Efficacy and adverse events of selective serotonin noradrenaline reuptake inhibitors in the management of postoperative pain: A systematic review and meta-analysis

Study objective: Selective-serotonin-noradrenaline-reuptake inhibitors (SSNRI) might be an interesting option for postoperative pain treatment. Objective was to investigate postoperative pain outcomes of perioperative SSNRI compared to placebo or other additives in adults undergoing surgery. Design: Systematic review of randomised controlled trials (RCT) with meta-analysis and GRADE assessment. Setting: Acute and chronic postoperative pain treatment. Patients: Adult patients undergoing surgery. Interventions: Perioperative administration of SSNRI. Measurements: Primary outcomes were postoperative acute pain at rest/during movement (measured on a scale from 0 to 10), number of patients with chronic postsurgical pain (CPSP) and with SSNRI-related adverse events. Main results: Fourteen RCTs (908 patients) were included. We have high-quality evidence that duloxetine has no effect on pain at rest at 2 h (MD:-0.02; 95% confidence interval (CI)-0.51 to 0.47), but probably reduces it at 48 h (MD:-1.16; 95%CI-1.78 to-0.54). There is low-and moderate-quality evidence that duloxetine has no effects on pain during movement at 2 h (MD:-0.42; 95%CI-1.53 to 0.69) and 48 h (MD:-0.91; 95% CI-2.08 to 0.26), respectively. We have very low-quality evidence that duloxetine might reduce pain at rest (MD:-0.45; 95%CI-0.74 to-0.15) and movement (MD:-1.19; 95%CI-2.32 to-0.06) after 24 h. We have low-quality evidence that duloxetine may reduce the risk of CPSP at 6 months (RR:0.35; 95%CI 0.14 to 0.90). There is moderate-quality evidence that duloxetine increases the risk of dizziness (RR:1.72; 95%CI 1.26 to 2.34). Conclusion: At the expense of a higher risk for dizziness, SSNRI may be effective in reducing postoperative pain between 24 and 48 h after surgery. However, the results of the meta-analyses are mostly imprecise and duloxetine might only be used in individual cases. Protocol registration: CRD42018094699