PT  - JOURNAL ARTICLE
AU  - Annemarieke de Jonghe
AU  - Barbara C. van Munster
AU  - J. Carel Goslings
AU  - Peter Kloen
AU  - Carolien van Rees
AU  - Reinder Wolvius
AU  - Romuald van Velde
AU  - Marcel Levi
AU  - Rob J. de Haan
AU  - Sophia E. de Rooij
AU  - Sophia E. de Rooij
AU  - on behalf of the Amsterdam Delirium Study Group
TI  - Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial
AID  - 10.1503/cmaj.140495
DP  - 2014 Jan 01
TA  - Canadian Medical Association Journal
PG  - cmaj.140495
4099  - http://www.cmaj.ca/content/early/2014/09/02/cmaj.140495.short
4100  - http://www.cmaj.ca/content/early/2014/09/02/cmaj.140495.full
AB  - 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. Interpretation: In this older population with hip fracture, treatment with melatonin did not reduce the incidence of delirium. Trial registration: Netherlands Trial Registry, NTR1576: MAPLE (Melatonin Against PLacebo in Elderly patients) study; www.trialregister.nl/trialreg/admin/rctview.asp?TC=1576