Table 7.

Drugs to treat disorders of sleep and wakefulness in PD

Intervention
Drug class/intervention strategy	Drug/intervention	Efficacy	Safety	Practice implications
Insomnia
Levodopa	Controlled‐release formulation of levodopa/carbidopa	Insufficient evidence	Acceptable risk without specialized monitoring	Investigational
Dopamine agonists	Pergolide	Insufficient evidence	Acceptable risk with specialized monitoring	Not useful
	Piribedil	Insufficient evidence	Acceptable risk without specialized monitoring	Investigational
	Rotigotine	Likely efficacious	Acceptable risk without specialized monitoring	Possibly useful
Hypnotics	Eszopiclone	Insufficient evidence	Acceptable risk without specialized monitoring1	Possibly useful a
Melatonin	3‐5 mg	Insufficient evidence	Acceptable risk without specialized monitoring	Possibly useful b
	50 mg	Insufficient evidence	Insufficient evidence	Investigational
Nonpharmacological interventions	Continuous positive airway pressure c	Likely efficacious	Acceptable risk without specialized monitoring	Possibly useful
Excessive daytime somnolence and sudden onset of sleep
Psychoactive drugs	Modafinil	Insufficient evidence	Insufficient evidenced	Possibly useful e
	Caffeine	Insufficient evidence	Acceptable risk without specialized monitoring	Investigational
Nonpharmacological interventions	Continuous positive airway pressure c	Likely efficacious	Acceptable risk without specialized monitoring	Possibly useful

^aAlthough there is insufficient evidence for eszopiclone to be rated for the treatment of insomnia in PD, it can improve global and sleep outcomes for insomnia disorder, and it can be associated with associated with infrequent but serious harms such as fractures and major injury.179 Therefore, the practice implication is suggested to be possibly useful.

^bAlthough there is insufficient evidence for melatonin to be rated for the treatment of insomnia in PD, it provided significant benefits on measures of insomnia compared to placebo in patients with PD and insomnia. Moreover, melatonin has not only been approved in the European Union (EU) for patients aged 55 or older suffering from primary insomnia but also has been available over the counter in the United States since the mid‐1990s. Therefore, the practice implication is “possibly useful.”

^cRecommendations apply for PD patients with obstructive sleep apnea.

^dRare cases of serious or life‐threatening rash, including Stevens‐Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms have been reported in adults and children in worldwide postmarketing experience. Estimates of the incidence rate for these serious skin reactions in the general population range between 1 to 2 cases per million‐person years. Psychiatric adverse events have been reported in patients treated with modafinil with many, but not all, patients having had a prior psychiatric history; postmarketing adverse events associated with the use of modafinil have included mania, delusions, hallucinations, suicidal ideation, and aggression, some resulting in hospitalization.2

^eModafinil provided significant benefits on measures of excessive daytime somnolence when compared with placebo in patients with PD and excessive daytime somnolence2 and a recent meta‐analysis of 3 trials evaluating modafinil, which were also included in the previous review,2 showed a significant reduction in sleepiness, as assessed by the Epworth Sleepiness Scale.94