Unraveling the Nuances of Excessive Daytime Sleepiness, Narcolepsy, OSA

A recent review examined the challenges of treating excessive daytime sleepiness (EDS) due to obstructive sleep apnea (OSA) and narcolepsy.

EDS is defined as unintentional sleepiness or inability to maintain wakefulness, impairing functional ability, but because of the subjectivity associated with self-reported EDS, prevalence in the general population is difficult to estimate.

The authors said that a recent population-based study showed that 33% of participants self-reported EDS at baseline; 28% of those without EDS at baseline developed EDS during the 5-year study period. Younger age and depression were independent predictors of incident EDS, and the degree of EDS fluctuated over time.

EDS, if not caused by insufficient sleep, could stem from medical or sleep disorders or may be an adverse effect of medications. Disorders linked to EDS include OSA, alveolar hypoventilation, restless leg syndrome, periodic limb movement disorder, circadian rhythm disorder, narcolepsy, idiopathic hypersomnia, and Kleine-Levin syndrome.

Narcolepsy and OSA are diagnosed through polysomnography and multiple sleep latency testing, but finding the primary cause of EDS can be challenging and may involve multiple factors.

Untreated OSA can show polysomnographic findings that are similar to narcolepsy, but the effects of sleep deprivation and certain medications can affect the polysomnographic results, leading to misdiagnosis.

In addition, narcolepsy and OSA can occur as comorbid disorders. If EDS persists despite adequate treatment for either disorder, a comorbid diagnosis should be sought.

The prevalence of OSA is common, estimated in the North American general adult population to range from 9% to 38%. The prevalence of narcolepsy is much lower, estimated at 0.07% to 0.20%.

The pathophysiology of type 1 narcolepsy (NT1) is characterized by destruction of hypocretin/orexin-producing neurons and reduced levels of hypocretin/orexin in the cerebrospinal fluid, possibly due to an autoimmune mechanism, although no direct evidence has been found.

The arguments that support this theory are linked to a strong association between NT1 and the HLA-DQB1*0602 allele and polymorphisms.

The origins of type 2 narcolepsy (NT2) is unknown, although it is thought to stem from less extensive damage to hypocretin/orexin. Most patients with NT2 have normal hypocretin levels, but NT2 seems to be a heterogeneous disorder.

Repeated upper airway obstruction leading to arousals and sleep fragmentation is thought to result in EDS in patients with OSA.

Daily occurrence of EDS for at least 3 months is required in order to be diagnosed with narcolepsy, and a diagnosis requires objective testing.

Management is generally achieved through nonpharmacological and pharmacological therapies. Patients should be encouraged to maintain an adequate and consistent sleep schedule; medications that cause insomnia or sleepiness should be avoided. In addition, weight loss should be encouraged if patients are overweight or obese, especially if the patient has comorbid OSA.

While there is no cure for narcolepsy, symptomatic relief is achieved through various medications. Wake-promoting drugs such as modafinil or sodium oxybate are a main therapy for EDS; in addition, stimulant medications may be used. Stimulant therapy approved specifically for narcolepsy includes solriamfetol, armodafinil, and modafinil.

Continuous positive airway pressure (CPAP) is the gold standard for treating OSA; however, its efficacy depends significantly on patient compliance and hours of usage. Although sleepiness improves with CPAP therapy in patients with comorbid narcolepsy and OSA, narcolepsy-related EDS is not expected to respond to CPAP.

One challenge clinicians face is prescribing stimulants to elderly populations. Studies of stimulant medications and cardiovascular risk did not include patients older than 65 years, the authors wrote, so the effect of preexisting cardiac conditions in the elderly population is unclear. In addition, these studies are confounded by healthy user bias. The authors said additional research on use of stimulants in the elderly, especially in patients with OSA on CPAP with residual daytime sleepiness, is needed.

In the pediatric population, EDS is required for the diagnosis of narcolepsy. In younger children, EDS may present as behavior problems or concentration difficulties.

Reference

Sahni AS, Carlucci M, Malik M, Prasad B. Management of excessive sleepiness in patients with narcolepsy and OSA: current challenges and future prospects [published online October 23, 2019]. Nat Sci Sleep. doi: 10.2147/NSS.S218402.