Selective serotonin reuptake inhibitors and tricyclic antidepressants in the acute treatment of chronic depression and dysthymia: a systematic review and meta-analysis

J Affect Disord. 2013 Jan 10;144(1-2):7-15. doi: 10.1016/j.jad.2012.06.007. Epub 2012 Sep 7.


Introduction: Chronic depression represents a substantial portion of depressive disorders and is associated with severe consequences. This review examined the efficacy and acceptability of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in the treatment of chronic depression. Additionally, the comparative effectiveness of the two types of antidepressants has been examined.

Methods: A systematic search was conducted in the following databases: CENTRAL, MEDLINE, EMBASE, ISI Web of Science, BIOSIS, PsycINFO, and CINAHL. Primary efficacy outcome was a response to treatment; primary acceptance outcome was dropping out of the study. Only randomized controlled trials were considered.

Results: We identified 20 studies with 22 relevant comparisons. 19 studies focused on samples with a majority of dysthymic patients. Both SSRIs and TCAs are efficacious in terms of response rates when compared to placebo (Benefit Ratio [BR]=1.49; p<0.001 for SSRIs and BR=1.74; p<0.001 for TCAs) and no statistically significant differences between the active drugs and placebo in terms of dropout rates could be found. No differences in effectiveness were found between SSRIs and TCAs in terms of response rates (BR=1.01; p=0.91), yet, SSRIs showed statistically better acceptability in terms of dropout rates than TCAs (Odds Ratio [OR]=0.41; p=0.02).

Limitations: The methodological quality of the primary studies was evaluated as unclear in many cases and more evidence is needed to assess the efficacy of SSRIs and TCAs in patients suffering from chronic forms of depression other than dysthymia.

Conclusions: This systematic review provides evidence for the efficacy of both SSRIs and TCAs in the treatment of chronic depression and showed a better acceptability of SSRIs.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Chronic Disease
  • Depressive Disorder / drug therapy*
  • Dysthymic Disorder / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors