Utility and Barriers to Clozapine Use: A Joint Study of Clinicians’ Attitudes From Singapore and Hong Kong

Shushan Zheng, MBBS, MRCPsych (UK); Jimmy Lee, MBBS, MMed (Psych), MCI; Sherry Kit Wa Chan, MBBS, MRCPsych (UK)

J Clin Psychiatry 2022;83(4):21m14231

ABSTRACT

Objective: This study aimed to survey clinicians’ attitudes in Singapore and Hong Kong toward clozapine and elucidate the barriers to its prescription in patients with treatment-resistant schizophrenia.

Methods: All clinicians in psychiatry in both regions were invited through email to participate in an anonymous online survey. The survey collected information on the participants’ characteristics, their experience with clozapine initiation, perceived usefulness of clozapine, barriers to clozapine initiation, and factors that might improve clozapine use. Data collection took place between December 2018 and March 2019 in Singapore and September 2019 and February 2020 in Hong Kong.

Results: A total of 261 clinicians (156 in Singapore, 105 in Hong Kong) responded to the survey. The majority of participants believed that clozapine was an effective and satisfactory treatment for schizophrenia. Clinicians were most concerned about the need for frequent blood monitoring (84.5% in Singapore; 87.5% in Hong Kong), clozapine’s tolerability (51.9% in Singapore; 61.6% in Hong Kong), and medical complications (54.8% in Singapore; 49.1% in Hong Kong). Compared to Hong Kong, more clinicians in Singapore endorsed an underutilization of clozapine (67.9% in Singapore; 51.4% in Hong Kong) and a greater need for outpatient resources in terms of clinic and administrative support (74.4% in Singapore; 59.0% in Hong Kong) to improve clozapine prescription.

Conclusions: The underutilization of clozapine in treatment-resistant schizophrenia remains a concern in both regions. An integrated clozapine service that addresses the system barriers and clinicians’ confidence in prescribing clozapine and managing its adverse effects would greatly improve the utilization of clozapine.

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References (40)

