View the Expanded Table: Some Oral Drugs for Chronic Insomnia

Cognitive behavioral therapy for insomnia (CBT-I) is recommended for initial treatment of chronic insomnia. CBT-I includes stimulus control, sleep education and hygiene, sleep restriction, relaxation training, and cognitive therapy. When CBT-I alone is not effective, pharmacologic treatment should be added.

The FDA has approved daridorexant (Quviviq – Idorsia), an orexin receptor antagonist, for treatment of sleep-onset and/or sleep-maintenance insomnia in adults. Daridorexant is the third orexin receptor antagonist to be approved for this indication; suvorexant (Belsomra) and lemborexant (Dayvigo) were approved earlier.

The FDA has approved lemborexant (Dayvigo – Eisai), an orexin receptor antagonist, for treatment of sleep-onset and/or sleep-maintenance insomnia in adults. It is the second orexin receptor antagonist to be approved for this indication; suvorexant (Belsomra) was the first.

Patients who receive pretravel advice can reduce their risk for many travel-related conditions. Vaccines recommended for travelers are reviewed in a separate issue.

View the Expanded Table: Some Drugs for Altitude Illness, Jet Lag, and Motion Sickness

Cognitive behavioral therapy for insomnia (CBT-I) is recommended for initial treatment of chronic insomnia. Pharmacologic treatment should be used in addition to CBT-I when CBT-I alone is not effective.

View the Expanded Table: Some Oral Hypnotics for Insomnia

Pharmacological treatment of insomnia includes prescription drugs, non-prescription medications, and "natural" remedies. Behavioral approaches such as cognitive behavioral therapy, which are not discussed here, are also used. Pharmacologic treatment and behavioral therapy are often combined.

Patients planning to travel to other countries often ask for information about prevention of diarrhea, malaria, and other travel-related conditions. Vaccines recommended for travelers based on their destination, length of stay, and planned activities were reviewed in a previous issue.

The FDA has approved suvorexant (Belsomra – Merck), the first orexin receptor antagonist to become available in the US, for treatment of sleep-onset and/or sleep-maintenance insomnia.

The FDA has required the manufacturer of eszopiclone (Lunesta – Sunovion), a benzodiazepine receptor agonist approved for the treatment of insomnia, to lower the current recommended starting dose to 1 mg for both men and women because a new study found that an evening dose of 3 mg can impair driving skills, memory, and coordination for more than 11 hours.1 Eszopiclone’s half-life is longer than that of any other drug in its class, which includes zolpidem (Ambien, and generics) and zaleplon (Sonata, and generics).

All benzodiazepine receptor agonists may impair performance the next morning, including driving.2 Anterograde amnesia and complex sleep-related behaviors without conscious awareness may also occur. Hallucinations have been reported. Like the benzodiazepines, benzodiazepine receptor agonists are schedule IV controlled substances; withdrawal, dependence, and abuse can occur.

1. FDA Drug Safety Communication. FDA warns of next-day impairment with sleep aid Lunesta (eszopiclone) and lowers recommended dose. Available at www.fda.gov. Accessed May 29, 2014.

2. Drugs for insomnia. Treat Guidel Med Lett 2012; 10:57.

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On January 10, 2013, the FDA issued a news release to announce that it was requiring the manufacturers of the zolpidem-containing products Ambien, Ambien CR, Edluar and Zolpimist, which are all approved for treatment of insomnia, to lower the doses for women and to recommend in their labeling consideration of a lower dose for men. No change will be required in the dose of Intermezzo, a low-dose sublingual formulation of zolpidem for middle-of-the-night awakening, which is already recommended in a lower dose for women.

Pharmacological treatment of insomnia includes prescription drugs, non-prescription medications and "natural" remedies. Behavioral changes are often needed as well.

The FDA has approved a new low-dose sublingual tablet formulation of the benzodiazepine receptor agonist zolpidem tartrate (Intermezzo – Transcept/Purdue) for treatment of insomnia due to middle-of-the-night awakening. Ambien and other zolpidem formulations available in the US are labeled for use only at bedtime.

Zolpidem oral spray (Zolpimist – NovaDel/ECR), a new formulation of the oral hypnotic zolpidem tartrate (Ambien, and others), has been approved by the FDA for short-term treatment of insomnia characterized by difficulty falling asleep.

