No snooze button on treating sleep disorders

Pharmacists can help recognize, resolve common sleep problems that can lead to health problems

Missing a few winks of sleep may seem just a nuisance, but it’s really something patients should be worried about. It’s also a problem that pharmacists can help recognize and resolve.

“Sleep in general has been ignored in the past,” said Rachel Salas, MD, Assistant Professor of Neurology and Assistant Director of the Sleep Disorders Center at the Johns Hopkins School of Medicine in Baltimore. “Studies have shown that more educated providers tend to ask their patients about sleep problems and address their issues related to sleep patterns and habits, [thereby] treating the patient’s whole well-being just like [the recommendations for] nutrition and exercise.”

Many of the advances of modern life contribute to the different sleep problems clinicians find in an estimated 30% to 40% of Americans. Air travel, shift work, smartphones buzzing and vibrating in the night, television and the internet—all contribute to insomnia, hypersomnia (sleeping during the day), parasomnia (disruptive sleep), circadian rhythm disturbances, narcolepsy, or sleep apnea. One-half of patients have chronic sleep disturbance.

For people who sleep for far less than 8 hours each night or who have jobs or lifestyles that require them to sleep during the day, physiologic or psychological problems may ensue eventually in the form of fatigue, headache, irritability, inattentiveness, or narcolepsy. More serious health problems can also develop, including hypertension and other cardiovascular disorders.

Scope of the problem

The most prevalent sleep disorder in the United States is insomnia. As currently defined, insomnia affects approximately 10% to 15% of the population. “This ratio may increase because of the changes in the definition of insomnia” in the recently published 5th edition of the Diagnostic and Statistical Manual of Mental Disorders, Salas warned.

In the pediatric population, the diagnosis of sleep apnea is rising due to an increased incidence of obesity among children, while teenagers exhibit a higher incidence of circadian rhythm disturbances than younger children because of the increased time they spend on electronic devices.

Salas is one of a handful of physicians at Johns Hopkins involved in treating patients with sleep disorders and working to discover more clues to the causes and cures for these disorders. She sees about 1,200 patients with sleep disorders in the clinic each year, mainly for insomnia, sleep apnea, circadian rhythm disturbances, and narcolepsy.

Effects of sleep deprivation

Adverse events associated with insomnia are many—motor-vehicle accidents, depression, abuse of alcohol and other sedatives, decreased cognitive function and health-related quality of life, and increased risk of headache, migraine, and, in patients with acute stroke, suicidality.

Decreased sleep duration has also been linked to increased risk for hypertension. Getting fewer than 5 hours per night is associated with a doubling of risk of hypertension among adults.

A study by Indra Narang, MB, BCh, MD, and colleagues published in the Canadian Medical Association Journal last November revealed that sleep disturbances in healthy adolescents are associated with increased cardiovascular risk factors. A Danish study by Tina Kold Jensen, PhD, and colleagues published in April in the American Journal of Epidemiology found a negative association between sleep disturbances and semen quality in approximately 1,000 healthy young men.

The most alarming evidence comes from a population-based study by Yong Liu, MD, and colleagues published in BMC Public Health in January. The researchers found that insufficient sleep was positively correlated with coronary heart disease, obesity, asthma, diabetes mellitus, stroke, hypertension, and arthritis in more than 375,000 U.S. adults.

Identifying the problems

Some causes of sleep disturbance are self-induced: poor sleep habits or sleep environments, psychological factors (e.g., depression, anxiety, post-traumatic stress disorder, personality disorders), physical disorders (e.g., sleep apnea, seizures, gastroesophageal reflux, chronic pain), and pharmacotherapy (e.g., antihypertensive agents, thyroid hormone, anticonvulsant drugs, corticosteroids, antidepressants). Genetics can also be involved. A few genes have already been identified to have a role in sleep apnea, circadian rhythm disturbance, and narcolepsy.

Making an accurate diagnosis is difficult because sleep-related symptoms may overlap with those produced by patients’ other medical problems. It winds up being a “chicken-or-egg” situation. For example, sleep apnea in children typically affects their attention and behavior. Once the sleep problem is correctly identified and treated, the behavioral problems tend to disappear. The signs and symptoms of restless legs syndrome (RLS) can also affect patients’ sleep. When symptoms are managed, sleep will improve.

Sleeping better

Although there are a few pharmacological options that may provide some relief, none deliver the goods without a price. Until a more promising solution can be discovered to better manage sleep problems in this country, Salas believes that health professionals should help patients identify their aberrant sleep patterns and recognize the importance of sleep in their lives.

A key to success in treating sleep disorders is the patient’s willingness to change behaviors that may trigger the problems. Just as with recommendations for exercise and diet in management of cardiovascular health, patients have trouble changing their lifestyles to accommodate better sleep hygiene.

Cognitive behavioral therapy (CBT) is comparable or more beneficial than pharmacological treatment for sleep disorders, especially insomnia, Salas explained. “One of the biggest frustrations with nonpharmacological therapies so far is that CBT takes about 8 to 10 sessions to truly work, but insurance does not cover those sessions provided by psychologists or psychotherapists,” Salas said. To avoid the out-of-pocket cost for treatment, patients may opt to choose pharmacological options.

None of the available agents is ideal, however, including the frequently prescribed zolpidem. FDA has recently warned of reduced mental alertness the day after zolpidem administration and of patients not remembering negative or highly arousing nocturnal activities while on the drug. Short- or immediate-acting benzodiazepines are typically recommended for a short-term treatment of insomnia, but there is a high risk for tolerance and dependence with using this class of medication. Patients are given those therapies for a longer duration than recommended.

“Tolerance is always an issue, especially with medications for insomnia and narcolepsy, or idiopathic hypersomnia,” Salas warned. Opioids are a treatment option for sleep problems with RLS but have similar problems of tolerance and dependence, in addition to constipation.

Most OTC medications for insomnia contain antihistamines such as diphenhydramine and doxylamine. These agents are not recommended for long-term management of insomnia because of adverse effects such as residual daytime sedation, cognitive impairment, and delirium.

An interesting new orphan drug, tasimelteon, is being investigated for its effect on circadian-rhythm sleep disorder that frequently affects the blind. Phase III trials have shown that the drug can reset the circadian clock and thereby improve the overall quality of nighttime sleep and reduce daytime sleepiness among these patients. The drug, not yet approved by FDA, could someday prove useful for treating transient disturbances such as those caused by jet lag and night-shift work.

Into the future

As one of a few research areas for sleep disorders, Salas and her colleagues at Johns Hopkins School of Medicine are investigating the role of glutamate in hyperarousal using transcranial magnetic stimulation. This could increase understanding of the excitability of patients with RLS and ultimately lead to identification of new nonpharmacologic (noninvasive cortical stimulation) or pharmacologic (glutamine modulators) therapies. Her team is also investigating the physiology of patients with chronic migraine in an effort to understand the relationship between sleep problems and the threshold for headache.

Pharmacists often hear patients joke, “Sleep is overrated” or “Why would I want to spend a third of my life sleeping?” Increasingly, medical research is showing how important sleep is in maintaining health and optimizing the quality of the other two-thirds of life.

Through a combination of health lifestyle choices by patients, nonpharmacologic interventions, and medications used properly, pharmacists can help patients get the winks they need.