Hostname: page-component-7c8c6479df-ph5wq Total loading time: 0 Render date: 2024-03-18T13:13:11.631Z Has data issue: false hasContentIssue false

The prevalence of agranulocytosis and related death in clozapine-treated patients: a comprehensive meta-analysis of observational studies

Published online by Cambridge University Press:  12 March 2019

Xiao-Hong Li
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & the Advanced Innovation Center for Human Brain Protection, Beijing Anding Hospital, School of Mental Health, Capital Medical University, Beijing, China
Xiao-Mei Zhong
Affiliation:
The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
Li Lu
Affiliation:
Unit of Psychiatry, Centre of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China
Wei Zheng
Affiliation:
The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
Shi-bin Wang
Affiliation:
Guangdong Mental Health Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
Wen-wang Rao
Affiliation:
Unit of Psychiatry, Centre of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China
Shuai Wang
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & the Advanced Innovation Center for Human Brain Protection, Beijing Anding Hospital, School of Mental Health, Capital Medical University, Beijing, China
Chee H. Ng
Affiliation:
Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia
Gabor S. Ungvari
Affiliation:
University of Notre Dame Australia, Fremantle, Australia Division of Psychiatry, Medical School, University of Western Australia, Perth, Australia
Gang Wang*
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & the Advanced Innovation Center for Human Brain Protection, Beijing Anding Hospital, School of Mental Health, Capital Medical University, Beijing, China
Yu-Tao Xiang*
Affiliation:
Unit of Psychiatry, Centre of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China
*
Author for correspondence: Yu-Tao Xiang, E-mail: xyutly@gmail.com; Gang Wang, E-mail: gangwangdoc@gmail.com
Author for correspondence: Yu-Tao Xiang, E-mail: xyutly@gmail.com; Gang Wang, E-mail: gangwangdoc@gmail.com

Abstract

Background

Clozapine treatment increases the risk of agranulocytosis, but findings on the epidemiology of agranulocytosis have been inconsistent. This meta-analysis examined the prevalence of agranulocytosis and related death in clozapine-treated patients.

Methods

A literature search in the international (PubMed, PsycINFO, and EMBASE) and Chinese (WanFang, Chinese National Knowledge Infrastructure, and Sinomed) databases was conducted. Prevalence estimates of agranulocytosis and related death in clozapine-treated patients were synthesized with the Comprehensive Meta-Analysis program using the random-effects model.

Results

Thirty-six studies with 260 948 clozapine-treated patients published between 1984 and 2018 were included in the meta-analysis. The overall prevalence of agranulocytosis and death caused by agranulocytosis were 0.4% (95% CI 0.3–0.6%) and 0.05% (95% CI 0.03–0.09%), respectively. The prevalence of agranulocytosis was moderated by sample size, study quality, year of publication, and that of data collection.

Conclusions

The prevalence of clozapine-associated agranulocytosis is low. Agranulocytosis-related death appears rare.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

PROSPERO registration No.: CRD42017068158.

