Effects of Melatonin on Sleep Quality and Patient-Reported Outcomes After Arthroscopic Rotator Cuff Surgery: A Prospective Randomized Controlled Trial

Abstract

Background: Sleep disturbance is a significant symptom associated with both rotator cuff tears and arthroscopic rotator cuff repair. Melatonin has been shown to be safe and effective in managing multiple sleep disorders, including secondary sleep disorders, with relatively minor adverse effects and lack of addictive potential. Purpose: To investigate the effects of oral melatonin on postoperative sleep quality after arthroscopic rotator cuff repair. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This was a prospective randomized clinical trial evaluating patients undergoing arthroscopic rotator cuff repair. Exclusion criteria included history of alcohol abuse, current antidepressant or sedative use, revision rotator cuff repair, severe glenohumeral arthritis, and concurrent adhesive capsulitis. Patients were randomly assigned in a 1:1 ratio to 1 of 2 groups: 5-mg dose of melatonin 1 hour before bedtime or standard sleep hygiene (≥6 hours per night, avoiding caffeine and naps in the evening). Patients in the melatonin group took their assigned melatonin dose for 6 weeks beginning the day of surgery. Patient-reported outcome assessments, including the Pittsburgh Sleep Quality Index (PSQI), the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and the Single Assessment Numeric Evaluation (SANE), and pain medication charts were collected preoperatively as well as at 2 weeks, 6 weeks, 3 months, 4 months, and 6 months postoperatively. Numeric variables were analyzed using paired and unpaired t tests, with significance set at P < .05. Results: Eighty patients were included for final analysis (40 in the control group, 40 in the melatonin group). Patient characteristics such as age, sex, race, body mass index, and laterality did not differ significantly ( P≥ .05). Preoperative ASES, SANE, and PSQI scores did not differ between groups ( P≥ .055). PSQI scores were significantly lower (better quality sleep) in the melatonin group at the 6-week postoperative period ( P = .036). There was a positive correlation between how patients rated the intensity of their pain and the PSQI at the 6-week postoperative period (0.566). The PSQI question regarding sleep quality was found to be significantly lower in the melatonin group at the 3-month, 4-month, and 6-month postoperative periods ( P = .015, P = .041, and P≤ .05, respectively). SANE scores were significantly lower in the melatonin group ( P = .011) at 6 weeks and then higher in the melatonin group ( P = .017) at 6 months. ASES scores were significantly higher in the melatonin group at 4 and 6 months ( P = .022 and P = .020, respectively). Lastly, patients who were randomized into the melatonin group were found to use significantly less narcotic medication at the 4-month postoperative period ( P = .046). Conclusion: Melatonin use after arthroscopic rotator cuff repair led to improved sleep quality (PSQI) in the early postoperative period as well as improved functional outcomes (ASES and SANE scores) and decreased narcotic use in the later postoperative period. Patients with significant sleep disturbances associated with rotator cuff repairs may benefit from the use of melatonin. Registration: NCT04278677 (ClinicalTrials.gov identifier).

Improvement of Sleep Disturbance After Rotator Cuff Repair Occurs at 3 Months

“…Cho et al 5 reported that zolpidem reduced the need for rescue analgesia after RCR with no associated risk. Similarly, Perez et al 21 reported that melatonin improved sleep quality and functional recovery while reducing opioid use after RCR.…”

Improvement of Sleep Disturbance After Rotator Cuff Repair Occurs at 3 Months

“…Cho et al 5 reported that zolpidem reduced the need for rescue analgesia after RCR with no associated risk. Similarly, Perez et al 21 reported that melatonin improved sleep quality and functional recovery while reducing opioid use after RCR.…”

Efficacy and effectiveness of melatonin for the management of musculoskeletal pain: a systematic review and meta-analysis of placebo and active controlled trials

“… 1 , 2 , 5 , 9 , 18 , 19 , 21 , 23 , 26 , 33 – 36 , 39 , 41 , 42 , 48 , 49 , 54 , 55 , 58 , 64 , 68 All studies used a parallel-arm RCT design including 14 placebo-controlled trials. Seven trials were conducted in Iran, 9 , 19 , 34 , 35 , 48 , 49 , 55 5 in United States, 18 , 27 , 39 , 42 , 56 3 in Russia, 36 , 41 , 59 2 in Brazil, 64 , 68 2 in Egypt, 1 , 21 1 in China, 23 1 in Iraq, 33 1 in Turkey, 2 and 1 in India. 5 Melatonin was administered orally in all studies, except one study where the drug was administered through transdermal patch.…”

“… 12 In postoperative studies where melatonin was administered only once, we selected the time point at which outcome was assessed closest to 24 hours after surgery for analysis. Although we attempted to extract data for medium (>3 months but <12 months) and long-term (≥12 months) follow-ups, only one trial reported outcomes at medium-term time points (4 and 6 months), 56 while all others provided short-term follow-up data only. Sensitivity analyses were conducted to assess the robustness of the findings by including only studies with low risk of bias.…”

Systematic Review on Antidepressant Use and Bleeding Risk After Dental Extractions: Evidence Gaps and Clinical Implications

