New discoveries for an old drug: a review of recent olanzapine research

ABSTRACT

Objective: Based on a substantial literature, olanzapine appears to be one of the most efficacious antipsychotics marketed in the United States, with only clozapine clearly more advantageous. However, olanzapine is marred by an equally substantial literature demonstrating a metabolic burden of olanzapine, particularly for weight gain. With the publication of successful strategies to limit olanzapine induced weight gain, a reassessment of the clinical utility of olanzapine appears warranted. The purpose of this paper is to review recent evidence for olanzapine, highlighting use in both schizophrenia and other conditions, safety and supporting the use of olanzapine above 20 mg/day, focusing on studies published since our previous reviews in 2008 and 2009.

Data Sources: The US National Library of Medicine’s PubMed resource (https://www.ncbi.nlm.nih.gov/pubmed/) was searched using the text word ‘olanzapine’ for all English-language articles published between 2008 to July 2019, inclusive with a specific focus on double-blind randomized controlled trials and meta-analyses. In addition, we examined the review articles for other reports of interest that may have been missed by our initial search.

Data Extraction: The studies were evaluated based on efficacy and safety data.

Results: Use of olanzapine may be decreasing but remains common overall. Evidence continues to support both the relative efficacy advantage and weight gain/metabolic disadvantages of olanzapine in schizophrenia, and recent research supports olanzapine’s use in treating anorexia nervosa and chemotherapy-induced nausea. The evidence for high dose olanzapine dosages >20 mg remains limited. Non-pharmacological options, such as dietary counseling and exercise, appear to be efficacious in addressing antipsychotic-induced weight gain. Topiramate, metformin and possibly the olanzapine-samidorphan combination also appear helpful.

Conclusions: Olanzapine remains a useful antipsychotic, but requires with careful monitoring. Further research is needed to compare the different options available to mitigate olanzapine-induced weight gain and to evaluate potential synergism between pharmacological and non-pharmacological treatments.

KEYWORDS:

• Antipsychotic
• olanzapine
• schizophrenia
• weight gain

Declaration of interest

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Dr. Kantrowitz reports having received consulting payments within the last 24 months from Krog & Partners Incorporated, IQVIA, Alphasights, Charles River Associates, Putnam Associates, Piper Jaffray, MEDACorp, Simon Kucher, LifeSci Capital, ECRI Institute and BVF Partners. He has served on the Aristada Schizophrenia Advisory Board for Alkermes.

He has conducted clinical research supported by the NIMH, Sunovion, the Stanley Foundation, Takeda, Taisho, Lundbeck, Boehringer Ingelheim, NeuroRX, Teva and Lilly within the last 24 months. He owns a small number of shares of common stock in GlaxoSmithKline.In the past 5 years, Leslie Citrome has engaged in collaborative research with, or received consulting or speaking fees, from: Acadia, Alexza, Alkermes, Allergan, AstraZeneca, Avanir, BioXcel, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Eli Lilly, Forum, Genentech, Impel, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Luye, Merck, Medivation, Mylan, Neurocrine, Novartis, Noven, Osmotica, Otsuka, Pfizer, Indivior/Reckitt Benckiser, Reviva, Shire, Sunovion, Takeda, Teva, Valeant, Vanda.

Ms. Deckler and Dr. Meftah report no relevant conflicts.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.