An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder

Leslie Citrome,1 Christine Graham,2 Adam Simmons,2 Ying Jiang,2 Mark S Todtenkopf,2 Bernard Silverman,2 Lauren DiPetrillo,2 Hannah Cummings,2 Lei Sun,2 David McDonnell3 1Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA; 2Alkermes, Inc., Waltham, MA, USA;...

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Autores principales:	Citrome L, Graham C, Simmons A, Jiang Y, Todtenkopf MS, Silverman B, DiPetrillo L, Cummings H, Sun L, McDonnell D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	antipsychotic agents clinical efficacy olanzapine opioid antagonists safety weight gain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/a8c9473278d14e10b367a12fc711ddf4
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spelling	oai:doaj.org-article:a8c9473278d14e10b367a12fc711ddf42021-12-02T14:57:24ZAn Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder1178-2021https://doaj.org/article/a8c9473278d14e10b367a12fc711ddf42021-09-01T00:00:00Zhttps://www.dovepress.com/an-evidence-based-review-of-olzsam-for-treatment-of-adults-with-schizo-peer-reviewed-fulltext-article-NDThttps://doaj.org/toc/1178-2021Leslie Citrome,1 Christine Graham,2 Adam Simmons,2 Ying Jiang,2 Mark S Todtenkopf,2 Bernard Silverman,2 Lauren DiPetrillo,2 Hannah Cummings,2 Lei Sun,2 David McDonnell3 1Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA; 2Alkermes, Inc., Waltham, MA, USA; 3Alkermes Pharma Ireland Limited, Dublin, IrelandCorrespondence: Leslie Citrome 11 Medical Park Drive, Suite 102, Pomona, NY, 10970, USATel +1-845-362-2081Email citrome@cnsconsultant.comAbstract: Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is limited by the risk of significant weight gain and metabolic effects. OLZ/SAM, a combination of olanzapine and samidorphan, was recently approved in the United States for the treatment of adults with schizophrenia or BD-I. OLZ/SAM provides the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data characterizing pharmacokinetics, antipsychotic efficacy, weight mitigation efficacy, safety, and long-term treatment effects. In an acute exacerbation of schizophrenia, OLZ/SAM and olanzapine provided similar symptom improvements versus placebo at week 4. In stable outpatients with schizophrenia, OLZ/SAM treatment resulted in significantly less weight gain, reducing the risk for clinically significant weight gain and waist circumference increases of ≥ 5 cm by half, compared with olanzapine at week 24. Based on open-label extension studies, OLZ/SAM is safe and well tolerated for up to 3.5 years of treatment, while maintaining schizophrenia symptom control and stabilizing weight. The olanzapine component of OLZ/SAM was bioequivalent to branded olanzapine (Zyprexa); adjunctive OLZ/SAM had no clinically significant effects on lithium or valproate pharmacokinetics. Additionally, OLZ/SAM had no clinically relevant effect on electrocardiogram parameters in a dedicated thorough QT study. Overall, safety and tolerability findings from clinical studies with OLZ/SAM indicate a similar safety profile to that of olanzapine, with the exception of less weight gain. As OLZ/SAM contains the opioid antagonist samidorphan, it is contraindicated in patients using opioids and in those undergoing acute opioid withdrawal. Clinical trial results from more than 1600 subjects support the use of OLZ/SAM as a new treatment option for patients with schizophrenia or BD-I.Keywords: antipsychotic agents, clinical efficacy, olanzapine, opioid antagonists, safety, weight gainCitrome LGraham CSimmons AJiang YTodtenkopf MSSilverman BDiPetrillo LCummings HSun LMcDonnell DDove Medical Pressarticleantipsychotic agentsclinical efficacyolanzapineopioid antagonistssafetyweight gainNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 2885-2904 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antipsychotic agents clinical efficacy olanzapine opioid antagonists safety weight gain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	antipsychotic agents clinical efficacy olanzapine opioid antagonists safety weight gain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Citrome L Graham C Simmons A Jiang Y Todtenkopf MS Silverman B DiPetrillo L Cummings H Sun L McDonnell D An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder
description	Leslie Citrome,1 Christine Graham,2 Adam Simmons,2 Ying Jiang,2 Mark S Todtenkopf,2 Bernard Silverman,2 Lauren DiPetrillo,2 Hannah Cummings,2 Lei Sun,2 David McDonnell3 1Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA; 2Alkermes, Inc., Waltham, MA, USA; 3Alkermes Pharma Ireland Limited, Dublin, IrelandCorrespondence: Leslie Citrome 11 Medical Park Drive, Suite 102, Pomona, NY, 10970, USATel +1-845-362-2081Email citrome@cnsconsultant.comAbstract: Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is limited by the risk of significant weight gain and metabolic effects. OLZ/SAM, a combination of olanzapine and samidorphan, was recently approved in the United States for the treatment of adults with schizophrenia or BD-I. OLZ/SAM provides the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data characterizing pharmacokinetics, antipsychotic efficacy, weight mitigation efficacy, safety, and long-term treatment effects. In an acute exacerbation of schizophrenia, OLZ/SAM and olanzapine provided similar symptom improvements versus placebo at week 4. In stable outpatients with schizophrenia, OLZ/SAM treatment resulted in significantly less weight gain, reducing the risk for clinically significant weight gain and waist circumference increases of ≥ 5 cm by half, compared with olanzapine at week 24. Based on open-label extension studies, OLZ/SAM is safe and well tolerated for up to 3.5 years of treatment, while maintaining schizophrenia symptom control and stabilizing weight. The olanzapine component of OLZ/SAM was bioequivalent to branded olanzapine (Zyprexa); adjunctive OLZ/SAM had no clinically significant effects on lithium or valproate pharmacokinetics. Additionally, OLZ/SAM had no clinically relevant effect on electrocardiogram parameters in a dedicated thorough QT study. Overall, safety and tolerability findings from clinical studies with OLZ/SAM indicate a similar safety profile to that of olanzapine, with the exception of less weight gain. As OLZ/SAM contains the opioid antagonist samidorphan, it is contraindicated in patients using opioids and in those undergoing acute opioid withdrawal. Clinical trial results from more than 1600 subjects support the use of OLZ/SAM as a new treatment option for patients with schizophrenia or BD-I.Keywords: antipsychotic agents, clinical efficacy, olanzapine, opioid antagonists, safety, weight gain
format	article
author	Citrome L Graham C Simmons A Jiang Y Todtenkopf MS Silverman B DiPetrillo L Cummings H Sun L McDonnell D
author_facet	Citrome L Graham C Simmons A Jiang Y Todtenkopf MS Silverman B DiPetrillo L Cummings H Sun L McDonnell D
author_sort	Citrome L
title	An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder
title_short	An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder
title_full	An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder
title_fullStr	An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder
title_full_unstemmed	An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder
title_sort	evidence-based review of olz/sam for treatment of adults with schizophrenia or bipolar i disorder
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/a8c9473278d14e10b367a12fc711ddf4
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An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder

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