“…As a result, there is a significant gap in the literature regarding the perioperative bleeding risk for this population in dental contexts [22][23][24]. Similar exclusion practices have been observed in randomized controlled trials of arthroscopic rotator cuff surgery, abdominal hysterectomy, and prospective observational studies following elective spinal surgery [25][26][27][28]. The mechanisms underlying this association are still being investigated; however, it is widely believed that serotonergic antidepressants inhibit platelet aggregation by depleting intraplatelet serotonin, an essential component of clot formation.…”

Improvement of Sleep Disturbance After Rotator Cuff Repair Occurs at 3 Months

“…Cho et al 5 reported that zolpidem reduced the need for rescue analgesia after RCR with no associated risk. Similarly, Perez et al 21 reported that melatonin improved sleep quality and functional recovery while reducing opioid use after RCR.…”

Efficacy and effectiveness of melatonin for the management of musculoskeletal pain: a systematic review and meta-analysis of placebo and active controlled trials

“… 1 , 2 , 5 , 9 , 18 , 19 , 21 , 23 , 26 , 33 – 36 , 39 , 41 , 42 , 48 , 49 , 54 , 55 , 58 , 64 , 68 All studies used a parallel-arm RCT design including 14 placebo-controlled trials. Seven trials were conducted in Iran, 9 , 19 , 34 , 35 , 48 , 49 , 55 5 in United States, 18 , 27 , 39 , 42 , 56 3 in Russia, 36 , 41 , 59 2 in Brazil, 64 , 68 2 in Egypt, 1 , 21 1 in China, 23 1 in Iraq, 33 1 in Turkey, 2 and 1 in India. 5 Melatonin was administered orally in all studies, except one study where the drug was administered through transdermal patch.…”

“… 12 In postoperative studies where melatonin was administered only once, we selected the time point at which outcome was assessed closest to 24 hours after surgery for analysis. Although we attempted to extract data for medium (>3 months but <12 months) and long-term (≥12 months) follow-ups, only one trial reported outcomes at medium-term time points (4 and 6 months), 56 while all others provided short-term follow-up data only. Sensitivity analyses were conducted to assess the robustness of the findings by including only studies with low risk of bias.…”

Systematic Review on Antidepressant Use and Bleeding Risk After Dental Extractions: Evidence Gaps and Clinical Implications

“…As a result, there is a significant gap in the literature regarding the perioperative bleeding risk for this population in dental contexts [22][23][24]. Similar exclusion practices have been observed in randomized controlled trials of arthroscopic rotator cuff surgery, abdominal hysterectomy, and prospective observational studies following elective spinal surgery [25][26][27][28]. The mechanisms underlying this association are still being investigated; however, it is widely believed that serotonergic antidepressants inhibit platelet aggregation by depleting intraplatelet serotonin, an essential component of clot formation.…”

Improvement of Sleep Disturbance After Rotator Cuff Repair Occurs at 3 Months

“…Cho et al 5 reported that zolpidem reduced the need for rescue analgesia after RCR with no associated risk. Similarly, Perez et al 21 reported that melatonin improved sleep quality and functional recovery while reducing opioid use after RCR.…”

Efficacy and effectiveness of melatonin for the management of musculoskeletal pain: a systematic review and meta-analysis of placebo and active controlled trials

“… 1 , 2 , 5 , 9 , 18 , 19 , 21 , 23 , 26 , 33 – 36 , 39 , 41 , 42 , 48 , 49 , 54 , 55 , 58 , 64 , 68 All studies used a parallel-arm RCT design including 14 placebo-controlled trials. Seven trials were conducted in Iran, 9 , 19 , 34 , 35 , 48 , 49 , 55 5 in United States, 18 , 27 , 39 , 42 , 56 3 in Russia, 36 , 41 , 59 2 in Brazil, 64 , 68 2 in Egypt, 1 , 21 1 in China, 23 1 in Iraq, 33 1 in Turkey, 2 and 1 in India. 5 Melatonin was administered orally in all studies, except one study where the drug was administered through transdermal patch.…”

“… 12 In postoperative studies where melatonin was administered only once, we selected the time point at which outcome was assessed closest to 24 hours after surgery for analysis. Although we attempted to extract data for medium (>3 months but <12 months) and long-term (≥12 months) follow-ups, only one trial reported outcomes at medium-term time points (4 and 6 months), 56 while all others provided short-term follow-up data only. Sensitivity analyses were conducted to assess the robustness of the findings by including only studies with low risk of bias.…”

Systematic Review on Antidepressant Use and Bleeding Risk After Dental Extractions: Evidence Gaps and Clinical Implications

“…As a result, there is a significant gap in the literature regarding the perioperative bleeding risk for this population in dental contexts [22][23][24]. Similar exclusion practices have been observed in randomized controlled trials of arthroscopic rotator cuff surgery, abdominal hysterectomy, and prospective observational studies following elective spinal surgery [25][26][27][28]. The mechanisms underlying this association are still being investigated; however, it is widely believed that serotonergic antidepressants inhibit platelet aggregation by depleting intraplatelet serotonin, an essential component of clot formation.…”