title: Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  Several studies have reported antidepressant effects of anti-inflammatory treatment; however, the results have been conflicting and detrimental adverse effects may contraindicate the use of anti-inflammatory agents.
  
  
  OBJECTIVE
  To systematically review the antidepressant and possible adverse effects of anti-inflammatory interventions.
  
  
  METHODS
  Trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO, Clinicaltrials.gov, and relevant review articles.
  
  
  METHODS
  Randomized placebo-controlled trials assessing the efficacy and adverse effects of pharmacologic anti-inflammatory treatment in adults with depressive symptoms, including those who fulfilled the criteria for depression.
  
  
  METHODS
  Data were extracted by 2 independent reviewers. Pooled standard mean difference (SMD) and odds ratios (ORs) were calculated.
  
  
  METHODS
  Depression scores after treatment and adverse effects.
  
  
  RESULTS
  Ten publications reporting on 14 trials (6262 participants) were included: 10 trials evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (n=4,258) and 4 investigated cytokine inhibitors (n=2,004). The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms (SMD, -0.34; 95% CI, -0.57 to -0.11; I2=90%) compared with placebo. This effect was observed in studies including patients with depression (SMD, -0.54; 95% CI, -1.08 to -0.01; I2=68%) and depressive symptoms (SMD, -0.27; 95% CI, -0.53 to -0.01; I2=68%). The heterogeneity of the studies was not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, -0.29; 95% CI, -0.49 to -0.08; I2=73%) on remission (OR, 7.89; 95% CI, 2.94 to 21.17; I2=0%) and response (OR, 6.59; 95% CI, 2.24 to 19.42; I2=0%). Among the 6 studies reporting on adverse effects, we found no evidence 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.
  
  
  CONCLUSIONS
  Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain. 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.
authors.affiliation: Research Department P, Aarhus University Hospital, Risskov, Denmark2Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Köhler
authors.affiliation: Mental Health Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Benros
authors.affiliation: Mental Health Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Nordentoft
authors.affiliation: Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York5Peter Munk Cardiac Centre and the Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Farkouh
authors.affiliation: Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York6School of Medicine, St George's University, St George's, Grenada.
authors.forename: Rupa L
authors.initials: RL
authors.lastname: Iyengar
authors.affiliation: Research Department P, Aarhus University Hospital, Risskov, Denmark2Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.affiliation: Mental Health Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Krogh
mesh_terms: D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D000893:Anti-Inflammatory Agents