A Combination of Olanzapine and Samidorphan in Adults With Bipolar I Disorder and Schizophrenia: Overview of Clinical Data
Author Type(s)
Faculty
Document Type
Abstract
Publication Date
4-2021
DOI
10.1017/S1092852920002771
Journal Title
Bipolar Disorders
Department
Psychiatry and Behavioral Sciences
Abstract
Objectives
Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is hindered by significant weight gain. A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data. Methods
The OLZ/SAM development program consists of 18 phase 1–3 clinical studies evaluating antipsychotic and weight mitigation efficacy of OLZ/SAM, along with pharmacokinetics, safety, and tolerability. Safety evaluation also included metabolic laboratory assessments. Results
OLZ/SAM significantly improved psychotic symptoms (measured by Positive and Negative Syndrome Scale); improvements were similar to that observed with olanzapine vs placebo. OLZ/SAM resulted in significantly less weight gain than olanzapine. Additionally, 2 long-term phase 3 extension studies confirmed the durability of antipsychotic effect, as well as stabilization of weight and metabolic parameters in those continuing treatment. Supporting the potential use of OLZ/SAM in BD-I, OLZ/SAM or olanzapine resulted in bioequivalent olanzapine plasma concentrations, and OLZ/SAM did not affect lithium or valproate pharmacokinetics. OLZ/SAM treatment had no clinically relevant effects on ECG parameters (including QTc interval). OLZ/SAM and olanzapine safety were similar, except for reduced weight gain with OLZ/SAM; no additional safety risks were identified. Conclusion
Data across 18 OLZ/SAM studies in >1600 subjects support an antipsychotic efficacy and safety profile for OLZ/SAM that is similar to olanzapine, with significantly less weight gain than olanzapine. OLZ/SAM is a potential new treatment for schizophrenia and BD-I patients needing efficacious long-term treatment with reduced risk of weight gain.
Disciplines
Medicine and Health Sciences
Recommended Citation
Citrome, L., Graham, C., Simmons, A., Jiang, Y., Todtenkopf, M. S., Silverman, B. L., DiPetrillo, L., Cummings, H., Sun, L., & McDonnell, D. (2021). A Combination of Olanzapine and Samidorphan in Adults With Bipolar I Disorder and Schizophrenia: Overview of Clinical Data. Bipolar Disorders, 26 (2), 170. https://doi.org/10.1017/S1092852920002771
