Co-prescription of the anticonvulsant gabapentin is associated with an increased risk of opioid-related death in people who are prescribed opioid painkillers, according to a new study published in PLOS Medicine.
Gabapentin is often used together with opioids to treat chronic pain, but both drugs have been shown to suppress breathing, a potentially deadly side-effect. Additionally, gabapentin use may also increase the amount of opioid absorbed by the body, effectively increasing the opioid dose.
In a case-control study among people who were prescribed opioid analgesics in Ontario, Canada, Dr. Tara Gomes of the University of Toronto, Canada, and colleagues, compared 1,256 opioid users who died of an opioid-related cause (cases) with 4,619 matched controls who also used opioids, but did not die of an opioid-related cause during the study period. Overall, 12.3% of cases (155 of 1,256) and 6.8% of controls (313 of 4,619) were prescribed gabapentin in the prior 120 days. After adjusting for additional risk factors, the authors found that the combination of gabapentin and opioid exposure was associated with a 49% higher risk of dying from an opioid overdose than opioid use alone (adjusted odds ratio 1.49; 95% confidence interval 1.18 to 1.88, p<0.001).
The authors caution that this study was limited to a population of individuals eligible for public drug coverage in Ontario, which disproportionately represented low-income neighborhoods. Additionally, the study could not assess drug adherence or account for drugs obtained outside the government reimbursement system (e.g., cash payments or illicit purchases). As with all observational studies, unmeasured confounding may influence the findings, in particular confounding by indication (for example, if pain from more severe underlying illness were a reason for gabapentin co-prescription). However, a sensitivity analysis found no additional risk of opioid-related death for patients co-prescribed opioids and nonsteroidal anti-inflammatory drugs, suggesting that this potential drug-drug interaction is specific to opioids and gabapentin.
"Clinicians should consider carefully whether to continue prescribing this combination of products, and when deemed necessary, should closely monitor their patients and adjust opioid dose accordingly."
This study was funded by a grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC; Grant #06673; TG, DNJ, MMM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
TA is supported by a New Investigator Award from the Canadian Institutes for Health Research (CIHR). DNJ has provided expert opinion on medicolegal matters, some of which have involved opioids (in no instances has DNJ engaged in paid work for or against opioid manufacturers.) Income received from speaking or expert testimony is tithed by The Sunnybrook Department of Medicine as part of their academic practice plan. MMM has served on advisory boards and reports honoraria from Bristol-Myers Squibb, Eli Lilly and Company, Glaxo Smith Kline, Hoffman La Roche, Novartis, Novo Nordisk, Pfizer, and Astra Zeneca, all outside the submitted work. WvdB received honoraria from Lundbeck, Indivior, Mundipharma, Novartis, Bioproject, Eli Lilly and Pfizer. All other authors report no conflicts of interest.
Gomes T, Juurlink DN, Antoniou T, Mamdani MM, Paterson JM, van den Brink W (2017) Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study. PLoS Med 14(10): e1002396. https://doi.org/10.1371/journal.pmed.1002396
Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
Sunnybrook Research Institute, Toronto, Ontario, Canada
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada
Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada
Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The
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