1. Elkis, H, Buckley, PF. Treatment-resistant schizophrenia. Psychiatr Clin North Am 2016; 39: 239–265.
Google Scholar | Crossref | Medline2. Samara, MT, Nikolakopoulou, A, Salanti, G, et al. How many patients with schizophrenia do not respond to antipsychotic drugs in the short term? An analysis based on individual patient data from randomized controlled trials. Schizophr Bull 2019; 45: 639–646.
Google Scholar | Crossref | Medline3. Huhn, M, Nikolakopoulou, A, Schneider-Thoma, J, et al. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet 2019; 394: 939–951.
Google Scholar | Crossref | Medline4. Every-Palmer, S, Nowitz, M, Stanley, J, et al. Clozapine-treated patients have marked gastrointestinal hypomotility, the probable basis of life-threatening gastrointestinal complications: a cross sectional study. EBioMedicine 2016; 5: 125–134.
Google Scholar | Crossref5. Dhillon, R, Bastiampillai, T, Tee, K, et al. Clozapine and associated QTc prolongation. Aust NZ J Psychiatry 2011; 45: 1098–1099.
Google Scholar | SAGE Journals | ISI6. Kang, UG, Kwon, JS, Ahn, YM, et al. Electrocardiographic abnormalities in patients treated with clozapine. J Clin Psychiatry 2000; 61: 441–446.
Google Scholar | Crossref | Medline | ISI7. Perdigues, SR, Quecuti, RS, Mane, A, et al. An observational study of clozapine induced sedation and its pharmacological management. Eur Neuropsychopharmacol 2016; 26: 156–161.
Google Scholar | Crossref | Medline8. Taylor, DM, Barnes, TR, Young, AH. The Maudsley prescribing guidelines in psychiatry. 13th ed. Hoboken, NJ: John Wiley & Sons, 2018.
Google Scholar9. Varma, S, Bishara, D, Besag, FM, et al. Clozapine-related EEG changes and seizures: dose and plasma-level relationships. Ther Adv Psychopharmacol 2011; 1: 47–66.
Google Scholar | SAGE Journals10. Haring, C, Neudorfer, C, Schwitzer, J, et al. EEG alterations in patients treated with clozapine in relation to plasma levels. Psychopharmacology (Berl) 1994; 114: 97–100.
Google Scholar | Crossref | Medline | ISI11. Dzahini, O, Singh, N, Taylor, D, et al. Antipsychotic drug use and pneumonia: systematic review and meta-analysis. J Psychopharmacol 2018; 32: 1167–1181.
Google Scholar | SAGE Journals | ISI12. Couchman, L, Morgan, PE, Spencer, EP, et al. Plasma clozapine, norclozapine, and the clozapine:norclozapine ratio in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 1993-2007. Ther Drug Monit 2010; 32: 438–447.
Google Scholar | Crossref | Medline | ISI13. Hiemke, C, Bergemann, N, Clement, HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry 2018; 51: 9–62.
Google Scholar | Crossref | Medline14. Chong, SA, Tan, CH, Khoo, YM, et al. Clinical evaluation and plasma clozapine concentrations in Chinese patients with schizophrenia. Ther Drug Monit 1997; 19: 219–223.
Google Scholar | Crossref | Medline | ISI15. Ng, CH, Chong, SA, Lambert, T, et al. An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels. Int Clin Psychopharmacol 2005; 20: 163–168.
Google Scholar | Crossref | Medline | ISI16. Matsuda, KT, Cho, MC, Lin, KM, et al. Clozapine dosage, serum levels, efficacy, and side-effect profiles: a comparison of Korean-American and Caucasian patients. Psychopharmacol Bull 1996; 32: 253–257.
Google Scholar | Medline17. Eiermann, B, Engel, G, Johansson, I, et al. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol 1997; 44: 439–446.
Google Scholar | Crossref | Medline | ISI18. Jaquenoud Sirot, E, Knezevic, B, Morena, GP, et al. ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine. J Clin Psychopharmacol 2009; 29: 319–326.
Google Scholar | Crossref | Medline | ISI19. Kuoppamäki, M, Syvälahti, E, Hietala, J. Clozapine and N-desmethylclozapine are potent 5-HT1C receptor antagonists. Eur J Pharmacol 1993; 245: 179–182.
Google Scholar | Crossref | Medline | ISI20. Bærentzen, S, Casado-Sainz, A, Lange, D, et al. The chemogenetic receptor ligand clozapine N-oxide induces in vivo neuroreceptor occupancy and reduces striatal glutamate levels. Front Neurosci 2019; 13: 187.
Google Scholar | Crossref | Medline21. Kida, N , et al. Policy research on comprehensive support for persons with severe and chronic mental illness-clozapine usage guidelines study: health and labour science research grants- disability policy research project (Japan) (in Japanese), https://mhlw-grants.niph.go.jp/project/27291/1 (2019).
Google Scholar22. Guy, W . ECDEU assessment manual for psychoparmacology. Washington, DC: US Department of Health, Education, and Welfare, Public Health Service, 1976, pp.76–338.
