ABSTRACT
Background: Clozapine is the drug of choice indicated for treatment-resistant schizophrenia (TRS), but delays in initiation and underutilization might have affected its effectiveness in practice. In this study, we sought to examine the clinical outcomes of patients on clozapine treatment and if a delay in initiation was associated with poorer outcomes.
Methods: This study was conducted at a tertiary mental health institution in patients aged 21 to 80 years from January 2016 to October 2019 who were on a stable dose of clozapine for 2 weeks. All patients were assessed using the Structured Clinical Interview for DSM-IV-TR (SCID-I) to ascertain diagnoses of schizophrenia and schizoaffective disorder. Each patient was assessed on the Positive and Negative Syndrome Scale (PANSS) and Social Occupational Functioning Assessment Scale (SOFAS). Past antipsychotic treatment trials were obtained from the medical records. Symptom remission status was defined using the PANSS symptom criteria proposed by Andreasen and colleagues in 2005. Functional remission was defined as a SOFAS score ≥ 60.
Results: A total of 159 individuals with schizophrenia or schizoaffective disorder were recruited. The mean age of patients was 40.01 years, and the majority of patients were male (64.2%) and Chinese (85.5%). Thirty-seven patients (23.3%) achieved symptom remission, and 101 (63.5%) achieved functional remission. The median number of antipsychotic trials before clozapine initiation was 6 (interquartile range, 5–8). Patients in either symptom or functional remission had shorter time periods and fewer numbers of antipsychotic trials before first clozapine initiation. However, the trend was statistically significant only for median number of antipsychotic trials in the functional remission (P = .027) and symptom remission (P = .011) groups.
Conclusion: Our study found a significant delay in the initiation of clozapine despite current guidelines indicating it for TRS. This delay might have contributed to the poorer clinical outcomes. Further research is needed to provide a clearer understanding of clozapine delay, evaluate its impact on outcomes, and find ways to improve access to clozapine.
J Clin Psychiatry 2023;84(5):22m14588
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References (37)
- Polese D, Fornaro M, Palermo M, et al. Treatment-resistant to antipsychotics: a resistance to everything? psychotherapy in treatment-resistant schizophrenia and nonaffective psychosis: a 25-year systematic review and exploratory meta-analysis. Front Psychiatry. 2019;10:210. PubMed CrossRef
- Howes OD, McCutcheon R, Agid O, 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(3):216–229. PubMed CrossRef
- Lee J, Takeuchi H, Fervaha G, et al. Subtyping schizophrenia by treatment response: antipsychotic development and the central role of positive symptoms. Focus Am Psychiatr Publ. 2016;14(3):396–402. PubMed CrossRef
- Siskind D, McCartney L, Goldschlager R, et al. Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. Br J Psychiatry. 2016;209(5):385–392. PubMed CrossRef
- Asenjo Lobos C, Komossa K, Rummel-Kluge C, et al. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010;(11):CD006633. PubMed CrossRef
- Manschreck TC, Redmond DA, Candela SF, et al. Effects of clozapine on psychiatric symptoms, cognition, and functional outcome in schizophrenia. J Neuropsychiatry Clin Neurosci. 1999;11(4):481–489. PubMed CrossRef
- McGurk SR. The effects of clozapine on cognitive functioning in schizophrenia. J Clin Psychiatry. 1999;60(suppl 12):24–29. PubMed
- Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: a meta-analysis. Schizophr Res. 2005;73(2–3):139–145. 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). (published correction appears in Arch Gen Psychiatry.2003 Jul;60(7) Arch Gen Psychiatry. 2003;60(1):82–91. PubMed CrossRef
- Meltzer HY. Suicide in schizophrenia, clozapine, and adoption of evidence-based medicine. J Clin Psychiatry. 2005;66(4):530–533. PubMed CrossRef
- Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet. 2009;374(9690):620–627. PubMed CrossRef
