Buprenorphine and Thiothixene: 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
Thiothixene
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 that can slow your breathing and make you sleepy. Thiothixene is an older antipsychotic that also causes drowsiness and can slow down your gut and bladder. Taken together, these effects can add up. That means more sedation, slower breathing, and a higher chance of serious constipation or trouble emptying your bladder.
The good news: this can be managed. Your care team may keep an eye on how sleepy you feel, watch your breathing, and check that your gut and bladder are working. Please don't stop either medicine on your own. Just talk with your pharmacist or doctor so they can help you take both safely.
Effect: Additive CNS and respiratory depression, plus additive anticholinergic effects on gastric motility raising the risk of urinary retention, severe constipation, and paralytic ileus.
Mechanism: Pharmacodynamic. Buprenorphine (opioid MAT agent) and thiothixene (sedating, anticholinergic antipsychotic) both depress the CNS; thiothixene adds antimuscarinic GI/bladder effects. Neither is a prodrug in a way that alters this direction.
- Severity/Evidence: Major; probable (epidemiologic overdose-death data).
- Management: Do not deny MAT. Prefer discontinuing/tapering the CNS depressant to lowest effective dose or an alternative; monitor sedation, respiratory rate, bowel and bladder function.
What happens
Increased risk of respiratory and CNS depression and an increased risk of paralytic ileus
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). Analysis of nationwide aggregate death certificate data spanning 2010 to 2014 showed that most overdose fatalities involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the overdose death risk associated with concomitant CNS depressants varies between buprenorphine and methadone remains unknown. Patients on CNS depressant therapy, thiothixene included, should not be refused MAT drugs (such as methadone and buprenorphine). While combined use raises the likelihood of serious adverse effects, overdose, and death, denying MAT access can heighten the 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 is required, exercise caution in monitoring and management; options include tapering the CNS depressant to the lowest effective dose or turning to alternative treatments for anxiety or insomnia2. In addition, giving buprenorphine together with thiothixene (an anticholinergic agent) can produce urinary retention or severe constipation, potentially leading to paralytic ileus. Watch for indications of urinary retention or diminished gastric motility when buprenorphine and thiothixene are used together 1.
Why it happens (mechanism)
Additive CNS depression; additive effects on gastric motility
How to manage this interaction
Keep taking both as prescribed unless your prescriber tells you otherwise. Medication-assisted treatment is important and should not be withheld.
- Your team may prefer to reduce, taper, or replace the sedating medicine (thiothixene) when it is safe to do so, using the lowest effective dose or an alternative.
- Expect closer monitoring for excess drowsiness and slowed breathing.
- Watch for severe constipation, bloating, belly pain, or trouble urinating, and report these promptly.
- Avoid alcohol and other sedatives unless cleared by your care team.
Raise any of these symptoms with your pharmacist or prescriber so your doses can be adjusted and individualized.
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 analyzed the risk of fatal overdose, non-overdose related mortality, and all-cause mortality in MAT prescribed patients (aged 18 to 50), comparing periods during which CNS depressants were prescribed with periods without CNS depressant therapy. The findings showed an increased 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 considered statistically significant. Although the results demonstrated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were coadministered, only the data for fatal overdose and all-cause mortality were considered 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 for the drugs 2.
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 frequently 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 accounted for. It remains unknown whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 2.
Common questions
Can I take Buprenorphine and Thiothixene together?
Combining buprenorphine and thiothixene adds up sedation and breathing risk and can cause serious constipation or trouble urinating; keep taking both as prescribed but stay in close contact with your care team, who can lower or swap the sedating drug and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Thiothixene 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 Thiothixene interaction managed?
Keep taking both as prescribed unless your prescriber tells you otherwise. Medication-assisted treatment is important and should not be withheld. Your team may prefer to reduce, taper, or replace the sedating medicine (thiothixene) when it is safe to do so, using the lowest effective dose or an alternative. Expect closer monitoring for excess drowsiness and slowed breathing. Watch for severe const… 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 Thiothixene 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 (2)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. 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 Thiothixene
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