to 13.54) and in the medium term (9 weeks to 6 months) of 4.04 (95% CI 2.81 to 5.8). Relative risk of relapse after 6 months was 1.70 (95% CI 1.44 to 2.01).
Cognitive behavioural therapy (CBT)
NICE found evidence that, compared with standard care, CBT was effective in reducing rehospitalization rates at up to 18 months after the end of treatment. Robust evidence indicated that the duration of hospitalization was also reduced (by 8.26 days on average). CBT reduced symptom severity both at end of treatment and at up to 12 months' follow up. Robust small-to-medium effects were found for reductions in depression when CBT was compared with both standard care and other active treatments. Furthermore, compared with treatment as usual, there was some evidence for improvements in social functioning up to 12 months.
Family intervention
NICE found evidence from 32 randomized controlled trials with 2429 participants that, compared with standard care or treatment as usual, risk of relapse was reduced. Length of treatment ranged from 6 weeks to 13 months. The number needed to treat was 4 (95% CI 3.23 to 5.88); for every four people who received family therapy (for up to 13 months), relapse was prevented in one person. In addition, family intervention reduced hospital admissions during treatment and reduced the severity of symptoms both during, and for up to 24 months after, the intervention.
Arts therapy
NICE found consistent evidence that arts therapies were effective for reducing negative symptoms compared with any other control. Some evidence indicated that the medium-to-large effects found at the end of treatment were sustained at up to 6 months' follow up.
Scenario: Managing relapse
Scenario: Managing relapse of schizophrenia
Management
How do I manage people with established schizophrenia who relapse?
For people with an established diagnosis of schizophrenia who relapse, undertake a risk assessment and:
For people who have a treatment care plan (or similar plans, such as the wellness recovery action plan and personal wellness plan) — manage according to the plan and where possible comply with their advance statement.
The advance statement is written and signed when the person is well. It sets out how they would prefer to be treated (or not treated) if they were to become ill in the future.
If in doubt about how to proceed, consider seeking advice from the key clinician or care coordinator stated in the crisis plan.
For people who do not have a treatment care plan:
If the person is judged to be at high risk of harm to themselves or others, arrange same-day specialist assessment. Depending on local service arrangements, this may be carried out at home by liaison with a crisis resolution or home treatment team or require hospital admission.
If the person needs to be admitted to hospital, every attempt should be made to persuade them to go voluntarily.
If admission is necessary but the person declines, compulsory admission may be arranged under sections 2, 3, or 4 of the Mental Health Act.
If the person is judged not to be at immediate risk of harm to themselves or others, urgently refer for a specialist assessment to:
The crisis intervention or home treatment team or acute day-hospital if available and the person has been previously diagnosed with schizophrenia, or
The community mental health service if the crisis intervention or home treatment team is not available or not appropriate. See Mental health services for more information.
For people with anxiety problems or insomnia who are awaiting referral, consider short-term treatment with an anxiolytic or hypnotic.
Mental Health Act
Mental Health Act
The Mental Health Act allows compulsory admission of people who:
Have a mental disorder of a nature and degree that warrants treatment in hospital, and
Need to be admitted in the interests of their own health or safety, or for the protection of other people.
Compulsory admission is arranged using the appropriate section of the Mental Health Act:
Section 2 allows compulsory admission for up to 28 days for assessment.
Section 3 allows compulsory admission for up to 6 months for treatment.
Sections 2 and 3 require an application from an Approved Mental Health Professional (AMHP, formerly an Approved Social Worker), or, rarely, the person's nearest relative, and recommendations from two doctors; one of whom is section 12-approved (usually a psychiatrist) and one who has previous acquaintance with the individual (usually the person's GP if at all practicable).
Ideally, the person should be examined jointly by the two doctors with the AMHP also present. Where this is not possible, each doctor may carry out a separate examination. If the AMHP is not present, it is essential that at least one of the doctors discusses the person with the AMHP.
Section 4 is used in exceptional cases to permit compulsory admission for up to 72 hours if there is urgent necessity, and undesirable delay would occur while trying to arrange admission under section 2.
It requires an application from an AMHP (or, rarely, the person's nearest relative) and just one medical recommendation, preferably from a doctor with previous acquaintance (usually the GP).
Section 136 may be used by police to take people from a public place to a place of safety and enable examination by a registered medical practitioner and interview by an AMHP. The person's GP, where known, may be informed.
Details of guidance and forms for the most common sections of the Mental Health Act can be accessed from the Department of Health website, as well as details of amendments made in the Mental Health Act 2007.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidance issued by the National Institute for Health and Clinical Excellence (NICE), Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care [National Collaborating Centre for Mental Health, 2009].
Advance statements
Although decisions in advance statements can be overridden using the Mental Health Act, NICE advises that healthcare professionals should endeavour to honour advance decisions and statements wherever possible.
Risk assessment
How do I assess risks in people with schizophrenia?
For people with schizophrenia, the decision to refer for same-day specialist assessment or urgent specialist assessment within a few days is determined by the risk of harm to themselves and to other people.
Assess the risk of suicide by:
Identifying factors that increase the risk of suicide, including:
Previous suicide attempts.
Precipitants for suicide, such as problems at work or school, conflict or breakdown in relationships, bereavement, or risk of imprisonment.
Poor adherence to treatment.
