Doxepin plasma concentrations: is there really a therapeutic range?

J Clin Psychopharmacol. 2001 Aug;21(4):432-9. doi: 10.1097/00004714-200108000-00011.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / blood*
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Doxepin / adverse effects
  • Doxepin / blood*
  • Doxepin / therapeutic use*
  • Female
  • Germany
  • Health Knowledge, Attitudes, Practice
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Surveys and Questionnaires

Substances

  • Antidepressive Agents, Tricyclic
  • Doxepin