Q&A: Brown psychiatrists on the unintended, fatal consequences of mixing psychiatric meds

PROVIDENCE, R.I. [Brown University] - While the U.S. has seen a decline in the overall number of overdose deaths, the news on drug use is not all trending positively, and researchers at Brown University's Warren Alpert Medical School are focused on an emerging contributor to fatal overdoses.

In recent commentary published in the Journal of Addiction Medicine, Madeline Benz and Brandon Gaudiano highlighted the prevalence of psychotropic polypharmacy - the use of multiple psychiatric medications at the same time - which they say is an underappreciatedfactor in overdose mortality rates.

In this Q&A, Benz, an assistant professor of psychiatry and human behavior (research), and Gaudiano, a professor of behavioral and social sciences and of psychiatry and human behavior, discussed the dangers of mixing drugs and what can be done to address this growing public health challenge.

Q: What are the risks of using multiple prescription psychiatric medications at once?

Gaudiano: It's important to state up front that psychiatric medications can be highly beneficial when prescribed appropriately and taken as directed. The key risk is often not just polypharmacy in general, but specific combinations of medications with known risk, such as sedating or cognitively impairing substances, including alcohol, opioids, benzodiazepines and sleep medications. Our aim here is not to suggest that all medication combinations are unsafe, but to raise awareness that certain combinations can increase overdose risk and need to be carefully considered.

Right now, we're focusing a lot on the big, clearly identified opioids, or on medications in the headlines like ketamine. We're missing an opportunity to have a major public health impact by highlighting other drugs that, when combined or misused, also pose risks. This motivates us to talk about this issue.

Q: How did you begin studying psychotropic polypharmacy and its effects?

Benz: My research has been primarily at the nexus of substance use and suicide, and I started to notice that the narrative about the overdose epidemic was primarily around illicit fentanyl, heroin and polysubstance use involving opioids. We were missing this whole group of people who were coming into the office and talking about overdoses on psychiatric medications, and overdoses with these combinations of such psychiatric medications and other substances.

Q: Can you describe some of the most significant dangers associated with mixing drugs?

Benz: One of the big dangers is with drug interactions. We know that when you have two substances that are taken either together or in close proximity, you have not just the effects of one and the other, but a compounded impact of how the chemicals are interacting. The other problem is the ways in which these substances interact don't simply cause problems from a chemical standpoint, but also from a behavioral one. One pathway by which these combinations may contribute to overdose risk is through the lowering of inhibitions, as people are more inclined to add more drugs.

This also creates a gray area for what may be considered intentional or unintentional overdoses. We have for a long time conceptualized overdose intentionality as this binary choice: either we totally planned on doing it, and that's where the suicide focus comes in, or it was 100% an accident, and that's where the opioid field tends to focus. However, from a clinical context, we see a lot of patients who will come in and they'll say they weren't really trying to die, but they didn't care about living either.

Q: How prevalent is psychotropic polypharmacy in overdoses?

Benz: We've seen an increase in psychiatric medications in intentional overdoses. Antidepressants were the most implicated prescription substance in intentional overdoses in 2022, and we also have seen an increase in the co-prescription of psychiatric medications. They're happening in parallel, which suggests there's some overlap.

Q: What can be done to address this issue nationally?

Benz: We need to ask how we can work collaboratively with patients to reduce unnecessary prescriptions, or whether we can use one [drug] that may address multiple symptoms. There's room for pharmacists to be involved as well, so it doesn't just have to be at the prescriber level, but also at the point where it's dispensed. We've seen this process work for de-prescribing certain medications for geriatric patients because of increased fall risk among older folks.

It is also important to consider behavioral treatment options, which we know are evidence-based but are not used as frequently. Treatments like cognitive behavioral therapy have a strong evidence base for treating depression, anxiety and chronic pain. So if a doctor knows that a patient is dealing with multiple comorbidities, we can explore a more overarching therapeutic approach.

For patients, it's important to be honest with your provider about any medications that you're taking from other prescribers. Also, something as simple as just asking to understand what the medication is for is very helpful.

The full Q&A is published on the Warren Alpert Medical School website.