Anticonvulsants in the treatment of bipolar mania

A series of antiepileptic drugs have been investigated in terms of their ability to treat mania (with later applications for the treatment of bipolar depression and prevention of relapses). These include divalproex, carbamazepine, oxcarbazepine, gabapentin, lamotrigine, levetiracetam, tiagabine, topiramate and zonisamide. Although these drugs are all antiepileptic in action, they bring about these effects by different mechanisms; in particular, their impact on GABA differs significantly. Perhaps for this reason, their impact on mania varies greatly, with double-blind significant results evident only for valproate, carbamazepine and oxcarbazepine. Only valproate and carbamazepine are approved by the US FDA for use in mania; oxcarbazepine has never been found significantly effective in large-scale studies. Of the other options, both gabapentin and topiramate failed in large-scale investigations; tiagabine failed in small sample reports. Although lamotrigine has been successful in the prevention of depression relapse in bipolar disorder, it has not been effective in treating mania. Finally, there are no findings of large scale double-blind studies on the use of levetiracetam and zonisamide. A review of the kinetics, side effects and complications of the antiepileptic drugs indicates that carbamazepine is useful, and has adverse event benefit over all other options. The potential of zonisamide awaits further testing.