Previous changes

January 2022 — reviewed. A literature search was conducted in November 2021 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. Updated literature has been incorporated to provide supporting evidence for the guidance. Addition of a differential diagnosis section. Minor changes to prescribing advice in line with manufacturer's guidance (SmPC for Tegretol). No major changes to the clinical recommendations have been made.

January 2018 — minor update. Revised SPC for Tegretol (carbamazepine) - all formulations, information regarding drug interactions updated as per revised SPC.  

February to March 2017 — reviewed. A literature search was conducted in February 2017 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made.

December 2016 — minor update. Information that carbamazepine levels may be increased when taken concomitantly with antivirals, such as ritonavir, has been added to the drug interactions section of this topic, in line with the manufacturer's Summary of Product Characteristics.

December 2014 — minor update. Minor typographical error corrected.

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. 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 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.

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.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 January 2022.

HTAs (Health Technology Assessments)

No new HTAs since 1 January 2022.

Economic appraisals

No new economic appraisals relevant to England since 1 January 2022.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 January 2022.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 January 2022.

New policies

No new national policies or guidelines since 1 January 2022.

New safety alerts

No new safety alerts since 1 January 2022.

Changes in product availability

No changes in product availability since 1 January 2022.

Basis for recommendation

The information on the diagnosis of trigeminal neuralgia is based on expert opinion in three narrative review articles [Zakrzweska, 2014; Zakrzewska, 2015; Besi, 2019] and in an information leaflet Trigeminal neuralgia: an overview from the Trigeminal Neuralgia Association UK [Trigeminal neuralgia association UK, 2016].

How should I manage a person with trigeminal neuralgia?

• If there are red flag symptoms and signs that may suggest a serious underlying cause, admit, or refer urgently for specialist assessment, depending on clinical judgement.
• Assess the person for signs of depression. For more information, see the CKS topic on Depression.
• If there are no red flag symptoms and signs, offer the person carbamazepine.
  • Carbamazepine is the only licensed anticonvulsant medication with proven efficacy to treat trigeminal neuralgia.
  • Initiate therapy at 100 mg up to twice daily, and titrate in steps of 100–200 mg every 2 weeks, until pain has been relieved.
  • 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).
  • Modified release preparations may be useful, particularly if the person experiences breakthrough pain at night. A usual dose is 600–800 mg in two divided doses (maximum dosage 1600 mg daily in two divided doses).
  • Once the pain is in remission, the dosage should be gradually reduced to the lowest possible maintenance level, or the drug can be discontinued until a further attack occurs.
  • For further information on contraindications and cautions, adverse effects, drug interactions, and monitoring with carbamazepine, see the section on Prescribing information.
• If carbamazepine is contraindicated, ineffective, or not tolerated, seek specialist advice. 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.
  • Specialist initiated medications may include other anticonvulsant medications such as oxcarbazepine, lamotrigine, topiramate, gabapentin and pregabalin, or non-anticonvulsant medications such as baclofen.
• Arrange early follow up to assess the progress made with dose titration, and the tolerability and effectiveness of the treatment. Timing of follow up should be based on clinical judgement.
• 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 use of carbamazepine.
  • That a daily pain diary may be useful to help people learn to manage their pain.
• Consider referring the person to a neurologist or specialist pain service 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).

How should I follow up a person with trigeminal neuralgia?

• Assess the progress made with dose titration, and the tolerability and effectiveness of treatment.
  • Ask about the current dose of carbamazepine, any problems they have experienced titrating the dose upwards, and confirm that they understand the titration process.
  • Ask about tolerability and adverse effects, and whether these 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 daily activities (including self care, general tasks and demands, interpersonal interactions and relationships, mobility, eating, 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 neurologist.
• If the treatment is 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 neurologist.
  • 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 neurologist at any stage, if:
  • They have severe pain.
  • Their pain significantly limits their daily activities (including self care, general tasks and demands, interpersonal interactions and relationships, mobility, and sleeping).
  • The person has atypical clinical features (for example burning pain between paroxysms, loss of sensation, or any abnormal neurological signs).

Contraindications and cautions

• Do not prescribe carbamazepine to people:
  • With a known hypersensitivity to carbamazepine or structurally related drugs (for example tricyclic antidepressants) or any other component of the formulation.
  • With atrioventricular block.
  • With a history of bone marrow depression.
  • With a history of hepatic porphyrias.
  • Taking a monoamine oxidase inhibitor.
• Prescribe carbamazepine with caution to people:
  • At risk of suicide.
  • With cardiac disease.
  • With a history of haematological reactions to other drugs.
  • With a history of absence and myoclonic seizures.
  • With a history of skin reactions.
  • Who are susceptible to angle-closure glaucoma.
  • Who are pregnant. Follow MHRA safety advice on antiepileptic drugs in pregnancy.  
• Consider vitamin D supplementation in patients who are immobilized for long periods or who have inadequate exposure to sun/low dietary calcium.

