Is Anticonvulsant Treatment of Mania a Class Effect? Data from Randomized Clinical Trials

Abstract

Our aim was to evaluate the efficacy and tolerability of anticonvulsant agents for the treatment of acute bipolar mania and ascertain if their effects on mania are a "class" effect. We conducted a systematic review of randomized controlled trials (RCTs) with placebo or active comparator, in acute bipolar mania in order to summarize available data on anticonvulsant treatment of mania/mixed episodes. We searched (PubMed/MEDLINE) with the combination of the words "acute mania" and "clinical trials" with each one of the following words: "anticonvulsants/antiepileptics,""valproic/valproate/divalproex,""carbamazepine,""oxcarbazepine,""lamotrigine,""gabapentin,""topiramate,""phenytoin,""zonisamide,""retigabine,""pregabalin,""tiagabine,""levetiracetam,""licarbazepine,""felbamate," and "vigabatrin." Original articles were found until November 1, 2008. Data from 35 randomized clinical trials suggested that not all anticonvulsants are efficacious for the treatment of acute mania. Valproate showed greater efficacy in reducing manic symptoms, with response rates around 50% compared to a placebo effect of 20-30%. It appears to have a more robust antimanic effect than lithium in rapid cycling and mixed episodes. As valproate, the antimanic effects of carbamazepine have been demonstrated. Evidences did not support the efficacy of the gabapentin, topiramate as well as lamotrigine as monotherapy in acute mania and mixed episodes. Oxcarbazepine data are inconclusive and data regarding other anticonvulsants are not available. Anticonvulsants are not a class when treating mania. While valproate and carbamazepine are significantly more effective than placebo, gabapentin, topiramate, and lamotrigine are not. However, some anticonvulsants may be efficacious in treating some psychiatric comorbidities that are commonly associated to bipolar illness.

Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry

“…A point that needs to be stressed is that while antipsychotics seem to possess a 'class effect' restricted to the treatment of acute mania (possibly an antidopaminergic effect) [89], there is no such an effect in anticonvulsants concerning any phase of BP [168,417]. Each anticonvulsant may possess a very distinct mode of pharmacologic action and should be considered separately.…”

Investigating psychotropic properties of antiepileptic drugs

“…Most of them have demonstrated good efficacy in the treatment of acute mania, in particular CBZ [62], PHT [63], OXC [64] and possibly ZNS [65], although results for the latter are still controversial [66]. It will be, thus, of interest to have data on new compounds such as ESL and LCM.…”

Mood-Stabilizing Agents

“…Best established as antimanic agents are valproate and carbamazepine, whereas lamotrigine lacks antimanic effects but has long-term bene fi ts, especially to protect against recurrences of bipolar depression, topiramate lacks bene fi cial effects in bipolar disorder, and the status of oxcarbazepine remains uncertain Anticonvulsants [ 79,289,350,351,373 ] . These clinical fi ndings of apparent differential ef fi cacy in epilepsy, with or without ef fi cacy in bipolar disorder, encourage consideration of action mechanisms that may differentiate the apparent subtypes based on their spectrum of clinical effects.…”

“…Several anticonvulsant drugs developed to treat epilepsy are effective in various phases of bipolar disorder [ 8,148,188,289 ] . Three such agents are FDA approved (Tables 3.2 …”