A commentary on the efficacy of olanzapine for the treatment of schizophrenia: the past, present, and future

Abstract

Olanzapine is a second-generation atypical antipsychotic with proven efficacy for the treatment of schizophrenia. Approved in 1996, olanzapine is one of the most studied antipsychotics, resulting in a considerable amount of clinical data across diverse patient populations. Despite the fact that olanzapine is associated with a known risk of metabolic side effects, including weight gain, many clinicians continue to prescribe olanzapine for the treatment of schizophrenia with the expectation of additional therapeutic antipsychotic efficacy relative to other first-line atypical antipsychotics. The goal of this narrative is to revisit the role of oral olanzapine in the management of patients with schizophrenia, including those with recently diagnosed schizophrenia (“first-episode”), those with an established schizophrenia diagnosis who experience acute exacerbations, those receiving long-term antipsychotic treatment as a maintenance intervention, and those with suboptimal response to antipsychotic treatment, including treatment resistance. Collectively, data from published literature support the favorable efficacy of olanzapine compared with other first- and second-generation antipsychotics, including lower rates of treatment discontinuation and clinically meaningful improvements in the symptoms of schizophrenia. The development of antipsychotic medications with the favorable efficacy of olanzapine, but with reduced weight gain, could address a major unmet need in the treatment of schizophrenia.

Keywords:

• antipsychotic
• efficacy
• metabolic dysregulation
• weight gain

Abbreviations

BPRS, Brief Psychiatric Rating Scale; CATIE, Clinical Antipsychotic Trials of Intervention Effectiveness; CGI, Clinical Global Impression; EUFEST, European First-Episode Schizophrenia Trial; FDA, US Food and Drug Administration; NNT, number needed to treat; PANSS, Positive and Negative Syndrome Scale; SOHO, Schizophrenia Outpatient Health Outcomes.

Acknowledgments

This study was sponsored by Alkermes, Inc. Medical writing and editorial support was provided by Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by Alkermes, Inc. Alkermes, Inc. is developing a combination product of olanzapine and samidorphan for the treatment of schizophrenia, and has funded the development of this manuscript.

Disclosures

LC has, in the past 5 years, engaged in collaborative research with, or received consulting or speaking fees, from: Acadia, Alexza, Alkermes, Allergan, AstraZeneca, Avanir, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Forum, Genentech, Intra-Cellular Therapeutics, Janssen, Jazz, Lundbeck, Merck, Medivation, Mylan, Neurocrine, Novartis, Noven, Otsuka, Pfizer, Indivior/Reckitt Benckiser, Reviva, Shire, Sunovion, Takeda, Teva, Valeant, Vanda. In the past 12 months, consultant: Acadia, Alkermes, Allergan, Indivior, Intra-Cellular Therapeutics, Janssen, Lundbeck, Merck, Neurocrine, Noven, Osmotica, Otsuka, Pfizer, Shire, Sunovion, Takeda, Teva, Vanda. In the past 12 months, speaker: Acadia, Alkermes, Allergan, Janssen, Lundbeck, Merck, Neurocrine, Otsuka, Pfizer, Shire, Sunovion, Takeda, Teva. Stocks (small number of shares of common stock): Bristol-Myers Squibb, Eli Lilly, J & J, Merck, Pfizer purchased >10 years ago. Royalties: Wiley (Editor-in-Chief, International Journal of Clinical Practice), UpTo Date (reviewer), Springer Healthcare (book). JPM serves on advisory boards for Neurocrine and Alkermes. MST, DM, and PJW are full-time employees of Alkermes, Inc., and may own stock in the company.