Treatments

Carbamazepine

In this section:

Key points | Benefits and Harms | Comment

Top

Key points

  • For GRADE evaluation of interventions for Trigeminal neuralgia, see table.
  • Carbamazepine is considered the gold-standard for the initial medical treatment of trigeminal neuralgia symptoms.
  • Carbamazepine has been shown to increase pain relief compared with placebo, but also increases adverse effects, such as drowsiness, dizziness, rash, liver damage, and ataxia.
  • Although studies evaluating durability of response with carbamazepine are lacking, consensus expert opinion suggests that it may have a greater than 50% failure rate for long-term (5-10 years) pain control.
  • Based on the strength of published evidence, carbamazepine remains the best supported standard medical treatment for trigeminal neuralgia.
Top

Benefits and harms

Carbamazepine versus placebo:

We found one systematic review (search date 2010), which identified three crossover RCTs.[23] We found another systematic review (search date 1994), which examined the number of people who withdrew from RCTs of carbamazepine versus placebo because of adverse effects.[24]

Pain relief

Carbamazepine compared with placebo Carbamazepine for 5 to 14 days seems to be more effective at relieving pain compared with placebo (moderate-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect size (for ORs and RRs)Favours
Pain improvement

[23]

Systematic review

208 people with trigeminal neuralgia

3 RCTs in this analysis

Other comment

RCTs were crossover design

Any pain improvement, 5–14 days

80/102 (78%) with carbamazepine

14/106 (13%) with placebo

RR 5.87

95% CI 3.58 to 9.61

P <0.00001

NNT 2

95% CI 1 to 2

large

carbamazepine

No data from the following reference on this outcome.[24]

Psychological distress

No data from the following reference on this outcome.[23][24]

Ability to perform normal activities

No data from the following reference on this outcome.[23][24]

Adverse effects
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect size (for ORs and RRs)Favours
Adverse effects

[23]

Systematic review

154 people with trigeminal neuralgia

2 RCTs in this analysis

Other comment

RCTs were crossover design

Death

with carbamazepine

with placebo

Other comment

1 RCT reported 4 deaths in those taking carbamazepine (2 with presumed cardiovascular problems, 1 frontal lobe glioblastoma, and 1 of progressive generalised debilitating disease), another RCT reported 1 death with carbamazepine, which was associated with a cardiovascular condition; the review did not report whether any deaths occurred in the placebo group

Significance not reported

[23]

Systematic review

164 people with trigeminal neuralgia

2 RCTs in this analysis

Other comment

RCTs were crossover design

Adverse effects

with carbamazepine

with placebo

Other comment

1 RCT reported dizziness and some drowsiness in 47% of those taking carbamazepine (absolute numbers not reported), Another RCT reported rash in 3 people taking carbamazepine; the review did not report whether any adverse effects occurred in the placebo group

Significance not reported

[24]

Systematic review

People with trigeminal neuralgia

Adverse effects

with carbamazepine

with placebo

Other comment

Significantly more people taking carbamazepine than placebo withdrew from the RCTs because of adverse effects

NNH for withdrawal 24

95% CI 14 to 112

not-calculated

placebo

Carbamazepine versus oxcarbazepine:

See option on Oxcarbazepine.

Carbamazepine versus baclofen:

See option on Baclofen.

Further information on studies

[23]All the RCTs were small and short-term, used simple measures for pain outcomes, and reported no quality-of-life outcomes. In addition, diagnostic criteria were not clearly stated, and previous treatment and duration of pain varied considerably.

Top

Comment

As Clinical Evidence was unable to perform a second appraisal of results retrieved by the contributor's search, we may have missed studies that could affect our overall assessment of this intervention.

Clinical guide:

We found one retrospective cohort study comparing long-term carbamazepine treatment versus stopping carbamazepine earlier.[25] The study did not show carbamazepine treatment to be beneficial in the long term (5–16 years) in people with trigeminal neuralgia. In another retrospective study of 178 people with classical trigeminal neuralgia receiving either carbamazepine or oxcarbazepine, with a mean follow-up of only 13 months, 2% of people taking carbamazepine failed to initially respond, and 27% of responders had adverse effects which either led to treatment interruption or dose reduction and subsequent discontinuation. After a mean follow-up of 13 months, 6% of people taking oxcarbazepine failed to initially respond, and 18% of responders discontinued owing to adverse effects.[26] While durability of response with carbamazepine has been poorly studied, consensus expert opinion suggests that it may have a greater than 50% long-term (5-10 years) failure rate for pain control.[25]

Adverse effects associated with carbamazepine treatment that are not mentioned in the Benefits and Harms table but have been described in observational studies include constipation, leucopenia, and abnormal liver function tests.[26][27]

Most clinicians believe that carbamazepine is the first-line medical treatment for trigeminal neuralgia. It has been widely advocated for use in primary care.[28] The National Institute for Health and Care Excellence (NICE) has published recommendations that state that carbamazepine should be offered as the initial pharmacological treatment for trigeminal neuralgia.[29] Clinicians should start or stop treatment by changing the dose in increments over several days to reduce common adverse effects. After starting treatment, a dose adjustment is often necessary at about 3 weeks owing to induction of liver enzymes. As carbamazepine is an enzyme inducer, NICE recommends a full blood count, measurements of electrolytes, liver enzymes, and vitamin D levels, and other tests of bone metabolism (e.g., serum calcium and alkaline phosphatase) every 2 to 5 years in those taking this drug.[30]

Drug safety alert:

(2008, carbamazepine) — Carbamazepine is associated with a risk of potentially life-threatening skin reactions, including Stevens-Johnson syndrome. The risk of carbamazepine-induced Stevens-Johnson syndrome is greater in people with the allele HLA-B*1502. The frequency of this allele varies worldwide and is highest in some Asian populations. Individuals of Han Chinese, Hong Kong Chinese, or Thai origin should be screened for HLA-B*1502 before starting treatment with carbamazepine.[31] Those who test positive for HLA-B*1502 should not start carbamazepine treatment unless the benefits clearly outweigh the risk of Stevens-Johnson syndrome.[32]