title: The efficacy and safety of antidepressants in inflammatory arthritis: a Cochrane systematic review.
abstract: OBJECTIVE
  To determine the efficacy and safety of antidepressants in pain management in patients with inflammatory arthritis (IA).
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PsychINFO for randomized controlled trials in adults with IA that compared any antidepressants (administered via any route) to another analgesic intervention or placebo. We also searched the 2008-2009 American College of Rheumatology and European League Against Rheumatism abstracts and performed a hand search of reference lists of relevant articles. Primary outcomes were patient-reported pain relief ≥ 30% and withdrawals due to adverse events. Two authors independently assessed methodological quality and extracted data. A risk of bias assessment was performed using methods recommended by the Cochrane Collaboration.
  
  
  RESULTS
  Eight trials (652 participants) in patients with rheumatoid arthritis (RA) and 1 trial in patients with ankylosing spondylitis (100 participants) were included in this review. The majority of studies were published in the late 1980s in patients with active disease receiving minimal disease-modifying antirheumatic drug therapy. All trials evaluated tricyclic antidepressants (TCA) and 2 studies included a selective serotonin uptake inhibitor. Seven of the 9 trials had high risk of bias, 2 were unclear, and metaanalysis was not performed due to trial heterogeneity. RA trials with short-term outcome (< 1 week) found no significant benefit of amitriptyline 25 mg in combination with dextropropoxyphene (DXP) 65 mg over placebo, and inferiority of amitriptyline + DXP versus DXP 130 mg [mean difference (MD) 10.0, 95% CI 0.4 to 19.6]. There was conflicting evidence regarding medium (1-6 wks) or longer-term (> 6 wks) benefits on pain. One trial in depressed patients with RA showed no significant difference between amitriptyline and paroxetine given for 8 weeks (65% vs 56% much or very much improved; RR 1.2, 95% CI 0.9 to 1.5). One trial found that amitriptyline was no better than placebo in reducing pain in patients with active AS over 2 weeks (MD -0.2, 95% CI -1.2 to 0.8). From 5 trials, withdrawals due to adverse events were not significantly different from placebo. However, there were significantly more minor adverse events in patients receiving TCA compared with those receiving a placebo (RR 2.3, 95% CI 1.2 to 4.4). These included somnolence, dizziness, dry mouth, and nausea.
  
  
  CONCLUSIONS
  Based upon 9 trials of high or unclear risk of bias, it is not possible to draw firm conclusions about the efficacy of TCA as analgesics for patients with IA. The use of these agents may be associated with adverse events that are generally mild and do not lead to cessation of treatment. High-quality trials are needed in this area.
authors.affiliation: Department of Rheumatology, Royal Prince Alfred Hospital, Level 4 QEII Building, Missenden Road, Camperdown NSW 2110, Australia. brichard@med.usyd.edu.au
authors.forename: Bethan L
authors.initials: BL
authors.lastname: Richards
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Whittle
authors.forename: Désirée M
authors.initials: DM
authors.lastname: van der Heijde
authors.forename: Rachelle
authors.initials: R
authors.lastname: Buchbinder
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D005104:Expert Testimony; D006801:Humans; D007391:International Cooperation; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D059408:Pain Management / Q000379:methods*
chemical_list: D000700:Analgesics; D000928:Antidepressive Agents