Pharmacologic therapy for insomnia is common and costly. It is estimated that 9 million American adults use prescription sleep aids and that more than 40 million prescriptions per year are written for these agents. Sales of zolpidem, the generic form of Ambien®, exceeded $2.8 billion dollars in 2011, while eszopiclone (Lunesta®) generated $912 million in sales. Prescription sleep aids remain one of the most heavily marketed direct-to-consumer medications.
Sleeping pills can work, but…
While sleeping pills can be highly effective for short-term use during stressful times or long-distance travel, long-term use of these agents is fraught with problems. Traditional sleep aids, such as barbiturates (phenobarbital or Luminal®), long-acting benzodiazepines (alprazolam or Xanax® and triazolam or Halcion®), opiate-based medications (laudanum) and potent hypnotics (chloral hydrate), have been largely displaced due to their high addiction potential and severe adverse side effects.
Newer benzodiazepine and non-benzodiazepine medications are extensively prescribed for insomnia, and their short durations of action may induce less risk of tolerance and abuse. Clonazepam (Klonapin®) and temazepam (Restoril®) are traditional benzodiazepines frequently prescribed for insomnia and do demonstrate improvement in the short term (less than one month). However, tolerance and dependency frequently develop, and long-term use can require prolonged tapering and result in rebound insomnia. Use of the lowest effective dose and alternating dosage schedules can diminish tolerance and potential for abuse, for example, taking the medication every other night or every third night.
Non-benzodiazepine Medications are Typically Safer
Newer non-benzodiazepine medications like zolpidem and eszopiclone have shown sustained positive effects on sleep latency, wake after sleep onset (WASO) and daytime symptoms without overt tolerance in patients treated, even when given nightly for less than six months. Behavioral side effects like parasomnias and amnestic events have been associated with zolpidem use, and psychological dependency on these newer agents is common with sustained use. Additionally, no evidence of sustained improvement of insomnia symptoms is seen once these agents are withdrawn.
Other Medications Used to Treat Insomnia
Over-the-counter antihistamines like diphenhydramine (Benadryl®) are frequently prescribed off-label for insomnia, but they have a hostile risk profile, especially in the elderly, that includes urinary retention, worsening of closed-angle glaucoma and unsteadiness of balance. Daytime “hangover” symptoms like fatigue and excessive sleepiness are also common. The same is true of antidepressants like trazodone (Desyrel®) and quetiapine (Seroquel®), which are commonly used to treat insomnia because of their ability to induce sleepiness. However, evidence of efficacy is lacking, and the side effect profiles for these drugs are complex.
Melatonin is a natural sleep-promoting substance made by the pineal gland and is instrumental in maintaining the normal sleep cycle in humans. The prescription drug ramelteon (Rozerem®) mimics the actions of melatonin on the body’s master clock, the suprachiasmatic nucleus (SCN) and induces sleep. Evidence suggests that patients using ramelteon may have lower risk of falling (no affect on balance) or confusion upon middle-of-the-night awakening, but its relatively low potency and high cost makes it a less desirable choice.
Suvorexant (Belsomra®) is the newest treatment option for insomnia. Suvorexant blocks the sites of action of the important wakefulness-promoting protein called orexin (hypocretin) to induce sleep. The U.S. Food and Drug Administration (FDA) approved it in August 2014 for use in adults with insomnia, although safety in children has not been established and it is contraindicated for use during pregnancy. The side effect profile of the medication submitted when suvorexant was undergoing FDA approval was relatively benign, although serious issues with amnesia, anxiety, hallucinations and parasomnias have been seen in post-marketing and may be an indication for discontinuation. This medication should also be avoided in patients with liver disease or those taking other medications (like digoxin), certain antibiotics or seizure medications (like phenytoin).