Bipolar mixed states and their treatment

Bipolar mixed states remain a nosologic dilemma, diagnostic challenge and neglected area of therapeutic research. While the outcome of mixed states is generally poorer than that of pure manic and depressive episodes, little is known about how to treat such a condition. The aim of this report is to investigate the results of clinical trials, including mixed bipolar patients, in order to provide some hints on the efficacy of the different compounds on this specific subpopulation. As a result of this research, it becomes clear that only dysphoric mania has been reasonably addressed in clinical trials, and unfortunately very little is known about the treatment of other mixed states. There is some indirect evidence that mixed mania may be more responsive to anticonvulsants than to lithium. Divalproate, and to a lesser extent carbamazepine, may be used either in monotherapy or as adjuncts to lithium. Use of other anticonvulsants, such as gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate or zonisamide is not yet supported by controlled data. The use of antidepressants is largely discouraged, as they may worsen this condition. On the other hand, atypical antipsychotics may be effective and safe either in monotherapy or in combination with lithium or valproate. Further research is urgently needed in this neglected area of psychiatry.