Use of Trazodone for Insomnia May Increase Suicide Risk in Veterans

Among more than 348,000 veterans taking medications prescribed for insomnia in the Veterans Health Administration system nationwide, the incidence of suicide attempts in the 12 months after starting treatment was higher for those taking trazodone than for those taking zolpidem and other commonly prescribed insomnia medications, Veterans Affairs (VA) researchers found.

Suicide attempts were 61% higher in veterans taking low-dose trazodone (<200 mg) than in those taking zolpidem in any dosage, according to research by Jill E. Lavigne, Ph.D., M.P.H., and colleagues at the Veterans Affairs Center of Excellence for Suicide Prevention in Canandaigua, N.Y. Lavigne, a VA health science specialist, is also a professor of pharmacy practice and administration at St. John Fisher College in Rochester, N.Y.

Lavigne’s group reviewed electronic medical records of VA patients aged 18 years and older who filled a first prescription for an insomnia medication in 2011 or 2012. They followed each veteran’s care for 12 months after the first insomnia prescription fill date or until the veteran was seen in an emergency room after a suicide attempt, was hospitalized for a suicide attempt, or died of any cause, the researchers reported in the Journal of General Internal Medicine.

The researchers found the incidence of suicide attempts within 12 months of first prescription fill was about 76 per 100,000 person-years in veterans taking trazodone, and about 51 per 100,000 person-years in veterans taking zolpidem. (The “person-years” statistic expresses incidence rates.) They saw no significant differences in suicide attempt risk among patients taking zolpidem, benzodiazepines, or sedating antihistamines.

“These findings,” they said, “provide empirical support for the American Academy of Sleep Medicine 2017 clinical practice guidelines discouraging the use of trazodone as a first-line therapy for insomnia” (Psychiatric News).

To ensure that the population they assessed was large enough to detect the rare event of a suicide attempt, Lavigne’s group included only veterans taking agents that made up at least 1% of filled prescriptions for sleep medications in the VA system in 2011 or 2012. These agents included low-dose trazodone, zolpidem, two first-generation antihistamines (hydroxyzine and diphenhydramine), and three benzodiazepines (diazepam, lorazepam, and temazepam).

The researchers included veterans who took antihistamines only if their prescription specified use at bedtime or for sleep or insomnia. They excluded veterans taking more than one medication for sleep as well as those who switched medications during the study period. They assessed outcomes only in veterans who filled and picked up their prescriptions at VA pharmacies.

The researchers excluded veterans who had a possible or confirmed suicide attempt in the 12 months before they received their first prescription for an insomnia medication. In analyzing data, they controlled for history of psychiatric disorders, comorbidities, central nervous system medications, and other factors.

Among 1,742,860 veterans who filled at least one prescription for an agent routinely used to treat insomnia in the VA in 2011 and 2012, 348,449 met the study criteria. Insomnia medications most often used by these veterans were trazodone, followed by benzodiazepines, antihistamines, and zolpidem. The veterans typically were white men in their late 50s or early 60s. About 1 in 4 had a VA disability rating of 50% or more, indicating a decrease of 50% or more in overall health and ability to function.

Trazodone’s use for insomnia, the researchers noted, eclipses its use as an antidepressant, even though it lacks Food and Drug Administration approval for the treatment of insomnia. “Physicians may prescribe trazodone off label for insomnia because patients have both insomnia and depression or because it is not a controlled substance,” Lavigne told Psychiatric News. Since insomnia may wax and wane, patients can start and stop taking this medication as needed. It’s also inexpensive, she noted. Trazodone may cause next-day drowsiness, however.

Trazodone carries an FDA warning label for risk of suicidal ideation and behavior, Lavigne noted. “Our study provides evidence,” she said, “that selecting a different medication may avoid this association.

“Clinical guidelines and evidence reviews strongly support nonpharmacologic interventions as first-line treatments for insomnia,” she noted, with cognitive-behavioral treatment for insomnia (CBT-I) the most highly recommended treatment. These guidelines suggest pharmacotherapy as second-line treatment after patients fail to improve or have an inadequate response to CBT-I or other behavioral treatment.

This study was supported by the Department of Veterans Affairs Office of Mental Health and Suicide Prevention. ■