Effectiveness of melatonin treatment for sleep disturbance in orthopaedic trauma patients: A prospective, randomized control trial

Published:October 13, 2022DOI:



      Explore sleep disturbance in postoperative orthopedic trauma patients and determine the impact of melatonin supplementation on postoperative sleep, pain, and quality of life.

      Materials and Methods

      In this prospective, randomized controlled trial at a Level I trauma center, 84 adult orthopedic trauma patients with operative fracture management were randomized 2-weeks postoperatively to either the melatonin or placebo group. Patients randomized to the melatonin group (42 subjects, mean age 41.8 ± 15.5 years) received 5 mg melatonin supplements. Patients in the placebo group (42 subjects, mean age 41.3 ± 14.0 years) received identical glucose tablets. Both groups were instructed to take the tablets 30 minutes before bed for 4 weeks and received sleep hygiene education and access to the Cognitive Behavioral Therapy for Insomnia (CBT-I) Coach app.

      Main Outcome Measures

      Our primary outcome was sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes were pain measured by the Visual Analog Scale (VAS), quality of life measured by the 36-Item Short Form Survey (SF-36), and opioid use.


      Patients in both groups had significant sleep disturbance (PSQI ≥ 5) at 2-weeks (83%) and 6-weeks (67%) postoperatively. PSQI improved by 3.3 points (p<0.001) at follow-up, but there was no significant difference between groups (melatonin PSQI = 5.6, placebo PSQI = 6.1, P = 0.615). Compared to placebo, melatonin did not affect VAS, SF-36, or opioid use significantly.


      Sleep disturbance is prevalent in orthopedic trauma patients. Melatonin treatment did not significantly improve subjective sleep quality, pain, quality of life or opioid use.

      Level of evidence

      Therapeutic Level I.


