High‑dose olanzapine versus clozapine for treatment‑resistant schizophrenia: A systematic review and meta‑analysis

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   Frontiers+6PubMed+6ScienceDirect+6

• Authors: Bijen Upadhyay, Sheila Abdolmanafi, Tanmay Bhatnagar, Mustafa Al Jnainati, Jana Al Jnainati, Partha Baral, and Muhammad Faisal Shakir PubMed

• Journal / Publication Date: General Hospital Psychiatry; published online July 9, 2025 (Volume 96, pages 140–150) Veterans Affairs+8PubMed+8Katalog plus+8

🔍 Summary

This review article systematically compares high‑dose olanzapine (≥20 mg/day) to clozapine as treatments for treatment‑resistant schizophrenia (TRS).

• Background: Clozapine is recognized as the gold‑standard for TRS but is underutilized due to strict hematological monitoring. High‑dose olanzapine is proposed as a potential alternative PubMed+1ScienceDirect+1.

• The authors conducted a PRISMA‑guided meta‑analysis, reviewing studies directly comparing the two approaches (up to February 2025) Katalog plus+9PubMed+9Frontiers+9.

• Outcomes examined included overall psychopathology (via PANSS or BPRS), positive and negative symptom subscales, and adverse events profile.

Key findings 

• Evidence across included studies is mixed, with some supporting high‑dose olanzapine efficacy in TRS, but not definitively equivalent to clozapine.

• Comparative efficacy and safety remain uncertain, reinforcing clozapine’s role as standard of care, although high‑dose olanzapine may be useful in some contexts.

💡 Clinical Implications

• Clozapine remains the first-line treatment for TRS; high-dose olanzapine may serve as an alternative in cases where clozapine is contraindicated or poorly tolerated.

• Decisions should consider side-effect profiles, monitoring requirements, and individual patient factors (e.g. metabolic risk).