Medline ® Abstracts for References 90-95

OBJECTIVE: To describe the treatment response with melatonin for rapid eye movement (REM) sleep behavior disorder (RBD) associated with other neurologic disorders.

BACKGROUND: Clonazepam has been considered the treatment of choice for RBD. However, an alternative treatment is desirable for those with RBD refractory to clonazepam, for those who experience intolerable side-effects with clonazepam, and for those in whom clonazepam precipitates or aggravates obstructive sleep apnea (OSA). To date, there is minimal published data and limited follow-up regarding the use of melatonin for patients with RBD associated with other neurologic syndromes and disorders.

DESIGN/METHODS: The response to melatonin treatment for RBD was reviewed on consecutive patients the investigators treated with this agent at Mayo Clinic Rochester from January 2000 to June 2001. The coexisting neurologic disorders, reasons for using melatonin, effective doses, side-effects, and duration of follow-up were also reviewed on all patients.

RESULTS: Fourteen patients were commenced on melatonin over the specified time period (13 male, median RBD onset age 56 years, range 20-77 years). The coexisting neurologic findings/disorders were dementia with Lewy bodies (n=7), mild cognitive impairment with mild parkinsonism (n=2), multiple system atrophy (n=2), narcolepsy (n=2), and Parkinson's disease (n=1). The reasons for using melatonin in these cases were incomplete response of RBD to clonazepam in six patients, existing cognitive impairment in five, intolerable side-effects with clonazepam in two, and 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. Five patients reported side-effects, which included morning headaches (2), morning sleepiness (2), and delusions/hallucinations (1); these symptoms resolved with decreased dosage. The mean duration of follow-up was 14 months (range 9-25 months), with eight patients experiencing continued benefit with melatonin beyond 12 months of therapy.

CONCLUSIONS: In this series, persistent benefit with melatonin beyond 1 year of therapy occurred in most but not all patients. Melatonin can be considered as a possible sole or add-on therapy in select patients with RBD. Prospective, long-term, controlled trials with melatonin are warranted in a larger number of patients with RBD associated with a variety of neurologic symptoms and disorders.

Rapid eye movement (REM) sleep behaviour disorder (RBD) has been suggested to predict the development of neurodegenerative disorders. Patients with RBD are acting out dream behaviour associated with loss of normal muscle atonia of REM sleep. The aim of the present study was to confirm that exogenous melatonin improves RBD. Eight consecutively recruited males (mean age 54 years) with a polysomnographically (PSG) confirmed diagnosis of RBD were included in a two-part, randomized, double-blind, placebo-controlled cross-over study. Patients received placebo and 3 mg of melatonin daily in a cross-over design, administered between 22:00 h and 23:00 h over a period of 4 weeks. PSG recordings were performed in all patients at baseline, at the end of Part I of the trial and at the end of Part II of the trial. Compared to baseline, melatonin significantly reduced the number of 30-s REM sleep epochs without muscle atonia (39% versus 27%; P = 0.012), and led to a significant improvement in clinical global impression (CGI: 6.1 versus 4.6; P = 0.024). Interestingly, the number of REM sleep epochs without muscle atonia remained lower in patients who took placebo during Part II after having received melatonin in Part I (-16% compared to baseline; P = 0.043). In contrast, patients who took placebo during Part I showed improvements in REM sleep muscle atonia only during Part II (i.e. during melatonin treatment). The data suggest that melatonin might be a second useful agent besides clonazepam in the treatment of RBD.

STUDY OBJECTIVES: REM sleep behavior disorder (RBD) is characterized by loss of the normal muscle atonia during REM sleep associated with disruptive motor activity related to the acting out of dreams. There is frequently injury to the patient or bed partner, and treatment is usually required. Clonazepam has been the first-line therapy for many years, with 2 large case series reporting efficacy with few side effects in the majority of patients. However, long-acting hypnotics in the elderly or those with cognitive impairment can be associated with adverse events especially unacceptable daytime sedation, confusion, and exacerbation of existing sleep apnea.

