Doxepin plasma concentrations: Is there really a therapeutic range?

Despite the introduction of numerous new agents, tricyclic antidepressants remain an important option for the treatment of depression. Doxepin is stil l in wide use, and determining its concentration is a standard procedure in many psychiatric clinics. Some widely cited reviews indicate a therapeutic range from 150 to 250 ng/mL, (parent plus desmethyl metabolite). The vast majority of the authors' patients fell short of these concentrations under customary doses. To resolve this issue, the authors' serum-level databank w as analyzed, a questionnaire was sent to U.S. and German psychiatric univer sity departments and laboratories, and the literature was reviewed. The mai n results were the following: (1) Only 9% of all samples analyzed (N = 217) displayed plasma levels (highperformance liquid chromatography) between 15 0 and 250 ng/mL; 88% were subtherapeutic. The mean doxepin + desmethyldoxep in steady-state serum concentration was 89 +/- 75 ng/mL (N = 32, doxepin >3 weeks). The mean daily dose was 143 +/- 30 mg. There was no correlation be tween concentrations and improvement. (2) A wide variety of recommendations is given by the different university departments (10-1,000 ng/mL). (3) Acc ording to the studies published to date, there is not enough evidence for r ecommending a therapeutic range. The preliminary suggestions given in some influential reviews have been widely adopted without critical re-evaluation . Compared with the concentrations found in the original studies, the thera peutic ranges suggested are too high. A methodologically sound study to det ermine a therapeutic range is required for the rational monitoring of this drug. Meanwhile, a preliminary working range of 50 to 250 ng/ml; is propose d on the basis critical reassessment of published data.