Aripiprazole and Buprenorphine: 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
Aripiprazole
Buprenorphine
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.
Taking aripiprazole (Abilify) together with buprenorphine can add up in two ways. Both drugs can affect the heart's electrical rhythm (something called the QT interval), and together they may slow down your breathing and make you very sleepy. In rare cases this can become serious.
This does not mean the combination can never be used. Your doctor and pharmacist can manage it by choosing the right doses, keeping an eye on you, and sometimes checking your heart rhythm. Please don't stop either medicine on your own. If you feel unusually drowsy, confused, dizzy, or notice slow or shallow breathing, get medical help right away and talk with your care team.
Effect: Additive risk of QT prolongation plus additive CNS and respiratory depression.
- Mechanism: Both agents can prolong the QT interval; buprenorphine is a CNS/respiratory depressant and aripiprazole contributes sedation. Pharmacodynamic (additive), not a metabolic prodrug issue.
- Direction/magnitude: Increased risk of profound sedation, respiratory depression, arrhythmia; magnitude unspecified but potentially fatal.
- Onset: Unspecified. Evidence: Probable.
- Management: Avoid where possible; use lowest effective doses, individualize, monitor sedation/respiration and consider ECG for QT. Do not withhold MAT solely for this reason; strongly consider prescribing naloxone.
What happens
An increased risk of QT interval prolongation and an increased risk of CNS and respiratory depression
Interaction Deep Dive
Do not combine buprenorphine with agents capable of prolonging the QT interval. When the two are used together, there is also a heightened likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing benzodiazepines or other CNS depressants is favored rather than using them alongside buprenorphine. For certain patients, either observation within a higher level of care or a taper may be suitable. For others, it may be suitable to slowly wean the patient off a prescribed benzodiazepine or other CNS depressant, or to reduce it to the lowest dose that remains effective. Should concurrent use be required, exercise caution in monitoring and management; weigh alternative treatments for anxiety or insomnia and give strong consideration to prescribing naloxone for emergency treatment of opioid overdose2. 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, drugs used for insomnia) face an increased 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 use of a CNS depressant. Whether the risk of overdose death from concomitant CNS depressant drugs varied between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive QT interval prolongation; additive CNS depression
How to manage this interaction
Your care team can manage this combination safely with a few common steps:
- Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Do not stop buprenorphine on your own.
- Doses may be adjusted and individualized, often aiming for the lowest effective dose.
- Your team may monitor you more closely and may check your heart rhythm with an ECG.
- They may discuss alternatives for anxiety or sleep if those are also being treated.
- Ask whether naloxone (emergency overdose rescue) is appropriate to have on hand.
Report severe drowsiness, confusion, or slow breathing right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) A Swedish epidemiological study found that patients who received methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) have an increased risk of death. Among MAT-prescribed patients (aged 18 to 50), the periods when CNS depressants were prescribed were compared with periods without CNS depressant therapy for risk of fatal overdose, non-overdose related mortality, and all-cause mortality, over the interval from July 1, 2005 to December 31, 2012. 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 showed a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were given together, only the data for fatal overdose and all-cause mortality 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 benzodiazepine cohort and the non-benzodiazepine cohort were not compared because the authors did not adjust for the indication of use of the drugs 3.
b) Based on 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 often cited as contributors in those deaths. Concurrent 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. 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 the number of buprenorphine-involved deaths, though confounding factors and differences in drug utilization were not taken into account. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is not known 3.
c) Thorough QT studies conducted with buprenorphine products have shown modest QT prolongation of 15 msec or less 1.
Common questions
Can I take Aripiprazole and Buprenorphine together?
Combining aripiprazole and buprenorphine can add up to heart-rhythm changes and dangerous sedation or slowed breathing, so keep both as prescribed but have your care team monitor you and consider having naloxone available. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Aripiprazole 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 Aripiprazole and Buprenorphine interaction managed?
Your care team can manage this combination safely with a few common steps: Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Do not stop buprenorphine on your own. Doses may be adjusted and individualized, often aiming for the lowest effective dose. Your team may monitor you more closely and may check your heart rhythm with an ECG. They may discuss alternatives f… 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 Aripiprazole 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 (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 Aripiprazole
Keep reading about Buprenorphine
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