References

Abanmy, NO, Al-Jaloud, A, Al-Jabr, A, Al-Ruwaisan, R, Al-Saeed, W and Fatani, S (2014) Clozapine-induced blood dyscrasias in Saudi Arab patients. International Journal of Clinical Pharmacy 36, 815–808.CrossRefGoogle ScholarPubMed
Alvir, JM, Lieberman, JA, Safferman, AZ, Schwimmer, JL and Schaaf, JA (1993) Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. The New England Journal of Medicine 329, 162167.CrossRefGoogle ScholarPubMed
Amar, A, Segman, RH, Shtrussberg, S, Sherman, L, Safirman, C, Lerer, B and Brautbar, C (1998) An association between clozapine-induced agranulocytosis in schizophrenics and HLA-DQB1*0201. International Journal of Neuropsychopharmacology 1, 4144.CrossRefGoogle ScholarPubMed
Arranz, B, Garriga, M, Garcia-Rizo, C and San, L (2018) Clozapine use in patients with schizophrenia and a comorbid substance use disorder: a systematic review. European Neuropsychopharmacology 28, 227242.CrossRefGoogle Scholar
Athanasiou, MC, Dettling, M, Cascorbi, I, Mosyagin, I, Salisbury, BA, Pierz, KA, Zou, W, Whalen, H, Malhotra, AK, Lencz, T, Gerson, SL, Kane, JM and Reed, CR (2011) Candidate gene analysis identifies a polymorphism in HLA-DQB1 associated with clozapine-induced agranulocytosis. Journal of Clinical Psychiatry 72, 458463.CrossRefGoogle ScholarPubMed
Atkin, K, Kendall, F, Gould, D, Freeman, H, Liberman, J and O'Sullivan, D (1996) Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland. The British Journal of Psychiatry 169, 483488.CrossRefGoogle ScholarPubMed
Balda, MV, Garay, OU, Papale, RM, Bignone, I, Bologna, VG, Brandolini, A, Prokopez, CR, Balasini, JI, Baldessarini, RJ and Daray, FM (2015) Clozapine-associated neutropenia and agranulocytosis in Argentina (2007–2012). International Clinical Psychopharmacology 30, 109114.CrossRefGoogle Scholar
Bankowski, Z, Bruppacher, R, Crusius, I, Gallagher, J, Kremer, G and Venulet, J (Reprinted 2000) REPORTING ADVERSE DURING REACTION Definitions of Terms and Criteria for Their Use. CIOMS (the Council for International Organizations of Medical Sciences), c/o World Health Organization, Geneva, Switzerland, 100.Google Scholar
Bastani, B, Alphs, LD and Meltzer, HY (1989) Development of the clozaril patient management system. Psychopharmacology 99(suppl), S122S125.CrossRefGoogle ScholarPubMed
Bastiampillai, T, Gupta, A, Chan, SK and Allison, S (2016) Changes for clozapine monitoring in the United States. Molecular Psychiatry 21, 858860.CrossRefGoogle ScholarPubMed
Boyle, MH (1998) Guidelines for evaluating prevalence studies. Evidence-Based Mental Health 1, 3740.CrossRefGoogle Scholar
Cao, XL, Wang, SB, Zhong, BL, Zhang, L, Ungvari, GS, Ng, CH, Li, L, Chiu, HF, Lok, GK, Lu, JP, Jia, FJ and Xiang, YT (2017) The prevalence of insomnia in the general population in China: a meta-analysis. PLoS ONE 12, e0170772.CrossRefGoogle ScholarPubMed
Chen, MJ (1991) The effect of psychotropic drugs on white blood cells: an analysis of 973 cases (in Chinese). Sichuan Mental Health 4, 3639.Google Scholar
Cooper, C, Balamurali, T and Livingston, G (2007) A systematic review of the prevalence and covariates of anxiety in caregivers of people with dementia. International Psychogeriatrics 19, 175195.CrossRefGoogle ScholarPubMed
Copolov, DL, Bell, WR, Benson, WJ, Keks, NA, Strazzeri, DC and Johnson, GF (1998) Clozapine treatment in Australia: a review of haematological monitoring. Medical Journal of Australia 168, 495497.CrossRefGoogle ScholarPubMed
Crilly, J (2007) The history of clozapine and its emergence in the US market: a review and analysis. History of Psychiatry 18, 3960.CrossRefGoogle ScholarPubMed
