One of the most extensive retrospective studies found that co-prescription of stimulants and opioids may be fueling a twin epidemic of overdose. Those prescribed stimulants require opioids at higher dosages for pain control and vice-versa.
Although opioid prescription rates have declined in recent years in the US, but opioid overdose-related deaths are still very common. There are several reasons for that, including a poor understanding of the opioid epidemic.
Opioids are still one of the most effective painkillers, especially for those living with chronic pain. For many patients, nothing seems to work except opioids.
When trying to understand opioid use disorder (OUD) and opioid overdose-related deaths, it is vital to understand that most patients are taking multiple medications. It also means that certain drugs might increase opioid overdose risk. Now, one of the new and most extensive studies to date shows that those who are prescribed stimulants to manage ADHD along with opioids are at a much greater opioid overdose risk.
This new study was published in The Lancet Regional Health – Americas. It looked into health claims of 3 million US patients who were prescribed stimulants and opioids. They believed that prescribing these drugs together may increase the risk of a twin epidemic.
Both of these drugs act very differently on the brain and have an opposing action. However, in some instances, doctors need to prescribe these drugs together. Stimulants are mainly used to manage ADHD, which is a diagnosis for a lifetime, often requiring prolonged or continuous treatment with these drugs. However, many of those living with ADHD may also develop chronic pain and require opioids to manage their pain. But, since these drugs have quite an opposing action, those taking stimulants may require higher dosages of opioids for pain control and vice-versa. That is why prescribing them together may increase the risk of a twin epidemic.
In the study, researchers analyzed 96 million opioid prescriptions and a total of 2.9 million patients. So, researchers analyzed a massive dataset, making their study quite robust.
Of course, things are not that simple, as there are many different kinds of opioids, like codeine, hydrocodone, methadone, oxycodone, morphine, and others. So, researchers had to calculate or standardize things using morphine milligram equivalents (MME) of opioid use by those patients. Hence, they had to use lots of computation.
In the study, researchers found that 160,243 or 5.5% of those on opioids were also prescribed stimulants. They found that those who were prescribed stimulants needed higher dosages of opioids. Further, using stimulants along with opioids means that doctors often need to increase opioid dosage. Additionally, individuals prescribed these drugs together were also more likely to be living with other mental health issues like anxiety and depression along with ADHD.
Nonetheless, even when correcting for these confounding factors, researchers found that prescribing stimulants to those taking opioids resulted in opioid dose escalation. This means that if doctors prescribe stimulants to those taking opioids, they are required to increase opioid dosage for adequate pain control.
So, this study suggests that the use of stimulants may increase the risk of opioid overdose and vice versa. This study could identify one of the reasons behind this twin epidemic.
Co-prescription of these drugs not only increasesthe risk of drug overdose but also increases the risk of mental health issues and cardiovascular events.
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
