Prescribing stimulants together with opioids raises overdose risk. A study of 2.9 million US patients appeared in The Lancet Regional Health – Americas. People who took stimulants needed higher opioid doses. Adding a stimulant pushed opioid doses up, even after other factors were taken out.
One of the largest studies of past records found that giving stimulants and opioids together may feed a twin epidemic of overdose. People on stimulants need more opioid to control pain, and the other way around.
Opioid prescribing has dropped in recent years in the US. Yet opioid overdose deaths are still very common. There are several reasons, including a poor grasp of the opioid epidemic.
Opioids are still one of the most effective painkillers, above all for people with chronic pain. For many patients, nothing else seems to work.
To understand opioid use disorder (OUD) and opioid overdose deaths, it is vital to know that most patients take several medicines. Some drugs might raise opioid overdose risk. Now one of the newest and largest studies to date shows something. People prescribed stimulants for ADHD along with opioids are at much higher risk of opioid overdose.
This new study appeared in The Lancet Regional Health – Americas. It looked at health records from 3 million US patients who took stimulants and opioids. The researchers thought giving these drugs together may raise the risk of a twin epidemic.
These two drugs act on the brain in very different, opposite ways. But sometimes doctors need to prescribe them together. Stimulants are mainly used for ADHD. ADHD is a lifelong diagnosis that often needs long or steady treatment with these drugs. Many people with ADHD may also develop chronic pain and need opioids for it. Because the drugs work in opposite ways, people on stimulants may need higher opioid doses for pain control, and the other way around. That is why prescribing them together may raise the risk of a twin epidemic.
In the study, researchers looked at 96 million opioid prescriptions and 2.9 million patients in all. That is a huge dataset, which makes the study quite strong.
Of course, it is not that simple. There are many kinds of opioids, like codeine, hydrocodone, methadone, oxycodone, morphine and others. So researchers had to put them on one scale using morphine milligram equivalents (MME). That took a lot of computing.
Researchers found that 160,243, or 5.5%, of people on opioids also took stimulants. People on stimulants needed more opioid. Using the two together often means doctors must raise the opioid dose. People on both drugs were also more likely to have anxiety and depression on top of ADHD.
Even after taking those other factors out, adding stimulants for people on opioids still pushed opioid doses up. So when doctors add a stimulant for someone on opioids, they must raise the opioid dose to control pain.
So this study suggests that stimulant use may raise the risk of opioid overdose, and the other way around. The study may have found one of the reasons behind this twin epidemic.
Giving these drugs together raises the risk of overdose. It also raises the risk of mental health problems and of heart and blood vessel problems.
Source:
Lee, S., Song, W., Bates, D. W., Urman, R. D., & Zhang, P. (2025). The recent trend of twin epidemic in the United States: A 10-year longitudinal cohort study of co-prescriptions of opioids and stimulants. The Lancet Regional Health – Americas, 44. https://doi.org/10.1016/j.lana.2025.101030
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