Anti-Inflammatory Treatment: Effect on Depression and Adverse Effects.



JAMA psychiatry published this systematic review and meta-analysis of randomized clinical trials done by Ole Kohler and colleagues in 2014. According to author, this is the largest study on anti-inflammatory treatment for depressive symptoms.



  • Recently studies have investigated the role of anti-inflammatory medications (NSAIDS and Cytokine Inhibitors) in improvement of antidepressant response.


  • NSAIDS inhibits COX-2, which inhibits the production of pro inflammatory cytokines.
  • Cytokine inhibitors acts directly on these pro inflammatory cytokines.


  • Only randomized placebo-controlled trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO,, and relevant review articles.
  • Anti-inflammatory treatment is defined as NASIDs, COX-2 inhibitors, pro-inflammatory cytokine inhibitors and Minocycline hydrochloride.

Results & Discussion:

  • 14 trials (6262 participants) included= 10 trials of NSAIDs (n = 4258) and 4 trials of cytokine inhibitors (n = 2004).
  • The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms compared with placebo.
  • This effect was observed in studies including patients with depression and depressive symptoms.
  • NSAIDS were associated with better antidepressant effects in general, whereas a statistical trend favored cytokine inhibitors.
  • Subanalyses emphasized the antidepressant properties of the selective COX-2 inhibitor celecoxib on remission and response.
  • NSADIS are known to increase the risk of GI and CV adverse effects; and Cytokine inhibitors are known to increase the risk for infections. Among the 6 studies reporting on adverse effects, no evidence found of an increased number of gastrointestinal or cardiovascular events after 6 weeks or infections after 12 weeks of anti-inflammatory treatment compared with placebo.
  • All trials were associated with a high risk of bias owing to potentially compromised internal validity.* All randomized studies emphasized the adjunctive antidepressant effects of Calecoxib within first 6-8 weeks of antidepressant treatment– this is suggested to be most pronounced in patients with increased pro-inflammatory markers.

    * Note: Not all studies reported adverse effects, thereby complicating the assessment. Also the treatment lasted only 6-12 weeks, which is too short to detect relevant adverse effects. SO RESULTS SHOULD BE INTERPRETED CAUTIOUSLY. 

Other agents with possible anti-inflammatory potential (speculative ?):

  • Aspirin: recent reviews emphasize favorable benefit to risk ration and better antidepressant effects (compared to selective COX-2 inhibitors)- but no randomize control trial published.
  • Statins
  • Minocycline– crosses blood brain barrier- but no randomize control trial published.
  • Pioglitazone
  • Modafinil
  • Polyunsaturated fatty acids


  • This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression.
  • Identification of subgroups that could benefit from such treatment might be warranted.

Source: JAMA Psychiatry 2014;71(12):1381-1391.


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Dr. Harvinder Singh, M.D. (Admin)

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