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Combination Therapy Shown to Improve Sleep Disturbance in Patients With Parkinson Disease


Among patients with advanced Parkinson disease and motor fluctuations, a combination of levodopa/carbidopa/entacapone was shown to improve motor and sleep symptoms.

Among patients with advanced Parkinson disease (PD) and motor fluctuations, a combination therapy of levodopa/carbidopa/entacapone (LCE) was shown to improve motor and sleep symptoms, according to study findings published today in the Journal of Movement Disorders.

Sleep-related symptoms are among the most common nonmotor symptoms in PD, affecting more than 75% of patients. As researchers note, the clinical features of sleep disturbance in patients with PD (PwP) are highly diverse, including insomnia, excessive daytime sleepiness, rapid eye movement sleep behavior disorder, and restless leg syndrome.

When addressing sleep symptoms among PwP, a common pharmacological strategy is to administer an additional dopaminergic agent before going to bed. Researchers note that this is usually prescribed for PwP who experience motor fluctuations at night, anticipating that relieving nighttime motor symptoms could improve sleep quality.

“In addition, dopamine plays an essential role in regulating the sleep-wake cycle. Thus, the dopaminergic agent is intended to correct sleep-wake cycle disruptions caused by PD-related dopamine depletion,” the researchers explained.

They sought to investigate the effects of using a levodopa triple combination agent, LCE, at bedtime on sleep quality in PwP with motor fluctuations. The study recruited 128 PwP with motor fluctuations who were assessed for motor (United Parkinson’s Disease Rating Scale [UPDRS]), nonmotor (Korean version of the Nonmotor Symptom Scale), and sleep-specific symptoms (Parkinson’s Disease Sleep Scale [PDSS]; the Epworth Sleepiness Scale; Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire [RBDSQ]).

In the study, the researchers compared the baseline characteristics of PwP with sleep disturbance (PDSS score < 120) and those without sleep disturbance (PDSS score ≥ 120). The intervention group included 39 patients with sleep disturbance who took LCE at bedtime and completed 3-month follow-ups. Changes in the scores of motor, nonmotor, and sleep symptom scales were analyzed over the 3-month period.

The investigators noted that participating PwP with sleep disturbance were at more advanced disease stages and had more severe motor, nonmotor, and sleep symptoms compared with those without sleep disturbance. In examining the intervention group, those given LCE at bedtime exhibited improvements in motor (UPDRS part III; P = .007) and sleep (total PDSS; P < .001) symptoms.

Sleep features that benefitted from LCE included nocturnal motor components (PDSS item 2; P = .005), insomnia (PDSS item 3; P < .001), and rapid eye movement behavior disorder (PDSS item 6, P = .002; RBDSQ, P < .001).

“Sleep disturbance is associated with more severe motor and nonmotor symptoms, and the use of LCE at bedtime is a possible treatment option for patients with PD who are experiencing sleep disturbance,” the study authors wrote. “Further clinical trials with objective sleep parameters and various regimens of levodopa to treat sleep disturbance of PD should be conducted.”


Park KW, Jo S, Lee SH, et al. Therapeutic effect of levodopa/carbidopa/entacapone on sleep disturbance in patients with Parkinson disease. J Mov Discord. Published online September 9, 2020. doi:10.14802/jmd.20055

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