Insomnia Drugs: Some More Dangerous Than Others

Fran Lowry

June 05, 2019

SCOTTSDALE, Arizona — When prescribing medications to treat insomnia, clinicians should be aware that some may be more dangerous than others, new research suggests.

In a study that examined the relative morbidity and mortality of medications used to treat insomnia, results showed that amitriptyline (multiple brands) and doxepin (multiple brands) were associated with very high morbidity and mortality indices. Quetiapine (Seroquel, AstraZeneca) and olanzapine (multiple brands) were associated with relatively high indices.

The safest medications were benzodiazepines and so-called z-drugs, such as eszopiclone (Lunesta, Suovion), zaleplon (Sonata, Pfizer), and zolpidem (multiple brands).

Dr J. Craig Nelson

Lead author J. Craig Nelson, MD, professor of psychiatry and the Leon J. Epstein MD Endowed Chair in Geriatric Psychiatry, University of California, San Francisco, told Medscape Medical News that insomnia is a common problem worldwide and that prescriptions for sedatives and hypnotics continue to rise. Deaths from excessive ingestion, either accidental or intentional, are also rising.

"Clinicians ought to consider which drugs have a greater hazard in patients who may be suicidal, where the risk of overdose is greater, and that there are differences among these drugs. The aim is to choose a safer drug," Nelson said.

The findings were presented here at the American Society of Clinical Psychopharmacology (ASCP) 2019 annual meeting.

Serious Outcomes Tripled

The investigators examined relative morbidity and mortality with regard to 42 medications used to treat insomnia, as shown in reports from 2000 to 2016 in the American Association of Poison Control Centers' National Poison Data System of single-drug exposures in individuals aged 12 years or older.

During that period, there were 876,662 single-substance exposures for the 42 medications. Serious outcomes rose 3.2-fold.

"That's a substantial increase, and it can't be explained by just an increase in the population. And it does appear that this group of drugs for insomnia is one of the groups that is showing the greatest increase in serious outcomes," Nelson said.

"These statistics make it imperative for clinicians to use extra caution in their prescribing habits, especially in vulnerable seniors," he added.

He noted that some of these medications are more harmful than others and that the morbidity and mortality indices associated with these drugs vary widely.

"Although the lower doses of these agents used for insomnia may be safe in limited quantities, the data suggest that a substantial portion of ingestions are large amounts," said Nelson.

"It was a bit of a surprise that quetiapine, one of the newer antipsychotics that is used for a variety of different conditions, was also relatively high on the list," he said.

When patients overdose, they often do so after taking the remaining amount of pills from a 30-day prescription. However, the researchers found that about one third of patients in their sample took more than a 1-month supply.

"They could be stockpiling a large supply over the years or else are getting pills elsewhere," Nelson said.

Most current guidelines for sleep problems encourage patients to first try sleep hygiene or cognitive-behavioral therapy for insomnia. Nevertheless, a lot of patients want a pill to help them sleep, Nelson noted.

Need for Clinician Awareness

Commenting on the findings for Medscape Medical News, session moderator Francisco Moreno, MD, professor of psychiatry, University of Arizona College of Medicine–Tucson and the College of Medicine–Phoenix, agreed that clinicians need to be aware of the increased rates of suicide from drugs indicated for treating insomnia.

"Yes, the medications that we are prescribing in our patients are very commonly utilized for suicidal intent or misused in ways that lead to overdoses of clinical significance," said Moreno, who was not involved with the research.

"Because of that, it becomes very important to be cautious in the doses and the amount of medication that we prescribe our patients in general, and specifically when it comes to sedating medications, hypnotic medications, and those that can be used to help people sleep," he said.

"Many of those have a liability for respiratory suppression that may lead to very serious morbidity and mortality complications," he said.

Nelson has financial relationships with Eisai, Janssen, Biohaven, and UpToDate. Moreno has disclosed no relevant financial relationships.

American Society of Clinical Psychopharmacology (ASCP) 2019: Abstract 3001861. Presented May 28, 2019.

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