Antidepressant drugs for prevention of acute and chronic postsurgical pain: early evidence and recommended future directions

Anesthesiology. 2014 Sep;121(3):591-608. doi: 10.1097/ALN.0000000000000307.


Background: This review evaluates trials of antidepressants for acute and chronic postsurgical pain.

Methods: Trials 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.

Results: Fifteen 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.

Conclusions: There 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.

Publication types

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

MeSH terms

  • Acute Disease
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Chronic Disease
  • Humans
  • Pain, Postoperative / prevention & control*
  • Randomized Controlled Trials as Topic


  • Antidepressive Agents