Clinical Topic A-Z Clinical Speciality

Trigeminal neuralgia

Trigeminal neuralgia
D014277Trigeminal Neuralgia
Neurological
2013-02-01Last revised in February 2013

Trigeminal neuralgia - Summary

Trigeminal neuralgia occurs in the distribution of one or more branches of the fifth (trigeminal) cranial nerve.

Pain may occur infrequently (e.g. periods of remission may last years) or with a frequency of up to hundreds of times a day.

In 80–90% of cases, trigeminal neuralgia is thought to be caused by compression of the trigeminal nerve by a loop of artery or vein.

Almost twice as many women are affected by trigeminal neuralgia than men. The incidence increases with age and is rare in people younger than 40 years of age.

Complications include depression, and inability to eat causing weight loss.

Features of trigeminal neuralgia include paroxysmal attacks of pain which may be precipitated from trigger areas or by trigger factors.

There is no clinically evident neurological deficit.

Attacks are stereotyped in the individual patient.

'Atypical' or 'mixed' trigeminal neuralgia occurs when there is a persistent discomfort between paroxysms or sensory loss.

The drug of choice for the treatment of trigeminal neuralgia is carbamazepine:

Dose should be titrated until pain is relieved. In the majority of people a dose of 200 mg three or four times a day is sufficient to prevent paroxysms of pain (maximum dosage 1600 mg daily).

If carbamazepine is inappropriate, ineffective, or not tolerated, specialist advice should be sought, or referral made to a neurologist or a specialist in pain management. A daily pain diary may be useful to help people learn to manage their pain.

When the pain is in remission, the dose of carbamazepine should be reduced, and gradually withdrawn if the person remains pain-free for 1 month.

Referral to a neurosurgeon, neurologist, or specialist in pain management (with an interest in trigeminal neuralgia) should be made if any of the following apply:

They have severe pain.

Their pain significantly limits their daily activities and participation.

Atypical clinical features (e.g. burning pain between paroxysms, loss of sensation, abnormal neurological signs) are present.

Carbamazepine is inappropriate, ineffective, or not tolerated.

Trigeminal neuralgia occurs in a person younger than 40 years of age.

Have I got the right topic?

216months3060monthsBoth

This CKS topic covers the management of trigeminal neuralgia in adults (excluding pregnant or breastfeeding women).

This CKS topic does not cover the management of other causes of facial pain, including trigeminal neuropathic pain (also called atypical odontalgia).

There are separate CKS topics on Migraine, Neuropathic pain - drug treatment, Palliative cancer care - pain, Post-herpetic neuralgia, and Shingles.

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

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in February 2013

March 2014 — minor update. The recommendation to consider gabapentin if carbamazepine is inappropriate, ineffective, or not tolerated has been changed in line with the updated NICE guideline on pharmacological treatment of neuropathic pain [NICE, 2013]. Specialist advice or referral is now recommended in this case.

January 2014 — minor update. Minor text changes to reflect the updated Summary of Product Characteristics for carbamazepine tablets regarding the maximum recommended daily dose for management of trigeminal neuralgia [ABPI Medicines Compendium, 2013] and minor typographical error corrected.

October 2012 to February 2013 — reviewed. A literature search was conducted in September 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. Pregabalin has been added to the treatment options.

Previous changes

September 2010 — minor update. A Prescribing information section has been included in this topic. Issued in September 2010.

June to November 2008 — converted from CKS guidance to CKS topic structure. The evidence base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. There have been no major changes to the recommendations.

April 2008 — minor update. Update to the text in medicines management to reflect recent MHRA advice regarding genetic testing for carbamazepine. Issued May 2008.

July 2007 — minor update. Clarification of when to refer for an MRI head scan to exclude a structural cause has been included. Issued in August 2007.

June 2007 — minor update. Gabapentin is now licensed up to a maximum dose of 3600 mg per day for the treatment of peripheral neuropathic pain. Issued in June 2007.

