Buprenorphine and Molindone: 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
Molindone
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 opioid-treatment medicine, and molindone is an antipsychotic. Both can make you sleepy and slow your breathing. When taken together, those effects can add up, and in serious cases that can lead to very deep sedation or dangerously slow breathing.
This does not mean you can't take both. It means your care team wants to keep a close eye on things. Please don't stop or change either medicine on your own. Watch for unusual drowsiness, confusion, or slow or shallow breathing, and let your doctor or pharmacist know if you notice these. Your team can adjust doses and monitoring to keep you safe.
Mechanism: additive CNS and respiratory depression. Buprenorphine is a partial mu-opioid agonist; molindone is a dopamine antagonist antipsychotic with sedative properties. Neither is a prodrug relevant here, so this is a pharmacodynamic (not PK) interaction.
- Direction: combined depressant effect increased.
- Severity/evidence: major; probable.
- Risk: profound sedation, respiratory depression, coma, death (data largely from opioid MAT plus CNS depressants).
- Management: use lowest effective doses; monitor for respiratory depression and sedation; consider higher level of care if needed. Do not withhold MAT solely to avoid this interaction.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the combined effect on the central nervous system can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored rather than using them alongside buprenorphine. Depending on the situation, it may be suitable to observe the patient in a higher level of care or to institute a taper. In other situations, it may be appropriate to slowly withdraw a patient from a prescribed CNS depressant or to reduce the dose to the lowest amount that remains effective. Should concurrent use be required, exercise careful monitoring and management, and think about alternative approaches for managing 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 an elevated risk of death. Analysis of pooled nationwide death certificate records spanning 2010 to 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of fatal overdose from concomitant CNS depressant drugs varied between buprenorphine and methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this safely with the right precautions.
- Keep taking both as prescribed unless your doctor tells you otherwise.
- Your team may use the lowest effective dose of each drug and monitor you more closely, including in a higher level of care if needed.
- Watch for extreme drowsiness, confusion, or slow/shallow breathing, and get help right away if these occur.
- Ask your pharmacist before adding anything else that causes drowsiness (alcohol, sleep aids, other sedatives).
If you are on buprenorphine for opioid treatment, do not stop it out of fear of this interaction. Talk with your prescriber about the safest plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study reported that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, drugs used to treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, investigators examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed with periods without CNS depressant therapy in MAT-prescribed 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 MAT and benzodiazepine treatment; however, these data were not regarded as statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the data for fatal overdose and all-cause mortality were deemed statistically significant; 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 of the drugs 3.
b) According to a study of aggregate nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were often reported as contributors to those deaths. Concurrent ALPRAZolam use was reported 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 involving buprenorphine. Of these 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 methadone-involved deaths was 10 times the number of buprenorphine-involved deaths, although confounding factors and differences in drug utilization 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 Molindone together?
Taking buprenorphine and molindone together can stack up sedation and slow breathing, so use the lowest effective doses and watch for excessive drowsiness or breathing problems. Keep both as prescribed and coordinate any changes with your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Molindone 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 Molindone interaction managed?
Your care team can manage this safely with the right precautions. Keep taking both as prescribed unless your doctor tells you otherwise. Your team may use the lowest effective dose of each drug and monitor you more closely, including in a higher level of care if needed. Watch for extreme drowsiness, confusion, or slow/shallow breathing, and get help right away if these occur. Ask your pharmacist b… 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 Molindone 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 Molindone
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