Meltzer HY. Treatment-resistant schizophrenia—the role of clozapine. Curr Med Res Opin. 1997;14(1):1–20. PubMed CrossRef
Agid O, Arenovich T, Sajeev G, et al. An algorithm-based approach to first-episode schizophrenia: response rates over 3 prospective antipsychotic trials with a retrospective data analysis. J Clin Psychiatry. 2011;72(11):1439–1444. PubMed CrossRef
Lehman AF, Lieberman JA, Dixon LB, et al; American Psychiatric Association; Steering Committee on Practice Guidelines. Practice Guideline for the Treatment of Patients With Schizophrenia, Second Edition. Am J Psychiatry. 2004;161(suppl):1–56. PubMed
Siskind D, Orr S, Sinha S, et al. Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis. Br J Psychiatry. 2022;220(3):115–120. PubMed
Chan SKW, Chan HYV, Honer WG, et al. Predictors of treatment-resistant and clozapine-resistant schizophrenia: a 12-year follow-up study of first-episode schizophrenia-spectrum disorders. Schizophr Bull. 2021;47(2):485–494. PubMed CrossRef
Warnez S, Alessi-Severini S. Clozapine: a review of clinical practice guidelines and prescribing trends. BMC Psychiatry. 2014;14(1):102. PubMed CrossRef
Vos T, Haby MM, Magnus A, et al. Assessing cost-effectiveness in mental health: helping policy-makers prioritize and plan health services. Aust N Z J Psychiatry. 2005;39(8):701–712. PubMed CrossRef
Kirwan P, O’Connor L, Sharma K, et al. The impact of switching to clozapine on psychiatric hospital admissions: a mirror-image study. Ir J Psychol Med. 2019;36(4):259–263. PubMed CrossRef
Siskind D, Reddel T, MacCabe JH, et al. The impact of clozapine initiation and cessation on psychiatric hospital admissions and bed days: a mirror image cohort study. Psychopharmacology (Berl). 2019;236(6):1931–1935. 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
Tang C, Subramaniam M, Ng BT, et al. Clozapine use in first-episode psychosis: The Singapore Early Psychosis Intervention Programme (EPIP) perspective. J Clin Psychiatry. 2016;77(11):e1447–e1453. PubMed CrossRef
Howes OD, Vergunst F, Gee S, et al. Adherence to treatment guidelines in clinical practice: study of antipsychotic treatment prior to clozapine initiation. Br J Psychiatry. 2012;201(6):481–485. PubMed CrossRef
Alessi-Severini S, Le Dorze J-A, Nguyen D, et al. Clozapine prescribing in a Canadian outpatient population. PLoS One. 2013;8(12):e83539. PubMed CrossRef
Shah P, Iwata Y, Brown EE, et al. Clozapine response trajectories and predictors of non-response in treatment-resistant schizophrenia: a chart review study. Eur Arch Psychiatry Clin Neurosci. 2020;270(1):11–22. PubMed CrossRef
Gee S, Vergunst F, Howes O, et al. Practitioner attitudes to clozapine initiation. Acta Psychiatr Scand. 2014;130(1):16–24. PubMed CrossRef
Daod E, Krivoy A, Shoval G, et al. Psychiatrists’ attitude towards the use of clozapine in the treatment of refractory schizophrenia: a nationwide survey. Psychiatry Res. 2019;275:155–161. PubMed CrossRef
Grover S, Balachander S, Chakarabarti S, et al. Prescription practices and attitude of psychiatrists towards clozapine: a survey of psychiatrists from India. Asian J Psychiatr. 2015;18:57–65. 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
Cheung EFC, Lam LCW, Hung SF. Mental health in Hong Kong: transition from hospital-based service to personalised care. Int Psychiatry. 2010;7(3):62–64. PubMed CrossRef
Nielsen J, Dahm M, Lublin H, et al. Psychiatrists’ attitude towards and knowledge of clozapine treatment. J Psychopharmacol. 2010;24(7):965–971. PubMed CrossRef
Leung JG, Cusimano J, Gannon JM, et al. Addressing clozapine under-prescribing and barriers to initiation: a psychiatrist, advanced practice provider, and trainee survey. Int Clin Psychopharmacol. 2019;34(5):247–256. PubMed CrossRef
Stahl SM. Clozapine: is now the time for more clinicians to adopt this orphan? CNS Spectr. 2014;19(4):279–281. PubMed CrossRef
Singh B, Hughes AJ, Roerig JL. Comfort level and barriers to the appropriate use of clozapine: a preliminary survey of us psychiatric residents. Acad Psychiatry. 2020;44(1):53–58. 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
Kalaria SN, Kelly DL. Development of point-of-care testing devices to improve clozapine prescribing habits and patient outcomes. Neuropsychiatr Dis Treat. 2019;15:2365–2370. PubMed CrossRef
Netherlands Clozapine Collaboration Group. Guideline for the Use of Clozapine [English version]. 2013. https://www.clozapinepluswerkgroep.nl/wp-content/uploads/2013/07/Guideline-for-the-use-of-Clozapine-2013.pdf
Schulte P. Risk of clozapine-associated agranulocytosis and mandatory white blood cell monitoring. Ann Pharmacother. 2006;40(4):683–688. PubMed CrossRef
Gee S, Gaughran F, MacCabe J, et al. Management of clozapine treatment during the COVID-19 pandemic. Ther Adv Psychopharmacol. 2020;10:2045125320928167. PubMed CrossRef
Zhang M, Owen RR, Pope SK, et al. Cost-effectiveness of clozapine monitoring after the first 6 months. Arch Gen Psychiatry. 1996;53(10):954–958. PubMed CrossRef
Siskind D, Honer WG, Clark S, et al. Consensus statement on the use of clozapine during the COVID-19 pandemic. J Psychiatry Neurosci. 2020;45(3):222–223. PubMed CrossRef
Chan SKW, So HC, Hui CLM, et al. 10-year outcome study of an early intervention program for psychosis compared with standard care service. Psychol Med. 2015;45(6):1181–1193. PubMed CrossRef
Ho CSH, Ho RCM, Mahendran R. The evolving mental health landscape in Singapore. Adv Psychiatr Treat. 2014;20(4):293–294. CrossRef
Hui C, Wong G, Lam Y, et al. Patient-clinician communication and needs identification for outpatients with schizophrenia in Hong Kong: role of the 2-COM Instrument. Hong Kong J Psychiatry. 2008;18(2):69–75.
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
Tang JY, Wong GH, Hui CL, et al. Early intervention for psychosis in Hong Kong—the EASY programme. Early Interv Psychiatry. 2010;4(3):214–219. PubMed CrossRef
Thien K, O’Donoghue B. Delays and barriers to the commencement of clozapine in eligible people with a psychotic disorder: a literature review. Early Interv Psychiatry. 2019;13(1):18–23. PubMed CrossRef
Maryan S, Harms M, McAllister E, et al. Comparison of clozapine monitoring and adverse event management in a psychiatrist-only and a clinical pharmacist-psychiatrist collaborative clinic. Ment Health Clin. 2019;9(2):70–75. PubMed CrossRef
Kelly DL, Love RC. Psychiatric pharmacist’s role in overcoming barriers to clozapine use and improving management. Ment Health Clin. 2019;9(2):64–69. PubMed CrossRef
Chan CY, Chua BY, Subramaniam M, et al. Clinicians’ perceptions of pharmacogenomics use in psychiatry. Pharmacogenomics. 2017;18(6):531–538. PubMed CrossRef
Hui CLM, Wong AKH, Leung WWT, et al. Psychiatrists’ opinion towards medication discontinuation in remitted first-episode psychosis: a multi-site study of the Asian Network for Early Psychosis. Early Interv Psychiatry. 2019;13(6):1329–1337. PubMed CrossRef