Plasma levels and antidepressive effect of imipramine

The relationship between the antidepressive effect of imipramine and the plasma concentrations of imipramine and the active metabolite desipramine was studied in 24 patients suffering from endogenous depression. After a placebo period of 7 days, the patients received imipramine, 75 mg 3 times a day. The dose was reduced in patients with pronounced side effects. Blood samples for drug assay were drawn in the morning, 15 hr after the last drug intake. Imipramine and desipramine in plasma were assayed by quantitative in situ thin-layer chromatography. Individual variations in plasma concentration were 20- to 30-fold in both imipramine and desipramine. Severity of depression was assessed on the Hamilton Rating Scale (HRS). Eleven of 12 patients who responded satisfactorily to the treatment (HRS post-treatment score less than 8) had plasma concentration of imipramine greater than or equal to 45 mug/L, and desipramine greater than 75 mug/L, whereas the 12 patients not responding satisfactorily (post-treatment score on HRS greater than or equal to 8) all had concentrations of imipramine or desipramine or both below these limits.