Study Links Gabapentinoids with Increased Drug Poisoning Risk When Combined with Other Medications

A new study published in PLOS Medicine has found that combining gabapentinoids with benzodiazepines or opioids significantly increases the risk of hospitalization for drug poisoning. The research analyzed prescription data from over 16,000 people in the UK.

Adding benzodiazepines to gabapentinoid treatment was associated with a doubling of hospitalization risk for drug poisoning. Adding opioids was linked to a 30% increase in risk.

Key Findings of the Study

Researchers reviewed UK prescription data from 2010 to 2020, focusing on 16,827 individuals who were prescribed gabapentinoids and had at least one drug poisoning hospitalization. They examined hospitalizations before, during, and after gabapentinoid prescriptions, including both intentional and accidental poisoning cases.

• The highest risk period for drug poisoning was observed in the 90 days before participants began taking gabapentinoids.
• Risk decreased somewhat after starting gabapentinoids but remained elevated for months.
• Widespread co-prescription: The analysis found that 89% of participants took gabapentinoids alongside opioids at some point, and 55% took them alongside benzodiazepines.

What Are Gabapentinoids?

Gabapentinoids, which include drugs like gabapentin and pregabalin, are prescribed for conditions such as epilepsy, nerve pain, and anxiety disorders. Their use for pain relief has grown significantly.

They are now the seventh most commonly prescribed medication in the United States, and their usage increased more than fourfold across 65 countries between 2008 and 2018.

What the Researchers Say

Lead author Dr. Kenneth Man noted the rapid rise in prescriptions: "Prescription rates for gabapentinoids have been increasing rapidly in recent years, as they are seen as a safe alternative to opioids. While they can be effective for pain relief and do have better perceived safety profiles than opioids, there are still substantial risks that clinicians and patients should be mindful of."

First author Dr. Andrew Yuen commented on the clinical implications: "A clinician's decision to prescribe gabapentinoids may sometimes be an attempt to minimize the risk of drug poisoning linked to opioids or other medications. While the risk of poisoning did decrease somewhat after patients began gabapentinoid treatment, they still faced an elevated risk... which suggests that clinicians need to remain vigilant to the risks."

"Our findings do not suggest that gabapentinoids are unsafe or should not be prescribed, but clinicians should be cautious when prescribing them, particularly if a patient is taking other medications as well." — Dr. Kenneth Man

Important Context and Warnings

The study authors clarify that it remains unclear if gabapentinoids directly cause drug poisoning. However, evidence suggests they might enhance the sedative effects of opioids and benzodiazepines. There is also evidence of abuse potential, particularly for people with a history of substance abuse.

Earlier this year, the UK's Medicines and Healthcare products Regulatory Agency strengthened warnings on gabapentinoids regarding addiction, dependence, withdrawal, and tolerance.

The study was supported by the NIHR UCLH Biomedical Research Centre and involved researchers from UCL School of Pharmacy, UCL Division of Psychiatry, UCLH, the University of Hong Kong, and Aston University.