Olanzapine/Samidorphan: New Drug Approved for Treating Bipolar I Disorder and Schizophrenia

To describe the approval of olanzapine/samidorphan, compare the clinical trial data, and summarize key findings, with a focus on impact to clinical practice.

A literature search of PubMed was performed (March 2006 to November 2021) using the following search terms: Lybalvi, olanzapine/samidorphan, olanzapine, antipsychotic, bipolar disorder, and schizophrenia. Product monographs, review articles, and randomized control trials were reviewed.

Relevant English-language studies conducted in humans were considered. Primary use of Phase III clinical drug approval trials preferred; supplementary trial analysis evaluated to provide context.

In June 2021, the Food and Drug Administration (FDA) approved Lybalvi^® (olanzapine/samidorphan) for indications including treatment of adults with schizophrenia and/or bipolar I disorder (acute manic episodes or acute episodes with mixed features) through the multi-stage ENLIGHTEN clinical trials. Participants were enrolled in 4-week, 24-week, and 52-week studies to evaluate the safety and efficacy of olanzapine/samidorphan. Subsequent secondary analysis evaluated metabolic effects.

This review details the pharmacologic, pharmacokinetic, associated dosing and indications, and adverse effects for the drug combination olanzapine/samidorphan. Better understanding of novel drug mechanisms will help to expand on the potential role and place for use in clinical practice.

When treating complex patients with schizophrenia, the olanzapine/samidorphan combination has limited effect on medication-induced weight gain often associated with antipsychotic olanzapine monotherapy. Additional studies are needed to further define the role of olanzapine/samidorphan in bipolar I disorder and clinical practice.