Substance abuse.
Presence or history of depression.
Agitation and fear of mental disintegration.
Low self esteem, hopelessness, or impulsivity; poor coping strategies for dealing with difficulties.
Environmental factors, such as social isolation or unemployment.
Family history of mental illness.
Identifying factors that reduce the risk of suicide, including:
Good social support.
Responsibility for children.
Assessing for suicidal ideation:
Ask 'Do you ever think about suicide?' and 'Do you hear voices commanding you to harm yourself?'
If the answer is 'yes', assess for suicidal intent.
Assessing for suicidal intent by asking:
Have you made any plans for ending your life?
Do you have the means for doing this available to you?
What has kept you from acting on these thoughts?
Assess the person's risk of unintentional harm to themselves caused by disorganized behaviour or poor judgement of risk due to their absorption with psychotic experiences and beliefs. This may leave them vulnerable to traumatic injuries, accidents, assault, or exploitation.
Determine the risk of harm to others by assessing:
The risk of violence towards others by asking about:
A history of violence or threats of violence.
Emotions related to violence, such as anger, hostility, or suspiciousness.
Persecutory delusions or hallucinations commanding them to harm other people.
Access to people identified in their delusions.
The risk of neglect of people dependant on them for care.
Basis for recommendation
Basis for recommendation
Assessment of risk of suicide
These recommendations are based on evidence from a systematic review [Hawton et al, 2005], and expert opinion taken from Suicide risk: a guide for primary care and mental health staff [Newcastle North Tyneside and Northumberland Mental Health NHS Trust, 2001].
Assessment of risk of harm to others
These recommendations are taken from Assessment and clinical management of risk of harm to other people, produced by the Royal College of Psychiatrists, and are based on expert opinion [RCPsych, 1996].
Scenario: The routine schizophrenia review
Scenario: The routine schizophrenia review
Overview of schizophrenia review
How should I conduct a routine schizophrenia review?
Most people with schizophrenia will be under specialist mental health supervision, usually with a Care Programme Approach. However, follow up in primary care is still needed, particularly to address the physical health needs of the individual.
Arrange to review all people with schizophrenia at least annually.
At the appointment, review the person's:
Continuity of primary and secondary care services.
Basis for recommendation
Basis for recommendation
The basis for each recommendation is discussed in the specific management section.
Ensuring continuity of care
How do I ensure continuity of primary and secondary care services for people with schizophrenia?
Most people with schizophrenia will have care shared between a specialist mental health team and primary care. Out of choice, a few people will be under primary care supervision only, once the diagnosis has been established and their management planned in secondary care.
To ensure follow up in primary care, include all people with schizophrenia on a register of serious mental illness and arrange a routine review at least annually.
Attempt to make contact (within 14 days) with people who do not attend.
If it is not possible to make contact despite reasonable efforts to do so, inform the person's key worker (who may be their psychiatrist, community psychiatric nurse, or social worker).
If the person is new to the area and is not known to local services, arrange a prompt referral to secondary care mental health services for assessment.
If the person is moving away from the catchment area to a different NHS Trust, ensure the secondary care provider is aware of this. The person's current secondary care provider should contact the new secondary care and primary care providers, and provide them with the current care plan.
Ensure the person has a documented care plan to refer to in the event of relapse.
For people under secondary care review who do not have a care plan, contact the team responsible for their management to obtain it.
For people managed solely in primary care who do not have a care plan, refer to secondary care.
Basis for recommendation
Basis for recommendation
These recommendations are based on the National Institute for Health and Clinical Excellence guideline, Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care [National Collaborating Centre for Mental Health, 2009] and the Quality and Outcomes Framework guidance for GMS contract 2012/13 [BMA and NHS Employers, 2012].
Physical health review
What should I do at a physical health review?
Assess the person's physical health annually.
More frequent review is needed if the person has a significant physical illness, or if there is a risk of physical illness because of substance misuse.
A physical health review should include:
Asking about symptoms that could be due to adverse effects of medication.
Blood tests. For more information see How should I monitor people taking antipsychotics?
Assessing cardiovascular risk (people with schizophrenia are at higher risk of cardiovascular disease than the general population). See the CKS topic on CVD risk assessment and management.
Weight and body mass index.
Blood pressure.
Smoking status.
Alcohol intake.
Substance misuse.
Note that smoking induces the metabolism of olanzapine and clozapine. If the person stops smoking, monitor for increased adverse effects and seek advice about dose adjustment if necessary.
There are separate CKS topics on Alcohol - problem drinking, CVD risk assessment and management, Diabetes - type 2, Hypertension - not diabetic, Lipid modification - CVD prevention, Obesity, and Smoking cessation.
Inform the secondary care team of the results of annual health screening.
Basis for recommendation
Basis for recommendation
These recommendations are based on the National Institute for Health and Clinical Excellence (NICE) guideline, Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care [National Collaborating Centre for Mental Health, 2009], the NICE guideline Psychosis with coexisting substance misuse, and the Quality and Outcomes Framework guidance for GMS contract 2012/13 [BMA and NHS Employers, 2012].
People with schizophrenia have high rates of mortality (approximately 50% above that of the general population), in part as a result of an increased incidence of suicide (about 10% die of suicide) and violent death, and in part as a result of an increased risk of physical health problems. People with schizophrenia are at increased risk of cardiovascular disease, Type 2 diabetes mellitus, and weight gain compared with the general population [National Collaborating Centre for Mental Health, 2009; BMA and NHS Employers, 2012].
Smoking
People with schizophrenia are more likely than the general population to smoke (61% compared with 33%) [BMA and NHS Employers, 2012].
Premature death and smoking-related diseases, such as respiratory disorders and heart disease, are more common among people with schizophrenia who smoke, than in the general population of smokers.
Information about the effect of smoking on olanzapine and clozapine reflects advice from the Medicines and Healthcare products Regulatory Agency (MHRA) [MHRA, 2009b]. Note that smoking induces the metabolism of olanzapine and clozapine because polycyclic aromatic hydrocarbons found in tobacco smoke are potent inducers of hepatic cytochrome P450 and a reduction in dose may be needed when the person stops smoking.
Weight gain and Type 2 diabetes mellitus
Compared with the general population, people with schizophrenia are less likely to exercise and are more likely to have a diet that is higher in fat and lower in fibre [National Collaborating Centre for Mental Health, 2009].
Some of the newer antipsychotic drugs (such as olanzapine) have a greater propensity to cause weight gain.
Both first-generation and second-generation antipsychotic drugs have been associated with an increased risk of diabetes, but the risk seems to be highest with second-generation antipsychotics, such as clozapine, quetiapine and olanzapine [Taylor et al, 2009; ABPI Medicines Compendium, 2011b].
The extent to which this excess mortality and high rate of disability are a result of the medications given for schizophrenia is unclear [National Collaborating Centre for Mental Health, 2009].
Substance misuse
In the UK, 9–35% of people with schizophrenia misuse alcohol or drugs [Menezes et al, 1996; Stefan et al, 2002].
Mental health review
What should I do at a mental health review?
Assess symptom control by:
Screening for psychotic symptoms by asking:
Do you hear voices when nobody is around?
Do you ever think that people are talking or gossiping about you, maybe even thinking about trying to get you?
Do you ever think that somehow people can pick up on what you are thinking or can manipulate what you are thinking?
Assessing for any deterioration in personal functioning by asking about any changes in academic achievement, work, social interaction, or personal care.
Assessing for depression and anxiety. If present, refer the person for further management. The urgency of the referral should be determined by a risk assessment.
Review adherence to and adverse effects from treatment. For further information on adverse effects, see Prescribing information.
Arrange annual monitoring of antipsychotic drugs if this is not carried out in secondary care.
Ask about illicit drug use and offer referral for specialist treatment where appropriate.
Arrange specialist review if compliance with medication is poor, symptoms are poorly controlled, or adverse effects are poorly tolerated.
Risk assessment
Risk assessment for admission
For people with schizophrenia, the decision to refer for same-day specialist assessment or urgent specialist assessment within a few days is determined by the risk of harm to themselves and to other people.
Assess the risk of suicide by:
Identifying factors that increase the risk of suicide, including:
Previous suicide attempts.
Precipitants for suicide, such as problems at work or school, conflict or breakdown in relationships, bereavement, or risk of imprisonment.
Poor adherence to treatment.
Substance abuse.
Presence or history of depression.
Agitation and fear of becoming worse.
Low self-esteem, hopelessness, or impulsivity; poor coping strategies for dealing with difficulties.
Environmental factors, such as social isolation or unemployment.
Family history of mental illness.
Identifying factors that reduce the risk of suicide, including:
Good social support.
Responsibility for children.
Assessing for suicidal ideation:
Ask 'Do you ever think about suicide?' and 'Do you hear voices commanding you to harm yourself?'
If the answer is 'yes', assess for suicidal intent.
Assessing for suicidal intent by asking:
Have you made any plans for ending your life?
Do you have the means for doing this available to you?
What has kept you from acting on these thoughts?
Assess the person's risk of unintentional harm to themselves caused by disorganized behaviour or poor judgement of risk due to psychotic experiences and beliefs. This may leave them vulnerable to traumatic injuries, accidents, assault, or exploitation.
Determine the risk of harm to others by assessing:
The risk of violence towards others by asking about:
A history of violence or threats of violence.
Emotions related to violence, such as anger, hostility, or suspiciousness.
Persecutory delusions or hallucinations commanding them to harm other people.
Access to people identified in their delusions.
The risk of neglect of people dependant on them for care.
Basis for recommendation
Basis for recommendation
These recommendations are based on the National Institute for Health and Clinical Excellence (NICE) guideline, Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care [National Collaborating Centre for Mental Health, 2009], the Quality and Outcomes Framework guidance for GMS contract 2012/13 [BMA and NHS Employers, 2012], and published expert opinion [Rethink, 2007].
Although specialist mental health services should undertake regular and full assessment of the mental health of their service users, GPs should also monitor the mental health of these people, so that they can be referred before crises arise, wherever possible.
Review is particularly important when the person is no longer being regularly reviewed by specialist mental health services.
Assessment of risk of suicide
These recommendations are based on evidence from a systematic review [Hawton et al, 2005], expert opinion taken from Suicide risk: a guide for primary care and mental health staff, and expert opinion [Newcastle North Tyneside and Northumberland Mental Health NHS Trust, 2001].
