Gabapentinoids up risk of suicidal behaviour, injuries and violent crimes
Use of gabapentinoids tends to induce suicidal behaviour and unintentional overdoses and may even lead to head/body injuries as well as road traffic incidents and offenses, suggests a study. Moreover, such associations are more robust with pregabalin than gabapentin.
“We found that gabapentinoids were associated with both increased and decreased risks of important adverse outcomes,” researchers said. “These associations varied with age and type of gabapentinoid.”
Of the 191,973 participants, 10,026 (5.2 percent) received treatment for suicidal behaviour or died from suicide, 17,144 (8.9 percent) had an unintentional overdose, 12,070 (6.3 percent) experienced a road traffic incident or offense, 70,522 (36.7 percent) presented with head/body injuries, and 7,984 (4.1 percent) were arrested for a violent crime during the study period. [BMJ 2019;365:l2147]
Within-individual analyses revealed the associations of gabapentinoid with higher risks of suicidal behaviour and death from suicide (age-adjusted hazard ratio [aHR], 1.26, 95 percent CI, 1.20–1.32), unintentional overdoses (aHR, 1.24, 1.19–1.28), head/body injuries (aHR, 1.22, 1.19–1.25), and road traffic incidents and offenses (aHR, 1.13, 1.06–1.20). Of note, the association with arrests for violent crime were less clear (aHR, 1.04, 0.98–1.11).
Separate analysis of gabapentinoids showed that pregabalin correlated with higher risks of all outcomes, while gabapentin correlated with reduced or no statistically significant risks. Furthermore, stratification by age revealed that those aged 15–24 years had an increased risk of all outcomes.
“Overall, gabapentinoids seem to be safe for a range of outcomes in older people,” researchers said. “However, the increased risks found in adolescents and young adults prescribed gabapentinoids, particularly for suicidal behaviour and unintentional overdoses, warrant further research.”
The varying results of the two study drugs could be explained by their different pharmacodynamic and pharmacokinetic profiles. For instance, pregabalin has a higher potency, greater bioavailability and faster absorption than gabapentin. [Clin Pharmacokinet 2010;49:661-669; Anesth Analg 2007;105:1805-1815; Can J Anaesth 2013;60:44-49; CNS Drugs 2014;28:491-496]
In addition, previous studies have shown an association between pregabalin use and withdrawal symptoms following rapid discontinuation, which could be related to suicidal behaviour. [Clin Neuropharmacol 2001;24:245-246; Eur J Clin Pharmacol 2013;69:1335-1342; Ther Adv Drug Saf 2014;5:38-56; Neuropsychiatr Dis Treat 2013;9:883-892]
There are also other reports confirming the association of gabapentinoids with overdoses and deaths. [N Engl J Med 2017;377:411-414; Drugs 2017;77:403-426; BMJ 2017;358:j4441; Psychother Psychosom 2011;80:118-122; Emerg Med J 2013;30:874; Eur J Clin Pharmacol 2013;69:1335-1342; Addiction 2016;111:1160-1174; Eur Neuropsychopharmacol 2017;27:1185-1215]
“If our findings are triangulated with other forms of evidence, clinical guidelines may need review regarding prescriptions for young people, and those with substance use disorders,” researchers said. “Further restrictions for off-label prescription may need consideration.”
The current population-based cohort study identified participants from the Swedish Prescribed Drug Register who collected prescriptions for gabapentinoids during 2006 to 2013. Stratified Cox proportional hazards regression was conducted to compare treatment periods with nontreatment periods within an individual.
Participants served as their own control; this accounted for time invariant factors and reduced confounding by indication. Researchers made additional adjustments by age, sex, comorbidities, substance use and use of other antiepileptics.