- Phenytoin is an effective anticonvulsant that has not previously been studied prophylactically in bipolar (BP) patients. Thus a study of phenytoin prophylaxis was undertaken and is herein reported. Bipolar patients were studied who had at least one episode per year in the previous 2 years despite ongoing prophylaxis. Patients were stable for a mean of 4 months (range 1-13) before entering the study. Phenytoin or placebo was added to their current therapy in a double-blind cross-over design for 6 months in each phase. Thirty observation periods of 6 months each were studied for 23 patients. Three patients had relapse on phenytoin and nine had relapse on placebo. There was a significant prophylactic effect of phenytoin in BP disorder [Cox's F-test for comparing survival in two groups: F(6, 18) = 3.44, p = 0.02]. This study suggests prophylactic effects of add-on phenytoin in BP illness. However, the number of patients was small and confirmation is necessary.