An overview of findings of the Stanley Foundation Bipolar Network (SFBN) and the Bipolar Collaborative Network (BCN): A focus on anticonvulsants
Author: Robert M. Post, on behalf of the Stanley Foundation Bipolar Network
Key contributors: Lori L. Altshuler, Mark A. Frye, Trish Suppes, Paul E. Keck, Jr., Susan L. McElroy,
Gabriele S. Leverich, Willem A. Nolen, Ralph Kupka, Jörg Walden, Heinz Grunze .
Correspondence and requests for reprints should be addressed to:
Robert M. Post
10 Center Drive
MSC 1272
Betheoda
MD 20892-1272
USA
Tel: +13014964805
Fax: +13014020052
E-mail: robert.post@nih.gov
Abstract
Introduction:
Following observations of the antimanic and mood stabilizing effects of the anticonvulsants carbamazepine and valproate, questions emerged as to whether these were general properties of anticonvulsant drugs as a class, or only to selected agents.
Methods:
The Bipolar Collaborative Network (BCN) has conducted studies on anticonvulsant and other compounds using a variety of methods, ranging from double-blind, placebo-controlled studies (omega-3 fatty acids), to open, randomized comparisons (topiramate and sibutramine), to open adjunctive strategies to gain preliminary evidence of possible effectiveness and tolerability in patients with treatment-resistant bipolar illness (lamotrigine, gabapentin, tiagabine, topiramate, zonisamide, and levetiracetam).
Results:
Lamotrigine’s positive effects in BCN trials foreshadowed its Food and Drug Administration (FDA) approval. The three drugs that increase brain gamma-aminobutyric acid (GABA; gabapentin, tiagabine, and topiramate) do not have acute antimanic effectiveness, yet they may play some role in treating the many comorbidities of bipolar disorder. Topiramate and zonisamide have the positive side effect of weight loss. Tiagabine is associated with a risk of seizures. The potential mood stabilizing effects of zonisamide are more promising than levetiracetam and deserve further study. High dose omega-3 fatty acids (the eicosapentaenoic acid [EPA] form) were not superior to placebo.
Conclusions:
Antimanic efficacy is not a class effect of the anticonvulsant compounds, but some nonetheless may prove useful in the treatment of many of the comorbidities of bipolar disorder, including anxiety (panic, social phobia, post-traumatic stress disorder), eating disorders, alcohol abuse, and substance abuse disorders.
Key words: Anticonvulsants, Lamotrigine, Tiagabine, Topiramate, Omega-3 Fatty Acids,
Bipolar Disorder, Comorbidity
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