New Study Highlights the Relationship Between Risk for Suicide and Prescription Drugs

November 8, 2019

A team of researchers, led by the University of Chicago’s Dr. Robert Gibbons, examined the relationship between 922 prescription drugs and 43,978 suicidal events. The findings were published in the Harvard Data Science Review. Dr. J. John Mann, Paul Janssen Professor of Translational Neuroscience (in Psychiatry and in Radiology) at Columbia University Vagelos College of Physicians and Surgeons and senior author of this paper, breaks down some of the key takeaways.

Columbia Psychiatry: Rates of suicide in the United States have been steadily rising for the past 16 years. Which prescription drugs show a statistically significant increase in suicide attempts?

Dr. Mann: 10 out of 922 drugs evaluated showed increased risk. Among the strongest increased risk signals identified were alprazolam, butalbital, hydrocodone, and the codeine/promethazine mixture.

Columbia Psychiatry: On the contrary, how many drugs had an association with a decrease in suicide risk?

Dr. Mann: 44 drugs showed lower risk. The list includes a large group of FDA approved antidepressants: selective serotonin reuptake inhibitor (SSRI) antidepressants citalopram, escitalopram, fluoxetine, and sertraline; the mixed serotonin and norepinephrine reuptake inhibitors (SNRI) venlafaxine, desvenlafaxine, and duloxetine; bupropion, an aminoketone that inhibits norepinephrine reuptake; mirtazapine, a noradrenergic alpha2-adrenergic antagonist; trazodone, a serotonin 5-HT2A receptor antagonist and reuptake inhibitor; and the tricyclic doxepin. The list also contains several antipsychotic medications and the vitamin folic acid, to name a few.

Columbia Psychiatry: What kind of data was used to come up with these statistics?

Dr. Mann: We used a within-person incident-user cohort design to simultaneously examine the relationship between 922 drugs and 43,978 suicidal events (suicide attempts and intentional self-harm, including fatalities if they resulted in a medical claim) using medical claims for private health insurance (MarketScan) from 2003–2014, for over 150 million people. Suicidal events were identified based on the following ICD-9 codes (E950-E959).

Columbia Psychiatry: How will these findings impact drug safety surveillance going forward?

Dr. Mann: Older methods did not allow valid, sensitive statistical assessment of such large drug data bases. High-dimensional drug safety surveillance using extensive observational data is feasible and our methods generate statistically and clinically significant signals of possible risks and benefits of drugs on suicide risk. 

Columbia Psychiatry: Where does the research go from here?

Dr. Mann: Thirty of the 44 drugs with decreased risk are approved psychotropic medications, providing both a degree of validation of the method and reassurance to clinicians about the effectiveness and safety of these drugs in suicidal patients. This method can be used for other outcomes and monitor all FDA-approved drugs for things like drugs causing sudden cardiac death as opposed to protecting against sudden cardiac death.

“What we’ve done is come up with an alternative approach to drug safety surveillance that could be used by any agency, country or formulary,” said Robert Gibbons, PhD, the Director of the Center for Health Statistics at the University of Chicago and lead author of the study, to UChicago Medicine. “We simultaneously did this analysis on all 922 drugs, and from that model we can back out the risks for each one individually.”


suicide risk, prescribed medication