Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.
OBJECTIVE
Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide.


METHODS
This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System.


RESULTS
Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression.


CONCLUSIONS
The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.
From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C.
W Vaughn
WV
McCall
From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C.
Ruth M
RM
Benca
From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C.
Peter B
PB
Rosenquist
From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C.
Mary Anne
MA
Riley
From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C.
Laryssa
L
McCloud
From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C.
Jill C
JC
Newman
From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C.
Doug
D
Case
From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C.
Meredith
M
Rumble
From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C.
Andrew D
AD
Krystal
D000328:Adult; D000368:Aged; D002423:Cause of Death; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006993:Hypnotics and Sedatives / Q000506:poisoning* / Q000627:therapeutic use*; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D012306:Risk; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000401:mortality; D059020:Suicidal Ideation; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data*; D014481:United States; D014486:United States Food and Drug Administration; D000092864:Suicide Prevention
D006993:Hypnotics and Sedatives
Sleep; Suicide