Donepezil in treatment-resistant bipolar disorder

Background: A considerable percentage of patients with bipolar disorder do not respond or do not tolerate conventional treatment. Cholinesterase (ChE) inhibitors have been suggested to possess depressogenic and antimanic prop erties. Methods: We report a case series of treatment-resistant bipolar patients (n = 11) to whom we administered the ChE inhibitor donepezil. Four patients m et criteria for current manic episode, 5 for mixed episode, I for hypomanic episode, and I for major depressive episode. Donepezil was added to curren t medication on an open-label basis. Ratings were based on a retrospective chart review. Results: Of the II patients, 6 (54.5%) demonstrated marked improvement (imp rovement in CGI-S greater than or equal to 2), 3 (27.2%) demonstrated sligh t improvement; I did not respond, and I did not tolerate the medication. Am ong those patients who had marked improvement (i.e., responders, n = 6), im provement was observed within 2 weeks or less in 5 of them (83%). Patients experienced only minor side effects, Conclusions: These pilot data suggest the efficacy and safety of donepezil in the treatment of bipolar disorder To our knowledge this is the first pub lished report on the use of donepezil in the treatment of mood disorders. C ontrolled, randomized, double-blind studies are necessary to validate these preliminary observations. (C) 1999 Society of Biological Psychiatry.