Clinical implications of imipramine plasma levels for depressive illness

Sixty depressed nonschizophrenic patients were admitted to a research unit. Following one drug-free week and one week of placebo, patients received 3.5 mg/kg of imipramine hydrochloride for 28 days. Plasma levels of imipramine and its metabolite desipramine hydrochloride (desmethylimipramine) were measured three times weekly and the relationship between plasma steady-state levels and clinical outcome was examined. Steady-state levels ranged from 50 to 1,050 ng/ml. There was a statistically and clinically significant relationship between plasma levels and response. The relationship existed across the entire sample, and was accentuated when the bipolar and unipolar nondelusional populations were examined. Because a strong relationship between sex and outcome was observed, the unipolar nondelusional patients were stratified by sex and a significant relationship still persisted. Only the unipolar delusional patients failed to demonstrate an association between blood level and clinical response.