Perioperative duloxetine improves postoperative outcomes after anterior talofibular ligament repair for chronic lateral ankle instability for patients with depression: A prospective randomized clinical trial

Background: Recent studies have indicated that depression is associated with persistent postoperative pain and decreased satisfaction following foot and ankle surgery. This study aimed to evaluate the effect of perioperative duloxetine on postoperative outcomes of anterior talofibular ligament (ATFL) surgical repair for chronic ankle instability (CAI) in patients with depression. We further sought to evaluate patients' satisfaction and side effects related to duloxetine. Material and methods: Patients undergoing ATFL repair were screened for depression preoperatively with the Patient Health Questionnaire (PHQ-9). Among 249 patients who underwent arthroscopic or open surgical Brostrom repair of the ATFL, 120 patients were identified as being "possibly depressed" and were included in the study. Sixty patients were randomly assigned to the duloxetine group (one day preoperatively and for 6 weeks postoperatively), and the other sixty were randomized to the placebo group. Painkillers and opioid consumption, pain scores, and patient satisfaction were recorded at 12, 24, 48, and 72 hours postoperatively and at follow-up visits 1, 3, and 6 months after surgery. Patient-reported outcome measures (PROMs) were assessed preoperatively and at 3, 6, 12 and 24 months postoperatively. Duloxetine-related side effects such as nausea/vomiting and fatigue were also recorded. Results: The patients in the duloxetine group reported a significantly longer time to rescue analgesic and reduced opioid requirements (including celecoxib, pregabalin, acetaminophen, and tramadol). The patients experienced decreased pain intensity and greater satisfaction with their pain management at 24, 48, 72 h and 1 and 3 months after surgery (p < 0.05). The duloxetine group also had significantly better clinical and functional outcomes at 3 and 6 months of follow-up compared to the placebo group (p < 0.05). The occurrence and rate of symptoms of duloxetine side effects were not significant. Discussion: Depression is an important factor to consider and address because its presence before surgery can predict poor postoperative outcomes, including more severe postoperative pain, persistent postoperative pain, and increased consumption of painkillers and opioids. Conclusion: Perioperative administration of duloxetine following ATFL repair for CAI in patients with depression increased the time to first postoperative rescue analgesic request and reduced both opioid consumption and postoperative pain. This approach also led to a high level of patient satisfaction. In addition, duloxetine improved the quality of recovery without leading to significant side effects. Level of evidence: I; prospective randomized controlled trial.