Rasagiline improves sleep disorders in Parkinson's disease

Objective: To evaluate the effects of levodopa–rasagiline combination therapy versus levodopa therapy alone in the treatment of sleep disorders in Parkinson's disease (PD). Background: Sleep disorders including sleep fragmentation, REM sleep behaviour, and complex paroxysmal nocturnal motor behavioral disorders are common in PD, and they may precede by decades motor symptoms. Classical antiparkinsonian drugs have shown limited effectiveness in controlling these symptoms. Rasagiline is a monoamine oxidase inhibitor (MAO-I) that ameliorates the symptoms of PD by inhibiting striatal dopamine metabolism. MAO-I are also able to increase melatonin levels in the pineal gland, and may therefore contribute to modulate wakefulness/sleep patterns and circadian rhythms. Methods: We performed a 12-weeks study in 38 patients (mean age:63-64 years; mean disease duration:1.92-2.15 years; Schwab and England activities of daily living scores: approximately 90%). Patients were randomly assigned to: levodopa (200-300 mg daily) (group A) or levodopa–rasagiline (200-300 mg+1 mg) (group B). Sleep parameters were recorded by means of PD Sleep Scale (PDSS) and sleep diaries. Results: The clinical characteristics at baseline of patients are summarized in Fig.1. Almost all patients reported difficulties in initiating and maintaining sleep. Mean total PDSS score was 104.7±21.5 in group A and 103.9±21.8 in group B, correlating with Hoehn&Yahr score (p=0.004).After 12 weeks, patients in group B showed a marked improvement on several aspects of sleep dysfunction, compared to patients in group A (p=0.019). In particular, patients in group B reported a lower sleep latency (Fig.2A), fewer night awakenings (Fig.2B) and longer total sleep duration (Fig.2C). When comparing scores for each item in the PDSS at 12 weeks, the most notable improvements in the treatment of sleep dysfunction referred to items 8 (nocturia), 10 (limb paresthesias), 11 (cramps), 14 (non restorative sleep), 15 (daytime sleepiness): patients in group B reported a lower score, indicating a diminished severity of those symptoms (Fig.2D). Conclusions: Our monocentric study, though small-sized, demonstrates the effectiveness of levodopa–rasagiline combination therapy as a treatment for sleep dysfunction in PD, which will hopefully be confirmed by larger studies.