January 2007 — typographical error corrected. Issued in January 2007.

October 2005 — minor technical update. Issued in November 2005.

March 2005 — reviewed. Validated in June 2005 and issued in July 2005.

January 2002 — reviewed. Validated in March 2002 and issued in April 2002.

October 1998 — written. Validated in November 1998 and issued in December 1998.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 September 2012.

HTAs (Health Technology Assessments)

No new HTAs since 1 September 2012.

Economic appraisals

No new economic appraisals relevant to England since 1 September 2012.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analyses since 1 September 2012.

Primary evidence

No new randomized controlled trials published in the major journals since 1 September 2012.

New policies

No new national policies or guidelines since 1 September 2012.

New safety alerts

No new safety alerts since 1 September 2012.

Changes in product availability

No changes in product availability since 1 September 2012.

Goals and outcome measures

Goals

Early recognition of symptoms suggestive of trigeminal neuralgia

Making an accurate diagnosis and excluding similar conditions

Making an accurate assessment (e.g. of severity)

Appropriate treatment in primary care settings

Appropriate referral to secondary care or other specialist service

Providing appropriate advice to patients

Background information

Definition

What is it?

Trigeminal neuralgia is defined as a unilateral, severe, short-lasting pain of the face [Zakrzewska, 2010].

Trigeminal neuralgia occurs in the distribution of one or more branches of the fifth (trigeminal) cranial nerve [Zakrzewska and Linskey, 2009].

Typically, the maxillary or mandibular branches are affected, either alone or in combination. Involvement of the ophthalmic branch alone is uncommon [Bennetto et al, 2007]. Only 3% of cases are bilateral.

Pain may occur infrequently (for example periods of remission may last years) or with a frequency of up to hundreds of times a day. Paroxysms of pain can be triggered by a number of factors including eating, talking, and touching or washing the face [Zakrzewska and Linskey, 2009].

'Atypical' or 'mixed' trigeminal neuralgia occurs when there is a persistent discomfort between paroxysms or sensory loss, and is more often refractory to treatment than classic trigeminal neuralgia [Nurmikko and Eldridge, 2001; Bennetto et al, 2007].

Causes

What causes it?

In 80–90% of cases, trigeminal neuralgia is thought to be caused by compression of the trigeminal nerve by a loop of artery or vein; another 5–10% of cases are attributed to tumours, multiple sclerosis, abnormalities of the skull base, or arteriovenous malformations [Bennetto et al, 2007].

Risk factors

What are the risk factors?

Risk factors include:

Multiple sclerosis.

Hypertension.

Female sex.

Almost twice as many women are affected by trigeminal neuralgia as men. The incidence increases with age and is rare in people less than 40 years of age [Bennetto et al, 2007; Zakrzewska, 2010].

Complications

What are the complications?

Complications include depression, and inability to eat causing weight loss.

Diagnosis

Diagnostic criteria for trigeminal neuralgia

Diagnosis

How do I diagnose trigeminal neuralgia?

Use the International Headache Society's diagnostic criteria to diagnose classical trigeminal neuralgia:

A: Paroxysmal attacks of pain lasting from a fraction of a second to 2 minutes, affecting one or more divisions of the trigeminal nerve and fulfilling criteria B and C.

B: Pain has at least one of the following characteristics:

Intense, sharp, superficial, or stabbing.

Precipitated from trigger areas or by trigger factors.

C: Attacks are stereotyped in the individual patient.

D: There is no clinically evident neurological deficit.

E: Not attributed to another disorder.

Pain may occur infrequently (for example periods of remission may last years) or with a frequency of up to hundreds of times a day. Paroxysms of pain can be triggered by a number of factors including eating, talking, and touching or washing the face.

'Atypical' or 'mixed' trigeminal neuralgia occurs when there is a persistent discomfort between paroxysms or sensory loss.

Basis for recommendation

Basis for recommendation

The diagnostic criteria for classical trigeminal neuralgia are those of the International Headache Society [Headache Classification Subcommittee of the International Headache Society, 2005].