Assessment of risk of harm to others
These recommendations are taken from Assessment and clinical management of risk of harm to other people, produced by the Royal College of Psychiatrists, and are based on expert opinion [RCPsych, 1996].
Social needs review
What social needs should I review?
Ask the person about the support they receive from family and carers, and consider referral to the community mental health service to manage any conflict or difficulties that could trigger a relapse.
Ensure that people with schizophrenia and their carers are well informed about the support available to them; to help them back into work or education, their housing options, entitlement to benefits, and entitlement to drive.
MIND (www.mind.org.uk) and Rethink (www.rethink.org) have local self-help groups, and their websites provide practical advice. The following fact sheets are freely available from Rethink:
Work and mental illness: getting back to work
Housing options for people with mental illness
Inform the person that they must not drive during an acute psychotic episode, and that they must tell the Driver and Vehicle Licensing Agency (DVLA) about their illness. The General Medical Council guidelines advise breaking patient confidentiality and informing the DVLA if the person cannot understand that driving during psychosis is unsafe (usually because of lack of insight into their illness) or if the person refuses to stop driving.
For more detailed guidance, see the DVLA 'At a glance' guide.
Ensure that the family and carers have been offered:
Family intervention therapy — refer to community mental health services if this is required.
An assessment of the carer's needs, including physical, social, and mental health needs.
An assessment of the needs of any children, siblings, and vulnerable adults in the family, including young carers.
Enitlement to drive
Entitlement to drive
Group 1 entitlement — re-licensing can be considered when all of the following conditions can be satisfied:
The person has remained well and stable for at least 3 months.
The person is adherent to treatment.
The person is free of adverse effects of medication which would impair driving.
The person has a favourable specialist report.
People with a history of instability or poor adherence to treatment will require a longer period off driving.
Group 2 entitlement — re-licensing (such as for heavy goods or public service vehicles) would usually only be considered if the person has been well and stable for 3 years. However, mitigating factors will be considered in individual cases.
Antipsychotic drugs can cause sedation, poor concentration, and extrapyramidal symptoms, all of which can impair driving. Careful assessment is therefore needed to determine whether adverse effects of medication will impair driving. This is usually undertaken by specialist mental health services.
Basis for recommendation
Basis for recommendation
These recommendations are based on the National Institute for Health and Clinical Excellence guideline, Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care [National Collaborating Centre for Mental Health, 2009], the Quality and Outcomes Framework guidance for GMS contract 2012/13 [BMA and NHS Employers, 2012], and the NICE guideline Psychosis with coexisting substance misuse [NICE, 2011].
Eligibility to drive
These recommendations are based on guidance issued by the Driver and Vehicle Licensing Agency [DVLA, 2010].
Scenario: Women of childbearing age
Scenario: Women of childbearing age with schizophrenia
Pregnancy (planned and unplanned)
How should I manage a woman with schizophrenia who is planning a pregnancy or has an unplanned pregnancy?
Refer the woman to the community mental health service for an assessment and discussion of drug treatment.
Do not alter or stop drug treatment without seeking specialist advice.
Explain to the woman that she may be advised to:
Remain on her current drug treatment throughout conception, pregnancy, and birth.
Switch to another drug treatment.
Stop or reduce the dose of her medication.
Explain that the strategy which is chosen will depend on her wishes, and on the advice of the medical team who need to balance the risks of under treatment (relapse) with the risk of harming the unborn child by remaining on drug treatment.
Discuss the likelihood that sleep and routine will be disturbed after the baby is born. Plan for practical support after the baby is born (from the woman's family, organizations such as SureStart, and social services) so that the woman gets enough rest and sleep.
For women who are planning a pregnancy, also give general pre-conception advice (such as smoking and alcohol consumption) and prescribe folic acid.
For more detailed information, see the CKS topic on Pre-conception - advice and management.
Basis for recommendation
Basis for recommendation
Referral
Referral to the community mental health service is recommended because this team needs to balance the risks of under treatment (relapse) with any possible risks of harming the fetus. The woman will require an assessment to decide whether it is appropriate to stop drug treatment, switch to another antipsychotic, or increase the dose of the drug as the pregnancy progresses.
Dose increases may be required in the third trimester (blood volume expands by around 30%).
Women who have a history of psychosis, particularly if they have experienced repeated relapses, may be best maintained on antipsychotics during and after the pregnancy [Taylor et al, 2007].
This may minimize fetal exposure by avoiding the need for higher doses, should relapse occur.
Safety of antipsychotics
Older first-generation antipsychotics are generally considered to have a minimal risk of teratogenicity; however, the evidence to support this is weak [Taylor et al, 2007]. The widespread use of first-generation antipsychotics over several decades suggest that the risk is small.
Data on second-generation antipsychotics are limited but suggest that clozapine, olanzapine, risperidone, and quetiapine are not teratogenic.
There is most experience with chlorpromazine (constipation and sedation can be a problem), trifluoperazine, haloperidol, olanzapine, and clozapine (gestational diabetes may be a problem with both second-generation antipsychotics).
Risk of not treating psychosis in pregnancy
The risks of not treating psychosis include [Taylor et al, 2007]:
Harm to the woman through poor self-care, lack of engagement with obstetric care, poor judgement, or impulsive acts.
Harm to the fetus or neonate.
