Drugs other than those used for epilepsy for treating trigeminal neuralgia

Review question

The purpose of this review was to assess the effects of non-antiepileptic drugs in trigeminal neuralgia.


Trigeminal neuralgia is a condition that affects the trigeminal nerve, the nerve which provides sensation in the skin of the face. The condition causes a sudden, severe, stabbing facial pain near the nose, lips, cheek, eye or ear. The incidence of trigeminal neuralgia is three to five new cases per 100,000 people each year. Standard treatment is with drugs that are used to treat epilepsy (antiepileptic drugs) but non-antiepileptic drugs, such as baclofen and tocainide, have been used to treat trigeminal neuralgia since the 1970s.

Study characteristics

After a wide search for studies, we identified four trials involving 139 participants in total that met our criteria for inclusion in the review. Three randomised controlled trials compared the three different non-antiepileptic drugs tizanidine, tocainide and pimozide with carbamazepine, which is the standard drug treatment. No new trials were identified for the update of this review in 2013.

Results and quality of the evidence

Tizanidine did not produce significantly more benefit than carbamazepine according to low-quality evidence. The reporting of the tocainide trial did not allow us to assess whether the drug helped the pain of trigeminal neuralgia, but studies that were not part of this review suggest that this treatment can have serious harmful effects on the blood. Side effects of pimozide were very common but there was low-quality evidence that it was more effective than carbamazepine. In a fourth trial there was low-quality evidence that proparacaine hydrochloride eye drops did not show any significant benefit.

There is insufficient evidence from randomised controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. Further well-designed randomised controlled trials are needed to establish whether non-antiepileptic drugs are beneficial in trigeminal neuralgia.

The searches for the review are up to date to May 2013.

Authors' conclusions: 

There is low-quality evidence that the effect of tizanidine is not significantly different than that of carbamazepine in treating trigeminal neuralgia. Pimozide is more effective than carbamazepine, although the evidence is of low quality and the data did not allow comparison of adverse event rates. There is also low-quality evidence that 0.5% proparacaine hydrochloride eye drops have no benefit over placebo. Limitations in the data for tocainide prevent any conclusions being drawn. There is insufficient evidence from randomised controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. More research is needed.

Read the full abstract...

Trigeminal neuralgia was defined by the International Association for the Study of Pain as a sudden, usually unilateral, severe, brief, stabbing recurrent pain in the distribution of one or more branches of the fifth cranial nerve. Standard treatment is with anti-epileptic drugs. Non-antiepileptic drugs have been used in the management of trigeminal neuralgia since the 1970s. This is an update of a review first published in 2006 and previously updated in 2011.


To systematically review the efficacy and tolerability of non-antiepileptic drugs for trigeminal neuralgia.

Search strategy: 

On 20 May 2013, for this updated review, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2013, Issue 4), MEDLINE (January 1966 to May 2013), EMBASE (January 1980 to May 2013), LILACS (January 1982 to May 2013) and the Chinese Biomedical Retrieval System (1978 to May 2013). We searched clinical trials registries for ongoing trials.

Selection criteria: 

We included double-blind, randomised controlled trials in which the active drug was used either alone or in combination with other non-antiepileptic drugs for at least two weeks.

Data collection and analysis: 

Two authors decided which trials fitted the inclusion criteria and independently graded risk of bias. We assessed the quality of the evidence according to the GRADE criteria for this update.

Main results: 

In this 2013 update, we updated the searches, but identified only two new ongoing studies. The review includes four trials involving 139 participants. The primary outcome measure in each was pain relief. Three trials compared one of the oral non-antiepileptic drugs tizanidine, tocainide or pimozide with carbamazepine. The quality of evidence for all outcomes for which data were available was low. In a trial of tizanidine involving 12 participants (one dropped out due to unrelated disease), one of five participants treated with tizanidine and four of six treated with carbamazepine improved (risk ratio (RR) 0.30, 95% confidence interval (CI) 0.05 to 1.89). Few side effects were noted with tizanidine. For pimozide, there was evidence of greater efficacy than carbamazepine at six weeks. Up to 83% of participants reported adverse effects but these did not lead to withdrawal; the report did not provide comparable data for carbamazepine. Limited data meant that we could not assess the effects of tocainide; however, data from non-randomised studies (not included in this review) indicate that serious haematological adverse events can occur. A trial involving 47 participants compared 0.5% proparacaine hydrochloride eyedrops with placebo but did not show any significant benefits, again according to low-quality evidence. The report did not mention adverse events. The proparacaine trial was at low risk of bias; the other trials were at unclear risk of bias overall.