Molero Y, Larsson H, D'Onofrio BM, et al. Associations between gabapentinoids and suicidal behaviour, unintentional overdoses, injuries, road traffic incidents, and violent crime: population based cohort study in Sweden. BMJ. 2019 Jun 12;365:l2147. doi: 10.1136/bmj.l2147. (Original study)

OBJECTIVE: To examine associations between gabapentinoids and adverse outcomes related to coordination disturbances (head or body injuries, or both and road traffic incidents or offences), mental health (suicidal behaviour, unintentional overdoses), and criminality.

DESIGN: Population based cohort study.

SETTING: High quality prescription, patient, death, and crime registers, Sweden.

PARTICIPANTS: 191 973 people from the Swedish Prescribed Drug Register who collected prescriptions for gabapentinoids (pregabalin or gabapentin) during 2006 to 2013.

MAIN OUTCOME MEASURES: Primary outcomes were suicidal behaviour, unintentional overdoses, head/body injuries, road traffic incidents and offences, and arrests for violent crime. Stratified Cox proportional hazards regression was conducted comparing treatment periods with non-treatment periods within an individual. Participants served as their own control, thus accounting for time invariant factors (eg, genetic and historical factors), and reducing confounding by indication. Additional adjustments were made by age, sex, comorbidities, substance use, and use of other antiepileptics.

RESULTS: During the study period, 10 026 (5.2%) participants were treated for suicidal behaviour or died from suicide, 17 144 (8.9%) experienced an unintentional overdose, 12 070 (6.3%) had a road traffic incident or offence, 70 522 (36.7%) presented with head/body injuries, and 7984 (4.1%) were arrested for a violent crime. In within-individual analyses, gabapentinoid treatment was associated with increased hazards of suicidal behaviour and deaths from suicide (age adjusted hazard ratio 1.26, 95% confidence interval 1.20 to 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 offences (1.13, 1.06 to 1.20). Associations with arrests for violent crime were less clear (1.04, 0.98 to 1.11). 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 on age, increased hazards of all outcomes were associated with participants aged 15 to 24 years.

CONCLUSIONS: This study suggests that gabapentinoids are associated with an increased risk of suicidal behaviour, unintentional overdoses, head/body injuries, and road traffic incidents and offences. Pregabalin was associated with higher hazards of these outcomes than gabapentin.

Discipline Area Score
Neurology 6 / 7
Pediatrics (General) 6 / 7
Psychiatry 6 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
FM/GP/Mental Health 6 / 7
Public Health 6 / 7
Comments from MORE raters

FM/GP/Mental Health rater

The presence of increased risks of dangerous behaviours suggests the need of reviewing guidelines for gabapentinoid treatment, especially in young people and in fragile portions of population.

FM/GP/Mental Health rater

The design does not allow adjustments for important interactions such as alcohol or other substance use. Difficult to decifer whether these are direct effects or the result of unsafe use of medication in combination with other substances, particularly for the younger group.

Neurology rater

This is a well designed study. Many more details of outcomes associated with an increased risk with gababentinoids are reported including suicidal behavior, unintentional overdoses, head/body injuries, and road traffic incidents and offenses. The period of the study extends from 2006-2018. In addition, pregabalin was associated with higher hazards for these outcomes than gabapentin. Physicians must better communicate with patients and their caregivers about these unintended side effects.

Psychiatry rater

Physicians who prescribe pregabalin should be aware of the risks associated with the agent.
Comments from EvidenceAlerts subscribers

Dr. Gregory Gray (7/1/2019 11:38 AM)

Further evidence that gabapentin and pregabalin are very different drugs

Dr. bruce macleod (6/25/2019 1:57 PM)

It would have been more useful to separate completed suicide from treated for suicidal behavior. There's a big difference and no way to evaluate them when combined. Also, why the age adjustment? And what was the effect on the stats?