Cariprazine and Methadone: 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
Methadone
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.
Methadone and cariprazine (Vraylar) can both slow down your brain and your breathing. When you take them together, those calming effects can add up. This may make you feel very drowsy, dizzy, or foggy, and in serious cases it can slow your breathing too much.
The good news is that your care team can manage this. It does not mean you have to give up your methadone, which is an important treatment. Please don't stop or change either medicine on your own. Instead, tell your pharmacist or doctor you take both, and watch for unusual sleepiness or trouble breathing. They can adjust things and keep a closer eye on you to keep you safe.
Mechanism: additive CNS depression. Both agents (methadone, a full mu-opioid agonist, and cariprazine, an atypical antipsychotic) independently produce sedation and respiratory depression; combined use is additive. Neither is a prodrug relevant to this pharmacodynamic interaction.
- Effect: increased risk of respiratory and CNS depression, sedation, overdose, and death.
- Evidence: theoretical/epidemiological (Swedish and US death-certificate data on opioid MAT plus CNS depressants); onset unspecified; severity major.
- Management: do not withhold MAT. Discontinuation of the CNS depressant is often preferred. If continued, use lowest effective cariprazine dose, monitor sedation and respiratory status, and consider alternatives for anxiety/insomnia.
What happens
Increased risk of respiratory and CNS depression
Interaction Deep Dive
A Swedish epidemiological investigation 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 for insomnia). Analysis of aggregate nationwide death certificate records spanning 2010 to 2014 showed that most overdose fatalities linked to buprenorphine and methadone also involved concurrent CNS depressant use. Whether buprenorphine and methadone differ in their overdose death risk when combined with CNS depressants remains unknown. Individuals being treated with CNS depressants, cariprazine among them, should not be refused access to MAT medications (such as methadone and buprenorphine). While combining these agents raises the likelihood of serious adverse effects, overdose, and death, denying MAT access may result in greater 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 reducing the CNS depressant to the lowest effective dose or turning to alternative therapies for anxiety or insomnia1.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination is used sometimes, and your team can manage it safely. The main goal is to keep your opioid treatment (methadone) while lowering the added sedation risk.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop your methadone on your own.
- Your care team may monitor you more closely for drowsiness or slowed breathing.
- They may adjust and individualize your cariprazine dose to the lowest effective amount, or consider an alternative if it is being used for anxiety or sleep.
- Tell your pharmacist or doctor right away about heavy sedation, confusion, or breathing trouble, and avoid alcohol or other sedatives.
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 received 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, investigators examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed to periods without CNS depressant therapy in MAT patients (aged 18 to 50). The analysis 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) with MAT combined with benzodiazepine treatment; however, these findings were not deemed statistically significant. Although the results also indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the fatal overdose and all-cause mortality figures 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 for which the drugs were used 1.
b) In a study analyzing pooled nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone together with other CNS depressants were often cited as contributors to these 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 documented 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 methadone-involved deaths was 10 times that of buprenorphine-involved deaths, though confounding factors and differences in drug utilization were not taken into account. Whether the risk of overdose death with concurrent CNS depressant drugs differs between buprenorphine and methadone remains unknown 1.
Common questions
Can I take Cariprazine and Methadone together?
Methadone and cariprazine both depress the brain and breathing, so together they raise the risk of oversedation and, rarely, dangerous slowed breathing. Keep taking both as prescribed, avoid other sedatives and alcohol, and ask your care team to monitor you and tailor the dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cariprazine and Methadone 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 Methadone interaction managed?
This combination is used sometimes, and your team can manage it safely. The main goal is to keep your opioid treatment (methadone) while lowering the added sedation risk. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop your methadone on your own. Your care team may monitor you more closely for drowsiness or slowed breathing. They may adjust and individualize… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Cariprazine or Methadone 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 Methadone
Keep reading about Cariprazine
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist