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3 - Initiating Clozapine

Published online by Cambridge University Press:  19 October 2021

Jonathan M. Meyer
Affiliation:
University of California, San Diego
Stephen M. Stahl
Affiliation:
University of California, San Diego
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Summary

The decision to start clozapine therapy derives from the accepted, evidence-based uses for this medication including treatment-resistant schizophrenia spectrum disorders, schizophrenia patients with a history of suicidality, schizophrenia spectrum patients with persistent aggression, treatment-resistant mania, and psychosis associated with Parkinson’s disease (see Chapter 1). As was discussed in Chapter 1, the greatest conundrum in determining whether a schizophrenia patient is truly resistant to other treatment is high rates of nonadherence, with subtherapeutic plasma antipsychotic levels seen in 35–44% of outpatients deemed to have treatment-resistant illness. Once a patient is a candidate based on clinical criteria, patients and caregivers must be educated about the unique benefits of clozapine, its common adverse effects, and the demands of monitoring. With many outpatients this is a conversation that is often performed over an extended period as patients try and fail other options and come to trust the clinician’s suggestion that the benefits of clozapine outweigh the burdens of treatment. An important principle to guide these discussions is that significant delays in starting clozapine may reduce the likelihood of response in treatment-resistant schizophrenia. A review of response rates among 90 patients who remained on clozapine for at least 3 months found that the response rate was 82% for those who started clozapine within 2.8 years of meeting clinical criteria for treatment resistance, but fell to 31% when clozapine was started > 2.8 years after reaching this benchmark.

Type
Chapter
Information
The Clozapine Handbook
Stahl's Handbooks
, pp. 60 - 77
Publisher: Cambridge University Press
Print publication year: 2019

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References

McCutcheon, R., Beck, K., D’Ambrosio, E., et al. (2018). Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia. Acta Psychiatrica Scandinavica, 137, 3946.Google Scholar
Yoshimura, B., Yada, Y., So, R., et al. (2017). The critical treatment window of clozapine in treatment-resistant schizophrenia: Secondary analysis of an observational study. Psychiatry Research, 250, 6570.CrossRefGoogle ScholarPubMed
Krakowski, M. I., Czobor, P., Citrome, L., et al. (2006). Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Archives of General Psychiatry, 63, 622629.Google Scholar
Nielsen, J., Young, C., Ifteni, P., et al. (2016). Worldwide differences in regulations of clozapine use. CNS Drugs, 30, 149161.Google Scholar
Ifteni, P., Nielsen, J., Burtea, V., et al. (2014). Effectiveness and safety of rapid clozapine titration in schizophrenia. Acta Psychiatrica Scandinavica, 130, 2529.Google Scholar
Rostami-Hodjegan, A., Amin, A. M., Spencer, E. P., et al. (2004). Influence 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. Journal of Clinical Psychopharmacology, 24, 7078.Google Scholar
de Leon, J., Schoretsanitis, G., Smith, R. L., et al. (2022). An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels. Pharmacopsychiatry, 55, 7386.CrossRefGoogle Scholar
Haslemo, T., Eikeseth, P. H., Tanum, L., et al. (2006). The effect of variable cigarette consumption on the interaction with clozapine and olanzapine. European Journal of Clinical Pharmacology, 62, 10491053.CrossRefGoogle ScholarPubMed
Jann, M. W., Grimsley, S. R., Gray, E. C., et al. (1993). Pharmacokinetics and pharmacodynamics of clozapine. Clinical Pharmacokinetics, 24, 161176.CrossRefGoogle ScholarPubMed
Guitton, C., Kinowski, J. M., Abbar, M., et al. (1999). Clozapine and metabolite concentrations during treatment of patients with chronic schizophrenia. Journal of Clinical Pharmacology, 39, 721728.Google Scholar
Takeuchi, H., Powell, V., Geisler, S., et al. (2016). Clozapine administration in clinical practice: Once-daily versus divided dosing. Acta Psychiatrica Scandinavica, 134, 234240.Google Scholar
Olesen, O. V. and Linnet, K. (2001). Contributions of five human cytochrome P450 isoforms to the N-demethylation of clozapine in vitro at low and high concentrations. Journal of Clinical Pharmacology, 41, 823832.CrossRefGoogle Scholar
Poyraz, C. A., Ozdemir, A., Saglam, N. G., et al. (2016). Rapid clozapine titration in patients with treatment refractory schizophrenia. Psychiatry Quarterly, 87, 315322.CrossRefGoogle ScholarPubMed
Suzuki, T., Uchida, H., Watanabe, K., et al. (2011). Factors associated with response to clozapine in schizophrenia: A review. Psychopharmacology Bulletin, 44, 3260.Google Scholar
Cummings, J., Isaacson, S., Mills, R., et al. (2014). Pimavanserin for patients with Parkinson’s disease psychosis: A randomised, placebo-controlled phase 3 trial. Lancet, 383, 533540.Google Scholar
Parkinson Study Group. (1999). Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. New England Journal of Medicine, 340, 757763.CrossRefGoogle Scholar
The French Clozapine Parkinson Study Group. (1999). Clozapine in drug-induced psychosis in Parkinson’s disease. The French Clozapine Parkinson Study Group. Lancet, 353, 20412042.Google Scholar
Ronaldson, K. J., Fitzgerald, P. B. and McNeil, J. J. (2015). Clozapine-induced myocarditis, a widely overlooked adverse reaction. Acta Psychiatrica Scandinavica, 132, 231240.Google Scholar
Golden, G. and Honigfeld, G. (2008). Bioequivalence of clozapine orally disintegrating 100-mg tablets compared with clozapine solid oral 100-mg tablets after multiple doses in patients with schizophrenia. Clinical Drug Investigation, 28, 231239.Google Scholar
Taylor, D. M., Smith, L., Gee, S. H., et al. (2012). Augmentation of clozapine with a second antipsychotic – A meta-analysis. Acta Psychiatrica Scandinavica, 125, 1524.Google Scholar
Luo, S., Michler, K., Johnston, P., et al. (2004). A comparison of commonly used QT correction formulae: The effect of heart rate on the QTc of normal ECGs. Journal of Electrocardiology, 37(Suppl), 8190.CrossRefGoogle ScholarPubMed
Kim, D. D., White, R. F., Barr, A. M., et al. (2018). Clozapine, elevated heart rate and QTc prolongation. Journal of Psychiatry and Neuroscience, 43, 7172.Google Scholar
Vandenberk, B., Vandael, E., Robyns, T., et al. (2016). Which QT correction formulae to use for QT monitoring? Journal of the American Heart Association, 5, e003264.Google Scholar
Rohde, C., Polcwiartek, C., Kragholm, K., et al. (2018). Adverse cardiac events in out-patients initiating clozapine treatment: a nationwide register-based study. Acta Psychiatrica Scandinavica, 137, 4753.Google Scholar
de Leon, J. (2005). Benztropine equivalents for antimuscarinic medication. American Journal of Psychiatry, 162, 627.Google Scholar
Nielsen, J. and Meyer, J. M. (2012). Risk factors for ileus in patients with schizophrenia. Schizophrenia Bulletin, 38, 592598.Google Scholar

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