The mental health of the woman in the perinatal period influences fetal well-being, obstetric outcome, and child development.
Breastfeeding
What issues should I consider if a woman is breastfeeding?
If the woman would like to breastfeed and is taking an antipsychotic, seek specialist advice from the UK Drugs in Lactation Advisory Service:
Telephone 0121 311 1974, or 0121 378 2211.
In general, antipsychotics are present in breast milk in amounts too small to be harmful. However, minor adverse effects have been described or are expected to occur in infants. Animal studies indicate possible adverse effects of these drugs on the developing nervous system.
The decision to breastfeed will depend upon several factors, such as whether the woman is taking a single antipsychotic or more than one, and whether the baby is premature or has gone to term.
Basis for recommendation
Basis for recommendation
CKS recommends contacting the UK Drugs in Lactation Advisory Service because the decision to breastfeed when taking antipsychotics is complicated and individual circumstances vary. The woman may be taking a single antipsychotic or more than one, and the baby may be premature or unwell.
In general, antipsychotics are present in breast milk in amounts too small to be harmful. However, minor adverse effects have been described or are expected to occur in infants. Animal studies indicate possible adverse effects of these drugs on the developing nervous system [UKMiCentral, 2004; BNF 57, 2009].
Adverse effects of maternal drugs in the neonate
What adverse effects of maternal drug treatment should I be aware of in the neonate?
Babies of women who have taken psychotropic drugs during pregnancy may experience adverse drug effects, drug toxicity, or withdrawal symptoms, which may vary in severity and duration. Symptoms in the baby to be aware of include:
Floppy baby syndrome.
Irritability.
Constant crying.
Shivering or tremor.
Restlessness.
Increased tone.
Feeding and sleeping difficulties.
Respiratory distress.
Seizures (rarely).
If any of these occur, seek specialist paediatric advice.
Basis for recommendation
Basis for recommendation
This recommendation is based on published guidance from the National Institute for Health and Clinical Excellence, Antenatal and postnatal mental health [National Collaborating Centre for Mental Health, 2007] and a drug safety update from the Medicines and Healthcare products Regulatory Agency (MHRA) [MHRA, 2011b].
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).
Available antipsychotics
Antipsychotics are available as oral preparations or depot injections. They are classified as first-generation antipsychotics (typical) and second-generation antipsychotics (atypical). For more information, see Table 1.
Antipsychotics are thought to exert their effects by blocking dopamine-2 receptors in the brain; however, their exact mode of action is unknown. Antipsychotics also have significant effects on acetylcholine, histamine, norepinephrine, and serotonin pathways. They can cause extrapyramidal symptoms (EPS) and a wide range of other adverse effects.
In general, second-generation antipsychotics are associated with fewer EPS than first-generation antipsychotics. However, second-generation antipsychotics are associated with several other important adverse effects, such as weight gain, glucose intolerance, and hyperprolactinaemia.
Previous guidance issued by the National Institute for Health and Clinical Excellence (NICE) [NICE, 2002] recommended second-generation antipsychotics (for example olanzapine, risperidone, or quetiapine) in some situations as first-line treatment for schizophrenia because of their lower potential for EPS.
NICE reviewed the evidence for the use of antipsychotics in schizophrenia and concluded that choosing the most appropriate drug and formulation for an individual is more important than the drug group (first or second generation) [National Collaborating Centre for Mental Health, 2009]. This was based on evidence from updated systematic reviews (particularly with regard to other adverse effects, such as metabolic disturbance) and new evidence from effectiveness (pragmatic) trials [Lieberman et al, 2005; Jones et al, 2006].
The only exception to this was clozapine, for which NICE found strong evidence to support its use in people who do not respond adequately to other antipsychotics. Clozapine is always initiated and monitored in secondary care.
Table 1. Antipsychotics available to prescribe.| Oral first generation(typical) | Oral second generation(atypical) | Antipsychotic depot injections* |
|---|---|---|
| BenperidolChlorpromazineFlupenthixolHaloperidolLevomepromazinePericyazinePerphenazinePimozideProchlorperazineSulpirideTrifluoperazineZuclopenthixol acetateZuclopenthixol | AmisulprideAripiprazoleClozapineOlanzapinePaliperidoneQuetiapineRisperidoneZotepine | Flupenthixol decanoateFluphenazine decanoateHaloperidolPipotiazine palmitateRisperidoneZuclopenthixol decanoate |
Monitoring
Antipsychotics are always initiated in secondary care, where baseline measurements are taken. Regular monitoring may be done in primary or secondary care, depending on locally agreed shared care guidelines or the person's care plan.
Regular monitoring is required in primary care for:
Body weight — 3 months after starting treatment, then every 12 months, or more often if the person is gaining weight rapidly.
Serum electrolytes and urea including creatinine and estimated glomerular filtration rate — every 12 months.
Full blood count — every 12 months.
Blood lipids — 3 months after starting treatment, then every 12 months.
Plasma glucose — 4–6 months after starting treatment, then every 12 months. Additionally for clozapine and olanzapine repeat after the first month of treatment. Ask about symptoms of hyperglycaemia (such as polydipsia, polyuria, and increased appetite).
Blood pressure — frequently during dose titration.
Not required for amisulpride, aripiprazole, trifluoperazine, and sulpiride.
Electrocardiography — after dose changes. Ideally, also annually.
