Initiating treatment with modafinil for control of excessive daytime sleepiness in patients switching from methylphenidate: an open-label safety study assessing three strategies.

RATIONALE

Modafinil is a first-line wake-promoting medication and a useful therapeutic alternative to psychostimulant medications for excessive daytime sleepiness.

OBJECTIVE

This 5-week, randomized, open-label study evaluated three strategies for switching patients from methylphenidate, a commonly used psychostimulant, to modafinil.

METHODS

Patients ( n=40) with excessive daytime sleepiness related to narcolepsy, who had received previous treatment with methylphenidate, were switched from methylphenidate to modafinil (200 mg/day followed by 400 mg/day) without a washout period between treatments, with a 2-day washout period between treatments, or by using a taper-down/titrate-up protocol. Adverse events were recorded throughout the study, and Epworth Sleepiness Scale scores were determined at the end of the study.

RESULTS

The majority of patients (95%) were successfully switched to modafinil. At the study end point, mean Epworth Sleepiness Scale scores were <12 for each treatment group. All three switching strategies were well tolerated, with adverse events mild or moderate in nature. Adverse events most frequently reported during modafinil treatment were among those seen previously in large-scale, placebo-controlled studies. There were no meaningful differences among the treatment groups in the frequency or severity of adverse events or in their relationship to modafinil treatment. Only one patient discontinued modafinil treatment because of a treatment-related adverse event (i.e. moderate headache); another patient discontinued due to insufficient efficacy.

CONCLUSIONS

Switching from methylphenidate to modafinil was well tolerated with or without a washout period or when the methylphenidate dose is gradually tapered during initiation of modafinil therapy. Daytime wakefulness was maintained in patients who have switched from methylphenidate to modafinil. These data suggest that patients with narcolepsy may be switched from methylphenidate to modafinil with few complications and inconveniences.