The statement that pain may occur infrequently (for example periods of remission may last years) or with a frequency of up to hundreds of times a day, and paroxysms of pain can be triggered by a number of factors including eating, talking, and touching or washing the face, is derived from an evidence-based review [Zakrzewska and Linskey, 2009].

The statement that 'atypical' or 'mixed' trigeminal neuralgia occurs when there is a persistent discomfort between paroxysms or sensory loss is based on expert opinion from narrative reviews [Nurmikko and Eldridge, 2001; Bennetto et al, 2007].

Management

Management

Scenario: Management : covers the management of people with trigeminal neuralgia in primary care.

Scenario: Management

Scenario: Management of trigeminal neuralgia

216months3060monthsBoth

Treatment

How should I treat trigeminal neuralgia?

Offer carbamazepine (licensed for trigeminal neuralgia).

Start at 100 mg twice daily and slowly titrate the dosage up until pain is relieved (for example increase by a maximum of 100 mg every 3 days, according to tolerability and efficacy).

In the majority of people a dosage of 200 mg three or four times a day is sufficient to prevent paroxysms of pain (maximum dosage 1600 mg daily).

Once the pain is in remission, the dosage should be gradually reduced to the lowest possible maintenance level. The maximum recommended dose is 1200 mg daily.

Modified release preparations may be useful at night if the person experiences breakthrough pain.

For further information on contraindications and cautions, adverse effects, drug interactions, and monitoring, see prescribing information.

If carbamazepine is inappropriate, ineffective, or not tolerated, consider seeking specialist advice and consider early referral to a specialist pain service or a condition-specific service.

Do not offer any other drug treatment unless advised to do so by a specialist. However, other treatments initiated by a specialist may be continued in primary care under a multidisciplinary care plan or a local shared-care agreement.

Arrange early follow up to assess the progress made with dose titration, and the tolerability and effectiveness of the the treatment. Use clinical judgement to decide how soon to follow up the person.

Advise the person:

On the importance of dosage titration, and the titration process, providing written information if possible. Explain that the treatment does not work immediately; it commonly takes weeks to titrate up to an effective dose.

On the possible adverse effects associated with carbamazepine.

That a daily pain diary may be useful to help people learn to manage their pain.

Consider referring the person to a specialist pain service and/or a relevant clinical speciality (for example neurology, diabetology, or oncology) if:

They have severe pain.

Their pain significantly limits their participation in daily activities (including self care, general tasks and demands, interpersonal interactions and relationships, mobility, and sleeping).

Their underlying health condition has deteriorated.

Basis for recommendation

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline: Neuropathic pain — pharmacological management. The pharmacological management of neuropathic pain in adults in non-specialist settings [NICE, 2013], the American Academy of Neurology and the European Federation of Neurological Societies (AAN/EFNS) guidelines on the management of trigeminal neuralgia [Cruccu et al, 2008; Gronseth et al, 2008; Attal et al, 2010], expert opinion in review articles [Jorns and Zakrzewska, 2007; van Kleef et al, 2009; Zakrzewska, 2010; Zakrzewska and McMillan, 2011], and feedback from expert reviewers of this CKS topic.

Offering carbamazepine

NICE did not identify any evidence that met their inclusion criteria, on the effectiveness of carbamazepine for the treatment of neuropathic pain. However, the guideline development group (GDG) recognized that carbamazepine is the only drug currently licensed for this condition, and it is widely used in current practice. The GDG concluded that until new evidence becomes available, carbamazepine should be offered as initial treatment for trigeminal neuralgia [NICE, 2013].

AAN/EFNS guidelines [Cruccu et al, 2008; Gronseth et al, 2008; Attal et al, 2010] and a number of review articles recommend carbamazepine as the drug of choice to treat trigeminal neuralgia, and it is licensed for this purpose [Attal et al, 2006; Bennetto et al, 2007; Jorns and Zakrzewska, 2007; van Kleef et al, 2009; Zakrzewska, 2010; ABPI Medicines Compendium, 2013].

