Clozapine Use Among People With Psychotic Disorders Who Experience Specific Indications for Clozapine

Gregory E. Simon, MD, MPH; Rebecca C. Rossom, MD, MS; Esti Iturralde, PhD; Brian K. Ahmedani, MSW, PhD; Stephen C. Waring, DVM, PhD; Ashli A. Owen-Smith, SM, PhD; Stacy A. Sterling, DrPH, MSW; Kathleen Miley, PhD, MSN; Cheryl D. Stults, PhD; Yihe G. Daida, PhD; Frances L. Lynch, PhD, MSPH; Arne Beck, PhD; Katherine Sanchez, LCSW, PhD; Karen J. Coleman, PhD; Susan M. Shortreed, PhD

J Clin Psychiatry 2024;85(2):23m14833

Abstract

Objective: To examine rates of clozapine use among people with psychotic disorders who experience specific indications for clozapine.

Methods: Records data from 11 integrated health systems identified patients aged 18 years or older with recorded International Classification of Diseases, Tenth Revision, Clinical Modification, diagnoses of schizophrenia, schizoaffective disorder, or other psychotic disorder who experienced any of the 3 events between January 1, 2019, and December 31, 2019, suggesting indications for clozapine: a diagnosis of self-harm injury or poisoning, suicidal ideation diagnosed or in response to standardized assessments, and hospitalization or emergency department (ED) care for psychotic disorder despite treatment with 2 or more antipsychotic medications. Prescription dispensing data identified all clozapine use prior to or in the 12 months following each indication event. Analyses were conducted with aggregate data from each health system; no individual data were shared.

Results: A total of 7,648 patients with psychotic disorder diagnoses experienced at least 1 indication event. Among 1,097 experiencing a self-harm event, 32 (2.9%) had any prior clozapine use, and 10 (0.9%) initiated clozapine during the following 12 months. Among 6,396 with significant suicidal ideation, 238 (3.7%) had any prior clozapine use, and 70 (1.1%) initiated clozapine over 12 months. Among 881 with hospitalization or ED visit despite pharmacotherapy, 77 (8.7%) had any prior clozapine treatment, and 41 (4.7%) initiated clozapine over 12 months. Among those with significant suicidal ideation, rates of both prior clozapine treatment and subsequent initiation varied significantly by race and ethnicity, with rates among Hispanic and non-Hispanic Black patients lower than among non Hispanic White patients.

Conclusions: Initiating clozapine treatment is uncommon among people with psychotic disorders who experience events suggesting clozapine is indicated, with even lower rates among Black and Hispanic patients.

J Clin Psychiatry 2024;85(2):23m14833

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References (43)

