In January 2004, the wake-promoting agent,
modafinil, was approved in the US for the treatment of excessive
sleepiness (ES) associated with obstructive sleep apnoea/hypopnoea syndrome (
OSAHS) and
shift-work sleep disorder (SWSD), representing an expansion of its labelling from the initial indication for ES associated with
narcolepsy. A total of five randomised, placebo-controlled studies in these three disorders showed statistically significant benefits on various objective measures and subjective estimates of ES, including the Multiple Sleep Latency Test, Maintenance of Wakefulness Test, Epworth
Sleepiness Scale and Karolinska
Sleepiness Scale. Significant improvement was also seen in overall clinical condition (on the Clinical Global Impression of Change) and measures of sustained attention and reaction time (on the Psychomotor Vigilance Task). The clinical efficacy of
modafinil, combined with improved safety over
CNS stimulants, has made it the most prescribed medication for the treatment of ES associated with
narcolepsy.
Modafinil is the only medication approved for ES associated with
OSAHS and SWSD (for
OSAHS, it is indicated as an adjunct to standard treatments for the under-lying obstruction). Unlike many other medications used for ES,
modafinil is not known to be abused. The most common adverse event reported in clinical studies was
headaches; most were transient and mild-to-moderate in severity.
Modafinil also has the potential for interactions with other drugs metabolised via
cytochrome P450 enzyme pathways. Potential obstacles to the use of
modafinil include an under-recognition of ES and its consequences. Increased education, both of the public and the medical community, should improve the recognition and
therapy of ES.