Deng, SP, Wang, DB, Ji, LY and Zou, XH (1999) The comparison of leukocyte changes caused by clozapine and white blood cells in non medication users (in Chinese). China Pharmacist 2, 298299.Google Scholar
Dettling, M, Cascorbi, I, Opgen-Rhein, C and Schaub, R (2007) Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues for associations with human leukocyte class I and II antigens. Pharmacogenomics Journal 7, 325332.CrossRefGoogle Scholar
Duan, R (2007) Clinical analysis and nursing care of clozapine induced leukocyte reduction (in Chinese). Modern Medicine and Health 23, 1059.Google Scholar
Egger, M, Davey Smith, G, Schneider, M and Minder, C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315, 629634.CrossRefGoogle ScholarPubMed
Faay, MDM, Czobor, P and Sommer, IEC (2018) Efficacy of typical and atypical antipsychotic medication on hostility in patients with psychosis-spectrum disorders: a review and meta-analysis. Neuropsychopharmacology 43, 23402349.CrossRefGoogle ScholarPubMed
Fan, ZY, Cui, HS, Shen, AZ, Ju, FY, Tang, M, Bai, SZ, Yang, LL and Kong, LF (1992) White blood cell counts in 3113 psychotic patients with clozapine treatment (in Chinese). New Drugs and Clinical Remidies 30, 330331.Google Scholar
Gan, JG and Chen, HL (1995) Comparison of clozapine alone and in combination with lithium carbonate in patients with leukocyte depletion (in Chinese). Health Psychology 3, 1113.Google Scholar
Gaszner, P, Makkos, Z and Kosza, P (2002) Agranulocytosis during clozapine therapy. Progress in Neuro-Psychopharmacology & Biological Psychiatry 26, 603607.CrossRefGoogle ScholarPubMed
Gerbino-Rosen, G, Tompkins, DA, Nusser, L, Napolitano, B, Henderson, I and Kumra, S (2005) Hematological adverse events in clozapine-treated children and adolescents. Journal of the American Academy of Child and Adolescent Psychiatry 44, 10241031.CrossRefGoogle ScholarPubMed
Goldstein, JI, Jarskog, LF, Hilliard, C, Alfirevic, A, Duncan, L, Fourches, D, Huang, H, Lek, M, Neale, BM, Ripke, S, Shianna, K, Szatkiewicz, JP, Tropsha, A, van den Oord, EJ, Cascorbi, I, Dettling, M, Gazit, E, Goff, DC, Holden, AL, Kelly, DL, Malhotra, AK, Nielsen, J, Pirmohamed, M, Rujescu, D, Werge, T, Levy, DL, Josiassen, RC, Kennedy, JL, Lieberman, JA, Daly, MJ and Sullivan, PF (2014) Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. Nature Communications 5, 4757.CrossRefGoogle ScholarPubMed
He, JL, Mao, PX and Yan, GJ (2002) Agranulocytosis caused by clozapine (in Chinese). Journal of Clinical Psychiatry 12, 291.Google Scholar
Higgins, JP, Thompson, SG, Deeks, JJ and Altman, DG (2003) Measuring inconsistency in meta-analyses. BMJ 327, 557560.CrossRefGoogle ScholarPubMed
Honigfeld, G (1996) Effects of the clozapine national registry system on incidence of deaths related to agranulocytosis. Psychiatric Services 47, 5256.Google Scholar
Honigfeld, G, Arellano, F, Sethi, J, Bianchini, A and Schein, J (1998) Reducing clozapine-related morbidity and mortality: 5 years of experience with the clozaril national registry. Journal of Clinical Psychiatry 59(suppl. 3), 37.Google ScholarPubMed
Idanpaan-Heikkila, J, Alhava, E, Olkinuora, M and Palva, I (1975) Letter: clozapine and agranulocytosis. Lancet 2, 611.CrossRefGoogle ScholarPubMed
Ingimarsson, O, MacCabe, JH, Haraldsson, M, Jonsdottir, H and Sigurdsson, E (2016) Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland. BMC Psychiatry 16, 441.CrossRefGoogle ScholarPubMed
