Olanzapine/Samidorphan (Lybalvi) and Buprenorphine: Considerations for a Contradictory Combination: A Case Report

Samidorphan is an opioid receptor antagonist and naltrexone analogue that has been harnessed in unique ways. Samidorphan has been paired with olanzapine in the new oral agent Lybalvi, approved by the FDA in 2021 for the treatment of schizophrenia and bipolar I disorder. The addition of samidorphan to olanzapine has the intention of reducing olanzapine's metabolic side effects (ie, weight gain), however, samidorphan's antagonism of the mu opioid receptor can lead to complications in patients with opioid use disorder on agonist therapy. These complications include not just precipitated withdrawal, as explored in prior case studies, but also the risk of reduced opioid tolerance and overdose in the event of olanzapine/samidorphan (Lybalvi) discontinuation and concurrent opioid use.

A 42-year-old female with a history of opioid use disorder, posttraumatic stress disorder (PTSD), and bipolar disorder presented to an opioid treatment program for buprenorphine/naloxone (BUP/NX) continuation. On presentation, she was being treated with a combination of olanzapine/samidorphan (Lybalvi) for bipolar disorder and 18 mg/d of transmucosal BUP/NX for opioid use disorder. Due to concern for interaction between buprenorphine and samidorphan, she was gradually tapered to a lower dose of buprenorphine to allow for discontinuation of olanzapine/samidorphan then titrated to an effective buprenorphine dose for long-term treatment.

This case report outlines the safety concerns of utilizing an opioid antagonist (samidorphan) in conjunction with an opioid partial agonist (buprenorphine) and demonstrates the process for safe transition to an alternative regimen.