[ABPI, 2021; BNF, 2021]   

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

• Common adverse effects of carbamazepine include nausea and vomiting, sedation, dizziness, and ataxia.
  • These adverse effects are dose related and are most common at the start of treatment and in older people.
  • Switching to a modified-release preparation of carbamazepine may help to reduce the incidence of central nervous system adverse effects, such as sedation.
• Hypersensitivity reactions (including rash, pruritus, urticaria, angioedema and anaphylaxis):
  • Discontinue treatment if these occur.
  • Cross-sensitivity has been reported with other antiepileptic drugs (including oxcarbazepine, phenytoin, primidone, and phenobarbital).
• 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. Those who test positive should not start carbamazepine unless there is no other treatment option.
  • Testing for this allele should also be considered in people originating from Malaysia and the Philippines.
• 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) may 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 drug use, which may be seen as early as 1 week after starting treatment.
  • People taking carbamazepine and healthcare professionals should be alert to any mood changes, distressing thoughts, or feelings about suicide or self-harm at any point during treatment.
• Some of these adverse reactions (including headache, ataxia, drowsiness, nausea, vomiting, blurring of vision, dizziness, and allergic skin reactions) are dose related, and may be dose-limiting. These side-effects are more common at the start of treatment and in the elderly. 

[ABPI, 2021; BNF, 2021]   

Drug interactions

• 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.
• The plasma concentration of carbamazepine may be increased (with an increased risk of toxicity) by the concomitant use of certain drugs, including:
  • Acetazolamide.
  • Antidepressants — fluoxetine, fluvoxamine, paroxetine, trazodone.
  • Azole antifungals.
  • Antivirals — protease inhibitors for HIV treatment (for example ritonavir).
  • Cimetidine.
  • Ciprofloxacin.
  • Clarithromycin.
  • Danazol.
  • Dextropropoxyphene. 
  • Diltiazem.
  • Erythromycin.
  • Isoniazid.
  • Olanzapine.
  • Omeprazole
  • Verapamil.
  • Vigabatrin.
• Carbamazepine accelerates the metabolism of certain drugs, including (but not limited to): 
  • Azole antifungals — resulting in reduced levels of voriconazole and itraconazole.
  • 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.
  • Direct acting oral anti-coagulants (DOACs; rivaroxaban, dabigatran, apixaban, and edoxaban) may lead to reduced plasma concentrations of DOACs, which carries the risk of thrombosis. Closer monitoring is recommended.
  • Doxycycline — resulting in 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.
• Other interactions include:
  • Grapefruit juice — may increase plasma concentrations.
  • Lithuim — may result in enhanced neurotoxicity despite lithium plasma concentrations being within the therapeutic range.
  • Paracetamol — long term co-administration may result in hepatotoxicity. 
  • Primidone, progabide, quetiapine, valproic acid, valnoctamide, and valpromide — may result in raised plasma levels of the active metabolite carbamazepine-10,11-epoxide, increasing the risk of adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia). The dosage of carbamazepine should be adjusted accordingly and/or the plasma levels monitored when used concomitantly with these substances.

[Baxter, 2013; ABPI, 2021; BNF, 2021]

What monitoring is required?

• Serum carbamazepine levels should not be routinely monitored unless toxicity is suspected. 
• A full blood count should ideally be done before starting treatment, and periodically thereafter.
  • If the white blood cell or platelet count is low or decreased during treatment, the person and the full blood count should be closely monitored.
  • 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.
• Liver function tests should also be performed before commencing treatment and periodically thereafter, particularly in patients with a history of liver disease and in elderly patients.
  • The drug should be withdrawn immediately in cases of aggravated liver dysfunction or acute liver disease.
  • Some liver function tests in patients receiving carbamazepine may be found to be abnormal, particularly gamma glutamyl transferase. This is probably due to hepatic enzyme induction. Enzyme induction may also produce modest elevations in alkaline phosphatase. Observations of such liver function abnormalities are not an indication for carbamazepine withdrawal.
• Suicidal ideation and behaviour has been reported in patients treated with antiepileptic drugs. All patients receiving carbamazepine should be made aware of this risk. Should signs of suicidal ideation or behaviours present, medical advice should be sought and appropriate treatment should be considered.

[ABPI, 2021; BNF, 2021]