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Top-Ranked Treatments for Schizophrenia Aggression: Clozapine, Paliperidone and Olanzapine

MHD card with an amber network of antipsychotic drug nodes linked to a placebo node over a dark background, with a calming waveform: clozapine, paliperidone, and olanzapine reduced aggression in schizophrenia most, but confidence was low.

A 2026 analysis of 41 randomized studies involving 21,025 adults with schizophrenia found the largest estimated reductions in hostility and aggression for clozapine (standardized mean difference, or SMD, of −0.75), paliperidone (−0.62), and olanzapine (−0.60) vs. placebo.1 Confidence in every comparison was low or very low, the top 3 were not statistically separable, and most …

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Early Clozapine in Schizophrenia: 34% Lower Relapse Risk

Stylized illustration of a stopwatch overlaying schizophrenia treatment-stage icons, representing the multi-year delay before clozapine is offered to patients who already meet treatment-resistance criteria.

Clozapine has been the most effective antipsychotic in schizophrenia for almost 40 years, yet it is still routinely held back until patients have failed multiple alternatives over many years — a “third-line, after years of failure” default that a 2026 Current Opinion review by Davani et al. argues is no longer supported by the evidence.1 …

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Machine Learning Predicts Clozapine Initiation in Schizophrenia

Photoreal illustration of an electronic health record dashboard with clinical text and a model output highlighted, representing ML prediction in psychiatry.

Clozapine is the only medication with proven efficacy for treatment-resistant schizophrenia, yet most eligible patients wait years before starting it. A 2026 paper by Perfalk and colleagues trains a machine-learning model on routine electronic health record data to flag candidates earlier.1 Research Highlights Clozapine is the only evidence-based treatment for treatment-resistant schizophrenia (TRS), but the …

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