Medications and Suicide: High Dimensional Empirical Bayes Screening (iDEAS)

Abstract

The rate of suicide has been rising for 16 years and it is the 10th leading cause of death in the United States. Most suicides occur in the context of a psychiatric disorder (Bachmann, 2018), and yet the effect of many medications, including psychotropic medications, on suicide risk is intensely debated. The objective of this study is to develop a statistical surveillance methodology based on generalized mixed-effects regression models applied to analysis of large-scale medical claims and medical records that identifies drugs associated with increased and decreased risk of suicidal events. To this end, we use 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). Analysis of medical claims data for 922 drugs revealed statistically significant associations with suicidal events, including 10 drugs with increased rates and 44 with reduced rates following exposure. Among the strongest increased risk signals identified were alprazolam, butalbital, hydrocodone, and the codeine/promethazine mixture, and among the potentially most protective drugs were folic acid, mirtazapine, hydroxyzine, disulfiram, and naltrexone. 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. High-dimensional drug safety surveillance using extensive observational data is feasible and generates statistically and clinically significant signals of possible risks and benefits of drugs on suicide risk.Keywords: empirical Bayes, drug safety, suicide