Ji, YP and Gao, CF (2005) Clinical analysis of clozapine induced leukopenia. and agranulocytosis (in Chinese). Sichuan Mental Health 18, 239.Google Scholar
Kadasah, S, Arfin, M and Tariq, M (2011) HLA-DRB1 association with schizophrenia in Saudi Arabian patients. International Journal of Psychiatry in Clinical Practice 15, 112117.CrossRefGoogle ScholarPubMed
Kane, J, Honigfeld, G, Singer, J and Meltzer, H (1988) Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Archives Of General Psychiatry 45, 789796.CrossRefGoogle ScholarPubMed
Kang, BJ, Cho, MJ, Oh, JT, Lee, Y, Chae, BJ and Ko, J (2006) Long-term patient monitoring for clozapine-induced agranulocytosis and neutropenia in Korea: when is it safe to discontinue CPMS? Human Psychopharmacology: Clinical and Experimental 21, 387391.CrossRefGoogle ScholarPubMed
Kelly, DL, Kreyenbuhl, J, Dixon, L, Love, RC, Medoff, D and Conley, RR (2007) Clozapine underutilization and discontinuation in African Americans due to leucopenia. Schizophrenia bulletin 33, 12211224.CrossRefGoogle ScholarPubMed
Lahdelma, L, Ahokas, A, Andersson, LC, Suvisaari, J, Hovatta, I, Huttunen, MO and Koskimies, S (2001) Mitchell B. Balter Award. Human leukocyte antigen-A1 predicts a good therapeutic response to clozapine with a low risk of agranulocytosis in patients with schizophrenia. Journal of Clinical Psychopharmacology 21, 47.CrossRefGoogle Scholar
Lambertenghi Deliliers, G (2000) Blood dyscrasias in clozapine-treated patients in Italy. Haematologica 85, 233237.Google ScholarPubMed
Land, R, Siskind, D, McArdle, P, Kisely, S, Winckel, K and Hollingworth, SA (2017) The impact of clozapine on hospital use: a systematic review and meta-analysis. Acta Psychiatrica Scandinavica 135, 296309.CrossRefGoogle ScholarPubMed
Lau, KL and Yim, PH (2015) Neutropenia and agranulocytosis in Chinese patients prescribed clozapine. Eastern Asian Archivas of Psychiatry 25, 164167.Google ScholarPubMed
Legge, SE, Hamshere, ML, Ripke, S, Pardinas, AF, Goldstein, JI, Rees, E, Richards, AL, Leonenko, G, Jorskog, LF, Chambert, KD, Collier, DA, Genovese, G, Giegling, I, Holmans, P, Jonasdottir, A, Kirov, G, McCarroll, SA, MacCabe, JH, Mantripragada, K, Moran, JL, Neale, BM, Stefansson, H, Rujescu, D, Daly, MJ, Sullivan, PF, Owen, MJ, O'Donovan, MC and Walters, JTR (2017) Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia. Molecular Psychiatry 22, 15021508.CrossRefGoogle ScholarPubMed
Li, Q, Xiang, YT, Su, YA, Shu, L, Yu, X, Chiu, HF, Correll, CU, Ungvari, GS, Lai, KY, Ma, C, Wang, GH, Bai, PS, Li, T, Sun, LZ, Shi, JG, Chen, XS, Mei, QY, Li, KQ and Si, TM (2015) Antipsychotic polypharmacy in schizophrenia patients in China and its association with treatment satisfaction and quality of life: findings of the third national survey on use of psychotropic medications in China. Australian & New Zealand Journal of Psychiatry 49, 129136.CrossRefGoogle ScholarPubMed
Li, Y, Cao, XL, Zhong, BL, Ungvari, GS, Chiu, HF, Lai, KY, Zheng, W, Correll, CU and Xiang, YT (2016) Smoking in male patients with schizophrenia in China: a meta-analysis. Drug and Alcohol Dependence 162, 146153.CrossRefGoogle ScholarPubMed
Lieberman, JA and Alvir, JM (1992) A report of clozapine-induced agranulocytosis in the United States. Incidence and risk factors. Drug Safety 7, 12.CrossRefGoogle ScholarPubMed
Lieberman, JA, Yunis, J, Egea, E, Canoso, RT, Kane, JM and Yunis, EJ (1990) HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia. Archives Of General Psychiatry 47, 945948.CrossRefGoogle ScholarPubMed
