Olanzapine/Samidorphan-Associated Opioid Withdrawal Reported to US Poison Centers
James B. Leonard, Sheila MohebbiPurpose/Background:
Olanzapine/samidorphan is a combination medication indicated for the treatment of mood and psychotic symptoms with limited weight gain. Samidorphan is a mu-opioid receptor antagonist that is contraindicated in patients actively using opioids.
Methods/Procedures:
Retrospective evaluation of olanzapine/samidorphan cases reported to the National Poison Data System between May 1, 2021, and June 30, 2025. We reviewed coded data to identify those possibly describing a patient who experienced opioid withdrawal. Case notes were requested from individual poison centers, and clinical factors were extracted from the notes.
Findings/Results:
There were 426 cases reported to the National Poison Data System, of which 31 were patients experiencing opioid withdrawal. About half were male, and the median age was 45 years. Buprenorphine and methadone were the most common opioids that patients were previously taking. Opioid withdrawal lasted about 24 hours for most patients. Seven patients were intubated in the course of their withdrawal management.
Implications/Conclusions:
Precipitated opioid withdrawal is a known concern when initiating olanzapine/samidorphan in patients using opioids. Withdrawal may last about 24 hours and require inpatient treatment. Careful screening for opioid use may reduce the risk.