Trimipramine fails to exert antimanic efficacy: A case of the discrepancy between in vitro rationale and clinical efficacy

Standard mood stabilizers, such as lithium and haloperidol, and anticonvuls ants show effectiveness in a maximum of 60%-70% of acutely manic patients. Obviously, there is a clinical need to evaluate other treatment options. Cu rrent pathophysiologic concepts suggest that substances with an amelioratin g effect on dopaminergic hyperfunction, serotonergic hypofunction, or GABAe rgic hypofunction might be useful, as may be substances with calcium-antago nistic effects. In vitro, the antidepressant trimipramine exerts dopamine- and calcium-antagonistic properties. Therefore, we conducted an open trial to screen it for antimanic action. We found no clinical benefit in four acu tely manic patients receiving up to 400 mg/d of trimipramine. It is conclud ed that, at least in the case of trimipramine, the pharmacologic profile is not helpful in predicting potential effectiveness in mania.