Age of Diagnosis and Comorbid PLMD Predict Poor Response of REM Behavior Disorder to Clonazepam

Abstract

Previous studies have shown the therapeutic effects of clonazepam for rapid eye movement sleep behavior disorder (RBD), but they had several limitations such as the lack of clear definition of treatment outcomes and little information about adjuvant therapy. The aims of this study were to evaluate the treatment outcomes with clonazepam and to explore possible determinants of treatment response. We performed a retrospective medical chart review of 171 patients with RBD. All the participants underwent overnight polysomnography and completed questionnaires. The positive treatment response was defined as the absence of disruptive behaviors causing sleep-related injuries during the last year of follow-up. Among the 171 patients presented with disruptive behaviors, 155 (90.6%) experienced positive treatment responses. Of the responders, 18 (11.6%) received adjunctive medication due to insufficient therapeutic effect of clonazepam monotherapy. After adjusted analysis, an earlier age of diagnosis (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.64–0.86, P < .001) and comorbid periodic limb movement during sleep (OR = 4.96, 95% CI = 1.05–23.33, P = .043) were related to poor treatment response. Clinicians should recognize the predictors of poor treatment response and consider combination therapy for better prevention of sleep-related injuries in those who show unsatisfactory responses to clonazepam monotherapy.

Current Treatment Options for REM Sleep Behaviour Disorder

“…Table 1 summarizes the studies describing the effect of clonazepam in patients with RBD [1,2,[17][18][19][20][21][22][23][24][25][26][27][28]. Surprisingly, despite clonazepam being considered a first-line therapy for RBD (and according to the experience of the authors of this review, it is a useful drug for treating this condition), its efficacy in the treatment of iRBD has apparently not been proven in randomized trials.…”

Polysomnographic features associated with clonazepam and melatonin treatment in isolated REM sleep behavior disorder: Time for new therapeutic approaches?

“…reported that iRBD patients who phenoconverted to a parkinsonian disorder had significantly much higher PLMS index at baseline than iRBD patients who remained iRBD at follow‐up. In addition, the presence of PLMS has also been correlated with an increase in the percentage of RSWA in REM sleep, suggesting a greater severity of the disorder in these patients 54 and that PLMS during sleep increase with age 55,56 and are associated with striatal neurodegeneration and dopamine deficiency 57 …”

“…However, in these patients the best response for reducing PLMS was observed, compared to the other groups; this is very interesting considering that, in 1996, Schenck et al 53 reported that iRBD patients who phenoconverted to a parkinsonian disorder had significantly much higher PLMS index at baseline than iRBD patients who remained iRBD at follow-up. In addition, the presence of PLMS has also been correlated with an increase in the percentage of RSWA in REM sleep, suggesting a greater severity of the disorder in these patients 54 and that PLMS during sleep increase with age 55,56 and are associated with striatal neurodegeneration and dopamine deficiency. 57 The fact that the association of CLO and MLT acts positively on PLMS is a proof that they may be due to a complex mechanism not known, which however could involve supra and subtentorial networks.…”

REM Sleep Behavior Disorder and Other REM Parasomnias

“…Several observational studies demonstrated its ability to suppress dream enactment behavior in isolated RBD and secondary RBD. 5,56 While its mechanism in improving RBD is unclear, it may work through enhanced GABA-ergic and glycinergic inhibition of spinal motor neurons. 57 Clonazepam may improve some phasic movements but does not appear to improve overall RWA, simple motor movements, or vocalizations, suggesting other mechanisms may be involved in major motor event suppression, such as through altering dream content.…”

“…Its use stemmed from its ability to control other types of movements during sleep and waking states. Several observational studies demonstrated its ability to suppress dream enactment behavior in isolated RBD and secondary RBD 5,56 . While its mechanism in improving RBD is unclear, it may work through enhanced GABA-ergic and glycinergic inhibition of spinal motor neurons 57 .…”