Liu, SY (1996) Clinical investigation of granulocyte reduction induced by clozapine and chlorpromazine (in Chinese). Medical Journal of Chinese Civil Administration 8, 7172.Google Scholar
Long, J, Huang, G, Liang, W, Liang, B, Chen, Q, Xie, J, Jiang, J and Su, L (2014) The prevalence of schizophrenia in mainland China: evidence from epidemiological surveys. Acta Psychiatrica Scandinavica 130, 244256.CrossRefGoogle ScholarPubMed
Lu, MK, Hou, XX, Zhou, JD, Yin, ML, Xu, YP, Guo, M, Zhang, LD and Yan, HQ (1990) Analysis of 520 cases of leukocyte change caused by clozapine (in Chinese). Shanghai Archives of Psychiatry 2, 185187.Google Scholar
Lv, HM, Niu, FR, Zhou, ZL, Zhou, SG, Pan, LM, Sun, ZX, Yu, XF, Gu, LZ, Mei, QY, Li, XJ, Wei, XY, Feng, HP, Yu, DX, Wang, XZ, Wang, YC, Jiang, XL, Wang, ML, Yu, HX, Wu, JL, Huang, LQ, Zhan, JX, Zhang, LL, Ji, F, Cui, JJ, Zhan, QM, Sun, CY, Zhuang, XG, Fu, JG and Guang, SJ (1997) Rediscussion on side reaction of clozapine (in Chinese). Journal of Clinical Psychiatry 7, 4446.Google Scholar
Mata, DA, Ramos, MA, Bansal, N, Khan, R, Guille, C, Di Angelantonio, E and Sen, S (2015) Prevalence of depression and depressive symptoms Among resident physicians: a systematic review and meta-analysis. JAMA 314, 23732383.CrossRefGoogle ScholarPubMed
Munro, J, O'Sullivan, D, Andrews, C, Arana, A, Mortimer, A and Kerwin, R (1999) Active monitoring of 12 760 clozapine recipients in the UK and Ireland. Beyond pharmacovigilance. British Journal of Psychiatry 175, 576580.CrossRefGoogle ScholarPubMed
Myles, N, Myles, H, Xia, S, Large, M, Kisely, S, Galletly, C, Bird, R and Siskind, D (2018) Meta-analysis examining the epidemiology of clozapine-associated neutropenia. Acta Psychiatrica Scandinavica 138, 101109.CrossRefGoogle ScholarPubMed
Oyesanmi, O, Kunkel, EJ, Monti, DA and Field, HL (1999) Hematologic side effects of psychotropics. Psychosomatics 40, 414421.CrossRefGoogle ScholarPubMed
Peacock, L and Gerlach, J (1994) Clozapine treatment in Denmark: concomitant psychotropic medication and hematologic monitoring in a system with liberal usage practices. Journal of Clinical Psychiatry 55, 4449.Google Scholar
Pecenak, J, Novotny, V and Janik, P (2009) Results from the monitoring system for clozapine in Slovakia. European Neuropsychopharmacology 19, S527.CrossRefGoogle Scholar
Pringsheim, T, Jette, N, Frolkis, A and Steeves, TD (2014) The prevalence of Parkinson's disease: a systematic review and meta-analysis. Movement Disorders 29, 15831590.CrossRefGoogle ScholarPubMed
Shapiro, S, Issaragrisil, S, Kaufman, DW, Anderson, T, Chansung, K, Thamprasit, T, Sirijirachai, J, Piankijagum, A, Porapakkham, Y, Vannasaeng, S, Leaverton, PE and Young, NS (1999) Agranulocytosis in Bangkok, Thailand: a predominantly drug-induced disease with an unusually low incidence. Aplastic Anemia Study Group. American Journal of Tropical Medicine and Hygiene 60, 573577.CrossRefGoogle ScholarPubMed
Sing, CW, Wong, ICK, Cheung, BMY, Chan, JCY, Chu, JKP and Cheung, CL (2017) Incidence and risk estimate of drug-induced agranulocytosis in Hong Kong Chinese. A population-based case–control study. Pharmacoepidemiology and Drug Safety 26, 248255.CrossRefGoogle Scholar
Siskind, D, McCartney, L, Goldschlager, R and Kisely, S (2016) Clozapine v. First- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. British Journal of Psychiatry 209, 385392.CrossRefGoogle ScholarPubMed
Sultan, RS, Olfson, M, Correll, CU and Duncan, EJ (2017) Evaluating the effect of the changes in FDA guidelines for clozapine monitoring. Journal of Clinical Psychiatry 78, e933e939.CrossRefGoogle ScholarPubMed
Valevski, A, Klein, T, Gazit, E, Meged, S, Stein, D, Elizur, A, Narinsky, ER, Kutzuk, D and Weizman, A (1998) HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients. European Journal of Immunogenetics 25, 1113.CrossRefGoogle ScholarPubMed
Vermeulen, JM, van Rooijen, G, van de Kerkhof, MPJ, Sutterland, AL, Correll, CU and de Haan, L (2018) Clozapine and long-term mortality risk in patients with schizophrenia: a systematic review and meta-analysis of studies lasting 1.1–12.5 years. Schizophrenia Bulletin. doi: 10.1093/schbul/sby052.CrossRefGoogle Scholar
Volavka, J, Czobor, P, Sheitman, B, Lindenmayer, JP, Citrome, L, McEvoy, JP, Cooper, TB, Chakos, M and Lieberman, JA (2002) Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. American Journal of Psychiatry 159, 255262.CrossRefGoogle ScholarPubMed
Volavka, J, Czobor, P, Nolan, K, Sheitman, B, Lindenmayer, JP, Citrome, L, McEvoy, JP, Cooper, TB and Lieberman, JA (2004) Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or haloperidol. Journal of Clinical Psychopharmacology 24, 225228.CrossRefGoogle ScholarPubMed
Wahlbeck, K, Cheine, M, Essali, A and Adams, C (1999) Evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials. American Journal of Psychiatry 156, 990999.Google ScholarPubMed
Wang, YL (2002) The relationship between age and granulopenia induced by clozapine (in Chinese). Aeronautical and Astronautical Medicine 13, 231.Google Scholar
Wang, GF and Liu, YP (2005) Changes of white blood cells in 850 outpatients with schizophrenia taking clozapine or chlorpromazine (in Chinese). Guangdong Medicine 26, 15751576.Google Scholar
Winsper, C, Ganapathy, R, Marwaha, S, Large, M, Birchwood, M and Singh, SP (2013) A systematic review and meta-regression analysis of aggression during the first episode of psychosis. Acta Psychiatrica Scandinavica 128, 413421.CrossRefGoogle ScholarPubMed
Xu, SH (1984) Clozapine and agranulocytopenia (in Chinese). Chinese Journal of Neuropsychiatry 17, 271272.Google Scholar
Xu, WL, Wang, JL, Wu, EN and Chen, CX (2001) Comparative analysis of the effects of clozapine and chlorpromazine on white blood cells (in Chinese). Medical Journal of Chinese Civil Administration 13, 1213.Google Scholar
Yan, XL and Wu, HJ (2014) Effects of antipsychotics on peripheral blood leukocytes in patients with schizophrenia (in Chinese). Chinese Journal of Primary Medicine and Pharmacy 21, 3.Google Scholar
Yang, JS and Zhang, WL (1990) Clozapine and agranulocytosis (in Chinese). Shanghai Archives of Psychiatry 2, 190 + 189.Google Scholar
Zeng, ZX, Li, ZC, Liu, YY and Zhang, SC (1994) Effect of psychotropic drugs on leukocyte in 856 patients (in Chinese). Chinese Journal of Pharmacoepidemiology 3, 2023.Google Scholar
Zhang, YY, Zhang, GM and Yan, YJ (1997) Analysis of the effects of clozapine on white blood cells in 210 patients (in Chinese). Psychiatry in Shandong 10, 51.Google Scholar
Zhao, HR, Si, SY and Zhang, YY (1999) Comparison of the effects of clozapine and chlorpromazine on white blood cells (in Chinese). Chinese Journal of Nervous and Mental Diseases 25, 55.Google Scholar
Zheng, H (2000) Analysis of 29 cases of granulopenia or agranulocytosis of clozapine (in Chinese). Journal of Shantou University Medical College 13, 3334.Google Scholar
Zhu, RM, Wang, DB and Wu, Y (1992) Comparison of the effects of clozapine and chlorpromazine on white blood cells (in Chinese). Shanghai Archives of Psychiatry 4, 116117.Google Scholar
Supplementary material: File

Li et al. supplementary material

Figure S1

Download Li et al. supplementary material(File)
File 14.6 KB