Cariprazine and Buprenorphine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 16, 2026 · Source data updated Jul 16, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Cariprazine
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 (used for pain or opioid use disorder) and cariprazine (Vraylar, used for certain mental health conditions) can both slow down your brain and breathing. When you take them together, those slowing effects can add up. That may make you feel very sleepy or dizzy, and in serious cases it can make your breathing too slow.
The good news is that this is very manageable. Your care team may keep a closer eye on you or adjust your doses so both medicines stay safe. Please don't stop or change either one on your own. Just let your pharmacist or doctor know you take both, and tell them right away if you feel unusually drowsy, confused, or short of breath.
Mechanism: Additive CNS and respiratory depression. Buprenorphine is a partial opioid agonist; cariprazine is a CNS-active atypical antipsychotic. Effect is pharmacodynamic, not pharmacokinetic (neither is acting as a prodrug relevant here).
- Direction/effect: Increased risk of sedation, respiratory depression, overdose, and death.
- Evidence: Theoretical/epidemiologic (Swedish and US death-certificate data on MAT plus CNS depressants); onset unspecified.
- Management: Do NOT withhold MAT. Discontinuation of the CNS depressant is preferred where feasible; otherwise use lowest effective cariprazine dose or alternatives, and monitor sedation and respiratory status closely.
What happens
Increased risk of respiratory and CNS depression
Interaction Deep Dive
A Swedish epidemiological study found that mortality risk rises among patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also take benzodiazepines or other CNS depressants (for instance, agents used to treat insomnia). An analysis of pooled nationwide death certificate records spanning 2010 through 2014 showed that most overdose deaths involving buprenorphine or methadone also involved concurrent CNS depressant use. Whether buprenorphine and methadone differ in overdose death risk when combined with CNS depressants remains undetermined. Access to MAT drugs (such as methadone and buprenorphine) should not be withheld from patients being treated with CNS depressants, cariprazine included. While combining these agents raises the likelihood of serious adverse effects, overdose, and death, denying MAT access can result in a higher risk of morbidity and mortality tied to opioid use disorder. In the majority of situations, stopping the CNS depressant is the preferred approach. When concurrent use cannot be avoided, exercise careful monitoring and management; options include tapering the CNS depressant down to the lowest effective dose or turning to alternative treatments for anxiety or insomnia1.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination can be managed by your care team. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise, because stopping medication-assisted treatment on your own carries its own serious risks.
- Your team may monitor you more closely for excess sedation and breathing changes.
- Doses may be adjusted and individualized, often using the lowest effective dose of the CNS depressant or, where appropriate, an alternative treatment.
- Tell your pharmacist or prescriber about all sedating medicines, alcohol, or sleep/anxiety aids you use.
Seek help right away for severe drowsiness, confusion, or slow or shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) 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 example, medications used for insomnia) had an increased risk of death. From July 1, 2005 through December 31, 2012, investigators compared the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed versus periods without such therapy in MAT patients (aged 18 to 50). The findings showed a higher 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) when MAT was combined with benzodiazepine treatment; however, these data were not regarded as statistically significant. Although the results also indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of concurrent MAT and non-benzodiazepine use, 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. The authors did not compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication of use for the drugs 1.
b) An analysis of aggregate nationwide death certificate data from 2010 to 2014 identified 3495 drug overdose deaths reported in 2014. Methadone and other CNS depressants were often cited as contributors to those deaths. Concurrent use of alprazolam 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 that involved buprenorphine. Among 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 deaths involving methadone was 10 times that of deaths involving buprenorphine, though confounding factors and differences in drug utilization were not taken into account. It remains unknown whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 1.
Common questions
Can I take Cariprazine and Buprenorphine together?
Taking buprenorphine and cariprazine together can add up to dangerous drowsiness and slowed breathing, so keep both as prescribed and let your care team monitor you and tailor the doses. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cariprazine and Buprenorphine 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 Cariprazine and Buprenorphine interaction managed?
This combination can be managed by your care team. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise, because stopping medication-assisted treatment on your own carries its own serious risks. Your team may monitor you more closely for excess sedation and breathing changes. Doses may be adjusted and individualized, often using the lowest effective dose of t… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Cariprazine or Buprenorphine 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 (1)
- 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 Cariprazine
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