Anesthesiology, V 121 • No 3 591 September 2014 W ITH well more than 40 million surgeries annually in North America alone, postoperative pain causes con- siderable morbidity and substantially impacts healthcare uti- lization. 1 Postoperative pain is mediated at multiple neural sites and via multiple mechanisms. 2 hus, diferent analge- sics can only partially reduce postoperative pain. A multi- modal analgesic approach is commonly used 3,4 ; however, currently using agents such as opioids, 5 local anesthetics, 6 nonsteroidal antiinlammatory drugs, 7 acetaminophen, 8,9 ketamine, 10 and gabapentin/pregabalin 11–13 have various limitations. Many other agents have been evaluated for ei- cacy, but evidence has not warranted their routine use. hus, a continued search for safer, more efective agents for post- operative pain is needed. Antidepressants are commonly used for various chronic pain conditions 14,15 and are classiied according to chemical What We Already Know about This Topic • Antidepressants show eficacy in the treatment of chronic pain, but their safety and eficacy for analgesia in the periop- erative period have not been critically reviewed What This Article Tells Us That Is New • In a systematic review of 15 studies including approximately 1,000 patients, heterogeneity in drug, dose, timing, and outcome mea- sure as well as general low quality precludes deinitive conclusions although a majority of studies reported positive outcomes • There is insuficient evidence to support the routine use of an- tidepressants for analgesia in the perioperative period Copyright © 2014, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology 2014; 121:591-608 ABSTRACT Background: his review evaluates trials of antidepressants for acute and chronic postsurgical pain. Methods: Trials were systematically identiied using predeined inclusion and exclusion criteria. Extracted data included the following: pain at rest and with movement, adverse efects, and other outcomes. Results: Fifteen studies (985 participants) of early postoperative pain evaluated amitriptyline (three trials), bicifadine (two trials), desipramine (three trials), duloxetine (one trial), luoxetine (one trial), luradoline (one trial), tryptophan (four trials), and venlafaxine (one trial). hree studies (565 participants) of chronic postoperative pain prevention evaluated duloxetine (one trial), escitalopram (one trial), and venlafaxine (one trial). Heterogeneity because of diferences 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. he majority of positive trials did not report suicient data to estimate treatment efect sizes. Many studies had inadequate size, safety evaluation/reporting, procedure speciicity, and movement-evoked pain assessment. Conclusions: here is currently insuicient evidence to support the clinical use of antidepressants—beyond controlled inves- tigations—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 periop- erative antidepressant use. Future studies are needed to better deine the risk–beneit 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 speciicity, and assessment of movement-evoked pain relevant to postoperative functional recovery. (ANESTHESIOLOGY 2014; 121:591-608) This article is featured in “This Month in Anesthesiology,” page 3A. Submitted for publication January 20, 2014. Accepted for publication April 8, 2014. From the Department of Anesthesiology and Peri- operative 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 Anesthesiol- ogy and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland (S.R.); and Departments of Anesthesiol- ogy and Perioperative Medicine and Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada (I. Gilron). Antidepressant Drugs for Prevention of Acute and Chronic Postsurgical Pain Early Evidence and Recommended Future Directions Karen Wong, M.D., Rachel Phelan, M.Sc., Eija Kalso, M.D., D.Med.Sci., Imelda Galvin, M.B., Ba.O., Bc.H., M.Sc., David Goldstein, M.B., B.Ch., B.A.O., M.Sc., F.R.C.P.C., Srinivasa Raja, M.D., Ian Gilron, M.D., M.Sc. PAIN MEDICINE