Melatonin in elderly patients with insomnia. A systematic review.
BACKGROUND
Melatonin is a hormone and antioxidant produced by the pineal gland of which four neurobiological roles have been claimed in the aged population: anti-ageing agent; free-radical scavenger; regulator of circadian rhythm; endogeneous sleep-inducer. The "melatonin replacement" hypothesis states that 1) the well-evidenced age-related decline contributes to insomnia and that 2) replacement with physiological doses of melatonin improves sleep. The aim of this review was to determine the evidence for the efficacy of melatonin in elderly insomniacs.


METHODS
MEDLINE's database from 1990-2000 was searched with "melatonin", "geriatrics" and "(frail)-elderly" as major sub-headings. This resulted in 78 articles: only studies with empirical treatment data were reviewed (N = 12).


RESULTS
Six reports (abstract, research letter, retrospective case study, 3 open label studies) showed a trend towards efficacy of melatonin: sleep quality improved and in patients with Alzheimer's disease sundowning was reduced. In 6 double blind, randomised crossover trials, a total number of 95 patients (mean ages: 65-79 yrs) were treated. Melatonin doses ranged from 0.5 mg to 6 mg; most took a single dose 30-120 min before bedtime. In 3 studies a slow release form was used. Sleep quality was objectively measured by wrist actigraphy (n = 4) and polysomnography (n = 2), and additionally subjective sleep quality was assessed (n = 2). Sleep latency decreased significantly in 4 studies. In 3 studies other measures of sleep quality (sleep efficiency, total sleep time and wake time during sleep) improved. Subjective sleep quality did not improve. No early-morning sleepiness occurred. Comparison of the studies suggests that melatonin is most effective in elderly insomniacs who chronically use benzodiazepines and/or with documented low melatonin levels during sleep.


CONCLUSIONS
There is sufficient evidence that low doses of melatonin improve initial sleep quality in selected elderly insomniacs. However, larger randomized controlled trials, with less strict inclusion criteria are necessary to yield evidence of effectiveness (i.e. clinical and subjective relevance) in geriatric patients who suffer from insomnia, before wide-spread use can be advocated.
Olde Rikkert
M G
MG
Dept. Geriatric Medicine, University Hospital Nijmegen, Code 318, PO Box 9101, 6500 HB Nijmegen, The Netherlands. M.Olde-Rikkert@czzoger.azn.nl
Rigaud
A S
AS
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D016896:Treatment Outcome
D008550:Melatonin