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Olanzapine/Samidorphan-Associated Opioid Withdrawal Reported to US Poison Centers
James B Leonard1, Sheila Mohebbi2
1Washington Poison Center.
Journal of Clinical Psychopharmacology
|August 4, 2026
Summary
Olanzapine/samidorphan can cause precipitated opioid withdrawal in patients using opioids. This withdrawal typically lasts 24 hours and may require hospitalization, highlighting the need for careful opioid use screening.
Area of Science:
- Pharmacology
- Toxicology
- Clinical Medicine
Background:
- Olanzapine/samidorphan is a medication for mood and psychotic symptoms associated with limited weight gain.
- Samidorphan, a mu-opioid receptor antagonist component, is contraindicated in active opioid users due to withdrawal risks.
Purpose of the Study:
- To evaluate cases of precipitated opioid withdrawal associated with olanzapine/samidorphan use.
- To understand the clinical characteristics and management of opioid withdrawal in patients taking olanzapine/samidorphan.
Main Methods:
- Retrospective analysis of 426 cases reported to the National Poison Data System (May 2021-June 2025).
- Identification of cases describing opioid withdrawal, followed by detailed clinical data extraction from poison center notes.
Main Results:
- 31 out of 426 cases involved patients experiencing opioid withdrawal.
- Commonly used opioids included buprenorphine and methadone; withdrawal duration was approximately 24 hours.
- Seven patients required intubation for withdrawal management.
Conclusions:
- Precipitated opioid withdrawal is a significant risk when initiating olanzapine/samidorphan in opioid-using patients.
- Withdrawal symptoms can necessitate inpatient care and last around 24 hours.
- Thorough screening for prior opioid use is crucial to mitigate this risk.
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