PLoS Med
Gabapentinoids linked to early spike in drug poisoning risk
Clinical Takeaway: When initiating gabapentin or pregabalin, reassess overdose risk, avoid or carefully justify concurrent opioids or benzodiazepines, and intensively monitor patients during the first month of therapy.
Gabapentinoids are widely viewed as safer analgesic alternatives, yet more than 16,000 patients with poisoning events show that timing and combination therapy substantially shape real‑world risk.
Prescriptions for gabapentinoids have surged globally, but new evidence in PLoS Medicine suggests clinicians should be especially cautious around treatment initiation and co‑prescribing. In a self‑controlled case series using UK primary care, hospital, and mortality data, researchers analyzed 16,827 adults who experienced at least one all‑cause drug‑poisoning event between 2010 and 2020.
Compared with patients’ own baseline periods, the risk of drug poisoning was already elevated in the 90 days before starting a gabapentinoid, more than doubling during that window (adjusted incidence rate ratio [aIRR], 2.09). Risk remained high immediately after initiation, peaking in the first 28 days of treatment (aIRR, 1.81), before tapering to a more modest increase during longer‑term use (aIRR, 1.11).
Concomitant medications made a critical difference. Co‑administration with opioids increased poisoning risk by about 30%, while concurrent benzodiazepines were associated with a two‑fold increase. A secondary case‑case‑time‑control analysis supported these findings, showing a 36% higher odds of recent gabapentinoid exposure before a poisoning event.
“Our findings suggest that gabapentinoids are often started during periods of heightened vulnerability,” said senior author Kenneth Man, PhD, adding that “there are still substantial risks that clinicians and patients should be mindful of” when these drugs are combined or newly initiated.
Source: Yuen ASC, et al. (2026, April 16). PLoS Med. Association between gabapentinoid treatment, concurrent use with opioid or benzodiazepine and the risk of drug poisoning: A self-controlled case series study