In the absence of sleep deprivation (either because of behavioral or medical 
causes) or pharmacologically induced sleepiness, hypersomnia is a manifestation 
of one of the central disorders of hypersomnolence, such as narcolepsy types 1 
and 2, idiopathic hypersomnia, and recurrent hypersomnias such as Kleine-Levin 
syndrome. Narcolepsy and most primary hypersomnias are chronic conditions, thus, 
before committing an individual to chronic, possibly, life-long treatments, an 
accurate diagnosis is important. The key to effective management of hypersomnia, 
thus, lies in a thorough history, detailed physical examination, and appropriate 
diagnostic tests. Secondary causes of hypersomnia are expected to resolve once 
these disorders are treated. The treatment of central hypersomnias, on the other 
hand, is guided by a level of diagnostic certainty as to the etiology of the 
hypersomnia. Narcolepsy, for example, has well defined pathophysiologic and 
diagnostic criteria, including low levels of hypocretin in cerebrospinal fluid 
(CSF) and specific findings on a polysomnography/multiple sleep latency test 
(PSG/MSLT). For these patients, life-long therapy is the norm and involves 
initiating treatment usually with modafinil, armodafinil, or sodium oxybate, 
with methylphenidate, amphetamine-like stimulants, atomoxetine, or 
antidepressants used as second-line therapy. Pharmacologic therapy is usually 
done in concert with behavioral modifications such as scheduled napping for the 
best response. On the other hand, the etiology and pathophysiology of 
non-hypocretin-related hypersomnias (eg, idiopathic hypersomnia, Kleine-Levine 
syndrome) are unknown. For these reasons, treatment of these disorders is more 
challenging and less well defined. A trial of modafinil or armodafinil may be 
considered as first line therapy along with behavioral modifications. 
Methylphenidate, amphetamine-based stimulants, and even clarithromycin have also 
been used. There is no effective cure for hypersomnia, and the current therapy 
is purely symptomatic. Thus, initial patient education, addressing treatment 
expectations, as well as continued regular follow-up to monitor treatment 
response are vital to effective management of hypersomnia. The focus of this 
article is limited to a discussion of treatment of central disorders of 
hypersomnolence.