Fifty-one depressed inpatients, after 1 drug-free week, were treated for 5 weeks with imipramine 4 mg/kg day. Plasma levels of imipramine (IMI) and its active metabolite desmethylimipramine (DMI) were measured weekly, 15 hours after the last drug intake. Steady state blood levels (IMI + DMI) ranged from 60 to 585 ng/ml. The mean value for plasma concentration (IMI + DMI) at day 42 was 271 ng/ml. In the same way, therapeutic effectiveness was assessed every week using the Hamilton Rating Scale for Depression (HDRS). There was a significant correlation between plasma concentration and the decrease of Hamilton scores. The IMI/DMI ratio showed a responder-nonresponder difference; 86% patients with a ratio between 0.4 and 1 were responders. Conversely, most patients with a ratio below 0.4 or above 1 were nonresponders. The ideal ratio for clinical response would be 0.68. The ratio is a subject-specific feature, able to be an early predictor of clinical outcome.
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