Olanzapine and samidorphan combination treatment: A systematic review

Muhammad Youshay Jawad; Yazen Alnefeesi; Leanna M W Lui; Felicia Ceban; David C J Chen-Li; Kayla Teopiz; Saja Jaberi; Emily S Gillissie; Joshua D Di Vincenzo; Joshua D Rosenblat; Roger S McIntyre

doi:10.1016/j.jad.2022.01.004

Olanzapine and samidorphan combination treatment: A systematic review

J Affect Disord. 2022 Mar 15:301:99-106. doi: 10.1016/j.jad.2022.01.004. Epub 2022 Jan 7.

Affiliations

¹ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
² Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
³ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
⁴ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁵ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address: roger.mcintyre@uhn.ca.

PMID: 35007644
DOI: 10.1016/j.jad.2022.01.004

Abstract

Introduction: The overarching aim of this review is to synthesize the efficacy, tolerability, and weight-mitigation effects of the olanzapine/samidorphan (OLZ/SAM) combination treatment in adults with schizophrenia and bipolar disorder-I.

Methods: A systematic search of PubMed, Web of Science, Embase, and The Cochrane Library was conducted on August 15th, 2021. Studies were included if they investigated the use of OLZ/SAM treatment in patients with schizophrenia or bipolar disorder-I, and reported the clinical outcomes: efficacy, change in weight or waist circumference, tolerability, pharmacokinetics, or change in metabolic parameters. A narrative synthesis was undertaken of the data.

Results: Eight studies met the inclusion criteria. All identified studies were conducted in adults with schizophrenia. Compared to OLZ-monotherapy, OLZ/SAM was associated with decreased odds of developing clinically significant (>10%) weight gain (OR=0.50, 95% CI:0.31,0.80; p= 0.003) and increase in waist circumference (risk difference = -17.1% 95% CI:-26.3,-7.8) from baseline measurements respectively. In another study, OLZ was 2.7 times more associated with clinically significant weight gain as compared to OLZ/SAM (OR=2.73, 95% CI:1.11, 6.67; p = 0.023). The clinical efficacy of OLZ/SAM remained similar to OLZ with improved tolerability in both short- and long-term studies with no significantly altered pharmacokinetic properties of the constituent agents.

Conclusion: OLZ/SAM-treatment is associated with mitigated weight-gain liability when compared to OLZ-monotherapy in adults with schizophrenia. Additional studies are needed to ascertain patient acceptability, appropriate selection and sequencing of OLZ/SAM in the treatment algorithms for adults with schizophrenia (and BD-I), as well as to determine cost-effectiveness and long-term metabolic effects.

Keywords: Adverse effects; Bipolar disorder; Depression; Obesity; Olanzapine; Olanzapine/samidorphan; Samidorphan; Schizophrenia.

Publication types

Review
Systematic Review

MeSH terms

Adult
Antipsychotic Agents* / adverse effects
Benzodiazepines / adverse effects
Humans
Naltrexone / analogs & derivatives
Narcotic Antagonists / pharmacology
Olanzapine / adverse effects

Substances

Antipsychotic Agents
Narcotic Antagonists
Benzodiazepines
Naltrexone
3-carboxamido-4-hydroxynaltrexone
Olanzapine