Abstract: 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. 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.

Plain-language summary: 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. 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.