The combination of prescribed central nervous system stimulants—such as medications that treat ADHD symptoms—with opioid painkillers has been linked to a pattern of increased opioid consumption over time, according to a recent study.
In this analysis, researchers examined health insurance claims from nearly three million U.S. patients to investigate the impact of stimulant prescriptions on long-term use of opioids spanning ten years. This research aims to shed light on what is often referred to as the “dual epidemic” associated with combining these two classes of drugs—a practice that can significantly elevate the risk of fatal overdose.
Combining stimulants and opioids has been known to boost the likelihood of overdoses, but it was unclear whether this relationship represented a causative effect. To address this question, researchers conducted an extensive data analysis examining how these two drug types interact over extended periods.
“What we discovered is that patients who take both stimulants and opioids simultaneously tend to be prescribed higher doses of the latter,” explained Ping Zhang, the senior author of the study and an associate professor at The Ohio State University in computer science and biomedical informatics. “Moreover, our findings indicate that individuals initiating opioid use after taking a stimulant are more likely to eventually require higher opioid dosages.”
The research was published on February 17 in The Lancet Regional Health – Americas.
To conduct the study, researchers accessed data from MarketScan Commercial Claims and Encounters—a comprehensive U.S. health insurance database containing information about over twenty million patients and ninety-six million opioid prescriptions.
A sample group of two-point-nine million participants aged forty-four on average was selected for analysis based on their having at least two distinct opioid prescriptions between 2012 and 2021. The researchers standardized the wide range of oral opioids (including codeine, hydrocodone, methadone, oxycodone, morphine) to a common measure: morphine milligram equivalents (MME). This allowed them to quantify each participant’s monthly opioid consumption.
Wenyu Song, an instructor at Harvard Medical School and co-senior author of the study, had previously co-developed with other researchers the MME computation method from electronic health records. Seungyeon Lee, a PhD student in Zhang’s lab, employed statistical modeling to categorize participants into five groups based on their opioid dosage trajectory over ten years: very low-dose use, decreasing low-dose usage, increasing low-dose usage, escalating moderate dose usage and sustained high dose consumption.
“We observed that while some patients maintained stable low levels of opioid intake throughout the decade, others experienced varying patterns from minor increases to more substantial upticks in dosage,” Lee noted. “Among these groups, we identified several risk factors contributing to increased opioid use.”
Within the overall group of 2.9 million participants, approximately five percent (or one hundred sixty thousand patients) had also been prescribed stimulants at some point during the study period.
Incorporating the total number of monthly cumulative stimulant prescriptions into their model and statistical analysis significantly influenced the categorization outcomes. Certain characteristics linked to a higher likelihood of escalating opioid use emerged, including:
- Moderate-dose increasing and high-dose groups: These categories had higher overall MMEs and a proportionally greater number of patients with depression, anxiety, or ADHD diagnoses compared to other trajectory groups.
- Low-dose increasing group: This subset also exhibited a significantly larger percentage of individuals diagnosed with ADHD in contrast to those in the low-dose decreasing category.
The most common medical conditions tied to concurrent use of stimulants and opioids were depression paired with ADHD, or ADHD alongside chronic pain. “This finding underscores that many patients dealing with both attention-deficit/hyperactivity disorder (ADHD) and persistent health issues such as depression are at a higher risk when prescribed both types of medications,” Zhang emphasized.
The findings suggest stimulants could play a significant role in fueling the dual epidemic, prompting calls for regulatory changes regarding the prescribing practices for patients already on opioids. Co-administering prescription stimulants with opioids is not only associated with heightened risks of overdose but also increases susceptibility to cardiovascular events and mental health issues.
As part of Zhang’s Artificial Intelligence in Medicine Lab’s ongoing efforts aimed at improving patient care, this research informs the development of safer personalized treatment recommendations for individuals prescribed both types of medications. “Our goal is to minimize adverse drug interactions and improve real-world clinical outcomes,” he concluded.
This study was supported by funding from several institutions including the National Institute of General Medical Sciences, the National Institute on Drug Abuse, and the National Science Foundation.
