Too Many Pills, Too Little Attention: Emphasizing Psychotropic Polypharmacy in the Overdose Conversation

Despite a recent decline in overdose deaths, the United States continues to have the highest global overdose mortality rate. Polysubstance use-taking opioids along with other drugs-has been increasingly recognized as a key contributor to preventable overdose cases. We propose that psychotropic polypharmacy, or the co-use of multiple psychiatric medications, is emerging as a related but distinct and underappreciated issue that is crucial for continued progress in slowing the pace of the overdose epidemic. This commentary aims to center psychotropic polypharmacy in the overdose prevention conversation, given its high rates in the United States and an increasing prevalence of psychiatric prescription medications implicated in overdose deaths. We present evidence for multiple mechanisms through which psychotropic polypharmacy increases overdose risk, including drug-drug interactions, lethal means access in cases of suicidality, and desensitization to overdose-related behaviors. We also propose several potential solutions to address this public health crisis, including discontinuing inappropriate and unnecessary medications, broadening access to evidence-based nonpharmacological prevention strategies for persons at risk for overdose, and improving overdose monitoring and surveillance.