The recommended dose and titration is based on the British National Formulary [BNF 67, 2014], the manufacturers' Summary of Product Characteristics [ABPI Medicines Compendium, 2013], a review article [Bennetto et al, 2007], and feedback from expert reviewers of this CKS topic.

The recommendation that modified release carbamazepine may be useful at night is based on expert opinion in a review article [Zakrzewska, 2010].

Advice

The NICE GDG recommends, based on what is considered to be good medical practice, discussing the risks and benefits of treatment to ensure the person makes an informed decision about their treatment [NICE, 2013].

Feedback from an expert reviewer of the CKS topic suggests that keeping a pain diary may help people to feel in control and to understand how their pain responds to medication and when they may be experiencing a remission or relapse.

Early follow up

In the expert opinion of the NICE GDG, an early clinical review is important to assess the progress made with titration as well as the effectiveness and tolerability of treatment. This allows any necessary treatment adjustments to be made promptly in order to ensure optimal pain control [NICE, 2013].

CKS recommends using clinical judgement to decide how soon to follow up a person with neuropathic pain. This pragmatic advice is based on the fact that CKS recognizes that the urgency of a follow up will depend on several factors including the cause of neuropathic pain, severity of pain, treatment prescribed, and the complexity of the titration process.

Referral

NICE recommends considering referral (to specialist pain services or a condition-specific service) at any stage (including at initial presentation and at regular clinical reviews) if pain is severe, pain significantly limits daily activities and quality of life, or any underlying health condition has deteriorated, because [NICE, 2013]:

Specialist pain services provide comprehensive assessment and multi-modal management of all types of pain, including neuropathic pain.

A condition-specific service (for example oncology, neurology, or diabetology) will provide treatment for the underlying health condition that is causing neuropathic pain.

Treatments not recommended

The GDG was aware of other very poor quality studies on other drugs for trigeminal neuralgia, such as oxcarbazepine or lacosamide, which could potentially have less adverse effects or be better tolerated than carbamazepine. However, in the absence of robust, good-quality evidence, the GDG felt unable to recommend the use of these off-label drugs [NICE, 2013].

The GDG viewed trigeminal neuralgia to be particularly distinctive from other neuropathic pain conditions and felt that, based on their clinical experience, recommending any other treatments apart from carbamazepine (which is commonly used in current practice) would not be appropriate [NICE, 2013].

Follow up

How should I follow up a person being treated for trigeminal neuralgia?

Assess the progress made with dose titration, the tolerability, and the effectiveness of the current treatment.

Ask about the current dose of carbamazepine, any problems thay have experienced titrating the dose upwards, and confirm they understand the titration process.

Ask about the tolerability of adverse effects experienced and whether they tend to improve or persist with time following each dose increase.

Assess the effectiveness of the treatment by asking about:

The degree of pain.

The impact of the pain on participation in daily activities (including self care, general tasks and demands, interpersonal interactions and relationships, mobility, and sleeping).

Their mood (in particular, whether the person is depressed or anxious).

If the treatment is poorly tolerated, use clinical judgement to decide whether to:

Titrate the dose more slowly upwards (especially if adverse effects improve with time following each dose increase), or

Refer to a specialist pain service or a relevant clinical speciality (for example neurology, diabetology, or oncology services).

If the treatment is reasonably well tolerated, continue titrating the dose upwards until either pain is well controlled or the maximum tolerated dose has been reached.

If pain is poorly controlled on the maximum tolerated dose, refer to a specialist pain service or a relevant clinical speciality (for example neurology, diabetology, or oncology services).

If pain is well controlled, continue treatment. Consider gradually reducing the dose over time if the person remains pain-free for 1 month.

Consider referring the person to a specialist pain service or a relevant clinical speciality (for example neurology, diabetology, or oncology services) at any stage if:

They have severe pain.

