Current Drug Treatment Of Trigeminal Neuralgia: A Systematic Review

Background: Drug therapy of trigeminal neuralgia originated from the 1960s and played an important role in easing the pain of patients with trigeminal neuralgia. Today, the drugs used to treat trigeminal neuralgia are up more than 10 kinds and can be divided into antiepileptic drugs and non-antiepileptic drugs. Antiepileptic drugs are the first line drugs for the treatment of trigeminal neuralgia, commonly including carbamazepine, phenytoin, lamotrigine, and so on. Common non-antiepileptic drugs include pimozide, baclofen, and Tizanidine, etc. Although carbamazepine in the clinical treatment of trigeminal neuralgia is still the first choice of drug and the use of other drugs are also very extensive, there is still a lack of convincing systematic review to demonstrate the clinical effects and side effects of these drugs.Objectives: To collect the randomized controlled trials of the above-mentioned six drugs around the whole world from 1960s and make a systematic review to explore the exact clinical effects and side effects of every drug so as to guide clinicians to use drugs reasonably and regularly and provide a guidance for future designing of randomized controlled trials for the treatment of trigeminal neuralgia.Materials and Methods: According to strict standards of inclusion and exclusion criteria and search strategy made already, we searched the commonly used database of English and Chinese, such as MEDLINE,EMBASE,CBMdisc, by using computer, and related Chinese journals by hand, such as Chinese Journal of Stomatology. We also searched the published and unpublished literatures associated with conference and pharmaceutical factory and other grey literatures. Two different reviewers independently screened the studies for eligibility, evaluated the quality and extracted the data from the eligible studies with confirmation of cross-check. Different opinions were consulted by the third party. Meta-analysis was done by software of Revman 5.0. Datas were pooled using fixed effect model if there was no heterogeneity(p>0.05), otherwise , sensitivity analysis, subgroup analysis or randomized effect model was adopted. We would use qualitative analysis while the data could not be pooled.Results: Ten randomized studies published between 1966 and 1997, involving 281 patients were included. There were four randomized controlled trials studying carbamazepine, while there were two trials studying tizanidine and baclofen each and there was only one trial studying lamotrigine and pimozide each. We didn't find out even one trial about phenytoin. Because the drugs tested in the included studies were different and the outcome of each trials wasn't the same, we only had a Meta analysis on the effective rate of carbamazepine. Because different control drugs had been used in the studies investigating the same drugs, we did not undertake subgroup analysis. Instead, we described the characteristics of each individual trial only. The results showed that carbamazepine had exact clinical effects to ease the pain in patients. However, the long-term application of carbamazepine will have a wide range of side effects, the most common of which included dizziness, ataxia, lethargy, loss of appetite and constipation. Lamotrigine was superior to placebo (p=0.011) based on analysis of a composite efficacy index which compared the numbers of patients assigned greater efficacy on lamotrigine with those assigned greater efficacy on placebo, but the long term effects should be still observed. We found that baclofen significantly relieved the pain of patients of trigeminal neuralgia and L-baclofen made a marked decrease in the number of attacks of trigeminal neuralgia and had less side effects than racemic baclofen. Tizanidine was well tolerated, but the effects, if any, were inferior to those of carbamazepine. Lamotrigine is a possibility as an add on treatment, but common side effects were widely happened. Though phenytoin is considered the second drug of choice in trigeminal neuralgia after the failure of carbamazepine, our search did not show a single study with high level of evidence on phenytoin.Conclusion: There are still no high-quality randomized controlled trials on the clinical effects and side effects of drug treatment for trigeminal neuralgia. All of the ten trials we searched out had shortcomings, such as non-standardized trial design, lack of enough samples, short follow-up time, and so on. Available evidence collected from this systematic review indicates that carbamazepine is still the first line drug to treat trigeminal neuralgia though it has a wide range of side effects. There is no enough evidence to demonstrate the exact effect of phenytoin and no sufficient evidence to show that the effects of non-antiepileptic, such as baclofen and tizanidine, is superior to that of carbamazepine. However, they can be used as additional selective drugs when carbamazepine is not effective.