Is clozapine a medication that should only be used when all other medications have failed?

Do not think of clozapine as a last-resort option. The APA Practice Guideline for the Treatment of Patients with Schizophrenia recommends clozapine if:

  • a patient shows no or minimal response to two antipsychotic medications at an adequate dose.
  • the risk of suicide attempts or suicide remains substantial despite other treatments.
  • the risk for aggressive behavior remains high despite other treatments.

In fact, some studies suggest that if you delay the use of clozapine for patients who may benefit from it, it may lead to poorer treatment outcomes.

Learn more about common myths around clozapine. See our infographic on this topic.




  • American Psychiatric Association. (2020). The American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia, Third Edition 2020 [9/24/2020]. Available from:
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  • Yoshimura B., Yada Y., So R., Takaki M., Yamada N. (2017).The critical treatment window of clozapine in treatment-resistant schizophrenia: Secondary analysis of an observational study. Psychiatry Research, 250:65-70.
  • Cotes R., Janjua A., Broussard B., Lazris D., Khan A., Jiao Y., et al. (2021). A Comparison of Attitudes, Comfort, and Knowledge of Clozapine Among Two Diverse Samples of US Psychiatrists. Community Ment Health J, 58(3):517-525. doi: 10.1007/s10597-021-00847-0.
  • Schoretsanitis G., Kane J., Correll C., Marder S., Citrome L., Newcomer J., et al. (2020). Blood Levels to Optimize Antipsychotic Treatment in Clinical Practice: A Joint Consensus Statement of the American Society of Clinical Psychopharmacology and the Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie. J Clin Psychiatry, 81(3):19cs13169. doi: 10.4088/JCP.19cs13169.
  • Northwood K., Pearson E., Arnautovska U., Kisely S., Pawar M., Sharma M., et al. (2023). Optimising plasma clozapine levels to improve treatment response: an individual patient data meta-analysis and receiver operating characteristic curve analysis. British J Psychiatry, 222(6):241-5. doi: 10.1192/bjp.2023.27.
  • Rostami-Hodjegan A., Amin A., Spencer E., Lennard M., Tucker G., Flanagan R. (2004). Inuence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients. J Clin Psychopharmacol, 24(1):70-8. doi: 10.1097/
  • Manu P., Sarvaiya N., Rogozea L., Kane J., Correll C. (2016). Benign Ethnic Neutropenia and Clozapine Use: A Systematic Review of the Evidence and Treatment Recommendations. J Clin Psychiatry, 77(7):e909-16.
  • Cotes R. (2023). Are slow clozapine titrations safer than fast ones? Poster Presentation at the Schizophrenia International Research Society Annual Congress.
  • Cotes R., Goldsmith D. (2022). The Tortoise Beats the Hare: The Case for Slow Clozapine Titrations with Serial CRP Monitoring. Psychiatria Danubina, 34(3):428-9.
  • Ronaldson K., Fitzgerald P., Taylor A., Topliss D., Wolfe R., McNeil J. (2012). Rapid clozapine dose titration and concomitant sodium valproate increase the risk of myocarditis with clozapine: a case-control study. Schizophr Res, 141(2-3):173-8.
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