Their pain significantly limits their participation in daily activities (including self care, general tasks and demands, interpersonal interactions and relationships, mobility, and sleeping).

Atypical clinical features (for example burning pain between paroxysms, loss of sensation, or any abnormal neurological signs) are present.

Basis for recommendation

Basis for recommendation

These recommendations are based largely on the National Institute for Health and Care Excellence (NICE) guideline: Neuropathic pain — pharmacological management. The pharmacological management of neuropathic pain in adults in non-specialist settings [NICE, 2013].

Assessing progress made with dose titration, the tolerability, and the effectiveness of the current treatment

In the expert opinion of the NICE guideline development group (GDG), assessing progress made with dose titration, the tolerability, and the effectiveness of the current treatment is important, to allow any necessary treatment adjustments to be made promptly in order to ensure optimal pain control [NICE, 2013].

Poorly tolerated treatment

CKS recommends using clinical judgement if treatment is poorly tolerated. This pragmatic advice is based on the fact that slower titration may reduce the risk of intolerable adverse effects for some people whilst others may need to be referred.

Reasonably well tolerated treatment

The recommendations to continue treatment if pain is well controlled and to consider gradually reducing the dose over time if the improvement is sustained is based on the expert opinion of the NICE GDG [NICE, 2013].

Stopping treatment

CKS found no evidence on the duration of treatment. Feedback from expert reviewers varied in the amount of time for which treatment should be tried before reducing or stopping medication. Considering this and the Summary of Product Characteristics for carbamazepine [ABPI Medicines Compendium, 2013], CKS has made a practical recommendation.

Referral

NICE recommends considering referral at any stage (including at initial presentation and at regular clinical reviews) if pain is severe; pain significantly limits daily activities and quality of life; their underlying health condition has deteriorated; or treatment is inappropriate, ineffective, or not tolerated, because [NICE, 2013]:

Specialist pain services provide comprehensive assessment and multi-modal management of all types of pain, including neuropathic pain.

A condition-specific service (for example oncology, neurology, or diabetology) will provide treatment for the underlying health condition that is causing neuropathic pain.

Other criteria for referral are based on expert opinion in a review article [Bennetto et al, 2007] and feedback from an expert reviewer of this CKS topic.

The diagnosis of trigeminal neuralgia should be reviewed if medical treatment fails.

Surgical options should be considered if pain control cannot be achieved, or drugs cause unacceptable adverse effects. This should be done at the earliest possible stage if medical treatment fails.

An MRI (magnetic resonance imaging) scan is indicated in younger people, those with atypical symptoms, people who do not respond to initial therapy, or anyone for whom neurosurgery is being considered. CKS recommends referral to a specialist to ensure the correct scan is requested, and that interpretation is carried out by someone with appropriate expertise. CKS has used 40 years of age as a cut-off as the review states that trigeminal neuralgia is rare below this age.

Expert opinion in another review article is that if facial sensory loss or cranial nerve dysfunction cannot be attributed to a previous nerve injury, cerebral imaging is necessary [Nurmikko and Eldridge, 2001].

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).

Carbamazepine

Carbamazepine

Licensed indications

Is carbamazepine licensed for trigeminal neuralgia?

Carbamazepine is licensed for the treatment of trigeminal neuralgia in adults.

Basis for recommendation

This is based on the manufacturers' information [ABPI Medicines Compendium, 2012].

Contraindications and cautions

When should carbamazepine be avoided?

Carbamazepine is contraindicated in:

Known hypersensitivity to carbamazepine or structurally related drugs (for example tricyclic antidepressants) or any other component of the formulation.

People with atrioventricular block.

People with a history of bone marrow depression.

People with a history of hepatic porphyrias.

People taking a monoamine oxidase inhibitor.

Prescribe carbamazepine with caution if the person is at risk of suicide.

Basis for recommendation

Carbamazepine may suppress both atrioventricular conduction and ventricular automacity shortly after oral administration. It is therefore contraindicated in people with a history of atrioventricular block [Micromedex, 2009; ABPI Medicines Compendium, 2012].

