Hypnotic Medications Linked to Suicide Risk

A recent review found that hypnotic medications are associated with risks of suicide and suicidal ideation. The review, published in the American Journal of Psychiatry, examines the relationship between hypnotics and suicide – a term which encompasses suicidal ideation, behavior, and death.

Hypnotics are a class of psychoactive drugs, including benzodiazepines, that are often prescribed to induce sleep. Prior reviews have focused on the relationship between hypnotics and suicide, including some studies which found increased rates of suicide death among hypnotic users and that hypnotics could increase the risk of suicide through disinhibition. However, this is the first review to include case reports of suicide as related to hypnotics and considered adverse events as reported to the Food and Drug Administration (FDA).

Insomnia has been linked to suicide in a number of studies, a link that has been maintained even after for controlling for depressive symptoms. This relationship has lead to, in part, the assumption that treating insomnia should reduce suicide risk – therefore individuals who present with suicidal ideation or behavior are often treated with hypnotic medications. However, the authors state, “the proposition of routinely prescribing hypnotic drugs to depressed and suicidal patients is countered by the fact that hypnotics can be part of an intentional overdose or may induce or aggravate suicidal thoughts.” A concern exacerbated by the high numbers of Americans that have reported using hypnotics.

To better assess the link between hypnotics and suicide, the researchers conducted searches on PubMed and Web of Science crossing the terms “suicide” and “suicidal” with each of the agents and their approved labeling. The researchers also contacted the FDA and requested case reports for hypnotic-related suicide deaths. The medications they focused on for the review were all approved by the FDA and included flurazepam, temazepam, triazolam, estazolam, quazepam, zolpidem, zaleplon, eszopiclone, ramelteon, doxepin at 3mg and at 6mg, and suvorexant.

Their results are divided into toxicology studies in suicide victims, retrospective cohort studies on hypnotics and suicide, prospective cohort studies on hypnotics and suicide, and illustrative cases.

Their review of toxicology studies, in and outside of the United States, showed that hypnotics are “often involved in suicide deaths,” both when used with alcohol or by themselves. In retrospective cohort studies, the authors found that individuals using hypnotic medications were overrepresented among suicide victims, and prospective cohort studies also showed an association between suicide and the use of hypnotics. Their review of the prospective cohort studies included findings such as regular hypnotic use being an indicator of increased risk of mortality and the possibility benzodiazepines causing disinhibition.

Their findings are not without limitations, and the authors discuss weaknesses within the reviewed studies, such as lack of information about mental health diagnoses in participants, and the fact that some studies didn’t measure alcohol or substance abuse.

The authors argue that the implication that hypnotics exacerbate suicidal ideation is not as clear-cut as it first seems. Further, they state that hypnotics “may reduce or prevent suicidal ideation in persons with insomnia and mental illness.” However, the authors admit that the idea that hypnotics could reduce or prevent suicidal ideation has not been evaluated. The authors also include financial disclosures which point to financial support from the drug manufacturers who produce some of these medications.

 

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McCall, W. V., Benca, R. M., Rosenquist, P. B., Riley, M. A., McCloud, L., Newman, J. C., … & Krystal, A. D. (2016). Hypnotic medications and suicide: risk, mechanisms, mitigation, and the FDA. American journal of psychiatry, appi-ajp. (Abstract)