High-dose olanzapine safe against treatment-resistant schizophrenia

A new research by Louisa Gannon and colleagues offered preliminary support for the application of high-dose olanzapine in treatment-resistant schizophrenia (TRS), albeit the evidence base is limited. The findings of this study were published in Therapeutic Advances in Psychopharmacology.

Around 30% of persons with schizophrenia have treatment-resistant schizophrenia. Clozapine is the gold standard treatment for TRS, however it is not always appropriate, with some people experiencing adverse effects or being unable to participate in blood monitoring. Given the severe impact TRS may have on persons who suffer from it, different pharmaceutical approaches to treatment are required. As a result, this study was designed to undertake a literature evaluation on the effectiveness and tolerance of high-dose olanzapine (>20 mg daily) in adults with TRS.

Researchers examined PubMed/MEDLINE, Scopus, and Google Scholar for eligible studies published before April 2022. The inclusion criteria were satisfied by ten studies [five randomized controlled trials (RCTs), one randomized crossover trial, and four open label studies]. Data were collected for two primary objectives (efficacy and tolerability).

The key findings of this study were:

1. High-dose olanzapine was non-inferior to conventional therapy in four RCTs, three of which employed clozapine as the comparison.

2. In a double-blind crossover experiment, clozapine outperformed high-dose olanzapine.

3. Open-label trials found preliminary evidence to support the use of high-dose olanzapine.

4. In two RCTs, it was tolerated better than clozapine and chlorpromazine, and it was usually well tolerated in open-label trials.

This research demonstrates that when compared to other regularly used first- and second-generation antipsychotics, such as haloperidol and risperidone, high-dose olanzapine is superior for TRS. The findings are positive in contrast to clozapine for the use of high-dose olanzapine where clozapine administration is difficult, but bigger, better planned trials are needed to examine the comparative efficacy of both therapies. When clozapine is not contraindicated, there is insufficient evidence to support high-dose olanzapine equal to clozapine. Overall, olanzapine at large doses was well tolerated, with no significant adverse effects.

Reference:

Gannon, L., Reynolds, J., Mahon, M., Gaughran, F., & Lally, J. (2023). High-dose olanzapine in treatment-resistant schizophrenia: a systematic review. In Therapeutic Advances in Psychopharmacology (Vol. 13, p. 204512532311687). SAGE Publications. https://doi.org/10.1177/20451253231168788