Mandatory for haloperidol, pimozide, and sertindole; not required for antipsychotics with no effect, or a low-to-moderate effect on the QT interval, and no other risk factors for arrhythmia.
Prolactin — 6 months after starting treatment, then every 12 months. Also ask about symptoms of raised prolactin (these include low libido, sexual dysfunction, menstrual abnormalities, gynaecomastia, and galactorrhoea).
Not required for aripiprazole, clozapine, quetiapine, or olanzapine (less than 20 mg daily).
Liver function tests — every 12 months.
Creatinine phosphokinase — measure again only if neuroleptic malignant syndrome is suspected.
Tests which need to be done every 12 months may be carried out at the annual physical review.
Clozapine
People taking clozapine are managed exclusively in secondary care. Clozapine can cause neutropenia or agranulocytosis, and frequent monitoring of the full blood count is required (weekly for 18 weeks after starting treatment, then every 2 weeks for the next 18 weeks, and then every 4 weeks thereafter). This is carried out by the clozapine monitoring service.
Clarification / Additional information
Baseline measurements (taken in secondary care) include:
Body weight.
Serum electrolytes and urea.
Full blood count.
Blood lipids.
Plasma glucose.
Creatinine phosphokinase.
Blood pressure.
Not required for amisulpride, aripiprazole, trifluoperazine, and sulpiride.
Electrocardiography.
Not required for people taking conventional antipsychotic doses and without any evidence of other predisposing factors, such as relevant personal or family history, co-prescription of QT-prolonging drugs, or electrolyte imbalance.
Prolactin.
Not required for aripiprazole, clozapine, quetiapine, olanzapine (less than 20 mg daily), and ziprasidone.
Liver function tests.
Not required for amisulpride or sulpiride.
Basis for recommendation
These recommendations are based on published expert opinion from the Maudsley Prescribing Guidelines [Taylor et al, 2009].
Although not all antipsychotics are associated with dyslipidaemia, weight gain, or impaired fasting glucose, close monitoring is recommended because people with schizophrenia are at higher risk of diabetes and cardiovascular disease [National Collaborating Centre for Mental Health, 2009].
Adverse effects
Antipsychotics can cause a wide range of adverse effects. The risk varies with the type of antipsychotic (first generation or second generation) and the individual drug. Adverse effects include:
Extrapyramidal symptoms — more common with first-generation antipsychotics. They include:
Dystonic reactions (abnormal movements of the face and body).
Pseudoparkinsonism (tremor, bradykinesia, and rigidity).
Akathisia (motor restlessness).
Tardive dyskinesia — late-onset movement disorder that can occur with prolonged use of antipsychotics. It is characterized by rhythmical, involuntary movements, usually lip smacking and tongue rotating, although it can affect the limbs and trunk. It may be persistent and can sometimes worsen on treatment withdrawal.
Weight gain — common with all antipsychotics, but more frequent with second-generation antipsychotics. In general, clozapine has the greatest potential to cause weight gain, followed by olanzapine, then quetiapine and risperidone, and then amisulpride.
Dyslipidaemia — phenothiazines (such as chlorpromazine), clozapine, olanzapine, quetiapine, and risperidone all increase lipid levels.
Hyperprolactinaemia — may lead to galactorrhea, amenorrhoea, gynaecomastia, hypogonadism, sexual dysfunction, and an increased risk of osteoporosis. Hyperprolactinaemia occurs with both first- and second-generation antipsychotics, but of the newer antipsychotics, sertindole, quetiapine, ziprasidone, aripiprazole, and clozapine have no important effect on prolactin. Risperidone and amisulpride have potent prolactin-elevating effects.
Sedation — chlorpromazine, clozapine, promazine, and zotepine cause the highest incidence of sedation. Amisulpride, aripiprazole, sertindole, and sulpiride are associated with a very low incidence of sedation. Performance of skilled tasks (such as driving) may be affected; effects of alcohol are enhanced.
Anticholinergic effects (such as dry mouth, blurred vision, urinary retention, constipation, and cutaneous flushing) — chlorpromazine and clozapine have potent anticholinergic effects.
Postural hypotension — commonly associated with clozapine, chlorpromazine, quetiapine, and risperidone.
Hypertension — clozapine but there are also reports with aripiprazole, sulpiride, risperidone, and quetiapine. Hypertension can occur as:
A small, steady increase in blood pressure over time (may be associated with weight gain), or
An unpredictable, sharp increase in blood pressure on starting a new drug.
Reduced seizure threshold — seizures are a recognized adverse effect of antipsychotics (the higher the dose, the greater the risk). Clozapine carries the greatest risk.
Impaired glucose tolerance — more common in people with schizophrenia than in the general population, and has been associated with both first-generation and second-generation antipsychotic drugs [MHRA, 2011a]. Hyperglycaemia, and sometimes diabetes (including ketoacidosis and coma) can occur in people taking clozapine, olanzapine, risperidone, and quetiapine.
QT interval prolongation — the most widely reported cardiac conduction defect caused by antipsychotics and considered to be a class effect. It increases the risk of torsades de pointes, a potentially fatal arrhythmia. The information regarding QT prolongation is taken from a published review of antipsychotics by the Medicines and Healthcare products Regulatory Agency [MHRA, 2006].