The FDA has approved a new low-dose formulation of the tricyclic antidepressant doxepin (Silenor – Somaxon) for treatment of insomnia associated with sleep maintenance. The manufacturer claims that this dose retains the hypnotic effect of doxepin, without typical tricyclic adverse effects. Doxepin is available generically in higher-strength capsules and in a liquid formulation.

Edluar (Meda), a new sublingual tablet formulation of the benzodiazepine receptor agonist zolpidem (Ambien, and others), has been approved by the FDA for treatment of insomnia.

Patients planning to travel to other countries often ask physicians for information about appropriate vaccines and prevention of diarrhea and malaria. Guidelines are also available from the Infectious Diseases Society of America (IDSA).

The majority of patients with insomnia do not have a predisposing psychiatric disease. Rather, untreated insomnia may be a risk factor for development of psychiatric problems such as depression or anxiety.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment could also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

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Many drugs are used to treat insomnia, but for some patients nonpharmacological treatments such as changing sleep habits, relaxation training and cognitive therapy may be more effective and durable than treatment with drugs. Hypnotic drugs are generally FDA-approved only for short-term use, but in practice they often are taken much longer.

Zolpidem (Ambien - Sanofi-Aventis), a nonbenzodiazepine benzodiazepine receptor agonist, is the most frequently prescribed hypnotic in the US. As its patent approaches expiration, its manufacturer has received FDA approval to market an extended-release formulation of the drug, Ambien CR. The pharmacological rationale for doing so is that short-acting hypnotics like zolpidem are more effective at inducing sleep than they are at maintaining it.

Ramelteon (Rozerem - Takeda), a melatonin receptor agonist, has been approved by the FDA for treatment of insomnia characterized by difficulty falling asleep. Unlike all other prescription hypnotics, which are classified as schedule IV drugs, ramelteon is not a controlled substance.

Eszopiclone (Lunesta - Sepracor), a benzodiazepine-like drug, has been approved by the FDA for oral treatment of insomnia. It is the S-isomer of zopiclone (Imovane, and others in Canada), which has been available in other countries for almost 20 years. Unlike similar drugs such as zolpidem (Ambien) or zaleplon (Sonata), Lunesta is not being restricted in its labeling to short-term use. Like other hypnotics, eszopiclone is a schedule IV drug.

Breaking drug tablets in half is a common practice. In some cases, a lower drug dose may be as effective as a higher one, with fewer adverse effects. Sometimes tablets are split to achieve an intermediate dose between marketed strengths. When 2 tablet sizes cost the same, as they often do, splitting the larger size saves money. Is this a reasonable practice?

Patients planning to travel to other countries often ask physicians for advice about immunizations and prevention of diarrhea and malaria. More detailed advice for travelers is available from the Centers for Disease Control (CDC) at 877-FYI-TRIP (877-394-8747) or www.cdc.gov/travel. Recommendations for the treatment of parasitic diseases are available in the public reading room of The Medical Letter's web site.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment may also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

Older patients are especially susceptible to drug-induced cognitive impairment. They are more likely to be taking multiple drugs, to have higher blood levels of those drugs because of renal or hepatic dysfunction, and to have pre-existing cognitive problems that make it difficult to detect the role of drugs causing new symptoms or making old ones worse.

Superseded by Drugs of Choice Handbook
Many drugs are used to treat insomnia, but for some patients nonpharmacological treatments such as changing sleep habits, relaxation training and cognitive therapy may be more effective than drugs.

Zaleplon, a pyrazolopyrimidine hypnotic, was recently approved by the FDA for short-term treatment of insomia. Zaleplon, like zolpidem, is a non-benzodiazepine that binds to benzodiazepine receptors.

Superseded by Drugs of Choice Handbook
Insomnia is a commom complaint, particularly among the elderly. Many drugs are approved by the US Food and Drug Administration (FDA) for treatment of insomnia, including five benzodiazepines and zolpidem (Ambien), a non-benzodiazepine that binds to benzodiazepine receptors in the brain. Some drugs marketed for other indications, such as antihistamines, antidepressants and antipsychotics, are also used as hypnotics. For many patients, nonpharmacological treatment of insomnia may be more effective than drugs, especially in the long term (CM Morin et al, Am J Psychiatry, 151:1172, 1994).

Zolpidem (Ambien - Searle), an imidazopyridine hypnotic available in Europe for several years, was recently approved by the US Food and Drug Administration for short-term treatment of insomnia.