Third Generation Anticonvulsants in Bipolar Disorder: A Review of Efficacy and Summary of Clinical Recommendations

Background: To review the literature on efficacy of third generation anticonvulsants for treatment of bipolar disorder and provide clinical recommendations.

Method: Open and controlled studies, case reports, and case series on the efficacy of lamotrigine, gabapentin, topiramate, tiagabine, and zonisamide were located through electronic searches of several databases, by manual search of proceedings of international meetings, and through contacting authors of recent reports.

Results: Lamotrigine is the best studied anticonvulsant and has efficacy in acute bipolar depression and in longer term treatment of bipolar depression as well as rapid-cycling bipolar II disorder but not in acute mania. Open reports suggest usefulness of gabapentin as an adjunct in bipolar disorder, but double-blind trials failed to confirm efficacy in acute mania and treatment-resistant rapid-cycling bipolar disorder. Topiramate is reported to be effective in acute mania and rapid-cycling bipolar disorder in several open studies, but methodological problems in a double-blind study led to a failed study in acute mania. However, topiramate may lead to weight loss in some patients. Zonisamide deserves further investigation, but tiagabine does not appear to be useful in acute mania.

Conclusion: Lamotrigine clearly fills an unmet need in treating bipolar depression and rapid-cycling bipolar disorder. Other third generation anticonvulsants with the exception of tiagabine offer promise but require confirmation of their efficacy from double-blind studies.