Gabapentinoid use associated with suicidal behavior, other adverse outcomes
The association of gabapentinoid with outcomes including overdoses, injuries, and accidents was strongest in younger patients, whereas those ages 55 years and older had reduced or no association.
A recent study of gabapentinoids found that use is associated with increased hazards of suicidal behavior and other adverse outcomes, although most of the effect was attributed to pregabalin, not gabapentin.
Researchers used prescription, patient, death, and crime registers to examine 191,973 adolescents and adults ages 15 years and older who filled prescriptions for gabapentinoids (pregabalin or gabapentin) from 2006 through 2013 in Sweden. They assessed the association between the medications and suicidal behavior, unintentional overdoses of illicit drugs, alcohol, medications, or noxious and biological substances, head/body injuries, road traffic incidents and offenses, and arrests for violent crime. Individuals served as their own controls, and additional adjustments were made for age, sex, comorbidities, substance use, and use of other antiepileptic agents. Results were published online on June 12 by The BMJ.
During the study period, 10,026 (5.2%) participants died from suicide or were treated for suicidal behavior, 17,144 (8.9%) had an unintentional overdose, 12,070 (6.3%) had a road traffic incident or offense, 70,522 (36.7%) had head/body injuries, and 7,984 (4.1%) were arrested for a violent crime. Use of gabapentinoids was associated with increased hazards of suicidal behavior and deaths (age-adjusted hazard ratio [HR], 1.26; 95% CI, 1.20 to 1.32), unintentional overdoses (HR, 1.24; 95% CI, 1.19 to 1.28), head/body injuries (HR, 1.22; 95% CI, 1.19 to 1.25), and road traffic incidents and offenses (HR, 1.13; 95% CI, 1.06 to 1.20). Associations with arrests for violent crime were not significant (HR, 1.04; 95% CI, 0.98 to 1.11).
However, when the drugs were analyzed separately, pregabalin was linked to increased hazards of all outcomes, whereas gabapentin was associated with decreased or no statistically significant hazards. In age-stratified analyses, gabapentinoid use increased the hazard of suicidal behavior in people younger than age 55 years but showed reduced or no associations in those ages 55 years and older. Similarly, patients ages 15 to 34 years had increased hazards for the other outcomes, whereas those ages 55 years and older had reduced or no associations.
Limitations of the study included a lack of information on time-varying covariates (e.g., alcohol or drug use) and on treatment adherence, the study authors noted. In addition, the correlations they observed do not imply causation, they added.
Gabapentinoid prescribing rates have risen sharply in recent years, and evidence has suggested that the medications are being used, albeit ineffectively, as a substitute for opioids, an accompanying editorial noted. Despite valid concerns, gabapentinoids are a viable therapeutic option for many patients, although it may be time to rethink the term, the editorial said.
“The findings challenge the clinical utility of the broad categorisation ‘gabapentinoid’ and suggest it might be time to uncouple pregabalin and gabapentin for the purposes of legislation and guidelines. Both might need to be more specific about age group,” the editorialist wrote.