Early Treatment Phase with Gabapentinoids tied to Highest Poisoning Risk, suggests study

A new research published in the journal of PLoS Medicine found that patients starting gabapentinoids faced an increased risk of drug poisoning, particularly soon after initiation. This risk was further elevated when combined with benzodiazepines or opioids. The self-controlled case series study of 17,000 U.K. patients demonstrated a clear temporal association between starting therapy and increased poisoning events.

Gabapentinoids, including commonly prescribed drugs like gabapentin and pregabalin, have seen a sharp rise in global use over the past decade. While they are often viewed as safer alternatives to opioids to treat nerve pain, epilepsy, and anxiety, the growing data suggests they may carry their own risks, especially when combined with other medications.

This new study analyzed data from over 16,800 adults in the UK who had been prescribed gabapentinoids and later experienced a drug poisoning event between 2010 and 2020. This study used robust statistical methods and linked healthcare databases to examine how the timing of medication use could influence poisoning risk within the same individuals.

The findings revealed the risk of drug poisoning was nearly doubled in the first 28 days after starting gabapentinoids, when compared to periods when patients were not on the medication. Despite the risk gradually declining over time, it remained slightly elevated throughout continued treatment.

Also, the study found that the risk was already elevated in the 90 days before patients began gabapentinoid therapy. This suggests that individuals prescribed these medications may already be in a vulnerable state, possibly due to worsening health conditions or other underlying factors.

The dangers increased further when gabapentinoids were used along with other drugs. Co-prescription with opioids raised the risk of drug poisoning by about 30%, while combining them with benzodiazepines doubled the risk. These combinations are not uncommon in clinical practice, which raises important safety questions. This secondary analysis uses a different statistical approach, which confirmed the association between recent gabapentinoid use and increased poisoning risk.

After accounting for several changing factors such as age, season, and use of other medications, this study acknowledged limitations. Certain influences, like sudden life events or illicit drug use, could not be fully measured and may have contributed to the observed risks. Overall, the findings of this study suggest that patients starting gabapentinoids should be carefully monitored, particularly in the first month of treatment. 

Source:

Yuen, A. S. C., Chen, B., Chan, A. Y. L., Hayes, J. F., Osborn, D. P. J., Besag, F. M. C., Lau, W. C. Y., Wong, I. C. K., Wei, L., & Man, K. K. C. (2026). Association between gabapentinoid treatment, concurrent use with opioid or benzodiazepine and the risk of drug poisoning: A self-controlled case series study. PLoS Medicine, 23(4), e1005035. https://doi.org/10.1371/journal.pmed.1005035