Excessive daytime sleepiness in patients with obstructive sleep apnea remains a common and often debilitating problem, despite optimal use of continuous positive airway pressure treatment, according to Dr. Janine R.E. Vintch.

The two drugs most beneficial as adjunctive therapy for these patients are modafinil (Provigil) and armodafinil (Nuvigil). Both are approved by the Food and Drug Administration for the management of persistent sleepiness and fatigue in patients with sleep apnea who are compliant with their CPAP therapy, Dr. Vintch said at the annual meeting of the American College of Physicians.

In one study, 22% of patients with obstructive sleep apnea using effective CPAP – that is, CPAP for more than 6 hours per night – still had impaired daytime functioning because of excessive daytime sleepiness documented on objective tests, including the Multiple Sleep Latency Test. This persistent daytime somnolence can manifest as cognitive impairment, diminished vigilance, and increased rates of workplace and motor vehicle accidents.

Before turning to drug therapy, however, it’s crucial to rule out other causes of persistent daytime sleepiness. The No. 1 reason is the patient is less adherent to CPAP than claimed. Other possible explanations include an improperly fitting CPAP mask, poor sleep hygiene, depression, and additional sleep disorders, such as restless legs, said Dr. Vintch of the University of California, Los Angeles.

Modafinil is a novel wake-promoting agent approved in 2004 for the management of residual sleepiness in CPAP-compliant patients. In 2006 the American Academy of Sleep Medicine published a practice parameter on the medical therapy of obstructive sleep apnea that endorsed modafinil as a standard recommendation for this indication (Sleep 2006;29:1031-5). It has a low abuse potential. Its mechanism of action remains controversial. Modafinil is cleared by both the liver and kidneys, so lower doses are appropriate in patients with either hepatic or renal dysfunction.

Modafinil has several important interactions with other drugs. These medications include propranolol, diltiazem, phenytoin, carbamazepine, and diazepam; the levels of all these drugs are increased in patients on modafinil. Also, women of childbearing age who are on ethinyl estradiol need to be given an alternative method of contraception, she said.

The most common side effects attributed to modafinil are headache, nausea, and nervousness. The headaches typically disappear after the first 3 days of treatment.

Armodafinil is the R-isomer of modafinil. Its 10- to 15-hour half-life is slightly longer than modafinil’s. It has the same side effects as modafinil.

Long-term studies of both drugs have documented good safety and tolerability along with improved objective and subjective measures of wakefulness and cognition.

Dr. Vintch reported having no relevant financial relationships.