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Real-world clinical and cost-effectiveness of community clozapine initiation: mirror cohort study

Published online by Cambridge University Press:  19 April 2022

Emma Butler
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and South London and Maudsley NHS Foundation Trust, UK
Toby Pillinger
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and South London and Maudsley NHS Foundation Trust, UK
Kirsten Brown
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Faith Borgan
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Alice Bowen
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Katherine Beck
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Enrico D'Ambrosio
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’, Italy
Lisa Donaldson
Affiliation:
South London and Maudsley NHS Foundation Trust, UK
Sameer Jauhar
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and South London and Maudsley NHS Foundation Trust, UK
Stephen Kaar
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and South London and Maudsley NHS Foundation Trust, UK
Tiago Reis Marques
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, UK
Robert A. McCutcheon
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and South London and Maudsley NHS Foundation Trust, UK
Maria Rogdaki
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and South London and Maudsley NHS Foundation Trust, UK
Fiona Gaughran
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
James MacCabe
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and South London and Maudsley NHS Foundation Trust, UK
Rosalind Ramsay
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and South London and Maudsley NHS Foundation Trust, UK
David Taylor
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK and South London and Maudsley NHS Foundation Trust, UK
Paul McCrone
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Alice Egerton
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Oliver D. Howes*
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Medical Research Council London Institute of Medical Sciences, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, UK and South London and Maudsley NHS Foundation Trust, UK
*
Correspondence: Oliver Howes. Email: oliver.howes@kcl.ac.uk

Abstract

Background

Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.

Aims

The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.

Method

This was a naturalistic study of community patients recommended for clozapine treatment.

Results

Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).

Conclusions

These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.

