Fatalities associated with gabapentinoids in England (2004-2020)

The gabapentinoids were reclassified as Schedule II medications and Class C drugs in the UK in 2019 due to their potential misuse. In this study we examined deaths following gabapentinoid use in England reported to the National Programme on Substance Abuse Deaths. A total of 3051 deaths were reported (gabapentin: 913 cases; pregabalin: 2322 cases [both detected in 184 cases]). Prescribed and illicitly obtained gabapentinoids accounted for similar proportions of deaths (gabapentin illicit 38.0%, prescribed 37.1%; pregabalin illicit 41.0%, prescribed 34.6%). Opioids were co-detected in most cases (92.0%), and co-prescribed in a quarter (25.3%). Postmortem blood gabapentinoid concentrations were commonly (sub)therapeutic (65.0% of gabapentin cases; 50.8% of pregabalin cases). In only two cases was gabapentinoid toxicity alone attributed in causing death. Gabapentinoids alone rarely cause death. Clinically relevant doses can, however, prove fatal, possibly by reducing tolerance to opioids. Doctors and patients should be aware of this interaction. Gabapentinoid-opioid co-prescribing needs urgent revision.