Evaluation of the efficacy and safety of topiramate as adjunctive drug in the treatment of refractory partial seizures with Meta-analysis

Abstract

Background Epilepsy is a chronic neurological condition characterized by paroxysm of seizures due to abnormal electrical discharge from central nervous system neurons. Several new antiepileptic drugs (AEDs) were listed over the past two decades, and they were believed to be equally effective and have better tolerability and side effect profiles. This paper aims to evaluate the efficacy and safety of adjunctive topiramate in refractory partial seizures.  Methods Relevant research articles about randomized controlled trials of adjunctive topiramate in refractory partial seizures, with topiramate, Topamax, add-on treatment, adjunctive treatment, add-on therapy, adjunctive therapy, refractory partial seizure, refractory partial epilepsy both in Chinese and English as retrieval words, were retrieved from PubMed (1995-2014), Cochrane Central Register of Controlled Trials (CENTRAL, 1995-2014), The Cochrane Database of Systematic Reviews (CDSR, 1995-2014), China National Knowledge Infrastructure (CNKI, 1995-2014) and Wanfang Data (1999-2014). Two reviewers independently evaluated the quality of the included articles and abstracted the data. A Meta-analysis was conducted using RevMan 5.0 software.  Results According to the enrollment criteria, 13 prospective, randomized controlled clinical trials with a total of 1622 patients were finally selected. The proportions of patients with reduction in seizure frequency ≥ 50% (OR = 3.710, 95% CI: 2.870-4.810; P = 0.000), ≥ 75% (OR = 7.220, 95% CI: 3.310-15.750; P = 0.000) and seizure free (OR = 3.380, 95%CI: 1.720-6.640; P = 0.000) in topiramate group were significantly higher than that in control group. The treatment withdrawal ratio was significantly higher compared to placebo in 600 mg/d and 800 mg/d subgroups, but not in 200 mg/d subgroup (200 mg/d: OR = 2.170, 95%CI: 0.470-9.950, P = 0.320; 600 mg/d: OR = 2.090, 95%CI: 1.020-4.270, P = 0.040; 800 mg/d: OR = 8.000, 95%CI: 1.390-46.140, P = 0.020). The common side effects included somnolence, anorexia, ataxia, aprosexia, dizziness, fatigue, nausea, thinking abnormality, paraesthesia and weight loss. The occurrence rate of side effects in topiramate group was higher than that in control group.  Conclusions Topiramate is effective when added to existing therapy in patients with refractory partial seizures. The withdrawal rate of 200 mg/d topiramate is similar to control group. Compared with the control group, adverse effects are more common but mild or moderate, mainly related with the central nervous system. However, trials included in this study are of relatively short duration, and provide no evidence for the long-term efficacy of topiramate.

doi: 10.3969/j.issn.1672-6731.2014.11.007