Melatonin For Rem Sleep Disorder: Is It Safe?

REM sleep behaviour disorder (RBD) is a parasomnia associated with dream enactment, often involving violent or potentially injurious behaviours during REM sleep. Clonazepam has long been considered the first-line treatment option for RBD. However, evidence supporting melatonin therapy is expanding. Melatonin appears to be beneficial for the management of RBD, with reductions in clinical behavioural outcomes and a decrease in muscle tonicity during REM sleep. Melatonin also has a more favourable safety and tolerability profile than clonazepam, with limited potential for drug-drug interactions.

Melatonin reduces REM sleep without atonia in RBD

Melatonin is a hormone that is secreted by the pineal gland and follows a circadian rhythm. Its levels begin to rise shortly after nightfall and peak in the middle of the night. Its secretion is influenced by darkness, and can be reduced by environmental light, severe illness, pineal calcification, or advanced age.

Melatonin therapy has been shown to be beneficial for the management of REM sleep behaviour disorder (RBD). RBD is a parasomnia associated with dream enactment, often involving violent or potentially injurious behaviours. It is believed to be caused by brain-stem dysfunction, and the usual age of onset is between 40 and 70 years. RBD may also be seen in younger adults with narcolepsy or antidepressant use.

Melatonin therapy has been shown to reduce clinical behavioural outcomes and decrease muscle tonicity during REM sleep in patients with RBD. In one randomised, double-blind, placebo-controlled crossover trial, melatonin decreased the percentage of REM sleep without atonia from 39.2% to 26.8% compared to baseline. Another randomised, double-blind, placebo-controlled crossover trial found that melatonin decreased the percentage of REM sleep without atonia from 32% to 11% compared to baseline.

Melatonin doses of 3-12mg appear to be efficacious in reducing clinical RBD symptoms. It is generally well-tolerated with minimal adverse events, and has a more favourable safety and tolerability profile than clonazepam, which has long been the suggested first-line treatment option for RBD. Given its favourable side effect profile, melatonin can be an alternative when clonazepam is not tolerated or less ideal for use.

However, more placebo-controlled and active comparator trials are needed to confirm the benefits of melatonin therapy for RBD.

Melatonin doses of 3–12 mg appear efficacious in reducing clinical RBD symptoms

Melatonin doses of 3–12 mg have been found to be effective in reducing clinical RBD symptoms. In a study, 14 patients were given melatonin over a period of time, with 13 of them being male, and the median age of RBD onset being 56 years. The coexisting neurological findings/disorders were dementia with Lewy bodies, mild cognitive impairment with mild parkinsonism, multiple system atrophy, narcolepsy, and Parkinson's disease. The reasons for using melatonin in these cases were the incomplete response of RBD to clonazepam in six patients, existing cognitive impairment in five, intolerable side-effects with clonazepam in two, and the presence of severe obstructive sleep apnea and narcolepsy in one. With seven patients continuing to use clonazepam at 0.5-1.0 mg/night, RBD was controlled in six patients, significantly improved in four, and initially improved but subsequently returned in two; no improvement occurred in one patient and increased RBD frequency/severity occurred in one patient. The effective melatonin doses were 3 mg in two cases, 6 mg in seven cases, 9 mg in one case, and 12 mg in two cases.

In another study, melatonin therapy was found to be beneficial for the management of RBD with reductions in clinical behavioral outcomes and a decrease in muscle tonicity during REM sleep. The study also found that melatonin has a favorable safety and tolerability profile over clonazepam with limited potential for drug-drug interactions, which is an important consideration for elderly individuals with RBD receiving polypharmacy.

Melatonin has minimal side effects compared to clonazepam

Melatonin is a natural hormone that regulates the sleep-wake cycle and helps individuals fall asleep. It has been found to be beneficial in the management of REM sleep behaviour disorder (RBD) by reducing clinical behavioural outcomes and decreasing muscle tonicity during REM sleep.

On the other hand, clonazepam is a benzodiazepine that increases the action of a chemical messenger (GABA) to suppress abnormal and excessive nerve cell activity in the brain. It has long been suggested as the first-line treatment option for RBD.

While both medications are used to treat RBD, melatonin has a more favourable safety and tolerability profile compared to clonazepam. Melatonin has limited potential for drug-drug interactions, which is an important consideration, especially for elderly individuals with RBD who may be receiving multiple medications.

In terms of side effects, melatonin is generally well-tolerated with minimal adverse events. Common side effects of melatonin include sleepiness, trouble thinking, unsteadiness, nausea, dizziness, and sexual dysfunction. These side effects are typically mild, and no adverse events have been reported at the commonly used dose of 3 mg nightly.

In contrast, clonazepam is associated with more significant side effects and has the potential for drug interactions. It may increase the risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents, especially in elderly individuals. Additionally, clonazepam can cause nervous system side effects such as dizziness, drowsiness, and difficulty concentrating when combined with alcohol.

Therefore, melatonin has minimal side effects compared to clonazepam, making it a safer and more attractive treatment option for individuals with RBD, particularly those who are elderly or taking multiple medications.

Melatonin may be a suitable alternative for those who can't tolerate clonazepam

RBD is a parasomnia associated with dream enactment, often involving violent or potentially injurious behaviours during REM sleep. Clonazepam has long been considered the first-line treatment option, with an efficacy rate of nearly 90%. However, melatonin therapy has been found to be beneficial for managing RBD, reducing clinical behavioural outcomes and decreasing muscle tonicity during REM sleep.

Melatonin has a more favourable safety and tolerability profile than clonazepam, with limited potential for drug-drug interactions. This is especially important for elderly individuals with RBD who are receiving polypharmacy. Melatonin is generally well-tolerated, with minimal adverse events such as somnolence, headache, fatigue, and cognitive alteration. It can be an attractive treatment option, particularly for those who cannot tolerate clonazepam or for whom clonazepam is less ideal.

However, it is important to note that prospective clinical trials are necessary to establish conclusive evidence for the use of melatonin and clonazepam as RBD therapies.

More placebo-controlled and active comparator trials are needed to confirm benefit

Melatonin is a hormone that is secreted in a circadian rhythm from the pineal gland. Its secretion is influenced by dark environments, with melatonin serum levels beginning to rise shortly after nightfall and peaking in the middle of the night. The secretion may be reduced due to environmental light, severe illness, pineal calcification, or advanced age.

Melatonin appears to be beneficial for the management of REM sleep behaviour disorder (RBD), with reductions in clinical behavioural outcomes and a decrease in muscle tonicity during REM sleep. It has a more favourable safety and tolerability profile than clonazepam, which has long been the first-line treatment option for RBD. Melatonin has limited potential for drug-drug interactions, which is an important consideration for elderly individuals with RBD who are receiving polypharmacy.

However, more placebo-controlled and active comparator trials are needed to confirm the benefits of melatonin for RBD. While there is some evidence to support melatonin therapy, the majority of studies have small sample sizes and are limited in scope. For example, one study only included eight male subjects with a mean age of 54 years. Another study only included six subjects with a mean age of 54 years. These small sample sizes and specific demographics limit the generalisability of the findings.

Further research is needed to establish the evidence basis for melatonin and clonazepam as RBD therapies.

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