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

ABSTRACT

Standard mood stabilizers, such as lithium and haloperidol, and anticonvulsants show effectiveness in a maximum of 60%-70% of acutely manic patients. Obviously, there is a clinical need to evaluate other treatment options. Current pathophysiologic concepts suggest that substances with an ameliorating effect on dopaminergic hyperfunction, serotonergic hypofunction, or GABAergic hypofunction might be useful, as may be substances with calcium-antagonistic 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 acutely manic patients receiving up to 400 mg/d of trimipramine. It is concluded that, at least in the case of trimipramine, the pharmacologic profile is not helpful in predicting potential effectiveness in mania.