A potentially life-threatening side effect of carbamazepine may be the Stevens-Johnson syndrome and related dermatologie effects. Other anticonvulsants Newer anticonvulsants such as lamotrigine, gabapentin, and topiramatc have failed to demonstrate superiority over placebo in randomized controlled studies of bipolar mania, and there is practically no evidence to support the use of tiagabine, levetirazetam, pregabalin, or zonisamide. There is some limited evidence that, phenytoin may possess antimanic effects.40 Oxcarbazepine, structurally similar to carbamazepine, may possess antimanic effects,41 but licarbazepine, its main active

metabolite, failed in at least one placebo-controlled trial. Clearly, not all anticonvulsants are Inhibitors,research,lifescience,medical antimanics. Antipsychotics Antipsychotics have been used since their introduction in clinical practice for the treatment of acute mania. For years, though, the evidence base for this practice was extremely limited. Now, the US Food and Drug Administration

Inhibitors,research,lifescience,medical (FDA) has already approved six antipsychotics for the treatment of acute mania: chlorpromazine, olanzapine, risperidone, Inhibitors,research,lifescience,medical quetiapine, ziprasidone, and aripiprazole. Current, criteria for FDA approval include two multicenter, randomized, double-blind, placebo-controlled trials with adequate sample sizes supporting the safety and efficacy of these agents. These drugs are also approved for the treatment of mania, in most European countries and in most countries worldwide. Chlorpromazine Chlorpromazine is a first-generation antipsychotic that has been studied only in one small, placebo-controlled trial42 and a few comparative, randomized studies, versus lithium, haloperidol, and pimozide.43-45 The main problems related to Inhibitors,research,lifescience,medical chlorpromazine use are extrapyramidal symptoms, tardive dyskinesia (long-term), and hepatotoxicity. Haloperidol Only recently have the results of placebo-controlled trials with this drug become available. Studies conducted in the 1970s already suggested that it could be efficacious in mania, and recent trials have shown that it has Inhibitors,research,lifescience,medical strong antimanic properties,46,47 but it may also carry important side effects such

as extrapyramidal symptoms and tardive dyskinesia, among those others. It is particularly relevant to mention that, although haloperidol seemed to have a faster onset of antimanic action than other antipsychotics in several controlled trials, it also Cell Cycle inhibitor significantly reduced the time until first depressive recurrence in one of them.48 Haloperidol has been compared as monotherapy with placebo, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and as an add-on to placebo and risperidone.46-52 Clozapine Clozapine is the prototype of an atypical antipsychotic, but has not, been as widely studied as the others in its class, due to the risks of seizures and agranulocytosis. Thus, to date we have no double-blind clinical trials on clozapine in acute mania.