Plasma levels of zimelidine and norzimelidine in endogenous depression

A new serotonin uptake inhibitor zimelidine was studied in 16 endogenously depressed inpatients, who received 150 mg/kg orally during 3--6 weeks in a phase II-type study. Plasma concentrations of zimelidine and its main metabolite norzimelidine were determined twice a week. Ten patients obtained a well-defined steady-state plasma level within 1--2 weeks, while three patients still had increasing concentrations of both substances or only norzimelidine within the investigation period. In two patients, biochemical affection of the liver could be demonstrated during the treatment; one associated with moderate clinical symptoms (dizziness and fever), the other without clinical symptoms. Both patients recovered upon cessation of the zimelidine treatment. In the former patient, very high concentrations of zimelidine at the time of hepatic symptoms were demonstrated, while the latter patient was within the average concentration range. Other adverse reactions were mild and few, particularly with respect to anticholinergic effects. With the applied, probably suboptimal, dosage the therapeutic response was only satisfactory in five cases.