Stroke risk — Olanzapine and risperidone are associated with an increased risk of stroke in elderly people with dementia. The Committee on Safety of Medicines has advised [CSM, 2004] that:
For acute psychotic conditions in elderly people with dementia, risperidone should be limited to short-term use under specialist advice; olanzapine is not licensed for acute psychosis.
The possibility of cerebrovascular events should be considered carefully before treating people with a history of stroke or transient ischaemic attack; risk factors for cerebrovascular disease (e.g. hypertension, diabetes, smoking, and atrial fibrillation) should also be considered.
Venous thromboembolism (VTE) — antipsychotic use may be associated with an increased risk of VTE [MHRA, 2009a].
Data are insufficient to determine any difference in risk between second-generation and first-generation antipsychotics, or between individual drugs.
All possible risk factors for VTE should be identified before and during antipsychotic treatment and preventive measures undertaken.
Basis for recommendation
This information is mainly based on published expert opinion from the Maudsley Prescribing Guidelines [Taylor et al, 2009], the British National Formulary [BNF 62, 2011], and a manufacturer's Summary of Product Characteristics for quetiapine [ABPI Medicines Compendium, 2011a].
Managing common adverse effects
Managing common adverse effects
Managing adverse effects is an important aspect of care because they are a common cause of nonadherence to treatment. CKS recommends that people who may benefit from a dose reduction or switching drugs should be referred to specialist mental health services, or that advice should be sought.
Extrapyramidal symptoms (EPS)
Dystonia and parkinsonism can be alleviated by antimuscarinic drugs, such as procyclidine (these should not be prescribed routinely). Antimuscarinic drugs should be withdrawn 2–3 months after symptoms resolve, as their adverse effects increase cognitive deficit and there is potential for abuse. Seek advice before initiating treatment with an antimuscarinic, or start treatment and inform the person's specialist.
Alternatively, a drug that is less likely to cause EPS can be used (for example clozapine, olanzapine, or quetiapine).
Akathisia can often be relieved by reducing the dose of the antipsychotic. If this is ineffective, consider switching to a drug less likely to cause EPS. Alternatively, low-dose propranolol may be considered. Antimuscarinics are generally considered to be less helpful in treating akathisia.
Tardive dyskinesia (TD) — the emergence of acute EPS is a strong risk factor for later TD. The drug should be discontinued on appearance of early signs. Withdrawal of antimuscarinic drugs can sometimes improve TD. In addition, consider reducing the dose of antipsychotic. Switching to clozapine can slowly help to improve TD.
Dyslipidaemia
Offer dietary advice and consider treatment with a statin according to national guidelines. For more information, see the CKS topic on Lipid modification - CVD prevention. If moderate-to-severe hyperlipidaemia develops, consider switching to a drug less likely to cause dyslipidaemia, such as aripiprazole.
Weight gain
The social stigma associated with being overweight adds to the stigma experienced by people with schizophrenia and is a common reason for nonadherence. Calorie restriction or a low glycaemic diet may help to reduce weight gain. Alternatively, consider switching to a drug that is less likely to cause weight gain, such as aripiprazole or a first-generation antipsychotic.
Impaired glucose tolerance
Aripiprazole may be considered.
Hyperprolactinaemia
Because first-generation antipsychotics and the second-generation antipsychotics risperidone and amisulpride cause hyperprolactinaemia at doses substantially lower than those needed for therapeutic efficacy, dose reduction is not always effective. Aripiprazole, quetiapine, olanzapine, or clozapine may be considered. Olanzapine may transiently increase prolactin levels, but they usually return to normal.
QT interval prolongation
QT prolongation is the most widely reported cardiac conduction defect caused by antipsychotics and is considered to be a class effect. It increases the risk of torsades de pointes, a potentially fatal arrhythmia.
Avoid co-prescribing other drugs that are known to prolong the QT interval (for example tricyclic antidepressants, erythromycin, or antiarrhythmics), and monitor potassium levels at least annually.
People taking antipsychotics who experience palpitations or any other symptoms that suggest cardiac disease should undergo electrocardiography.
Consider dose reduction if the QT interval is prolonged.
Antimuscarinic adverse effects (such as dry mouth, blurred vision, urinary retention, constipation, and cutaneous flushing).
Tolerance may develop, but it is very variable, and these adverse effects are often poorly tolerated. Consider dose reduction or switching to amisulpride if problems persist.
Sedation
Tolerance to sedation usually develops.
Photosensitivity is common with chlorpromazine. Adequate use of sunscreen will prevent sunburn in affected people. Some high-factor sunscreens (sun protection factor 30 or above) are available on prescription. The prescription should be endorsed with ACBS.
Postural hypotension
Clozapine, chlorpromazine, and quetiapine are the most likely to be associated with postural hypotension. Discuss changing to an alternative antipsychotic with a mental health specialist.
Neutropenia
Stop the suspect drug if neutrophils fall below 1.5 x 109/L and seek urgent advice from a secondary care specialist.
Abnormal liver function tests (LFTs)
Stop the suspect drug if LFTs suggest hepatitis (transaminases rise to three times normal) or a functional change (prothrombin time or albumin are abnormal). Seek advice from a secondary care specialist.