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        • Swann M
        • Batty M
        • Hu G.
        Sleep Disturbance in Orthopaedic Trauma Patients.
        J Orthop Trauma. 2018; 32: 500-504
        • DeGutis J
        • Chiu C
        • Thai M
        • Esterman M
        • Milberg W
        • McGlinchey R.
        Trauma Sequelae are Uniquely Associated with Components of Self-Reported Sleep Dysfunction in OEF/OIF/OND Veterans.
        Behavioral Sleep Medicine. 2018; 16: 38-63
        • Wu H
        • Zhang F
        • Cheng W
        • Lin Y.
        Factors Related to Acute Anxiety and Depression in Inpatients with Accidental Orthopedic Injuries.
        Shanghai Arch Psychiatry. 2017; 29: 77-84
        • Liu H
        • Petukhova M
        • Sampson N.
        Association of DSM-IV posttraumatic stress disorder with traumatic experience type and history in the world health organization world mental health surveys.
        JAMA Psychiatry. 2017; : 270-281
        • Ross RJ
        • Ball WA
        • Sullivan KA
        • Caroff SN.
        Sleep disturbance as the hallmark of posttraumatic stress disorder.
        Am J Psychiatry. 1989; 146: 697-707
        • Ponsford J
        • Hill B
        • Karamitsios M
        • Bahar-Fuchs A.
        Factors influencing outcome after orthopedic trauma.
        J Trauma. 2008; 64: 1001-1009
        • Sprague S
        • Petrisor BA
        • Jeray KJ
        • et al.
        Factors Associated With Health-Related Quality of Life in Patients With Open Fractures.
        J Orthop Trauma. 2018; 32: e5-e11
        • Lu K
        • Barron JO
        • Israel H
        • Cannada LK.
        Sleep disturbances in orthopaedic trauma patients.
        OTA Int. 2019; 2: e040
        • Strand LB
        • Tsai MK
        • Gunnell D
        • Janszky I
        • Wen CP
        • Chang SS.
        Self-reported sleep duration and coronary heart disease mortality: A large cohort study of 400,000 Taiwanese adults.
        Int J Cardiol. 2016; 207: 246-251
        • Gottlieb DJ
        • Punjabi NM
        • Newman AB
        • et al.
        Association of sleep time with diabetes mellitus and impaired glucose tolerance.
        Arch Intern Med. 2005; 165: 863-867
        • Chien MY
        • Chen HC.
        Poor sleep quality is independently associated with physical disability in older adults.
        J Clin Sleep Med. 2015; 11: 225-232
        • Cronin AJ
        • Keifer JC
        • Davies MF
        • King TS
        • Bixler EO.
        Melatonin secretion after surgery.
        Lancet. 2000; 356: 1244-1245
        • Arendt J
        • Skene DJ.
        Melatonin as a chronobiotic.
        Sleep Med Rev. 2005; 9: 25-39
        • ichiro Aizawa K
        • T Kanai
        • Saikawa Y
        • et al.
        A novel approach to the prevention of postoperative delirium in the elderly after gastrointestinal surgery.
        Surg Today. 2002; 32: 310-314
        • Lee TYC
        • Curtin JP.
        The effects of melatonin prophylaxis on sensory recovery and postoperative pain following orthognathic surgery: a triple-blind randomized controlled trial and biochemical analysis.
        Int J Oral Maxillofac Surg. 2020; 49: 446-453
        • Javaherforoosh Zadeh F
        • Janatmakan F
        • Shafaeebejestan E
        • Jorairahmadi S
        Effect of Melatonin on Delirium After on-Pump Coronary Artery Bypass Graft Surgery: A Randomized Clinical Trial.
        Iran J Med Sci. 2021; 46: 120-127
        • Madsen MT
        • Hansen MV
        • Andersen LT
        • et al.
        Effect of Melatonin on Sleep in the Perioperative Period after Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.
        J Clin Sleep Med. 2016; 12: 225-233
        • Vij V
        • Dahiya D
        • Kaman L
        • Behera A.
        Efficacy of melatonin on sleep quality after laparoscopic cholecystectomy.
        Indian J Pharmacol. 2018; 50: 236-241
        • Kirksey MA
        • Yoo D
        • Danninger T
        • Stundner O
        • Ma Y
        • Memtsoudis SG.
        Impact of Melatonin on Sleep and Pain After Total Knee Arthroplasty Under Regional Anesthesia With Sedation: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.
        J Arthroplasty. 2015; 30: 2370-2375
        • Clarkson SJ
        • Yayac MF
        • Rondon AJ
        • Smith BM
        • Purtill JJ.
        Melatonin Does Not Improve Sleep Quality in a Randomized Placebo-controlled Trial After Primary Total Joint Arthroplasty.
        J Am Acad Orthop Surg. 2022; 30: e287-e294
        • Xu H
        • Zhang C
        • Qian Y
        • et al.
        Efficacy of melatonin for sleep disturbance in middle-aged primary insomnia: a double-blind, randomised clinical trial.
        Sleep Med. 2020; 76: 113-119
        • Kuhn E
        • Miller KE
        • Puran D
        • et al.
        A Pilot Randomized Controlled Trial of the Insomnia Coach Mobile App to Assess Its Feasibility, Acceptability, and Potential Efficacy.
        Behav Ther. 2022; 53: 440-457
        • Buysse DJ
        • Reynolds CF
        • Monk TH
        • Berman SR
        • Kupfer DJ.
        The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research.
        Psychiatry Res. 1989; 28: 193-213
        • Hughes CM
        • McCullough CA
        • Bradbury I
        • et al.
        Acupuncture and Reflexology for Insomnia: A Feasibility Study.
        Acupunct Med. 2009; 27: 163-168
        • Weinberg M
        • Mollon B
        • Kaplan D
        • Zuckerman J
        • Strauss E.
        Improvement in sleep quality after total shoulder arthroplasty.
        The Physician and Sportsmedicine. 2020; 48: 194-198
        • McDonnell LM
        • Hogg L
        • McDonnell L
        • White P.
        Pulmonary rehabilitation and sleep quality: a before and after controlled study of patients with chronic obstructive pulmonary disease.
        npj Prim Care Resp Med. 2014; 24: 1-5
        • Eadie J
        • van de Water AT
        • Lonsdale C
        • et al.
        Physiotherapy for Sleep Disturbance in People With Chronic Low Back Pain: Results of a Feasibility Randomized Controlled Trial.
        Archives of Physical Medicine and Rehabilitation. 2013; 94: 2083-2092
        • Longo UG
        • Berton A
        • De Salvatore S
        • et al.
        Minimal Clinically Important Difference and Patient Acceptable Symptom State for the Pittsburgh Sleep Quality Index in Patients Who Underwent Rotator Cuff Tear Repair.
        International Journal of Environmental Research and Public Health. 2021; 18: 8666
        • Zhou JN
        • Liu RY
        • van Heerikhuize J
        • Hofman MA
        • Swaab DF.
        Alterations in the circadian rhythm of salivary melatonin begin during middle-age.
        Journal of Pineal Research. 2003; 34: 11-16
        • Kain ZN
        • Caldwell-Andrews AA.
        Sleeping characteristics of adults undergoing outpatient elective surgery: a cohort study.
        J Clin Anesth. 2003; 15: 505-509
        • Yang H
        • Liu YJ
        • Ye JL
        • Zhao LH
        • Li LL
        • Hou XL.
        Evaluation of sleep disorder in orthopedic trauma patients: a retrospective analysis of 1129 cases.
        J Orthop Surg Res. 2021; 16: 344
        • Canfield MJ
        • Cremins MS
        • Vellanky SS
        • Teng R
        • Belniak RM.
        Evaluating the Success of Perioperative Self-Guided Meditation in Reducing Sleep Disturbance After Total Knee Arthroplasty.
        J Arthroplasty. 2021; 36 (S215-S220.e2)
        • Wade AG
        • Ford I
        • Crawford G
        • et al.
        Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety.
        BMC Med. 2010; 8: 51
        • Haimov I
        • Laudon M
        • Zisapel N
        • et al.
        Sleep disorders and melatonin rhythms in elderly people.
        BMJ. 1994; 309: 167
        • Hajak G
        • Rodenbeck A
        • Staedt J
        • Bandelow B
        • Huether G
        • Rüther E.
        Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia.
        J Pineal Res. 1995; 19: 116-122
        • Zhdanova IV
        • Wurtman RJ
        • Regan MM
        • Taylor JA
        • Shi JP
        • Leclair OU.
        Melatonin treatment for age-related insomnia.
        J Clin Endocrinol Metab. 2001; 86: 4727-4730
        • Dawson D
        • Rogers NL
        • van den Heuvel CJ
        • Kennaway DJ
        • Lushington K.
        Effect of sustained nocturnal transbuccal melatonin administration on sleep and temperature in elderly insomniacs.
        J Biol Rhythms. 1998; 13: 532-538
        • Luthringer R
        • Muzet M
        • Zisapel N
        • Staner L.
        The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia.
        Int Clin Psychopharmacol. 2009; 24: 239-249
        • Almeida Montes LG
        • Ontiveros Uribe MP
        • Cortés Sotres J
        • Heinze Martin G.
        Treatment of primary insomnia with melatonin: a double-blind, placebo-controlled, crossover study.
        J Psychiatry Neurosci. 2003; 28: 191-196
        • Schultz BJ
        • Tanner N
        • Shapiro LM
        • et al.
        Patient-Reported Outcome Measures (PROMs): Influence of Motor Tasks and Psychosocial Factors on FAAM Scores in Foot and Ankle Trauma Patients.
        J Foot Ankle Surg. 2020; 59: 758-762