title: Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial.
abstract: BACKGROUND
  Disturbance of the sleep-wake cycle is a characteristic of delirium. In addition, changes in melatonin rhythm influence the circadian rhythm and are associated with delirium. We compared the effect of melatonin and placebo on the incidence and duration of delirium.
  
  
  METHODS
  We performed this multicentre, double-blind, randomized controlled trial between November 2008 and May 2012 in 1 academic and 2 nonacademic hospitals. Patients aged 65 years or older who were scheduled for acute hip surgery were eligible for inclusion. Patients received melatonin 3 mg or placebo in the evening for 5 consecutive days, starting within 24 hours after admission. The primary outcome was incidence of delirium within 8 days of admission. We also monitored the duration of delirium.
  
  
  RESULTS
  A total of 452 patients were randomly assigned to the 2 study groups. We subsequently excluded 74 patients for whom the primary end point could not be measured or who had delirium before the second day of the study. After these postrandomization exclusions, data for 378 patients were included in the main analysis. The overall mean age was 84 years, 238 (63.0%) of the patients lived at home before admission, and 210 (55.6%) had cognitive impairment. We observed no effect of melatonin on the incidence of delirium: 55/186 (29.6%) in the melatonin group v. 49/192 (25.5%) in the placebo group; difference 4.1 (95% confidence interval -0.05 to 13.1) percentage points. There were no between-group differences in mortality or in cognitive or functional outcomes at 3-month follow-up.
  
  
  CONCLUSIONS
  In this older population with hip fracture, treatment with melatonin did not reduce the incidence of delirium.
  
  
  BACKGROUND
  Netherlands Trial Registry, NTR1576: MAPLE (Melatonin Against PLacebo in Elderly patients) study; www.trialregister.nl/trialreg/admin/rctview.asp?TC=1576.
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands. a.dejonghe@amc.uva.nl.
authors.forename: Annemarieke
authors.initials: A
authors.lastname: de Jonghe
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: van Munster
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands.
authors.forename: J Carel
authors.initials: JC
authors.lastname: Goslings
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Kloen
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands.
authors.forename: Carolien
authors.initials: C
authors.lastname: van Rees
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands.
authors.forename: Reinder
authors.initials: R
authors.lastname: Wolvius
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands.
authors.forename: Romuald
authors.initials: R
authors.lastname: van Velde
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Haan
authors.affiliation: Department of Internal Medicine, Geriatrics Section (de Jonghe, van Munster, de Rooij), Department of Surgery, Trauma Unit (Goslings), Department of Orthopedic Surgery (Kloen), Department of Internal Medicine (Levi) and Clinical Research Unit (de Haan), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Geriatrics (van Munster), Gelre Hospitals, Apeldoorn, The Netherlands; Department of Geriatrics (van Rees), Department of Orthopaedic Surgery (Wolvius) and Department of Surgery (van Velde), Tergooi Hospitals, Hilversum, The Netherlands.
authors.forename: Sophia E
authors.initials: SE
authors.lastname: de Rooij
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects / Q000379:methods; D003693:Delirium / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005593:Fracture Fixation, Internal / Q000009:adverse effects / Q000379:methods; D006620:Hip Fractures / Q000150:complications* / Q000601:surgery; D006801:Humans; D015994:Incidence; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*
chemical_list: D008550:Melatonin