- OBJECTIVE: Phenytoin, a classical anticonvulsant, shares with antimanic anticonvulsants the property of blockade of voltage-activated sodium channels. The authors therefore planned a trial of phenytoin for mania. METHOD: Patients with either bipolar I disorder, manic type, or schizoaffective disorder, manic type, entered a 5-week, double-blind controlled trial of haloperidol plus phenytoin versus haloperidol plus placebo. Of 39 patients, 30 completed at least 3 weeks and 25 completed 5 weeks. RESULTS: Significantly more improvement was observed in the patients receiving phenytoin. Added improvement with phenytoin in scores on the Brief Psychiatric Rating Scale and Clinical Global Impression was seen in the patients with bipolar mania but not those with schizoaffective mania. CONCLUSIONS: Blockade of voltage-activated sodium channels may be a common therapeutic mechanism of many anticonvulsants given for mania, and phenytoin may be a therapeutic option for some manic patients.