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. 2019 Jun 12:365:l2147.
doi: 10.1136/bmj.l2147.

Associations between gabapentinoids and suicidal behaviour, unintentional overdoses, injuries, road traffic incidents, and violent crime: population based cohort study in Sweden

Yasmina Molero  1   2   3 , Henrik Larsson  2   4 , Brian M D'Onofrio  2   5 , David J Sharp  6 , Seena Fazel  7
Affiliations

Associations between gabapentinoids and suicidal behaviour, unintentional overdoses, injuries, road traffic incidents, and violent crime: population based cohort study in Sweden

Yasmina Molero et al. BMJ. .

Abstract

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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Henrik Larsson reports grants from Shire and Evolan, and has served as a speaker for Shire, all outside of the submitted work.

Figures

Fig 1
Fig 1
Within-individual associations between gabapentinoid treatment and adverse outcomes
Fig 2
Fig 2
Within-individual associations between gabapentinoid treatment and adverse outcomes by age
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References

    1. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet 2010;49:661-9. 10.2165/11536200-000000000-00000 - DOI - PubMed
    1. Johansen ME. Gabapentinoid use in the United States 2002 through 2015. JAMA Intern Med 2018;178:292-4. 10.1001/jamainternmed.2017.7856 - DOI - PMC - PubMed
    1. Goodman CW, Brett AS. Gabapentin and pregabalin for pain - is increased prescribing a cause for concern? N Engl J Med 2017;377:411-4. 10.1056/NEJMp1704633 - DOI - PubMed
    1. Philippidis A. The top 15 best-selling drugs of 2016. Genetic Engineering & Biotechnology News. Accessed July, 2018: www.genengnews.com/the-lists/the-top-15-best-selling-drugs-of-2016/77900868, 2017.
    1. PMLIVE. Top 50 pharmaceutical products by global sales. Accessed July 10, 2018: www.pmlive.com/top_pharma_list/Top_50_pharmaceutical_products, 2017.

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