As of the 1st of June 2021, the entry for melatonin in the Poisons Standard was amended to enable the use of specific melatonin formulations under the Schedule 3 classification.
The following criteria must be met before supplying melatonin under the new Schedule 3 entry:
Melatonin tablets must be:
- Modified release containing 2 mg or less of melatonin in packs of no more than 30 tablets
- Used for the short-term treatment of primary insomnia (characterised by poor quality of sleep)
- Used as monotherapy in those aged 55 years or older
What is insomnia?
Some of the essential features of insomnia as described by the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) include a dissatisfaction with the quality or quantity of sleep and difficulty initiating sleep or maintaining sleep. These features should be present despite the adequate opportunity for sleep. Additionally, the poor sleep is associated with distress and/or functional impairment.
‘Primary insomnia’ results from an unknown cause and is not related to other factors such as a contributing medical condition (for example, sleep apnoea) or substance (for example, alcohol).
Australian data published in 2019 suggests that almost 60% of adults report at least one troubling sleep symptom (for example, difficulty staying asleep) on three or more nights of the week.
What is melatonin and how is it used in primary insomnia?
Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced primarily by the pineal gland in response to the influence of daily light exposure and darkness. One of melatonin’s key functions is to regulate sleeping and the circadian rhythm. During the day melatonin levels are relatively low, whereas the levels increase in the evening, and peak between 1:00 am and 4:00 am.
Research suggests that with increasing age the patterns of melatonin secretion and metabolism change, resulting in decreased nighttime melatonin concentrations. This decline in melatonin production that occurs with age led to the recommendation that it be used only in patients over 55 years old. Randomised controlled trial data support benefits from using modified-release (MR) melatonin in those aged 55 years or older, and a relative lack of benefit in younger groups. Benefits associated with the use of MR melatonin include improvement in quality of sleep, morning alertness, and reduced sleep onset latency. Between 30% to 50% of patients 55 years or older respond to the use of 2 mg of MR melatonin given 1 to 2 hours before bed compared to placebo.
When researchers investigated the efficacy of MR and immediate-release formulations of melatonin compared to other agents commonly available over-the-counter (including doxylamine, diphenhydramine and valerian), a 2015 systematic review suggests that the use of MR melatonin displays the most consistent evidence of benefit compared to placebo.
Has melatonin been associated with many side effects?
Adverse effects associated with melatonin occur with a relatively low frequency (comparable with placebo), and melatonin is considered to be well tolerated. Adverse effects that have been reported most frequently were headache, diarrhoea, upper and lower respiratory tract infections, nasopharyngitis, and arthralgia.
Of note, the use of melatonin does not reduce morning alertness, has not been found to be associated with impaired memory or disrupted psychomotor functioning, and has not been found to be associated with rebound insomnia on discontinuation.
Guidelines are available to support pharmacists in the provision of Schedule 3 melatonin, and pharmacists are encouraged to familiarise themselves with these resources. For example, the ‘Non-prescription medicine treatment guideline: Insomnia’ is available in the Australian Pharmaceutical Formulary (APF) and is also available on the Pharmaceutical Society of Australia (PSA) website.
Modules have been made available for pharmacists to complete, such as the Melatonin for Insomnia online module available on GuildEd – successful completion of this module can contribute up to 2 CPD points and is available from https://guilded.guild.org.au/course/view.php?id=1040.
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