title: Doxepin plasma concentrations: is there really a therapeutic range?
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Gernany. Stefan.Leucht@Lrz.tu-muenchen.de
authors.forename: S
authors.initials: S
authors.lastname: Leucht
authors.forename: W
authors.initials: W
authors.lastname: Steimer
authors.forename: S
authors.initials: S
authors.lastname: Kreuz
authors.forename: D
authors.initials: D
authors.lastname: Abraham
authors.forename: P J
authors.initials: PJ
authors.lastname: Orsulak
authors.forename: W
authors.initials: W
authors.lastname: Kissling
mesh_terms: D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004316:Doxepin / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D005260:Female; D005858:Germany; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D011795:Surveys and Questionnaires
chemical_list: D000929:Antidepressive Agents, Tricyclic; D004316:Doxepin