Benzodiazepine Use With Methadone Prolonged Heart Rhythm Intervals More Than Methadone Alone
Among 421 methadone maintenance patients, QTc prolongation occurred during early treatment but was clinically insignificant, except when patients also used benzodiazepines, which significantly increased QTc prolongation beyond methadone alone.
Quick Facts
What This Study Found
Four hundred twenty-one opiate addicts newly admitted to methadone maintenance were followed prospectively for 4.5 years. QTc intervals were measured at baseline and again at a steady methadone dose. QTc prolonged significantly from 424.5 ms at baseline to 438.6 ms at steady dose, but this prolongation was not affected by methadone dose level or treatment duration beyond 2 years.
The critical finding was that patients whose urine tested positive for benzodiazepine during steady-dose treatment had significantly greater QTc prolongation (p=0.003). Two patients who were benzodiazepine abusers died from undefined causes. Cannabis use was included as a variable but was not associated with additional QTc risk.
Key Numbers
421 patients. QTc: 424.5 ms baseline to 438.6 ms at steady dose (significant). Benzodiazepine positive: significantly greater QTc prolongation (p=0.003). Cannabis positive: no additional QTc effect. 2 benzodiazepine-abusing patients died (undefined causes).
How They Did This
Prospective cohort study of 421 newly admitted methadone patients at 2 clinics. 4.5-year follow-up. Baseline ECG within 28 days of admission. Follow-up ECG at steady methadone dose with negative or positive urine toxicology. QTc intervals compared across conditions.
Why This Research Matters
QTc prolongation can lead to fatal cardiac arrhythmias. This study identifies benzodiazepine co-use as a specific risk factor that clinicians should monitor in methadone patients. The finding that cannabis did not add QTc risk provides reassurance for methadone patients who also use cannabis.
The Bigger Picture
Methadone's QTc-prolonging effect is well recognized, but this study identified benzodiazepine co-use as an additive risk factor. Given that benzodiazepine use is common among methadone patients, this interaction has important clinical safety implications.
What This Study Doesn't Tell Us
Urine testing provides only a snapshot of substance use. Cannabis and benzodiazepine categories were combined in some analyses. The "undefined" deaths in benzodiazepine users cannot be definitively attributed to QTc prolongation. Not all patients had follow-up ECGs. Methadone dose was not randomized.
Questions This Raises
- ?Should all methadone patients be screened for benzodiazepine use with regular ECGs?
- ?Does the QTc prolongation from benzodiazepine + methadone translate to increased cardiac events?
- ?Should cannabis be viewed as relatively safe regarding cardiac rhythm in methadone patients?
Trust & Context
- Key Stat:
- Benzodiazepine use significantly increased QTc prolongation beyond methadone alone (p=0.003)
- Evidence Grade:
- Prospective cohort with objective ECG measurements; moderate evidence for benzodiazepine-methadone cardiac interaction.
- Study Age:
- Published in 2013. Guidelines for cardiac monitoring during methadone treatment have been updated based on this and similar findings.
- Original Title:
- Prospective study of QTc changes among former opiate addicts since admission to methadone maintenance treatment: benzodiazepine risk.
- Published In:
- Journal of addiction medicine, 7(6), 428-34 (2013)
- Authors:
- Peles, Einat(4), Linzy, Shirley, Kreek, Mary Jeanne, Adelson, Miriam
- Database ID:
- RTHC-00715
Evidence Hierarchy
Enrolls participants and follows them forward in time.
What do these levels mean? →Frequently Asked Questions
Is it dangerous to mix methadone with benzodiazepines?
This study adds cardiac risk to the already-known respiratory risk of combining these drugs. Patients using benzodiazepines with methadone showed significantly greater prolongation of QTc intervals (a heart rhythm measure), which can predispose to dangerous arrhythmias. Two patients in this study who abused benzodiazepines died from undefined causes. This combination requires careful medical monitoring.
Does cannabis affect heart rhythm in methadone patients?
In this study, cannabis use did not add additional QTc prolongation risk beyond methadone alone, in contrast to benzodiazepines which significantly increased the risk. This suggests that regarding heart rhythm specifically, cannabis is a lower-risk co-substance for methadone patients than benzodiazepines.
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Cite This Study
https://rethinkthc.com/research/RTHC-00715APA
Peles, Einat; Linzy, Shirley; Kreek, Mary Jeanne; Adelson, Miriam. (2013). Prospective study of QTc changes among former opiate addicts since admission to methadone maintenance treatment: benzodiazepine risk.. Journal of addiction medicine, 7(6), 428-34. https://doi.org/10.1097/ADM.0b013e3182a8a4f2
MLA
Peles, Einat, et al. "Prospective study of QTc changes among former opiate addicts since admission to methadone maintenance treatment: benzodiazepine risk.." Journal of addiction medicine, 2013. https://doi.org/10.1097/ADM.0b013e3182a8a4f2
RethinkTHC
RethinkTHC Research Database. "Prospective study of QTc changes among former opiate addicts..." RTHC-00715. Retrieved from https://rethinkthc.com/research/peles-2013-prospective-study-of-qtc
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.