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 properties. Methods: We report a case series of treatment-resistant bipolar patients (n = 11) to whom we administered the ChE inhibitor donepezil. Four patients met criteria for current manic episode, 5 for mixed episode, 1 for hypomanic episode, and 1 for major depressive episode. Donepezil was added to current medication on an open-label basis. Ratings were based on a retrospective chart review. Results: Of the 11 patients, 6 (54.5%) demonstrated marked improvement (improvement in CGI-S ≥ 2), 3 (27.2%) demonstrated slight improvement, 1 did not respond, and 1 did not tolerate the medication. Among those patients who had marked improvement (i.e., responders, n = 6), improvement 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 published report on the use of donepezil in the treatment of mood disorders. Controlled, randomized, double-blind studies are necessary to validate these preliminary observations.