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Olanzapine/samidorphan combo mitigates weight gain in phase 3 schizophrenia study

Key clinical point: Treatment with olanzapine/samidorphan combination is associated with significantly less weight gain than olanzapine monotherapy in patients with schizophrenia.

Major finding: At week 24, the least squares mean percent change was 4.21% for the olanzapine/samidorphan group and 6.59% for the olanzapine group (a difference of −2.38%; P = .003). The proportion of patients with 10% or more weight gain was significantly lower in the olanzapine/samidorphan vs. olanzapine group (17.8% vs. 29.8%; odds ratio, 0.50).

Study details: In this phase 3 trial, 561 patients with schizophrenia (age, 18-55 years) were randomly assigned (1:1) to receive olanzapine/samidorphan combination or olanzapine alone for 24 weeks.

Disclosures: The study was sponsored by Alkermes. The authors reported owning stock in, being an employee of, receiving support from, and/or consulting for Alkermes.


“Antipsychotic drugs, including olanzapine, are a foundational treatment for individuals with schizophrenia. Despite olanzapine’s robust efficacy demonstrated in multiple clinical trials, the compound is no longer widely used in clinical practice settings because of the associated risk of significant weight gain and metabolic complications such as diabetes. The key finding that olanzapine/samidorphan combination treatment was associated with less weight gain than olanzapine monotherapy has some important clinical implications. Clinicians considering olanzapine as a new-start therapeutic option might chose to initiate olanzapine/samidorphan combination therapy as one strategy to potentially minimize weight gain as a treatment complication. Additionally, patients who had previous good psychotic symptom response to olanzapine, but who were unable to sustain treatment due to unacceptable weight gain or metabolic complications might be candidates for a re-challenge with olanzapine/samidorphan combined therapy.”

Martha Sajatovic, MD

Professor of Psychiatry and of Neurology

Willard Brown Chair in Neurological Outcomes Research

Director, Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center

Case Western Reserve University School of Medicine


Correll CU et al. Am J Psychiatry. 2020 Aug 14. doi: 10.1176/appi.ajp.2020.19121279.