Pharmacology
Does taking gabapentin with opioids raise overdose death risk?
Open access · cc by · source: Europe PMC
People on prescription opioids who were also given gabapentin had about 50% higher odds of dying from an opioid overdose, with the greatest risk at moderate-to-high gabapentin doses.
Study at a glance
- Design
- Case-control — Nested case-control study within all Ontario public-drug-plan opioid recipients (1997-2013): coroner-confirmed accidental opioid deaths matched to up to four living opioid users on a disease risk index, age, sex, year and kidney disease; exposure was a gabapentin prescription in the prior 120 days.
- N
- N=5875 · 1,256 matched cases (opioid-related deaths) and 4,619 matched controls drawn from 2,914,971 opioid recipients; all were receiving opioids for non-cancer pain.
- Population
- Adults aged 15-105 eligible for Ontario public drug coverage (mostly under 65 and low-income) with an active opioid prescription and no cancer or palliative care.
- Outcome
- Odds of accidental opioid-related death with concomitant gabapentin versus opioids alone, overall and by gabapentin dose.
Structured fields used in claim comparison tables when every cited study has a complete layer.
Key findings
Gabapentin had been prescribed recently to 12.3% of those who died versus 6.8% of controls. Co-prescription was linked to 49% higher odds of opioid-related death (adjusted odds ratio 1.49); moderate and high gabapentin doses were linked to odds ratios of 1.56 and 1.58, low doses to a non-significant 1.32, and very high doses (2,500 mg a day or more) to 1.83. NSAID co-prescription showed no significant link, and in 2013 nearly half of Ontario gabapentin users also received an opioid.
Methodology
Using linked health records for everyone in Ontario who received publicly funded opioids between 1997 and 2013, the researchers identified people whose deaths the coroner confirmed were accidental and opioid-related. Each death was matched with up to four living opioid users of similar predicted risk, age, sex, year and kidney-disease history. They compared how often cases and controls had filled a gabapentin prescription in the previous 120 days, adjusting for opioid dose, other sedating drugs, alcohol use disorder and other health factors, and repeated the analysis for NSAIDs as a comparison drug that should not add risk.
Limitations
As an observational study it cannot prove gabapentin causes the deaths; people prescribed both drugs may differ in ways not captured, such as pain severity (confounding by indication). The sample was mostly low-income people under 65 on public drug coverage, so it may not generalise to all opioid users. Only dispensed, government-reimbursed prescriptions were seen, so adherence, cash or illicit drug use and the reason gabapentin was prescribed are unknown. The dose categories had overlapping confidence intervals, so the dose-response pattern is suggestive rather than firm.
How this study connects
Role on claims
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Additive respiratory depression is a real-world, dose-related hazard.
Combining sedating drugs raises risk: in an Ontario nested case-control study, gabapentin co-prescription with opioids was linked to 49% higher odds of opioid-related death (adjusted OR 1.49), rising to 1.83 at very high gabapentin doses, while NSAID co-prescription showed no link.
Evidence for the claim as stated.
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