Selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors as adjuncts for postoperative pain management: systematic review and meta-analysis of randomised controlled trials

We conducted a systematic review and meta-analysis to assess effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) as adjuncts for postoperative pain management. We searched seven databases and two trial registers from inception to February 2021 for RCTs that compared SSRIs or SNRIs with placebo or an active control for postoperative pain management. We included 24 RCTs with 2197 surgical patients (21 trials for SNRIs and three trials for SSRIs). Moderate-quality evidence found that, compared with placebo, SSRIs/SNRIs (majority SNRIs) significantly reduced postoperative pain within 6 h {weighted mean difference (WMD) –0.73 cm on a 10 cm VAS (95% confidence interval [CI]: –1.04 to –0.42)}, 12 h (–0.68 cm [–1.28 to –0.07]), 24 h (–0.68 cm [–1.16 to –0.20]), 48 h (–0.73 cm [–1.22 to –0.23]), 10 days to 1 month (–0.71 cm [–1.11 to –0.31]), 3 months (–0.64 cm [–1.05 to –0.22]), and 6 months (–0.95 cm [–1.64 to –0.25]), and opioid consumption within 24 h (WMD –12 mg [95% CI: –16 to –8]) and 48 h (–10 mg [–15 to –5]), and improved patient satisfaction (WMD 0.49 point on a 1–4 Likert scale [95% CI: 0.09 to 0.89]) without significant increase in adverse events. Selective serotonin reuptake inhibitors tended to be less effective despite non-significant subgroup effects. Serotonin–norepinephrine reuptake inhibitors as an adjunct to standard perioperative care probably provide small reduction in both acute and chronic postoperative pain and opioid consumption, and small improvement in patient satisfaction without increases in adverse events. The effects of SSRIs are inconclusive because of very limited evidence.