• Karen Wong, Rachel Phelan, Eija Kalso, Imelda Galvin, David Goldstein, Srinivasa Raja, and Ian Gilron.
• From the Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, Ontario, Canada (K.W., R.P., I. Galvin, D.G.); Department of Anaesthesia, Intensive Care Medicine, Emergency Medicine and Pain Medicine, Helsinki University Central Hospital, Helsinki, Finland (E.K.); Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland (S.R.); and Departments of Anesthesiology and Perioperative Medicine and Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada (I. Gilron).
• Anesthesiology. 2014 Sep 1;121(3):591-608.

BackgroundThis review evaluates trials of antidepressants for acute and chronic postsurgical pain.MethodsTrials were systematically identified using predefined inclusion and exclusion criteria. Extracted data included the following: pain at rest and with movement, adverse effects, and other outcomes.ResultsFifteen studies (985 participants) of early postoperative pain evaluated amitriptyline (three trials), bicifadine (two trials), desipramine (three trials), duloxetine (one trial), fluoxetine (one trial), fluradoline (one trial), tryptophan (four trials), and venlafaxine (one trial). Three studies (565 participants) of chronic postoperative pain prevention evaluated duloxetine (one trial), escitalopram (one trial), and venlafaxine (one trial). Heterogeneity because of differences in drug, dosing regimen, outcomes, and/or surgical procedure precluded any meta-analyses. Superiority to placebo was reported in 8 of 15 trials for early pain reduction and 1 of 3 trials for chronic pain reduction. The majority of positive trials did not report sufficient data to estimate treatment effect sizes. Many studies had inadequate size, safety evaluation/reporting, procedure specificity, and movement-evoked pain assessment.ConclusionsThere is currently insufficient evidence to support the clinical use of antidepressants-beyond controlled investigations-for treatment of acute, or prevention of chronic, postoperative pain. Multiple positive trials suggest the therapeutic potential of antidepressants, which need to be replicated. Other nontrial evidence suggests potential safety concerns of perioperative antidepressant use. Future studies are needed to better define the risk-benefit ratio of antidepressants in postoperative pain management. Higher-quality trials should optimize dosing, timing and duration of antidepressant treatment, trial size, patient selection, safety evaluation and reporting, procedure specificity, and assessment of movement-evoked pain relevant to postoperative functional recovery.

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