Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review

Acta Psychiatr Scand. 2014 Mar;129(3):163-79. doi: 10.1111/acps.12211. Epub 2013 Nov 11.


Objective: To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders].

Method: Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs).

Results: Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia.

Conclusion: Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology.

Keywords: anti-inflammatory; bipolar disorders; celecoxib; cyclooxygenase-1; cyclooxygenase-2; depression; infliximab; minocycline; non-steroidal anti-inflammatory drugs; salicylate; schizophrenia; tumor necrosis factor.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology*
  • Bipolar Disorder / drug therapy*
  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / pharmacology*
  • Depressive Disorder, Major / drug therapy*
  • Fatty Acids, Unsaturated / adverse effects
  • Fatty Acids, Unsaturated / pharmacology*
  • Humans
  • Minocycline / adverse effects
  • Minocycline / pharmacology*
  • Schizophrenia / drug therapy*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Cyclooxygenase Inhibitors
  • Fatty Acids, Unsaturated
  • Tumor Necrosis Factor-alpha
  • Minocycline