Increasing Worldwide Evidence of Harms Associated With Gabapentinoids, Particularly Pregabalin

With increased use of gabapentinoids (gabapentin and pregabalin) for a wide a variety of indications, there has been growing evidence of harms. Two recent studies—one in Sweden and the other in Australia—looked at national data to investigate harms associated with gabapentinoid use.

Swedish researchers used national data to investigate the association between receiving a gabapentinoid prescription and a variety of adverse outcomes from 2006 to 2013.

• Overall, 191,973 individuals (2.1% of the population aged ≥15) received ≥2 consecutive prescriptions for a gabapentinoid.
• Gabapentinoids were associated with suicidal behavior and deaths by suicide (age-adjusted hazard ratio [aHR], 1.26), unintentional overdoses (aHR, 1.24), head/body injuries (aHR, 1.22), and traffic incidents and offenses (aHR, 1.13).
• The hazards were highest for those aged 15–24 and among those prescribed pregabalin.

In Australia, researchers used national data to explore trends in adverse events associated with pregabalin between 2005 (when it first became available) and 2017, compared with gabapentin.

• Pregabalin dispensing increased from 132,000 in 2013 (when it was first covered under the national Pharmaceutical Benefits Scheme) to 353,000 in 2016, a 2.7-fold increase, while gabapentin remained stable and at much lower levels.
• There were a total of 1,158 intentional pregabalin poisonings reported to the Poisons Information Centre during this period, increasing from 0 in 2005 to 375 in 2016.
• There were a total of 88 pregabalin-associated deaths during this period; most also involved opioids (80%) and benzodiazepines (67%).

Comments: These studies highlight a number of harms associated with gabapentinoid use, particularly pregabalin. Clinicians should exercise caution before prescribing these medications, especially to younger people and those with substance use disorders.

Darius A. Rastegar, MD

References: Molero Y, Larsson H, D’Onofrio BM, et al. Associations between gabapentinoids and suicidal behavior, unintentional overdoses, road traffic accidents and violent crime: population based cohort study in Sweden. BMJ. 2019;365:I2147.

Cairns R, Schaffer AL, Ryan N, et al. Rising pregabalin use and misuse in Australia: trends in utilization and intentional poisonings. Addiction. 2019;114:1026–1034.