Insomnia Hypnotic Treatment Lowers Risk of Suicidal Ideation


Data show zolpidem use in 8-week insomnia trial reduced suicidal ideation in patients, even after trial randomization ended.

William McCall, MD

William McCall, MD

Previous studies have found insomnia as a risk factor in suicidal ideation, suicidal behavior, and death by suicide.

The relationship of suicide and insomnia has often been found in patients with depressive conditions, as well as being shown in patients with schizophrenia.

Investigators, led by William Vaughn McCall, MD of the Medical College of Georgia at Augusta University, found that psychiatrists treating insomnia in suicidal major depressive disorder (MDD) patients should consider the adjunctive use of hypnotic medication along with selective serotonin reuptake inhibitor (SSRI) in treatment.

The findings were presented in a session at the 2021 American Psychiatric Association Annual Meeting.

Current treatment methods for insomnia in patients with suicidal ideation include SSRIs, SNRIs, or bupropion. The American College of Physicians and the American Academy of Sleep Medicine recommend cognitive behavior therapy (CBT-I) for insomnia, but patient access is limited.

McCall and team hypothesized that the targeted treatment of insomnia with hypnotics, combined with an SSRI, would create a significant reduction in suicidal ideation, when compared to an SSRI alone.

Are Hypnotics Safe?

Investigators researched previous studies on the relationship between insomnia and suicidal ideation, with McCall calling it a “universal phenomenon” across geographics, age groups, and diagnoses.

The team chose to use hypnotic medication prescribing, rather than CBT-I, due to concerns of lack of treatment options for a greater public health concern.

They noted the evidence of hypnotics use in suicide death, generally in combination with other medications or alcohol.

However, there was no firm evidence found on one hypnotic being more likely to lead to suicide over another. Investigators said the association had an odds ratio of >2, but the interpretation is unresolved.

Other data show the suicide risk is maximized in the first few days of use, during the hours of peak drug effects.

Between the rates of prescribing for flunitrazepam, nitrazepam, zopiclone, and zolpidem, the associations were found to be the same, with approximately 1 suicide per million daily doses of each drug.

However, the team noted that strategic prescription of hypnotics to suicidal insomniac patients might reduce suicide risk, particularly with limited access to pills and constant follow-up.


Investigators designed a randomized controlled trial (RCT) of hypnotics in MDD outpatients who have significant insomnia and suicidal ideation.

The patients in the study were required to be medication free, with many having never taken a psychotropic and some already on an antidepressant, creating safety concerns.

Investigators implemented a 1-week medication-free baseline, so all patients started from the same position, without any incidence during the screening phase. Patients were also required to undergo a sleep apnea screening test.

A 1:1 randomization was stratified by site, gender, and prior suicide attempts. Patients with MDD must have a ≥ 20 score in the Hamilton Rating Scale for Depression (HRSD24), an Insomnia Severity Index score of >7, and a Beck Scale for Suicide Ideation score of ≥3, in a 0 – 38 scale.

In the open-label study, patients were given 20mg fluoxetine as an SSRI. Patients were then randomized at bedtime to be given either a zolpidem-controlled release or placebo.

The dose could be increased to 40 mg after the end of 4 weeks if the HRSD24 was >15, which happened 50% of the time, according to investigators.

Zolpidem treatment started at 6.25 mg concurrent to guidelines but could be doubled at the end of the first week if there were no therapeutic effects.

The patients were followed for 8 weeks and after the end of 8 weeks, the antidepressant was continued. Treatment of the hypnotic could be stopped or become an open-label treatment.

The blind was not broken for the investigators until after the study. Patients were followed up in a two-week period to monitor suicidal ideation.


The study included 103 patients, with 51 in the zolpidem group and 52 in the placebo group.

Patients in the study were predominantly female (52%), middle-aged (40.5 years), with 40% non-white participants. They had an overall high level of depression (29.1 HRSD) and insomnia symptoms (20.8), with mild to moderate suicidal ideation levels (12.0).

Adherence to treatment was positive, despite investigators concern of a haphazard approach to treatment regimen adherence.

“My thinking goes, if this person is thinking about taking their own life, what’s the motivation for them to actually stick to what they are supposed to do,” McCall said. “Nothing could have been further from the truth.

In the 103 patients, 90% completed all scheduled visits, with total completion rates in 86% of the zolpidem assigned group and 73% in the placebo group. Participants took 91% of all randomized study drugs and 94% of all prescribed SSRIs.

The flexible dosing of the study led to a zolpidem/placebo dose escalation in 73% of the zolpidem group and 72% of the placebo.

Most patients did not need to take zolpidem after the 8-week treatment for insomnia, but the SSRI was continued.

On the Insomnia Severity Index, the zolpidem and fluoxetine resulted in a superior reduction during treatment, even past the point of randomization.

On the Columbia Suicide Severity Rating Scale, an advantage was found for those assigned to zolpidem during the 8-week treatment with a reduction of suicide severity.


Investigators concluded that the targeted treatment of insomnia may result in a quicker resolution of suicidal ideation.

“I think we can say it is possible to safely recruit and retain suicidal, depressed patients with insomnia within a randomized controlled trial that has specific safety methods built into it,” McCall said.

The team said the future of treatment may require a much larger magnitude of study participants, but the treatment of insomnia with hypnotics may help mitigate suicidal ideation.

The study, “Addressing Insomnia in Psychiatric Practice: A Modifiable Risk Factor for Suicidal Ideation,” was presented online at the 2021 American Psychiatric Association Annual Meeting.

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