Google Scholar23. Takeuchi, H, Fervaha, G, Lee, J, et al. A preliminary examination of the validity and reliability of a new brief rating scale for symptom domains of psychosis: Brief Evaluation of Psychosis Symptom Domains (BE-PSD). J Psychiatr Res 2016; 80: 87–92.
Google Scholar | Crossref | Medline24. Takeuchi, H, Fervaha, G, Lee, J, et al. What symptom domains are associated with patient distress in schizophrenia? Schizophr Res 2016; 176: 329–330.
Google Scholar | Crossref | Medline25. American Psychiatric Association . Diagnostic and Statistical Manual of mental disorder 4 Text Revision (DSM-4-TR). Washington, DC: American Psychiatric Publishing, 2000, p.34.
Google Scholar26. Naber, D, Moritz, S, Lambert, M, et al. Improvement of schizophrenic patients’ subjective well-being under atypical antipsychotic drugs. Schizophr Res 2001; 50: 79–88.
Google Scholar | Crossref | Medline | ISI27. Watanabe, M, Matumura, H. Reliability and validity of subjective weii-being under neuroleptic drug treatmen short form, Japanese version (SWNS-J). Nihon Shinkei Seishin Yakurigaku Zasshi 2003; 6: 905–912. (in Japanese)
Google Scholar28. Hynes, C, Keating, D, McWilliams, S, et al. Staff information of Glasgow antipsychotic side-effects scale for clozapine - development and validation of a clozapine-specific side-effects scale. Schizophr Res 2015; 168: 505–513.
Google Scholar | Crossref | Medline29. Kitagawa, K, So, R, Nomura, N, et al. Reliability of the Glasgow Antipsychotic Side-effects Scale for Clozapine Japanese version (GASS-C-J). PLoS One 2020; 15: e0234864.
Google Scholar | Crossref | Medline30. Ng, W, Uchida, H, Ismail, Z, et al. Clozapine exposure and the impact of smoking and gender: a population pharmacokinetic study. Ther Drug Monit 2009; 31: 360–366.
Google Scholar | Crossref | Medline31. R Core Team . R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2020. https://www.R-project.org/ (accessed 10 November 2020).
Google Scholar32. Denney, W, Duvvuri, S, Buckeridge, C. Simple, automatic noncompartmental analysis: the PKNCA R package. J Pharmacokinet Pharmacodyn 2015; 42: 11–107, S165.
Google Scholar33. Patteet, L, Maudens, KE, Vermeulen, Z, et al. Retrospective evaluation of therapeutic drug monitoring of clozapine and norclozapine in Belgium using a multidrug UHPLC–MS/MS method. Clin Biochem 2014; 47: 336–339.
Google Scholar | Crossref | Medline34. Suhas, S, Kumar, V, Damodharan, V, et al. Do Indian patients with schizophrenia need half the recommended clozapine dose to achieve therapeutic serum level? An exploratory study. Schizophr Res 2020; 222: 195–201.
Google Scholar | Crossref | Medline35. Yusufi, B, Mukherjee, S, Flanagan, R, et al. Prevalence and nature of side effects during clozapine maintenance treatment and the relationship with clozapine dose and plasma concentration. Int Clin Psychopharmacol 2007; 22: 238–243.
Google Scholar | Crossref | Medline | ISI36. Olesen, OV, Thomsen, K, Jensen, PN, et al. Clozapine serum levels and side effects during steady state treatment of schizophrenic patients: a cross-sectional study. Psychopharmacology (Berl) 1995; 117: 371–378.
Google Scholar | Crossref | Medline | ISI37. Spina, E, Avenoso, A, Facciola, G, et al. Relationship between plasma concentrations of clozapine and norclozapine and therapeutic response in patients with schizophrenia resistant to conventional neuroleptics. Psychopharmacology (Berl) 2000; 148: 83–89.
Google Scholar | Crossref | Medline | ISI38. Sporn, AL, Vermani, A, Greenstein, DK, et al. Clozapine treatment of childhood-onset schizophrenia: evaluation of effectiveness, adverse effects, and long-term outcome. J Am Acad Child Adolesc Psychiatry 2007; 46: 1349–1356.
Google Scholar | Crossref | Medline | ISI39. Thorup, M, Fog, R. Clozapine treatment of schizophrenic patients - plasma concentration and coagulation factors. Acta Psychiatr Scand 1977; 55: 123–126.
Google Scholar | Crossref | Medline | ISI40. Uchida, H, Kapur, S, Mulsant, BH, et al. Sensitivity of older patients to antipsychotic motor side effects: a PET study examining potential mechanisms. Am J Geriatr Psychiatry 2009; 17: 255–263.
Google Scholar | Crossref | Medline | ISI41. Palmer, SE, McLean, RM, Ellis, PM, et al. Life-threatening clozapine-induced gastrointestinal hypomotility: an analysis of 102 cases. J Clin Psychiatry 2008; 69: 759–768.
Google Scholar | Crossref | Medline | ISI