METHODS: We reviewed 39 patients with confirmed RBD who were treated within our regional sleep center, assessing both efficacy and side effects of drug therapies.

RESULTS: Adverse effects were reported by 58% of the patients using clonazepam, with 50% either discontinuing the drug or reducing the dose. This prompted us review the side effects of clonazepam in detail and to look for alternative therapies. We report several novel and effective therapies, in particular zopiclone, ina series of patients under long-term follow-up for RBD.

CONCLUSIONS: There are alternatives to clonazepam therapy for RBD which can be as effective and may be better tolerated.

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia with clinical symptoms that include punching, kicking, yelling and leaping out of bed in sleep. Polysomnographic (PSG) finding showed REM sleep without muscle atonia. Clonazepam is generally used for treating RBD symptoms but melatonin was reported to be effective so we reconfirmed the effect of melatonin on RBD patients in the present study. We used melatonin (3-9 mg/day) which could ameliorate problem sleep behaviors remarkably, as well as %tonic activity in PSG variables. In the present study, melatonin was reconfirmed to be effective in RBD symptoms, especially for patients with low melatonin secretion, while its mechanism was not clearly known in the present study.

OBJECTIVE: REM sleep behavior disorder (RBD) is usually characterized by potentially injurious dream enactment behaviors (DEB). RBD treatment aims to reduce DEBs and prevent injury, but outcomes require further elucidation. We surveyed RBD patients to describe longitudinal treatment outcomes with melatonin and clonazepam.

METHODS: We surveyed and reviewed records of consecutive RBD patients seen at Mayo Clinic between 2008-2010 to describe RBD-related injury frequency-severity as well as RBD visual analog scale (VAS) ratings, medication dosage, and side effects. Statistical analyses were performed with appropriate non-parametric matched pairs tests before and after treatment, and with comparative group analyses for continuous and categorical variables between treatment groups. The primary outcome variables were RBD VAS ratings and injury frequency.

RESULTS: Forty-five (84.9%) of 53 respondent surveys were analyzed. Mean age was 65.8 years and 35 (77.8%) patients were men. Neurodegenerative disorders were seen in 24 (53%) patients and 25 (56%) received antidepressants. Twenty-five patients received melatonin, 18 received clonazepam, and two received both as initial treatment. Before treatment, 27 patients (60%) reported an RBD associated injury. Median dosages were melatonin 6 mg and clonazepam 0.5 mg. RBD VAS ratings were significantly improved following both treatments (p(m) = 0.0001, p(c) = 0.0005). Melatonin-treated patients reported significantly reduced injuries (p(m) = 0.001, p(c) = 0.06) and fewer adverse effects (p = 0.07). Mean durations of treatment were no different between groups (for clonazepam 53.9±29.5 months, and for melatonin 27.4±24 months, p = 0.13) and there were no differences in treatment retention, with 28% of melatonin and 22% of clonazepam-treated patients discontinuing treatment (p = 0.43).

CONCLUSIONS: Melatonin and clonazepam were each reported to reduce RBD behaviors and injuries and appeared comparably effective in our naturalistic practice experience. Melatonin-treated patients reported less frequent adverse effects than those treated with clonazepam. More effective treatments that would eliminate injury potential and evidence-based treatment outcomes from prospective clinical trials for RBD are needed.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia associated with dream enactment often involving violent or potentially injurious behaviors during REM sleep that is strongly associated with synucleinopathy neurodegeneration. Clonazepam has long been suggested as 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 behavioral outcomes and decrease in muscle tonicity during REM sleep. Melatonin also has a favorable safety and tolerability profile over clonazepam with limited potential for drug-drug interactions, an important consideration especially in elderly individuals with RBD receiving polypharmacy. Prospective clinical trials are necessary to establish the evidence basis for melatonin and clonazepam as RBD therapies.