Acetazolamide in bipolar affective disorders

Acetazolamide is a carbonic anhydrase inhibitor used for a variety of purposes, including adjunctively in the management of various types of epilepsy. A previous study on its psychotropic effects suggested the possibility of efficacy in atypical psychotic states, especially those characterized by cyclicity. In the present investigation, 16 patients with refractory affective symptomatology were treated with acetazolamide in a prospective open trial after exhaustive trials with antidepressants, lithium, carbamazepine, divalproex, and other anticonvulsants. Seven of the 16 (44%) responded positively, in some cases dramatically, for as long as 2 years. Analysis revealed that all of the responders were either in a depressive phase or in a rapid-cycling phase of a bipolar illness and that all had experienced partial positive response to at least one other anticonvulsant and were being maintained on anti-convulsant therapy when the response occurred. Salient theoretical issues are explored.