Hypnotic, Antidepressant Combo Shown to Reduce Suicidal Ideation in Patients With Severe Insomnia

Pairing a sedative with an antidepressant was shown to be potentially beneficial in patients with suicidal thoughts, chiefly those with severe insomnia, according to a study.

Pairing a sedative with an antidepressant was shown to be potentially beneficial in patients with suicidal thoughts, chiefly those with severe insomnia, according to a September study published in The American Journal of Psychiatry.

Lead study author Vaughn McCall, MD, chair of the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Augusta University, noted how more than 30 studies have correlated insomnia to suicidal thoughts or actions, yet this link has remained overlooked when treating patients with insomnia. “If your patient says their sleep problem is really bad and they have had thoughts of killing themselves, maybe they should have a targeted treatment for their insomnia,” said McCall in a statement.

Researchers examined the effectiveness of sleeping medication, when paired with an antidepressant, in 103 patients aged 18 to 65 years with major depressive disorder, insomnia, and suicidal thoughts. In the multisite parallel-arm randomized REST-IT (Reducing Suicidal Ideation Through Insomnia Treatment) study, participants were administered either a controlled-release zolpidem (zolpidem-CR) or a placebo over 8 weeks, in conjunction with an open-label selective serotonin reuptake inhibitor to compare efficacy on suicidal ideation:

  • Suicidal ideation served as the main outcome and was measured first by the Scale for Suicide Ideation, and second by the Columbia-Suicide Severity Rating Scale (C-SSRS)
  • Of the study group randomly assigned to either zolpidem-CR (N=51) or placebo (N=52), 64 were women and 39 were men with a mean age of 40.5 years

While study results exhibited no significant treatment effect on the Scale for Suicide Ideation (least squares mean estimate = -0.56, SE = 0.83, 95% CI = -2.19 to 1.08), the authors noted that the reduction in scores were significantly positively related to improvement in insomnia after accounting for the effect of other depression symptoms. Zolpidem-CR was shown to have a significant treatment effect indicated in the C-SSRS (least squares mean estimate = -0.26, SE = 0.12, 95% CI = -0.50 to -0.02), with an increased advantage in reducing suicidal ideation found in patients with more severe insomnia.

Zolpidem-CR further showed a robust anti-insomnia effect, particularly in patients with the most severe insomnia symptoms.

To combat suicidal ideation especially among patients with severe insomnia, the study highlights a possibly beneficial co-prescription of a hypnotic and an antidepressant. Further research into the effect of insomnia on suicide risk and how treating it reduces that risk was noted by McCall.

“Our results do suggest that, with proper safety procedures, it is possible to provide short-term relief of insomnia and more rapid reduction of suicidal ideation by time-limited prescribing of small quantities of hypnotics, without incurring major risk of emergent suicidal ideation, especially in those suicidal outpatients with major depression with the most severe insomnia,” wrote the authors.


McCall WV, Benca RM, Rosenquist PB, et al. Reducing suicidal ideation through insomnia treatment (REST-IT). [published online September 20, 2019]. Am J Psychiatry. doi: 10.1176/appi.ajp.2019.19030267.

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