SSRIs and TCAs are equally effective at treating chronic depression, but SSRIs have fewer side effects

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Major depression all too often develops a chronic course, with every episode making future relapse more likely (Gilmer et al., 2005). Dysthymic disorders represent a less severe, but more persistent form of depression lasting for at least two years. In the affective disorder spectrum, chronic forms are unsurprisingly associated with greater functional impairment and overall disease burden (Satyanarayana et al., 2009). Unfortunately, little is known about effective drug treatment for these chronic types of depression. A recent meta-analysis by von Wolff et al. (2012) aims to discuss usage of selective serotonin inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in the acute treatment of chronic depression and dysthymia.


The authors scanned important medical databases and journals for relevant studies, including ongoing or unpublished work. This boiled down to 20 primary trials comprising 2,918 patients. Risk of bias and study quality was assessed by independent raters. No publication bias was found.

Drug response was defined as minimally 50% decrease on a depression questionnaire 12 weeks after treatment start, while remission was classified as having sub-threshold scores. Dropout or experience of adverse effects was taken as a measure of drug acceptance. Benefits ratios (BRs) and odds ratios (ORs), 95% confidence intervals and numbers needed to treat (NNT) were calculated in accordance with statistical guidelines.


SSRIs are more effective than TCAs in the treatment of chronic depression and dysthymia

SSRIs have fewer side-effects than TCAs in the treatment of chronic depression and dysthymia

  • SSRIs were superior to placebo in terms of response  (BR = 1.49, CI: 1.29-1.72, NNT = 6) and remission (BR = 1.53, CI: 1.29-18, NNT = 7)
  • Dropout and rates of adverse effects did not differ between placebo and SSRIs (but there was statistical heterogeneity across primary studies and the authors therefore urge caution in interpreting these results)
  • TCAs were superior to placebo in terms of response (BR = 1.74, CI: 1.5-2.02, NNT = 4) and remission (BR = 1.77, CI: 1.24-2.53, NNT = 7)
  • While dropout rates did not differ between TCA and placebo, TCAs caused side effects significantly more often (OR = 2.87, CI: 1.83 – 4.5)
  • Efficacy (i.e. response + remission) did not differ significantly between SSRIs and TCAs, but SSRIs had lower rates of dropout (OR = 0.41, CI: 0.19-0.86, p = 0.02) and adverse effects (OR = 0.48, CI:  0.32-0.7, p < .001)
  • Analyses of depressive subgroups showed results held for all chronic depressive diagnoses


Similar results were obtained in terms of efficacy for both SSRIs and TCAs. […] In terms of acceptability, results demonstrated the superiority of SSRIs, as TCAs yielded significantly higher rates of dropouts and adverse events.


Drugs remain one of the leading treatment options for chronic depression and dysthymia

Antidepressants remain one of the leading treatment options for chronic depression and dysthymia

Sample sizes varied greatly, from 15 to 635, possibly leading to false negatives in underpowered studies and biasing of effect sizes. Moreover, female patients were overrepresented and there was heterogeneity in terms of age (34-69.9 years) and drug dosage regimen. In 6 of the 20 included studies, von Wolff et al. found a high risk of bias and in a further 10, assessment was not possible due to lack of information. Additionally, many studies did not report all outcome measures. For instance, only 4 studies comparing SSRIs to TCAs mentioned dropout rates.


Clearly, the results of this meta-analysis show possible benefits of using antidepressant medication in chronic forms of depressive disorders. In particular, they suggest SSRIs to be superior TCAs, not because of increased efficacy, but higher acceptability. However, when keeping the above-mentioned limitations in mind, it is clear that these conclusions are tentative. It is equally clear that more research in this area is desperately needed to ensure patients receive the best evidence-based treatment for their condition.


Von Wolff, A., Hölzel, L.P., Westphal, A., Härter, M., & Kriston, L. (2012). Selective serotonin reuptake inhibitors and tricyclic antidepressants in the acute treatment of chronic depression and dysthymia: A systematic review and meta-analysis. Journal of Affective Disorders, 144, 7-15. [PubMed abstract]

Gilmer, W.S., Trivedi, M.H., Rush, A.J., Wisniewski, S.R., Luther, J., Howland, R.H., Yohanna, D., et al.  (2005). Factors associated with chronic depressive episodes: a preliminary report from the STAR-D project. Acta Psychiatrica Scandinavica 112, 425–433. [PubMed abstract]

Satyanarayana, S., Enns, M.W., Cox, B.J., & Sareen, J. (2009). Prevalence and correlates of chronic depression in the Canadian Community Health Survey: Mental health and well-being. Canadian Journal of Psychiatry, 54, 389–398. [PubMed abstract]

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