Type
Paper
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists

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References

Howes, OD, McCutcheon, R, Agid, O, De Bartolomeis, A, Van Beveren, NJM, Birnbaum, ML, et al. Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry 2017; 174: 216–29.10.1176/appi.ajp.2016.16050503CrossRefGoogle Scholar
Siskind, D, Orr, S, Sinha, S, Yu, O, Brijball, B, Warren, N, et al. Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis. Br J Psychiatry 2022; 220: 115–20.10.1192/bjp.2021.61CrossRefGoogle ScholarPubMed
Iasevoli, F, Avagliano, C, Altavilla, B, Barone, A, D'Ambrosio, L, Matrone, M, et al. Disease severity in treatment resistant schizophrenia patients is mainly affected by negative symptoms, which mediate the effects of cognitive dysfunctions and neurological soft signs. Front Psychiatry 2018; 9: 553.10.3389/fpsyt.2018.00553CrossRefGoogle ScholarPubMed
Kennedy, JL, Altar, CA, Taylor, DL, Degtiar, I, Hornberger, JC. The social and economic burden of treatment-resistant schizophrenia: A systematic literature review. Int Clin Psychopharmacol 2014; 29: 6376.10.1097/YIC.0b013e32836508e6CrossRefGoogle ScholarPubMed
American Psychiatric Association. The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients with Schizophrenia. APA, 2018.Google Scholar
Barnes, TRE, Drake, R, Paton, C, Cooper, SJ, Deakin, B, Ferrier, IN, et al. Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2020; 34: 378.10.1177/0269881119889296CrossRefGoogle ScholarPubMed
National Institute for Health and Care Excellence. Schizophrenia: Core Interventions in the Treatment and Management of Schizophrenia in Primary and Secondary Care (update). NICE, 2009.Google Scholar
Mizuno, Y, McCutcheon, RA, Brugger, SP, Howes, OD. Heterogeneity and efficacy of antipsychotic treatment for schizophrenia with or without treatment resistance: a meta-analysis. Neuropsychopharmacology 2020; 45: 622–31.10.1038/s41386-019-0577-3CrossRefGoogle ScholarPubMed
Aitchison, KJ, Kerwin, RW. Cost-effectiveness of clozapine. Br J Psychiatry 1997; 171: 125–30.10.1192/bjp.171.2.125CrossRefGoogle ScholarPubMed
Hayhurst, K, Brown, P, Lewis, SW. The cost-effectiveness of clozapine: a controlled, population-based, mirror-image study. J Psychopharmacol 2002; 16: 169–75.10.1177/026988110201600208CrossRefGoogle ScholarPubMed
Hasan, AAH. The correlation between the quality of life and clinical variables among outpatients with schizophrenia. Psychiatry Res 2019; 271: 3945.10.1016/j.psychres.2018.09.062CrossRefGoogle ScholarPubMed
Warnez, S, Alessi-Severini, S. Clozapine: a review of clinical practice guidelines and prescribing trends. BMC Psychiatry 2014; 14: 102.10.1186/1471-244X-14-102CrossRefGoogle ScholarPubMed
Beck, K, McCutcheon, R, Stephenson, L, Schilderman, M, Patel, N, Ramsay, R, et al. Prevalence of treatment-resistant psychoses in the community: A naturalistic study. J Psychopharmacol 2019; 33: 1248–53.10.1177/0269881119855995CrossRefGoogle ScholarPubMed
Potkin, SG, Kane, JM, Correll, CU, Lindenmayer, J-P, Agid, O, Marder, SR, et al. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research. NPJ Schizophr 2020; 6: 1.10.1038/s41537-019-0090-zCrossRefGoogle Scholar
Gee, S, Vergunst, F, Howes, O, Taylor, D. Practitioner attitudes to clozapine initiation. Acta Psychiatr Scand 2014; 130: 1624.10.1111/acps.12193CrossRefGoogle ScholarPubMed
Verdoux, H, Quiles, C, Bachmann, CJ, Siskind, D. Prescriber and institutional barriers and facilitators of clozapine use: A systematic review. Schizophr Res 2018; 201: 1019.10.1016/j.schres.2018.05.046CrossRefGoogle ScholarPubMed
Nielsen, J, Dahm, M, Lublin, H, Taylor, D. Psychiatrists attitude towards and knowledge of clozapine treatment. J Psychopharmacol 2010; 24: 965–71.10.1177/0269881108100320CrossRefGoogle ScholarPubMed
Howes, OD, Vergunst, F, Gee, S, McGuire, P, Kapur, S, Taylor, D. Adherence to treatment guidelines in clinical practice: Study of antipsychotic treatment prior to clozapine initiation. Br J Psychiatry 2012; 201: 481–5.10.1192/bjp.bp.111.105833CrossRefGoogle ScholarPubMed
Tungaraza, TE, Farooq, S. Clozapine prescribing in the UK: views and experience of consultant psychiatrists. Ther Adv Psychopharmacol 2015; 5: 8896.10.1177/2045125314566808CrossRefGoogle ScholarPubMed
Beck, K, Mccutcheon, R, Bloomfield, MAP, Gaughran, F, Reis Marques, T, Maccabe, J, et al. The practical management of refractory schizophrenia - the Maudsley Treatment REview and Assessment Team service approach. Acta Psychiatr Scand 2014; 130: 427–38.10.1111/acps.12327CrossRefGoogle ScholarPubMed
O'Brien, A, Firn, M. Clozapine initiation in the community. Psychiatr Bull 2002; 26: 339–41.10.1192/pb.26.9.339CrossRefGoogle Scholar
Luchins, D, Hanrahan, P, Shinderman, M, Lagios, L, Fichtner, C. Initiating clozapine treatment in the outpatient clinic: service utilization and cost trends. Psychiatr Serv 1998; 49: 1034–8.10.1176/ps.49.8.1034CrossRefGoogle ScholarPubMed
Office for National Statistics. Population Estimates: Analysis Tool. Office for National Statistics, 2017 (https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesanalysistool).Google Scholar
Kaar, SJ, Natesan, S, McCutcheon, R, Howes, OD. Antipsychotics: Mechanisms underlying clinical response and side-effects and novel treatment approaches based on pathophysiology. Neuropharmacology 2020; 172: 107704.10.1016/j.neuropharm.2019.107704CrossRefGoogle ScholarPubMed
Taylor, D, Barnes, TRE, Young, AH. The Maudsley Prescribing Guidelines in Psychiatry (13th Edition). Wiley-Blackwell, 2018.Google Scholar
Kay, SR, Fiszbein, A, Opler, LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261–76.10.1093/schbul/13.2.261CrossRefGoogle Scholar
Wing, JK, Beevor, AS, Curtis, RH, Park, SBG, Hadden, S, Burns, A. Health of the Nation Outcome Scales (HoNOS): Research and development. Br J Psychiatry 1998; 172: 111810.1192/bjp.172.1.11CrossRefGoogle ScholarPubMed
World Health Organisation, . ICD-10 International Statistical Classification of Diseases and Related Health Problems 10th Revision: Schizophrenia, schizotypal and delusional disorders (F20-F29). WHO, 2016.Google Scholar
Tiihonen, J, Haukka, J, Taylor, M, Haddad, PM, Patel, MX, Korhonen, P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011; 168: 603–9.10.1176/appi.ajp.2011.10081224CrossRefGoogle Scholar
Siskind, D, Reddel, T, Maccabe, JH, Kisely, S. The impact of clozapine initiation and cessation on psychiatric hospital admissions and bed days: a mirror image cohort study. Psychopharmacology (Berl) 2019; 236: 1931–5.10.1007/s00213-019-5179-6CrossRefGoogle ScholarPubMed
Kirwan, P, O'Connor, L, Sharma, K, McDonald, C. The impact of switching to clozapine on psychiatric hospital admissions: a mirror-image study. Ir J Psychol Med 2019; 36: 259–63.10.1017/ipm.2017.28CrossRefGoogle ScholarPubMed
Land, R, Siskind, D, McArdle, P, Kisely, S, Winckel, K, Hollingworth, SA. The impact of clozapine on hospital use: a systematic review and meta-analysis. Acta Psychiatr Scand 2017: 135: 296309.10.1111/acps.12700CrossRefGoogle ScholarPubMed
Meltzer, HY, Cola, P, Way, L, Thompson, PA, Bastani, B, Davies, MA, et al. Cost effectiveness of clozapine in neuroleptic-resistant schizophrenia. Am J Psychiatry 1993; 150: 1630–8.Google ScholarPubMed
Honigfeld, G, Patin, J. A two-year clinical and economic follow-up of patients on clozapine. Psychiatr Serv 1990; 41: 882–5.10.1176/ps.41.8.882CrossRefGoogle ScholarPubMed
Percudani, M, Fattore, G, Galletta, J, Mita, PL, Contini, A, Altamura, AC. Health care costs of therapy-refractory schizophrenic patients treated with clozapine: a study in a community psychiatric service in Italy. Acta Psychiatr Scand 1999; 99: 274–80.10.1111/j.1600-0447.1999.tb07225.xCrossRefGoogle Scholar
BNF. Clozapine. Medicinal Forms. BNF, 2021 (https://bnf.nice.org.uk/medicinal-forms/clozapine.html).Google Scholar
Pillinger, T, McCutcheon, RA, Vano, L, Mizuno, Y, Arumuham, A, Hindley, G, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry 2020; 7: 6477.10.1016/S2215-0366(19)30416-XCrossRefGoogle ScholarPubMed
South London and Maudsley NHS Foundation Trust. Annual Report and Accounts. South London and Maudsley NHS Foundation Trust, 2020 (https://www.slam.nhs.uk/about-us/policy-and-publications/annual-report-and-accounts/).Google Scholar
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