Oxford, UK—A new observational study raises concerns about a link between treatment with gabapentinoids and increased risk of suicidal behavior, unintentional overdose, injuries, and road-traffic incidents.

The research from the University of Oxford and the Karolinska Institute in Sweden was published by The BMJ.

Prescriptions have risen dramatically for gabapentinoids, used to treat epilepsy, nerve pain, and anxiety disorders, according to the article, which also points out that those are among the top 15 drugs globally in terms of revenue.

Risks for adverse effects appear to be greatest in people aged 15 to 24 years, researchers note, leading them to suggest that treatment guidelines for young people be reviewed. Although previous studies have linked gabapentinoids to suicidal behavior and overdose-related deaths, results have been inconsistent and little data is available on longer term effects.

To remedy that, the international research team examined associations between gabapentinoids and a range of harms including suicidal behavior, unintentional overdose, injuries, road-traffic incidents, and violent crime.

Using national prescription, patient, death, and crime registers, the study team identified 191,973 patients aged 15 years and older who were prescribed pregabalin or gabapentin in Sweden between 2006 and 2013. The majority, 59%, of participants were women, and most were aged 45 years or older.

Researchers report that, during the study period, 5.2% of participants were treated for suicidal behavior or died from suicide, 8.9% experienced an unintentional overdose, 6.3% had a road-traffic incident or offense, 36.7% presented with head/body injuries, and 4.1% were arrested for a violent crime.

Results indicate that in within-individual analyses, gabapentinoid treatment was associated with increased hazards of suicidal behavior and deaths from suicide (age-adjusted hazard ratio 1.26; 95% CI, 1.20-1.32), unintentional overdoses (1.24; 1.19 to 1.28), head/body injuries (1.22; 1.19 to 1.25), and road-traffic incidents and offenses (1.13; 1.06-1.20).

Associations with arrests for violent crime were less clear (1.04; 0.98-1.11), however.

Researchers emphasized two important points:
• When the drugs were examined separately, pregabalin was associated with increased hazards of all outcomes, whereas gabapentin was associated with decreased or no statistically significant hazards.
• When stratifying by age, increased hazards of all outcomes were associated with participants aged 15 to 24 years.

“This study suggests that gabapentinoids are associated with an increased risk of suicidal behavior, unintentional overdoses, head/body injuries, and road traffic incidents and offences,” the authors conclude. “Pregabalin was associated with higher hazards of these outcomes than gabapentin.”

A linked editorial questions whether pregabalin and gabapentin should be considered separately for the purposes of legislation and guidelines but added that gabapentinoids “remain a valued therapeutic option for many people.”

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