Opioid users who also filled a benzodiazepine had about twice the odds of an overdose visit
Among 315,428 insured opioid users, the share also taking a benzodiazepine rose from 9 percent in 2001 to 17 percent in 2013. Concurrent use carried an adjusted odds ratio of 2.14 for an overdose emergency visit or admission.
Well-supported by good-quality research. how we score evidence
Caveat on this rating: Retrospective claims analysis: association, not causation, and the authors say so ("If this association is causal"). Privately insured adults under 65 only; the elderly and Medicaid populations, where both drugs are common, are not represented.
The label says the combination is dangerous. This is the study that put a number on it, in the year before the FDA required the boxed warning.
Significant findings
Sun and colleagues (BMJ, 2017) analysed claims for 315,428 privately insured people aged 18 to 64 who filled at least one opioid prescription between 2001 and 2013. Concurrent use meant the two prescriptions overlapped by at least one day. "9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users."
On the outcome: "Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P<0.001) among all opioid users." The odds ratio was 1.42 for intermittent opioid users and 1.81 for chronic users.
The authors' own conditional: "If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16)."
Worth asking
Two things this study is not. It is not a trial, so it cannot prove the benzodiazepine caused the overdoses; people prescribed both may differ in ways claims data cannot see. And it is not about street drugs; every exposure was a filled prescription from a doctor. That second point is the useful one. Both drugs came through a pharmacy, which means a pharmacist can see both. If you take either, ask the pharmacist to check for the other.
Source
Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis — Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S (2017)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1136/bmj.j760
DOI: 10.1136/bmj.j760
How this was scored
- Study design
- Cohort study
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 315,428
- 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 "strong evidence". Well-supported by good-quality research. It scores 74 out of 100 on our published rubric. One caveat travels with that badge: Retrospective claims analysis: association, not causation, and the authors say so ("If this association is causal"). Privately insured adults under 65 only; the elderly and Medicaid populations, where both drugs are common, are not represented. 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?
Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis — Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S (2017). Published in: Top-tier peer-reviewed journal. DOI: 10.1136/bmj.j760. 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: Cohort study. Funding: Independently funded. 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.