Opioid users co-prescribed gabapentin had about 50 percent higher odds of an opioid-related death
In Ontario, 12.3 percent of 1,256 opioid-related deaths had gabapentin prescribed in the prior 120 days, against 6.8 percent of matched opioid-using controls: adjusted odds ratio 1.49, rising to 1.58 at 1,800 mg a day or more.
Suggestive but preliminary. Not settled. how we score evidence
Caveat on this rating: Nested case-control in administrative data: association, not causation; residual confounding by pain severity or illness is possible. Ontario only, 1997 to 2013. The NSAID negative control strengthens but does not settle the causal reading.
The gabapentin label warns about breathing with opioids. This is the study behind the size of that risk.
Significant findings
Gomes and colleagues (PLoS Medicine, 2017) ran a population-based nested case-control study among opioid users in Ontario, Canada, from 1997 to 2013. Cases were opioid users who died of an opioid-related cause; each was matched with up to four opioid-using controls on age, sex, year, kidney disease and a disease risk index. "After matching, we included 1,256 cases and 4,619 controls."
"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 multivariable adjustment, co-prescription of opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI 1.61 to 2.47, p < 0.001; adjusted OR [aOR] 1.49, 95% CI 1.18 to 1.88, p < 0.001) compared to opioid prescription alone."
Dose mattered: moderate (900 to 1,799 mg daily) and high (1,800 mg or more) gabapentin "was associated with a nearly 60% increase in the odds of opioid-related death relative to no concomitant gabapentin use." The control comparison was clean: "we found no significant association between co-prescription of opioids and NSAIDs and opioid-related death," which is what you would expect if the gabapentin finding is about sedation rather than about being the kind of patient who takes a second drug.
The abstract's framing sentence: "Although gabapentin is widely perceived as safe, drug-induced respiratory depression has been described when gabapentin is used alone or in combination with other medications."
Worth asking
Case-control designs cannot prove cause, and the authors adjusted for what the databases could see. What the NSAID comparison adds is a negative control: a second painkiller that does not sedate showed no such association. If you take gabapentin for anxiety or sleep and an opioid is proposed, or the reverse, the question is whether the prescriber has weighed this study, and at what gabapentin dose.
Source
Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study — Gomes T, Juurlink DN, Antoniou T, Mamdani MM, Paterson JM, van den Brink W (2017)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1371/journal.pmed.1002396
DOI: 10.1371/journal.pmed.1002396
How this was scored
- Study design
- Case-control study
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- 5,875
- Preregistered
- not recorded
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "early signal". Suggestive but preliminary. Not settled. It scores 52 out of 100 on our published rubric. One caveat travels with that badge: Nested case-control in administrative data: association, not causation; residual confounding by pain severity or illness is possible. Ontario only, 1997 to 2013. The NSAID negative control strengthens but does not settle the causal reading. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study — Gomes T, Juurlink DN, Antoniou T, Mamdani MM, Paterson JM, van den Brink W (2017). Published in: Reputable peer-reviewed journal. DOI: 10.1371/journal.pmed.1002396. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Case-control study. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.