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Review
. 2022 Oct;38(5):304-313.
doi: 10.1177/87551225221114281. Epub 2022 Jul 29.

Olanzapine/Samidorphan: A New Option for the Treatment of Adults With Schizophrenia or Bipolar I Disorder

Huy Pham  1 , Halford Warlick  2 , Ricardo Bermudez  3 , Quan Nguyen  4 , Jose A Rey  5
Affiliations
Review

Olanzapine/Samidorphan: A New Option for the Treatment of Adults With Schizophrenia or Bipolar I Disorder

Huy Pham et al. J Pharm Technol. 2022 Oct.

Abstract

Objective: To review the pharmacology, pharmacokinetics, and efficacy and safety data of a combination of olanzapine and samidorphan (OLZ/SAM) for the treatment of schizophrenia and bipolar I disorder, which mitigates the possible unwanted side effects of weight gain associated with olanzapine (OLZ).

Data sources: The review was done with a bibliographic survey of studies using MEDLINE/PubMed (January 1999-May 2021) database using the keywords olanzapine and samidorphan. Abstracts, scientific posters, and information from the manufacturer's product labeling were evaluated for inclusion. Inclusion criteria: phase 2, phase 3, and open-labeled studies that evaluated the use of OLZ/SAM for the treatment of schizophrenia and bipolar I disorder.

Data synthesis: We have included one phase 2 dose-ranging exploratory study, two phase 3 efficacy and safety studies, and several open-label extension studies without a comparator. For the treatment of schizophrenia, OLZ/SAM and OLZ alone were analyzed in 2 randomized, double-blind comparison studies of approximately 960 patients. Analysis indicated that OLZ (5-20 mg)/SAM (10 mg) significantly mitigated the side effect of weight gain compared with OLZ alone (control) while maintaining antipsychotic efficacy. For bipolar I disorder, OLZ/SAM was approved as an acute treatment for manic or mixed episodes, as well as an adjunct to valproate or lithium for manic/mixed episodes based on bridging strategy allowed by the Food and Drug Administration.

Relevance to patient care and clinical practice: The combination of olanzapine and samidorphan demonstrated efficacy for the treatment of schizophrenia with a dosage range of 5 to 20 mg OLZ to a 10-mg fixed dose of samidorphan. Advantages of this drug combination include once-daily dosing, favorable tolerability, and most importantly, mitigation of weight gain, which may encourage adherence, when compared with OLZ alone.

Conclusion: The new combination treatment of OLZ/SAM is a unique antipsychotic formulation to provide the recognized efficacious treatment of OLZ, while mitigating the weight gain and possibly the weight-related adverse effects secondary to OLZ monotherapy.

Keywords: bipolar I disorder; olanzapine; samidorphan; schizophrenia; weight gain.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Rey is a paid consultant for Alkermes, maker of OLZ/SAM, his Conflict of Interest (COI) is minimal in this article as he only serves as an advisor for the writing and editing of this article.

Figures

Figure 1.
Figure 1.
Chemical structures of samidorphan and naltrexone.
See this image and copyright information in PMC

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