Melatonin is a natural hormone produced in the pineal gland in the brain. Its role is to regulate circadian rhythms of sleepiness and wakefulness. Once melatonin appears in the plasma it enters the brain and binds to melatonin receptors in the hypothalamus – melatonin 1 and melatonin 2 (MT1 and MT2). Research is ongoing about their role in sleep/wake regulation and circadian rhythms. Natural melatonin production declines with age and is lower in middle-aged and elderly patients with insomnia than in ‘good’ sleepers9795.
There is only one licensed formulation of melatonin in the UK (Circadin® 2mg prolonged-release tablet), licensed for short-term treatment of primary insomnia characterised by poor quality of sleep in patients aged 55 or over. Treatment with prolonged-release melatonin (Circadin) may be continued for up to 13 weeks.
Three randomised, double-blind trials showed that prolonged-release melatonin improved quality of sleep (QOS) and morning alertness when used for three weeks in patients aged 55 years and older414395. A further randomised trial looking at a subgroup of patients aged 65 to 80 demonstrated that subjective sleep latency was significantly shorter in patients receiving prolonged-release melatonin than in patients receiving placebo. Secondary outcomes (sleep maintenance, sleep quality, time of sleep onset and WHO-5 Wellbeing index) also showed improvements whilst there was no significant difference for total sleep time94.
Another small study comparing prolonged-release melatonin with the Z-drug zopiclone and placebo showed that in aircrew both melatonin and zopiclone were equally effective in inducing early circadian sleep without impacting on psychomotor performance69.
A study in 24 healthy volunteers concluded that prolonged-release melatonin does not affect postural instability, whereas postural instability was increased with zolipdem68.
In clinical trials, 48.8% of patients receiving prolonged-release melatonin reported an adverse event compared with 37.8% taking placebo. The most common were headache, nasopharyngitis, back pain, and arthralgia. Prolonged-release melatonin may also cause drowsiness19.