Istradefylline is recommended for morning use: a report of 4 cases.

We herein describe four cases of patients with Parkinson's disease who were treated with istradefylline (ISD) in the evening and had severe daytime sleepiness. The time to onset of sleepiness varied between 2 weeks to 3 months. All patients recovered after changing the timing of the ISD dosage from evening to morning. ISD is an A2A receptor antagonist with a caffeine-like arousal effect that may worsen the quality of sleep and thus increase daytime sleepiness. This report provides the first evidence of daytime sleepiness induced by evening ISD treatment. We propose that ISD should therefore only be used in the morning, particularly if taken by professional drivers.