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Clozapine Initiation for Schizophrenia: A Review of Clinical Effectiveness and Guidelines

Last updated: February 18, 2020
Project Number: RC1229-000
Product Line: Rapid Response
Research Type: Drug
Report Type: Summary with Critical Appraisal
Result type: Report


  1. What is the clinical effectiveness of clozapine during the initiation phase of therapy for adult patients with schizophrenia in outpatient, in-patient, and community settings?
  2. What are the evidence-based guidelines for monitoring adult patients with schizophrenia initiating clozapine therapy?​

Key Message

Three systematic reviews were identified regarding the clinical effectiveness of clozapine during the initiation phase, and three evidence-based guidelines were identified regarding monitoring of patients taking clozapine during the initiation phase.

The identified systematic reviews were of limited quality and focused primarily on cardiac complications during clozapine initiation. Side effects of clozapine included myocarditis, tachycardia, hypertension, hyperglycemia, and death. The average time until side effect onset ranged from 14 days to 7 weeks after clozapine initiation, with one study reporting heart rate changes after 2 to 3 days. There were no studies identified that reported on clozapine compared with other antipsychotics during the initiation phase.

The identified guidelines indicate and recommend monitoring of patients initiating clozapine, with recommendations varying in strength of evidence from randomized controlled trials to non-analytic studies and expert opinion. Non-graded evidence suggests assessments of patient history, weight, waist circumference, fasting plasma glucose, fasting lipid profile, prolactin, full blood count, electrocardiograms, electroencephalogram, pregnancy, and ophthalmological examinations for patients who have been prescribed antipsychotics. It was not clear what the strength of evidence for these specific assessments was.