Evidence that the SSRI dose response in treating major depression should be reassessed: a meta-analysis

Depress Anxiety. 2003;17(1):1-9. doi: 10.1002/da.10079.


The limitations in design and analysis of currently available dose-response studies of SSRI treatment of major depression have led to the conclusion that dose response is flat. We applied concepts from our companion article to determine if currently available data is consistent with a "potential" and an "expressed" dose response. Using these concepts, we performed a meta-analysis on all identifiable published fixed-dose and dose-escalation studies that reported the effect of different SSRI oral doses on efficacy. "Potential" dose response in fixed-dose studies with categorical response outcomes equaled a significant meta-analyzed slope of 3.1%/100 SSRI mg equivalents (SMEs) (SE=1.2%) or 7.8% across the dose range. Similar analysis in dose-escalation studies that reported categorical response data yielded a non-significant meta-analyzed slope of 3.7%/100 SMEs (SE=2.3%) or 9.3% across the dose range. Analyses of the "expressed" dose response demonstrated in the studies indicated a slope statistically equal to zero. The current analysis suggests a "potential" dose response can be demonstrated for SSRIs in treating major depression. The analysis suggests an "expressed" dose response could exist in best clinical practice. Study designs better tailored to address the relevant clinical question would test these hypotheses more appropriately than previous studies.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Depressive Disorder, Major / drug therapy*
  • Dose-Response Relationship, Drug
  • Humans
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*


  • Serotonin Uptake Inhibitors