Jonathan R. L. Schwartz

Effects of modafinil on wakefulness and executive function in patients with narcolepsy experiencing late-day sleepiness.

Objectives:A modafinil daily dosing strategy promotes wakefulness in narcolepsy patients experiencing excessive daytime sleepiness; however, some patients may continue to experience late-day sleepiness. Excessive sleepiness in narcolepsy is associated with cognitive impairment. Modafinil has improved executive function in other models of excessive sleepiness. This study evaluated the effects of once-daily vs. split doses of modafinil on wakefulness and of combined doses on executive function in narcolepsy patients experiencing late-day sleepiness despite satisfactory modafinil treatment earlier in the day. Methods:After a 2-week washout, 24 patients received 3 weeks of double-blind treatment with modafinil 400-mg once daily (7 AM) plus placebo (noon) or modafinil 600-mg split dose (400 mg, 7 AM; 200 mg, noon). Assessments included a Maintenance of Wakefulness Test (MWT) for individual regimens and the Wisconsin Card Sort Test (WCST) for treatments combined. Results:Modafinil 600-mg split dose was significantly more effective than modafinil 400-mg once daily in improving late-day MWT scores (5 PM–7 PM; P < 0.05). Significant mean (± SEM) reductions from baseline of 8.2 ± 2.7 in the total number of errors and 5.9 ± 1.9 in total percent of errors (P < 0.05, both) were demonstrated for modafinil on the WCST. Modafinil was well tolerated; adverse events included headache (n = 1), emotional lability (n = 1), bronchitis (n = 1), and accidental injury (n = 2), with no reports of insomnia. Conclusions:For patients with residual late-day sleepiness associated with narcolepsy, an additional 200-mg dose of modafinil taken at midday was effective in sustaining wakefulness throughout the entire waking day. Treatment with modafinil also significantly improved executive function.

Recognition and management of excessive sleepiness in the primary care setting

BACKGROUND Excessive sleepiness often goes unrecognized in the primary care setting despite its high prevalence and deleterious effects on both individual and public safety. Patients with neurologic and psychiatric illnesses, as well as those with acute and chronic medical conditions, plus those with sleep disorders, often have symptoms of excessive sleepiness, tiredness, and fatigue. Recognition and prompt treatment of these symptoms are important, even though their etiology may not be immediately understood. This review focuses on the underlying causes, consequences, identification, and treatment of excessive sleepiness. DATA SOURCES A search of the literature to 2007 was performed using the PubMed search engine. English-language articles were identified using the following search terms: excessive sleepiness, fatigue, circadian rhythm, obstructive sleep apnea, shift work disorder, narcolepsy, drowsy driving, and wakefulness. Additional references were identified through bibliography reviews of relevant articles. DATA SYNTHESIS Current assessments of the prevalence, consequences, and etiologies of excessive sleepiness, with leading treatment strategies, were extracted, reviewed, and summarized to meet the objectives of this article. CONCLUSIONS Excessive sleepiness is associated with a wide range of medical, neurologic, and psychiatric disorders frequently seen in primary care practice. Excessive sleepiness is a serious, debilitating, potentially life-threatening condition, yet also treatable, and it is important to initiate appropriate intervention as early as possible. Physicians should place increasing emphasis on the substantial benefits that accompany improvements in wakefulness.

Time to response with sodium oxybate for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy.

STUDY OBJECTIVES This post hoc analysis evaluated the time to response that can be expected with sodium oxybate (SXB) for treatment of excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy. METHODS Data were from a 4-week, double-blind, randomized, placebo-controlled trial (GHB-2; N = 136) of oral SXB 3 g, 6 g, and 9 g nightly, and its 12-month open-label extension (GHB-3). Two response definitions were utilized: ≥ 20% improvement in Epworth Sleepiness Scale (ESS) score (EDS responders), and ≥ 50% reduction in weekly cataplexy attacks (cataplexy responders). These thresholds were previously determined to be clinically relevant based on analysis of the relationship of Clinical Global Impression of Change with ESS and number of cataplexy attacks. Kaplan-Meier curves and median times to first response, based on above criteria, and to maximum response were estimated. RESULTS Among 86 patients randomized to SXB in GHB-2 and continued into GHB-3, 77.6% and 90.7% were EDS and cataplexy responders, respectively. The median (95% CI) times to first response were 37 (31-50) days for EDS and 25 (17-29) days for cataplexy, and median times to maximum response were 106 (85-164) days for EDS and 213 (94-279) days for cataplexy. GHB-3 results among 31 patients initially randomized to placebo were consistent with those treated with SXB throughout, but with longer times to maximum response. CONCLUSIONS Response onset, assessed as clinically meaningful improvements in EDS and cataplexy, was observed in most patients within 2 months; a longer period is needed to achieve maximum response. Clinicians should recognize that time to initial and maximum response may take weeks to months.

Armodafinil in the treatment of sleep/wake disorders

Excessive sleepiness (ES) is a major but underestimated public health concern associated with significant impairments in alertness/wakefulness and significant morbidity. The term ES has been used in the sleep medicine literature for years, but due to its nonspecific symptoms (ie tiredness or fatigue), it frequently goes unrecognized or is misdiagnosed in primary care. In some cases ES arises due to poor sleep habits or self-imposed sleep deprivation; however, ES is also a key component of a number of sleep/wake disorders and multiple medical and psychiatric disorders. Identification and treatment of ES is critical to improve the quality of life and well-being of patients and for the safety of the wider community. The inability of patients to recognize the nature, extent, and symptomatic profile of sleep/wake disorders requires vigilance on the part of healthcare professionals. Interventions to address ES and its associated impairments, treatment of the underlying sleep/wake disorder, and follow-up are a priority given the potential for serious consequences if left untreated. Wakefulness-promoting agents are available that treat ES associated with sleep/wake disorders. This review examines current approaches for managing this debilitating and potentially life-threatening condition, focusing on the place of armodafinil as a wakefulness-promoting agent.