Combining antidepressants for treatment-resistant depression: a review

J Clin Psychiatry. 2002 Aug;63(8):685-93. doi: 10.4088/jcp.v63n0805.

Abstract

Objective: Many patients with depression remain poorly responsive to antidepressant monotherapy. One approach for managing treatment-resistant depression is to combine antidepressants and to capitalize on multiple therapeutic mechanisms of action. This review critically evaluates the evidence for efficacy of combining antidepressants.

Method: A MEDLINE search of the last 15 years (up to June 2001), supplemented by a review of bibliographies, was conducted to identify relevant studies. Criteria used to select studies included (1) published studies with original data in peer-reviewed journals, (2) diagnosis of depression with partial or no response to standard treatments, (3) any combination of 2 antidepressants with both agents used to enhance antidepressant response, (4) outcome measurement of clinical response, and (5) sample size of 4 or more subjects.

Results: Twenty-seven studies (total N = 667) met the inclusion criteria, including 5 randomized controlled trials and 22 open-label trials. In the 24 studies (total N = 601) reporting response rates, the overall mean response rate was 62.2%. Methodological limitations included variability in definitions of treatment-resistant depression and response to treatment, dosing of medications, and reporting of adverse events.

Conclusion: There is limited evidence, mostly in uncontrolled studies, supporting the efficacy of combination antidepressant treatment. Further randomized controlled trials with larger sample sizes are required to demonstrate the efficacy of a combination antidepressant strategy for patients with treatment-resistant depression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Tricyclic / administration & dosage
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Clinical Trials as Topic
  • Cyclohexanols / administration & dosage
  • Cyclohexanols / therapeutic use
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Humans
  • Mianserin / administration & dosage
  • Mianserin / therapeutic use
  • Monoamine Oxidase Inhibitors / administration & dosage
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Morpholines / administration & dosage
  • Morpholines / therapeutic use
  • Psychiatric Status Rating Scales
  • Reboxetine
  • Research Design
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / therapeutic use
  • Treatment Outcome
  • Venlafaxine Hydrochloride

Substances

  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Cyclohexanols
  • Monoamine Oxidase Inhibitors
  • Morpholines
  • Serotonin Uptake Inhibitors
  • Mianserin
  • Venlafaxine Hydrochloride
  • Reboxetine