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
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.
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
