Effective Treatments For Rem Sleep Disorder

REM sleep behaviour disorder (RBD) is a parasomnia disorder characterised by nocturnal complex motor behaviour and a loss of muscle atonia during REM sleep. It is often a precursor to neurological disorders such as Parkinson's disease and Lewy body dementia. The current approach to treating RBD is twofold: firstly, to prevent injury and, secondly, to provide prognostic counselling and longitudinal follow-up surveillance for phenoconversion towards overt neurodegenerative disorders.

The most common treatment for RBD is a combination of melatonin and clonazepam, which are considered the first-line therapy. However, their efficiency has not been proven by randomised clinical trials. Melatonin has been shown to be more tolerable than clonazepam, and is often used to treat sleep disorders. Other treatments with anecdotal efficacy include temazepam, lorazepam, zolpidem, zopiclone, pramipexole, donepezil, ramelteon, agomelatine, cannabinoids, and sodium oxybate.

Clonazepam is a first-line treatment for REM sleep behaviour disorder (RBD)

Clonazepam is a highly successful first-line treatment for REM sleep behaviour disorder (RBD). It is effective in nearly 90% of patients, with 79% experiencing complete relief from symptoms and 11% experiencing partial relief. The drug works by enhancing the neurotransmitter gamma-aminobutyric acid (GABA) and has anxiolytic, anticonvulsant, and hypnotic properties. The initial dose is 0.5 mg at bedtime, which can be increased to 1-2 mg if ineffective. Treatment should be continued indefinitely as violent behaviours and nightmares relapse promptly when medication is discontinued.

Despite its high success rate, the long-term use of clonazepam in older adults should be carefully managed. Common side effects include daytime drowsiness, dizziness, and motor and balance impairments, which increase the risk of falling and fall-related injuries in elderly patients. In patients with RBD, the frequent association with neurodegenerative diseases may also increase this risk. Therefore, the correct management of dosage is essential to reducing the number of fall-related injuries.

While clonazepam has proven to be an effective treatment for RBD, its well-known side effects require attention. Timely clinical evaluations should be conducted to reduce residual effects and initiate treatment of associated neurodegenerative diseases as soon as possible.

Melatonin is also a first-line treatment for RBD

Melatonin is a hormone secreted by the pineal gland and is influenced by dark environments. It is a first-line treatment for REM sleep behaviour disorder (RBD) and is used to reduce clinical behavioural outcomes and decrease muscle tonicity during REM sleep.

Melatonin has a more favourable safety and tolerability profile than clonazepam, which is also a first-line treatment for RBD. This is because melatonin has limited potential for drug-drug interactions, which is an important consideration for elderly individuals with RBD who are receiving polypharmacy.

Melatonin is generally well-tolerated and has minimal adverse effects. It can be an alternative when clonazepam is not tolerated or less ideal for use.

Rivastigmine and 5-hydroxytryptophan are two anticholinesterase drugs that have shown short-term efficacy in treating RBD

Rivastigmine and 5-hydroxytryptophan are two anticholinesterase drugs that have shown efficacy in treating REM sleep behaviour disorder (RBD) in the short term.

Rivastigmine is a reversible acetylcholinesterase inhibitor that prevents the breakdown of acetylcholine, increasing its availability and duration of action in the central and peripheral nervous system. It is typically used to treat neurogenerative diseases such as Alzheimer's disease, Parkinson's disease, and Lewy body dementia. In the context of RBD, a double-blind, crossover pilot trial involving 12 patients with Parkinson's disease and RBD found that a patch of rivastigmine at a dose of 4.6 mg/24 hours for 3 weeks significantly reduced the mean frequency of RBD episodes. The drug was well-tolerated, with minor side effects related to peripheral cholinergic action.

Similarly, 5-hydroxytryptophan is a precursor of serotonin that has shown efficacy in treating RBD in patients with Parkinson's disease. A randomised, double-blind, placebo-controlled crossover trial involving 18 patients with Parkinson's disease and polysomnography-confirmed RBD found that 5-hydroxytryptophan improved clinical status and UPDRS part 2 scores. It also increased the total percentage of stage REM sleep without increasing RBD episodes and showed a trend towards reducing the arousal index and wake after sleep onset.

Herbal medicine yokukansan has shown promise in treating RBD

Yokukansan (YKS) is a traditional Japanese herbal medicine consisting of seven herbal ingredients: Japanese Angelica root, Uncaria hook, Cnidium rhizome, Atractylodes lancea rhizome, Poria sclerotium, Bupleurum root, and Glycyrrhiza. The effectiveness of YKS in treating behavioural and psychological symptoms of dementia and psychophysiological insomnia has been previously reported.

The detailed mechanisms of action of YKS are currently unclear. Reportedly, at least 25 ingredients in the methanol fraction of YKS extract have been identified in three-dimensional high-performance liquid chromatographic analysis. Thus, a mixture of various ingredients derived from seven medicinal herbs in YKS makes it more difficult to identify the specific positive mechanism of action for RBD symptoms. Descending glutamatergic projection from the sublaterodorsal tegmental nucleus to spinal and cranial motoneurons induces the phasic motor activation leading to the vigorous movements in patients with RBD. The glutamate uptake function of YKS suggests that the drug possibly reduces oneiric behaviour through the suppression of phasic muscle activity.

In a 2020 study, the mean total RBDQ-JP score significantly improved from 52.5 to 21.7 after treatment with YKS (mean dosage: 3.0 g/day), which was similar to the change after clonazepam treatment (from 43.8 to 21.3). On RBDQ-JP factor 1 (dream content), the mean score on five of six items significantly improved after treatment with YKS. There was no significant change in Short-Form Health Survey scores after treatment with either drug. Potassium concentrations were within the normal range in patients treated with YKS.

In a 2020 case report, YKS was studied as a potential alternative to clonazepam (CNZP) for RBD associated with dementia with Lewy bodies (DLB). The results of this study, although there were limitations due to the preliminary nature of the study, verified the hypothesis, indicating that YKS may provide a new therapeutic option for RBD associated with DLB.

Sodium oxybate is a treatment for RBD, though its effectiveness is limited to single case reports, short case series, or open-label studies

Sodium oxybate, also known as sodium 4-hydroxybutyrate or sodium 4-hydroxybutanoate, is a treatment option for RBD. It is the sodium salt of γ-hydroxybutyric acid and is typically used to treat sudden muscle weakness and excessive daytime sleepiness in patients with narcolepsy.

The effectiveness of sodium oxybate in treating RBD has been reported in single case reports, short case series, or open-label studies. For instance, a patient with RBD who was resistant to multiple therapies experienced long-term improvement in their RBD symptoms with sodium oxybate. Similarly, sodium oxybate has been shown to improve RBD symptoms in patients with Parkinson's disease and narcolepsy type 1. However, in the latter case, it reduced muscle activity during REM sleep but did not affect the frequency of motor episodes.

Sodium oxybate's mechanism of action in treating RBD is not yet fully understood. One hypothesis is that it interacts with the GABAB receptor as a GABAB agonist, potentially promoting muscle atonia during REM sleep. Another theory suggests that it may decrease REM sleep, as an initial study reported an increase in slow-wave sleep and a decrease in REM sleep with sodium oxybate.

Despite these promising findings, larger clinical trials are needed to establish the efficacy of sodium oxybate in treating RBD.

Frequently asked questions