Although rare, agranulocytosis and aplastic anaemia have been associated with carbamazepine when used for epilepsy [Micromedex, 2009; ABPI Medicines Compendium, 2012]. This risk may increase in people with a history of bone marrow suppression.

There appear to be no reports of adverse reactions during the concurrent use of MAOIs and carbamazepine. However, carbamazepine is structurally similar to the tricyclic antidepressants and there is a theoretical risk of a reaction similar to the serotonin syndrome. The manufacturers of carbamazepine (Tegretol®) therefore advise that concurrent use should be avoided [ABPI Medicines Compendium, 2012; Baxter and Preston, 2013].

There is a small increased risk of suicidal ideation and behaviour in people treated with antiepileptic drugs in several indications. The mechanism of this risk is not known, and the available data do not exclude the possibility of an increased risk for carbamazepine [MHRA, 2008b].

Adverse effects

What are the adverse effects and how can they be managed?

Common adverse effects include nausea and vomiting, sedation, dizziness, and ataxia.

These adverse effects are dose related and are most common at the start of treatment.

Switching to a modified-release preparation of carbamazepine may help to reduce the incidence of central nervous system adverse effects, such as sedation.

Allergic skin reactions (including urticaria, which may be severe) are also common:

Withdraw carbamazepine if the skin reaction worsens or is accompanied by other symptoms.

Rarely, serious dermatological adverse effects, including Stevens–Johnson syndrome and exfoliative dermatitis, can occur.

People who are of Han Chinese, Hong Kong Chinese, or Thai origin should be screened for the presence of the HLA–B*1502 allele before taking carbamazepine.

People who test positive should not start carbamazepine unless the benefits clearly outweigh the risks of Stevens–Johnson syndrome.

Hyponatraemia occurs in 20% of people taking carbamazepine. It is usually mild but in rare cases can lead to water intoxication accompanied by lethargy, vomiting, headache, and confusion.

Consider hyponatraemia if the person develops dizziness, drowsiness, confusion, nausea, muscle cramps, or seizures.

If hyponatraemia is suspected, reduce the dose or stop carbamazepine and manage according to severity of symptoms, duration, and state of hydration.

Leucopenia (very common) and other blood disorders (including thrombocytopenia, agranulocytosis, and aplastic anaemia) occur with carbamazepine treatment.

Advise people taking carbamazepine to seek immediate medical attention if they develop symptoms indicative of blood, hepatic, or skin disorders (for example fever, sore throat, rash, mouth ulcers, bruising, or bleeding).

There is a small risk of suicidal thoughts and behaviour associated with antiepileptic drugs, which may be seen as early as one week after starting treatment.

People taking carbamazepine and healthcare professionals should be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment.

Basis for recommendation

Information regarding adverse effects is taken from the British National Formulary, Micromedex, the Summary of Product Characteristics for Tegretol® and the Medicines and Healthcare products Regulatory Agency [MHRA, 2008b; Micromedex, 2009; ABPI Medicines Compendium, 2012; BNF 64, 2012].

Evidence from one small study (n = 61 people taking carbamazepine for the management of epilepsy) suggests that switching from standard-release to modified-release carbamazepine significantly reduces the incidence of central nervous system adverse effects (p = 0.001) and enables people to tolerate higher doses of carbamazepine [Miller et al, 2004].

The risk of carbamazepine-induced Stevens–Johnson syndrome is strongly associated with presence of the HLA–B*1502 allele in individuals of Han Chinese, Hong Kong Chinese, or Thai origin. The Medicines and Healthcare products Regulatory Agency therefore recommends that these individuals should be screened for the HLA–B*1502 allele before starting carbamazepine [MHRA, 2008a].

Drug interactions

What are the key drug interactions with carbamazepine?

The plasma concentration of carbamazepine may be increased (with an increased risk of toxicity) by the concomitant use of:

Azole antifungals.