Basis for recommendation
This information is mainly based on published expert opinion from the Maudsley Prescribing Guidelines [Taylor et al, 2009] and the British National Formulary [BNF 62, 2011].
QT interval prolongation
The information on how to manage QT prolongation is taken from guidance issued by the Medicines and Healthcare products Regulatory Agency [MHRA, 2006].
Interactions
CKS recommends that people requiring a change in the dose of their antipsychotic should be referred to specialist mental health services, or that advice should be sought.
The following interactions are common to all antipsychotics:
Drugs with a sedative action (such as alcohol, analgesics, tricyclic antidepressants, and sedating antihistamines) will enhance the sedative effects of antipsychotics.
Drugs with a hypotensive effect (for example antihypertensives) will enhance the hypotensive effect of antipsychotics.
Drugs that prolong the QT interval, such as antiarrhythmics, macrolides (for example erythromycin), and tricyclic antidepressants, may have a synergistic effect on the QT interval. Avoid co-prescribing drugs that prolong the QT interval. These drugs are contraindicated with sertindole therapy.
Diuretics may cause hypokalaemia, which may increase the risk of arrhythmias; monitor potassium levels in people taking diuretics.
Azole antifungals
Azole antifungals may increase levels of some antipsychotics, for example:
Aripiprazole levels are predicted to be increased by itraconazole and ketoconazole.
Haloperidol levels are increased by 30% or more by itraconazole.
Quetiapine levels are increased six-fold by ketoconazole.
Other azole antifungals are predicted to act similarly.
If azole antifungals are given concurrently with antipsychotics, monitor for signs of adverse effects of antipsychotics and consider reducing the dose as necessary.
The manufacturer of aripiprazole recommends halving the dose of aripiprazole if itraconazole or ketoconazole is given concomitantly.
Carbamazepine
Carbamazepine reduces plasma levels of clozapine, haloperidol, and risperidone by half. Carbamazepine also reduces levels of aripiprazole, fluphenazine, olanzapine, quetiapine, and sertindole.
Monitor the person's symptoms to ensure that antipsychotics remain effective.
Carbamazepine levels are increased by haloperidol, quetiapine, or risperidone, or chlorpromazine with amoxapine.
Monitor carbamazepine levels if these drugs are given together.
Grapefruit juice
Advise the person not to drink grapefruit juice if they are taking pimozide. Grapefruit juice increases the levels of pimozide, possibly leading to torsades de pointes potentially fatal arrhythmias.
Selective serotonin reuptake inhibitors (SSRIs)
SSRIs increase levels of some antipsychotics, for example:
Haloperidol levels are increased by 20–30% by fluoxetine and by 20–60% by fluvoxamine.
Risperidone levels are increased by fluvoxamine, fluoxetine, and paroxetine.
Sertindole levels are increased two- to three-fold by fluoxetine and paroxetine.
Clozapine and olanzapine levels are increased by fluoxetine, fluvoxamine, paroxetine, sertraline, and possibly citalopram.
Where antipsychotic drug levels are increased, the person should be monitored and the dose adjusted accordingly.
Stopping smoking
Smoking induces the metabolism of olanzapine and clozapine. If the person stops smoking, monitor for increased adverse effects and seek advice about dose adjustment if necessary.
Basis for recommendation
These recommendations are based on Stockley's drug interactions: a source book of interactions, their mechanisms, clinical importance and management [Baxter, 2010], and advice on stopping smoking from the Medicines and Healthcare products Regulatory Agency [MHRA, 2009b].
Evidence
Evidence
Supporting evidence
There is no supporting evidence section within this CKS topic.
Almost all recommendations for the primary care management of people with schizophrenia are based on guidance from the National Institute for Health and Clinical Excellence [National Collaborating Centre for Mental Health, 2009].
Search strategy
Scope of search
A full literature search was not required as this CKS topic is primarily based on the National Institute for Health and Clinical Excellence (NICE) guideline Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care [NICE, 2009]. Additional searches were requested for further evidence in the following areas:
Early detection of schizophrenia
Impact of return to work on outcome in schizophrenia
Assessment of risk (suicide, self-harm, harm to others)
Managing schizophrenia in primary care
Search dates
Guidelines: January 2006 – June 2009
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases.
exp schizophrenia/, schizophrenia.tw, schizophrenic.tw, psychosis.tw, psychoses.tw, psychotic.tw
early diagnosis/, early.tw, detect$.tw, diagnosis.tw
employment/, employment.tw, rehabilitation, vocational/
risk assessment/ or risk assessment.tw, violence/, violence.tw, suicide/, suicide.tw, neglect.tw, (harm ADJ to ADJ self).tw, (harm ADJ to ADJ others).tw, safety/, self-injurious behavior/, aggression/, aggression.tw, aggressive.tw
primary health care/, primary care.tw, primary healthcare.tw, primary health care.tw, general practice.tw, gp.tw, general practitioner$.tw, family practice/, physicians, family/
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSH subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Topic specific literature search sources
National Mental Health Development Unit
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
National Guidelines Clearinghouse
British Columbia Medical Association
Dutch College of General Practitioners
Institute for Clinical Systems Improvement
Guidelines International Network
National Library of Guidelines
National Health and Medical Research Council (Australia)
University of Michigan Medical School
Michigan Quality Improvement Consortium
National Resource for Infection Control
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
DynaMed
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
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