Drug Interaction: Inhibitory Effect of Neuroleptics on Metabolism of Tricyclic Antidepressants in Man

Abstract

Total urinary excretion of radioactivity after oral or intravenous administration of a test dose of ¹⁴C-imipramine was measured in eight patients. They were tested before, during, and after treatment with neuroleptics. Excretion diminished while the patients were being treated with perphenazine, haloperidol, or chlorpromazine, though not during flupenthixol treatment. Total urinary excretion of radioactivity and plasma levels of metabolites and unchanged drug were measured in five patients after a test dose of ¹⁴C-nortriptyline. Each patient was tested before and again during perphenazine treatment. In all patients perphenazine treatment caused: (1) decrease of total urinary excretion, (2) decreased plasma level of metabolites, and (3) increased plasma level of unchanged nortriptyline. These results indicate that neuroleptics inhibit the metabolism of tricyclic antidepressants in man.