Cimetidine.

Danazol.

Macrolide antibiotics (clarithromycin and erythromycin).

Selective serotonin reuptake inhibitors (fluoxetine and fluvoxamine).

Carbamazepine accelerates the metabolism of:

Ciclosporin — resulting in reduced levels of ciclosporin.

Clozapine — resulting in reduced plasma concentration of clozapine; also avoid concomitant use of drugs with potential for causing agranulocytosis.

Corticosteroids (systemic) — resulting in their reduced effect.

Doxycycline — resulting in their reduced effect.

Oestrogens and progestogens — resulting in reduced effect of oral contraceptives.

Thyroid hormones — requirements for thyroid hormones in hypothyroidism may be increased.

Tricyclic antidepressants — resulting in their reduced effect.

Simvastatin — consider increasing dose of simvastatin; statins metabolized by the same route as simvastatin may also have their levels reduced.

Warfarin — resulting in reduced anticoagulant effect.

The use of carbamazepine is not recommended in combination with monoamine oxidase inhibitors (MAOIs), or for 2 weeks after stopping an MAOI.

Avoid giving carbamazepine with diuretics — increased risk of hyponatraemia.

Basis for recommendation

Information regarding drug interactions with carbamazepine is taken from the British National Formulary, Micromedex, Stockley's drug interactions, and the Summary of Product Characteristics for Tegretol® [Micromedex, 2009; ABPI Medicines Compendium, 2012; BNF 64, 2012; Baxter and Preston, 2013].

Monitoring

What monitoring is required?

Serum carbamazepine levels should not be routinely monitored unless toxicity is suspected.

A full blood count, liver function tests, and urea and electrolyte measurements should be done before starting treatment and every 6 months during treatment.

Stop treatment if leucopenia develops that is severe, progressive, or accompanied by clinical symptoms (e.g. fever or sore throat), or if there is any evidence of significant bone marrow depression.

Stop treatment immediately if liver dysfunction develops.

Basis for recommendation

These recommendations are consistent with guideline sources, expert opinion, and the manufacturer's recommendations [London and South East Medicines Information Service et al, 2008].

There is no clear guidance regarding the frequency of monitoring for adverse effects in someone taking carbamazepine for trigeminal neuralgia; the recommendation to monitor every 6 months has been extrapolated from the National Institute for Health and Care Excellence guidance on bipolar disorder [NICE, 2006].

Evidence

Evidence

Supporting evidence

Carbamazepine

Evidence on carbamazepine

The National Institute for Health and Care Excellence (NICE) did not identify any good quality evidence on which to base specific recommendations for treating trigeminal neuralgia and concluded that until new evidence is available, carbamazepine should be offered as initial treatment for neuropathic pain, as per current routine practice. Adverse effects are commonly reported and may limit its use.

The NICE guideline development group (GDG) considered the clinical and economic evidence on different drug treatments for adults with trigeminal neuralgia [NICE, 2013].

No clinical or economic evidence was found that met the inclusion criteria specified in the review protocol.

The GDG was concerned by the lack of robust evidence on trigeminal neuralgia but recognized that carbamazepine is the only drug currently licensed for this condition, and it is widely used in current practice.

The GDG concluded that carbamazepine should be offered as initial treatment for trigeminal neuralgia.

For a full version of the clinical and economic evidence reviewed by the NICE GDG, see the full NICE guidance and the full appendices (C–L).

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of trigeminal neuralgia.

Search dates

May 2008 - September 2012

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

exp Trigeminal Neuralgia/, trigeminal neuralgia.tw

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)
Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

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

The Cochrane Library :

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

The Cochrane Library :

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

Bandolier

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

References

ABPI Medicines Compendium (2012) Summary of product characteristics for Tegretol Tablets 100mg, 200mg, 400mg. Electronic Medicines CompendiumDatapharm Communications Ltd. www.medicines.org.uk [Free Full-text]

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