Efficacy and Safety Outcomes of Different Plasma Clozapine and Norclozapine Levels in Schizophrenia Spectrum Disorder: A Dose-Response Meta-Analysis Exploring "critical" Levels.
Psychiatry ResJul 26, 2026 (epub)
Clinical ResearchPsychiatry
Michele Fornaro, Chiara Di Lorenzo, Dan Siskind et al.
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In 30 seconds
This dose-response meta-analysis examined the relationship between plasma clozapine and norclozapine levels and efficacy and safety outcomes in schizophrenia spectrum disorder, analyzing data from 34 studies with 134,111 participants. Key findings suggest specific clozapine concentration turning points for various outcomes, including a change in the Brief Psychiatric Rating Scale at 535 ng/mL.
Key findings
- Clozapine turning point for Brief Psychiatric Rating Scale change was 535 ng/mL.
- Positive and Negative Syndrome Scale total change occurred at 898 ng/mL.
- Tolerability was associated with a clozapine level of 707 ng/mL.
- Blood dyscrasia risk increased at 357 ng/mL.
Why it matters
Understanding the relationship between clozapine levels and clinical outcomes can guide clinicians in optimizing treatment for patients with schizophrenia spectrum disorders, emphasizing the importance of individualized therapeutic drug monitoring.