---
title: "Psych News Alert: Drug Combination Mitigates Weight Gain in Patients With Schizophrenia, Study Shows"
description: The combination of the antipsychotic olanzapine and samidorphan, an experimental agent that acts on opioid receptors in the brain, result...
image: https://alert.psychnews.org/hubfs/Imported_Blog_Media/DOCTOR%20COUNSELS%20PATIENT%20ABOUT%20PILLS%20iStock-1041147612-4.jpg
---

 3/12/19 12:00 AM

# Drug Combination Mitigates Weight Gain in Patients With Schizophrenia, Study Shows

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The combination of the antipsychotic olanzapine and samidorphan, an experimental agent that acts on opioid receptors in the brain, results in significantly lower weight gain than olanzapine plus placebo in patients with schizophrenia, according to a [report](https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2018.18030280) in *AJP in Advance*.

At the same time, olanzapine plus samidorphan demonstrated equal antipsychotic efficacy as olanzapine plus placebo. Olanzapine is highly effective for treating psychotic symptoms in people with schizophrenia but can cause significant weight gain resulting in metabolic disease.

“Antipsychotic-induced weight gain generally has a rapid onset and can occur in the first few weeks of treatment—an effect that was seen in all treatment groups during the first two weeks of this study,” wrote lead author William Martin, M.D., senior director of clinical development at Alkermes, manufacturer of samidorphan. “Thus, the addition of samidorphan mitigates olanzapine-associated weight gain but does not completely prevent it. Rather, treatment with olanzapine plus samidorphan changed the trajectory of weight gain over the remainder of the study period.”

In the study, 309 patients with schizophrenia had a one-week open-label treatment with olanzapine, followed by a 12-week double-blind treatment phase in which patients were randomly assigned to receive olanzapine plus placebo (n=75) or olanzapine plus samidorphan in these doses:5 mg (n=80), 10 mg (n=86), and 20 mg (n=68).

Patients in the olanzapine-plus-samidorphan groups experienced 37 percent lower weight gain than those in the olanzapine plus placebo group. Positive and Negative Symptom Scale (PANSS) scores were equivalent at follow-up for all groups. In addition, olanzapine plus samidorphan was generally well tolerated, with a safety profile similar to olanzapine plus placebo.

Olanzapine plus samidorphan at 10 mg/day was seen to be an effective dosage and superior to the 5 mg/day dosage. The 10 mg/day dosage was associated with a weight gain pattern similar to the 20 mg/day dosage, but overall adverse events were higher at 20 mg/day.

“The findings from this study identified 10 mg of samidorphan as the daily dose to further assess the mitigation of olanzapine-induced weight gain, and they support the continued development of olanzapine plus samidorphan in a phase 3 program,” the researchers concluded.

For related information see the *Psychiatric News* article “[Taking Some Antipsychotics During Pregnancy May Raise Risk of Gestational Diabetes](https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2018.pp5a3).”

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[schizophrenia](https://alert.psychnews.org/tag/schizophrenia), [ajp in advance](https://alert.psychnews.org/tag/ajp-in-advance), [olanzapine](https://alert.psychnews.org/tag/olanzapine), [metabolic disease](https://alert.psychnews.org/tag/metabolic-disease), [weight gain](https://alert.psychnews.org/tag/weight-gain), [samidorphan](https://alert.psychnews.org/tag/samidorphan)

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