Buprenorphine and Melperone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Melperone
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Buprenorphine is a strong pain and addiction-treatment medicine, and melperone is a sedating antipsychotic. Both can slow down your brain and your breathing. Taken together, that calming effect can stack up, and this can make you very drowsy, slow your breathing, or in serious cases cause dangerous or life-threatening problems.
The good news is that your care team can manage this. Please don't stop or change either medicine on your own. If you notice unusual sleepiness, confusion, or slow or shallow breathing, get help right away. Talk with your pharmacist or doctor so they can watch you closely and make sure your doses are right for you.
Mechanism: Additive CNS and respiratory depression. Buprenorphine is a partial opioid agonist; melperone is a sedating butyrophenone antipsychotic. Effect is pharmacodynamic (additive), not a prodrug or enzyme issue.
Direction/effect: Increased sedation, respiratory depression, profound sedation, potentially coma or death.
- Severity: Major; evidence probable.
- Onset: Unspecified.
- Management: Avoid concurrent use when possible; if necessary, use lowest effective doses and monitor for respiratory depression and sedation. Consider higher level of care or a taper. Do not withhold MAT from patients on CNS depressants; individualize dosing.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the CNS depressant effects can be additive, raising the likelihood of respiratory depression, profound sedation, coma, and death. Discontinuing CNS depressants is favored rather than using them at the same time. Depending on the situation, it may be suitable to observe the patient in a higher level of care or to implement a taper. In other circumstances, slowly weaning a patient off a prescribed CNS depressant or reducing it to the lowest effective dose may be appropriate. When concurrent use cannot be avoided, exercise caution in monitoring and management, and consider alternative treatments for anxiety or insomnia2. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for instance, medications used for insomnia) had a heightened risk of death. Based on an analysis of aggregate nationwide death certificate data spanning 2010 to 2014, most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of overdose death associated with concomitant CNS depressant drugs varied between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this combination safely with the right precautions.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop either one on your own.
- Your team may use the lowest effective dose of the sedating medicine, or gradually taper it, and may monitor you more closely.
- They may consider alternative options for anxiety or sleep if that medicine is being used for those reasons.
- Watch for severe drowsiness, confusion, or slow/shallow breathing and seek help right away.
Raise any daytime grogginess or breathing concerns with your pharmacist or doctor.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) An epidemiological study conducted in Sweden found that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, agents used to treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, researchers examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed compared with periods without CNS depressant therapy in MAT patients (aged 18 to 50). The findings showed a raised risk of all-cause mortality (adjusted hazard ratio (HR) 1.44; 95% CI, 0.93 to 2.23) and non-overdose related mortality (HR 1.74; 95% CI 1.00 to 3.01) with combined MAT and benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were given together, only the fatal overdose and all-cause mortality data reached statistical significance; HR 2.34 (95% CI, 1.37 to 3.99) and HR 1.33 (95% CI, 1.12 to 2.45), respectively. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not performed because the authors did not adjust for the indication of use for the drugs 3.
b) According to a study of pooled nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly cited as contributors to those deaths. Simultaneous ALPRAZolam use was noted in 18.1% of cases, followed by oxyCODONE (10.1%), cocaine (9.6%), heroin (9%), and diazePAM (6.6%). The FDA reported 322 drug overdose deaths in 2014 that involved buprenorphine. Of those 322 deaths, 32.9% involved ALPRAZolam, 17.4% involved clonazePAM, 11.2% involved diazePAM, 11.2% involved heroin, and 9.9% involved fentaNYL. The absolute number of deaths involving methadone was 10 times the number involving buprenorphine, although confounding factors and differences in drug use were not taken into account. Whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Buprenorphine and Melperone together?
Combining buprenorphine and melperone can dangerously add up their sedating and breathing-slowing effects, so use the lowest effective doses and have your care team monitor you closely. Watch for heavy drowsiness or slow breathing and get help immediately if it happens. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Melperone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Buprenorphine and Melperone interaction managed?
Your care team can manage this combination safely with the right precautions. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop either one on your own. Your team may use the lowest effective dose of the sedating medicine, or gradually taper it, and may monitor you more closely. They may consider alternative options for anxiety or sleep if that medicine is being… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Buprenorphine or Melperone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: SUBUTEX(R) sublingual tablets, buprenorphine sublingual tablets. Indivior Inc (per FDA), North Chesterfield, VA, 2021. DailyMed
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks. US Food and Drug Administration (FDA). Silver Spring, MD. 2017.
Keep reading about Buprenorphine
Keep reading about Melperone
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