Kreyenbuhl J, Buchanan RW, Dickerson FB, et al. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull. 2010;36(1):94–103. PubMed CrossRef
Warnez S, Alessi-Severini S. Clozapine: a review of clinical practice guidelines and prescribing trends. BMC Psychiatry. 2014;14:102. PubMed CrossRef
Stroup TS. Clozapine and evidence-based psychopharmacology for schizophrenia. JAMA Psychiatry. 2019;76(10):1007–1008. PubMed CrossRef
American Psychiatric Association. Practice Guideline for the Treatment of Patients With Schizophrenia. American Psychiatric Association; 2021.
National Institute for Health and Care Excellence. Psychosis and Schizophrenia in Adults: Prevention and Management. National Institute for Health and Care Excellence; 2014.
Remington G, Addington D, Honer W, et al. Guidelines for the pharmacotherapy of schizophrenia in adults. Can J Psychiatry. 2017;62(9):604–616. PubMed CrossRef
Forte A, Pompili M, Imbastaro B, et al. Effects on suicidal risk: comparison of clozapine to other newer medicines indicated to treat schizophrenia or bipolar disorder. J Psychopharmacol. 2021;35(9):1074–1080. PubMed CrossRef
Masuda T, Misawa F, Takase M, et al. Association with hospitalization and all cause discontinuation among patients with schizophrenia on clozapine vs other oral second-generation antipsychotics: a systematic review and meta-analysis of cohort studies. JAMA Psychiatry. 2019;76(10):1052–1062. PubMed CrossRef
Stroup TS, Gerhard T, Crystal S, et al. Comparative effectiveness of clozapine and standard antipsychotic treatment in adults with schizophrenia. Am J Psychiatry. 2016;173(2):166–173. PubMed CrossRef
Meltzer HY, Alphs L, Green AI, et al; International Suicide Prevention Trial Study Group. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry. 2003;60(1):82–91. PubMed CrossRef
Wilkinson ST, Trujillo Diaz D, Rupp ZW, et al. Pharmacological and somatic treatment effects on suicide in adults: a systematic review and meta-analysis. Depress Anxiety. 2022;39(2):100–112. PubMed CrossRef
Zuschlag ZD, Fowler CA, Devendorf A, et al. Clozapine utilization at the United States Veterans Health Administration: a descriptive report of prescribing patterns and patient characteristics among Operation Enduring Freedom/Operation Iraqi Freedom Veterans. Int Clin Psychopharmacol. 2020;35(6):322–328. PubMed CrossRef
Bareis N, Olfson M, Wall M, et al. Variation in psychotropic medication prescription for adults with schizophrenia in the United States. Psychiatr Serv. 2022;73(5):492–500. PubMed CrossRef
Stroup TS, Gerhard T, Crystal S, et al. Geographic and clinical variation in clozapine use in the United States. Psychiatr Serv. 2014;65(2):186–192. PubMed CrossRef
Jones GH, Mitchell BG, Bernard J, et al. History of suicide attempt and clozapine treatment in veterans with schizophrenia or schizoaffective disorder. Prim Care Companion CNS Disord. 2022;24(6):21m03231. PubMed CrossRef
Kelly DL, Freudenreich O, Sayer MA, et al. Addressing barriers to clozapine underutilization: a national effort. Psychiatr Serv. 2018;69(2):224–227. PubMed CrossRef
Farooq S, Choudry A, Cohen D, et al. Barriers to using clozapine in treatment resistant schizophrenia: systematic review. BJPsych Bull. 2019;43(1):8–16. PubMed CrossRef
Verdoux H, Quiles C, Bachmann CJ, et al. Prescriber and institutional barriers and facilitators of clozapine use: a systematic review. Schizophr Res. 2018;201:10–19. PubMed CrossRef
Gören JL, Rose AJ, Engle RL, et al. Organizational characteristics of Veterans Affairs clinics with high and low utilization of clozapine. Psychiatr Serv. 2016;67(11):1189–1196. PubMed
Whiskey E, Barnard A, Oloyede E, et al. An evaluation of the variation and underuse of clozapine in the United Kingdom. Acta Psychiatr Scand. 2021;143(4):339–347. PubMed CrossRef
Williams JC, Harowitz J, Glover J, et al. Systematic review of racial disparities in clozapine prescribing. Schizophr Res. 2020;224:11–18. PubMed CrossRef
de Freitas DF, Patel I, Kadra-Scalzo G, et al. Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records. Soc Psychiatr Psychiatr Epidemiol. 2022;57(7):1341–1355. CrossRef
Das-Munshi J, Bhugra D, Crawford MJ. Ethnic minority inequalities in access to treatments for schizophrenia and schizoaffective disorders: findings from a nationally representative cross-sectional study. BMC Med. 2018;16(1):55. PubMed CrossRef
Horvitz-Lennon M, Donohue JM, Lave JR, et al. The effect of race-ethnicity on the comparative effectiveness of clozapine among Medicaid beneficiaries. Psychiatr Serv. 2013;64(3):230–237. PubMed CrossRef
Manu P, Sarvaiya N, Rogozea LM, et al. Benign ethnic neutropenia and clozapine use: a systematic review of the evidence and treatment recommendations. J Clin Psychiatry. 2016;77(7):e909–e916. PubMed CrossRef
Dotson S, Shtasel D, Freudenreich O. Race–based medicine, clozapine, and benign (ethnic) neutropenia: a call for nuance. Psychiatr Serv. 2021;72(2):232–233. PubMed CrossRef
Coleman KJ, Stewart C, Waitzfelder BE, et al. Racial-ethnic differences in psychiatric diagnoses and treatment across 11 health care systems in the Mental Health Research Network. Psychiatr Serv. 2016;67(7):749–757. PubMed CrossRef
Ross TR, Ng D, Brown JS, et al. The HMO Research Network Virtual Data Warehouse: a public data model to support collaboration. EGEMS (Wash DC). 2014;2(1):1049. PubMed CrossRef
Simon GE, Shortreed SM, Boggs JM, et al. Accuracy of ICD-10-CM encounter diagnoses from health records for identifying self-harm events. J Am Med Inf Assoc. 2022;29(12):2023–2031. CrossRef
Simon GE, Coleman KJ, Rossom RC, et al. Risk of suicide attempt and suicide death following completion of the Patient Health Questionnaire depression module in community practice. J Clin Psychiatry. 2016;77(2):221–227. PubMed CrossRef
Mundt JC, Greist JH, Jefferson JW, et al. Prediction of suicidal behavior in clinical research by lifetime suicidal ideation and behavior ascertained by the electronic Columbia-Suicide Severity Rating Scale. J Clin Psychiatry. 2013;74(9):887–893. PubMed CrossRef
Posner K, Brown GK, Stanley B, et al. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168(12):1266–1277. PubMed CrossRef
Simon GE, Coleman KJ, Yarborough BJH, et al. First presentation with psychotic symptoms in a population-based sample. Psychiatr Serv. 2017;68(5):456–461. PubMed CrossRef
Schoenbaum M, Sutherland JM, Chappel A, et al. Twelve-month health care use and mortality in commercially insured young people with incident psychosis in the United States. Schizophr Bull. 2017;43(6):1262–1272. PubMed CrossRef
Remington G, Agid O, Foussias G, et al. Clozapine’s role in the treatment of first episode schizophrenia. Am J Psychiatry. 2013;170(2):146–151. PubMed CrossRef
Stokes I, Griffiths SL, Jones R, et al. Prevalence of treatment resistance and clozapine use in early intervention services. BJPsych Open. 2020;6(5):e107. PubMed CrossRef
Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika. 1934;26(4):404–413. CrossRef
Fisher RA. Statistical Methods for Research Workers. Oliver and Boyd; 1954.
Misra S, Etkins OS, Yang LH, et al. Structural racism and inequities in incidence, course of illness, and treatment of psychotic disorders among Black Americans. Am J Public Health. 2022;112(4):624–632. PubMed CrossRef
Givens JL, Houston TK, Van Voorhees BW, et al. Ethnicity and preferences for depression treatment. Gen Hosp Psychiatry. 2007;29(3):182–191. PubMed CrossRef
Tourtellotte R, Lim CT, Battista A. Advancing clozapine use in a community health system. Psychiatr Serv. 2022;73(12):1428. PubMed CrossRef
Carruthers J, Radigan M, Erlich MD, et al. An initiative to improve clozapine prescribing in New York State. Psychiatr Serv. 2016;67(4):369–371. PubMed CrossRef
Simon GE, Yarborough BJ, Rossom RC, et al. Self-reported suicidal ideation as a predictor of suicidal behavior among outpatients with diagnoses of psychotic disorders. Psychiatr Serv. 2019;70(3):176–183. PubMed CrossRef