- Tiihonen J, Wahlbeck K, Lönnqvist J, et al. Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study. BMJ. 2006;333(7561):224. PubMed CrossRef
- Essock SM, Frisman LK, Covell NH, et al. Cost-effectiveness of clozapine compared with conventional antipsychotic medication for patients in state hospitals. Arch Gen Psychiatry. 2000;57(10):987–994. 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
- Warnez S, Alessi-Severini S. Clozapine: a review of clinical practice guidelines and prescribing trends. BMC Psychiatry. 2014;14(1):102. PubMed CrossRef
- Nielsen J, Damkier P, Lublin H, et al. Optimizing clozapine treatment. Acta Psychiatr Scand. 2011;123(6):411–422. PubMed CrossRef
- Zheng S, Lee J, Chan SKW. Utility and barriers to clozapine use: a joint study of clinicians’ attitudes from Singapore and Hong Kong. J Clin Psychiatry. 2022;83(4):21m14231. PubMed CrossRef
- Bachmann CJ, Aagaard L, Bernardo M, et al. International trends in clozapine use: a study in 17 countries. Acta Psychiatr Scand. 2017;136(1):37–51. PubMed CrossRef
- Doyle R, Behan C, OʼKeeffe D, et al. Clozapine use in a cohort of first-episode psychosis. J Clin Psychopharmacol. 2017;37(5):512–517. PubMed CrossRef
- Varghese M T, Jyothi KS, Shaji KS, et al. Delaying clozapine: how long is too long? Gen Psychiatr. 2020;33(2):e100172. PubMed CrossRef
- First MB, Gibbon M. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). In: Hilsenroth MJ, Segal DL, Hersen M, eds. Comprehensive Handbook of Psychological Assessment. Vol 2. John Wiley & Sons, Inc; 2004:134–143.
- Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–276. PubMed CrossRef
- Lim K, Peh OH, Yang Z, et al. Large-scale evaluation of the Positive and Negative Syndrome Scale (PANSS) symptom architecture in schizophrenia. Asian J Psychiatr. 2021;62:102732. PubMed CrossRef
- Üstün TB, Kostanjsek N, Chatterji S, et al, eds. Measuring Health and Disability: Manual for WHO DIsability Assessment Schedule WHODAS 2.0. World Health Organization; 2010.
- Goldman HH, Skodol AE, Lave TR. Revising Axis V for DSM-IV: a review of measures of social functioning. Am J Psychiatry. 1992;149(9):1148–1156. PubMed CrossRef
- Andreasen NC, Carpenter WT Jr, Kane JM, et al. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162(3):441–449. PubMed CrossRef
- Glazer WM, Dickson RA. Clozapine reduces violence and persistent aggression in schizophrenia. J Clin Psychiatry. 1998;59(suppl 3):8–14. PubMed
- Frogley C, Taylor D, Dickens G, et al. A systematic review of the evidence of clozapine’s anti-aggressive effects. Int J Neuropsychopharmacol. 2012;15(9):1351–1371. PubMed CrossRef
- Nielsen J, Nielsen RE, Correll CU. Predictors of clozapine response in patients with treatment-refractory schizophrenia: results from a Danish Register Study. J Clin Psychopharmacol. 2012;32(5):678–683. PubMed CrossRef
- Yoshimura B, Yada Y, So R, et al. The critical treatment window of clozapine in treatment-resistant schizophrenia: secondary analysis of an observational study. Psychiatry Res. 2017;250:65–70. PubMed CrossRef
- Taylor DM, Young C, Paton C. Prior antipsychotic prescribing in patients currently receiving clozapine: a case note review. J Clin Psychiatry. 2003;64(1):30–34. PubMed CrossRef
- Wheeler AJ. Treatment pathway and patterns of clozapine prescribing for schizophrenia in New Zealand. Ann Pharmacother. 2008;42(6):852–860. PubMed CrossRef
- Zheng S, Chan SKW, Lee J. Managing treatment resistance in schizophrenia: a joint study in Hong Kong and Singapore. Front Psychiatry. 2022;13:1005373. 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
- 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
- Tungaraza TE, Farooq S. Clozapine prescribing in the UK: views and experience of consultant psychiatrists. Ther Adv Psychopharmacol. 2015;5(2):88–96. PubMed CrossRef
- Farhall J, Greenwood KM, Jackson HJ. Coping with hallucinated voices in schizophrenia: a review of self-initiated strategies and therapeutic interventions. Clin Psychol Rev. 2007;27(4):476–493. PubMed CrossRef
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