Treatment outcomes in REM sleep behavior disorder

Abstract

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.

FIGURE 1

Patient ratings of dream enactment behavior frequency and severity (visual analog scale, VAS) for melatonin and clonazepam, showing that both treatments comparably reduced RBD behaviors. The difference between pre-treatment and post-treatment RBD VAS ratings was statistically significant for both treatments (melatonin treated patients pre-treatment vs. post-treatment VAS scores, 6.68 vs. 4.22, p= 0.0001; clonazepam treated patients pre-treatment vs. post-treatment VAS scores, 6.53 vs. 4.15, p = 0.0005).

FIGURE 2

Percentage of RBD patients reporting comparatively worsened, neutral, or improved outcomes (mild, moderate, significant, or freedom from symptom) following treatment with melatonin or clonazepam. Both treatments showed overall subjective global improvements in RBD outcomes, with clonazepam trending toward a more significant proportion of patients achieving a moderate or greater level of improvement (clonazepam vs. melatonin, 78% vs. 48%, p=0.06). The frequency of reported complete suppression of RBD following treatment was similar (17% vs. 12%, p= 0.68).

FIGURE 3

Percentage of RBD patients reporting dream enactment behaviors, falls, and injury before and after treatment with melatonin or clonazepam. Statistically significant improvements were seen for melatonin in RBD DEB, falls, and injury. Trends toward similar improvements were seen with clonazepam treatment.

FIGURE 4

Percentage of RBD patients reporting injuries (either no injury, or mild, moderate, or marked injury) before and after treatment with melatonin or clonazepam. Melatonin treatment was associated with statistically significant reported reductions in injury severity, while clonazepam treatment demonstrated similar but non-statistically significant trends for severity of injury reduction.

FIGURE 5

Percentage of RBD patients reporting adverse effects (sleepiness, unsteadiness, trouble thinking, nausea, or sexual dysfunction) before and after treatment with melatonin or clonazepam. Adverse effects were more frequently reported following clonazepam than melatonin treatment, a group difference trending toward statistical significance (p=0.06).

FIGURE 6

Percentage of RBD patients reporting adverse effects by category for sleepiness, unsteadiness, trouble thinking, and dizziness, with either no report, or mild, moderate, or severe level of the adverse effect, during treatment with melatonin or clonazepam. Sleepiness, unsteadiness, dizziness, and trouble thinking were more frequently reported with clonazepam than melatonin treatment, but these differences did not achieve statistical significance.