A class of widely prescribed painkillers may carry hidden risks when combined with other medications, according to new research that is raising concerns among clinicians.

The study, published in PLOS Medicine, found that patients taking gabapentinoids—a group of drugs commonly used for nerve pain, epilepsy, and anxiety—face a significantly increased risk of drug poisoning when these medications are combined with others such as opioids or benzodiazepines.

Gabapentinoids, which include drugs like gabapentin and pregabalin, are often prescribed as safer alternatives to opioids. However, the study suggests that their interaction with other drugs may complicate that assumption.

Researchers found that patients who took benzodiazepines alongside gabapentinoids had double the risk of hospitalization due to drug poisoning. Meanwhile, combining gabapentinoids with opioids was associated with a 30% increase in risk.

“Our findings do not suggest that gabapentinoids are unsafe or should not be prescribed,” said Kenneth Man of University College London. “But clinicians should be cautious, particularly when patients are taking multiple medications, and should monitor them closely.”

The study analyzed nearly 17,000 patients in the U.K. who had been hospitalized for drug poisoning while on gabapentinoids. Although these cases represented a small fraction of all users, the patterns observed were notable: nearly 90% of patients had also taken opioids at some point, while more than half had used benzodiazepines alongside their gabapentinoid treatment.

Symptoms of drug poisoning can include loss of consciousness, breathing difficulties, and seizures—serious complications that often require emergency care.

Interestingly, researchers found that the risk of poisoning was highest in the period before patients were prescribed gabapentinoids. This suggests that doctors may have been using these drugs in an attempt to reduce risks associated with opioid or benzodiazepine use.

“A clinician’s decision to prescribe gabapentinoids may sometimes be an attempt to minimize the risk of drug poisoning linked to other medications,” said Andrew Yuen, a doctoral student involved in the study.

While the risk did decline somewhat after patients began gabapentinoid treatment, it remained elevated—highlighting the need for continued vigilance.

Experts say the exact mechanism behind the increased risk is still not fully understood. However, there is growing evidence that gabapentinoids may amplify the sedative effects of other drugs, particularly opioids and benzodiazepines, increasing the likelihood of overdose or poisoning.

As prescriptions for these medications continue to rise globally, the findings underscore an urgent need for more careful prescribing practices—and closer monitoring of patients navigating complex medication regimens.