Doxepin plasma concentrations:
is there really a therapeutic range?

Leucht S, Steimer W, Kreuz S,
Abraham D, Orsulak PJ, Kissling W.
Department of Psychiatry and Psychotherapy,
Klinikum rechts der
Isar der Technischen Universitat Munchen,
J Clin Psychopharmacol 2001 Aug;21(4):432-9


Despite the introduction of numerous new agents, tricyclic antidepressants remain an important option for the treatment of depression. Doxepin is still 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 was analyzed, a questionnaire was sent to U.S. and German psychiatric university departments and laboratories, and the literature was reviewed. The main results were the following: (1) Only 9% of all samples analyzed (N = 217) displayed plasma levels (high-performance liquid chromatography) between 150 and 250 ng/mL; 88% were subtherapeutic. The mean doxepin + desmethyldoxepin 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 between concentrations and improvement. (2) A wide variety of recommendations is given by the different university departments (10-1,000 ng/mL). (3) According to the studies published to date, there is not enough evidence for recommending 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 therapeutic ranges suggested are too high. A methodologically sound study to determine a therapeutic range is required for the rational monitoring of this drug. Meanwhile, a preliminary working range of 50 to 250 ng/mL is proposed on the basis of critical reassessment of published data.
Dumb drugs
Dothiepin overdose
Dothiepin v doxepine
Antidepressant toxicity
Selectivity or multiplicity?
Doxepin (Adepin): structure
Tricyclic antidepressants for depression

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