Indian Journal of Psychological Medicine
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Year : 2020  |  Volume : 42  |  Issue : 1  |  Page : 4-10

Do asian patients require only half of the clozapine dose prescribed for caucasians? A critical overview

1 Mental Health Research Center, Eastern State Hospital, Lexington, Kentucky, USA; Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain, and Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apóstol Hospital, University of the Basque Country, Vitoria, Spain
2 Department of Psychiatry, Christian Medical College, Vellore, Tamil Nadu, India; Institute of Mental Health, University of Nottingham, Nottingham, United Kingdom
3 Hazelwood Center, Louisville, Kentucky, USA
4 Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA
5 Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks; Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
6 Department of Psychiatry, The National Clinical Research Centre for Mental Disorders and Beijing Key Lab of Mental Disorders and Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China
7 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, and Substance Abuse Treatment Program, Atlanta VA Medical Center, Decatur, Georgia, USA
8 Department of General Psychiatry, Taipei City, Psychiatric Center, Taipei, Taiwan, and Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan
9 Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
10 School of Primary, Community and Social Care, Faulty of Medicine and Health Sciences, Keele University, Staffordshire, and Midlands Partnership NHS Foundation Trust, Staffordshire, United Kingdom
11 Department of Psychiatry, The Melbourne Clinic and St Vincent's Hospital, The University of Melbourne, Melbourne, Victoria, Australia
12 Laboratory of Clinical Psychopharmacology & The National Clinical Research Centre for Mental Disorders & Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
13 Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Correspondence Address:
Dr. Jose de Leon
Room 3A15A, Mental Health Research Center, Eastern State Hospital, 1350 Bull Lea Road, Lexington, Kentucky 40511

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPSYM.IJPSYM_379_19

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Since 1997, studies have found that Asians need lower clozapine doses than Caucasians. Caucasians with average clozapine metabolism may need from 300 to 600 mg/day to reach the therapeutic range (350 ng/ml). Thus, serum clozapine concentration-to-dose (C/D) ratios typically range between 0.60 (male smokers) and 1.20 (female non-smokers). A 2019 systematic review of clozapine levels demonstrated weighted mean C/D ratios of 1.57 in 876 East Asians and 1.07 in 1147 Caucasians (P <.001). In Asian countries, average clozapine doses are lower than 300 mg/day. After sex and smoking stratification in 5 Asian samples with clozapine concentrations, the clozapine dose required to reach 350 ng/ml in female non-smokers ranged from 145 to 189 mg/day and in male smokers, from 259 to 294 mg/day. Thus, in Asian patients with average metabolism (with no inducers other than smoking, with no inhibitors, and in the absence of extreme obesity), the dose needed for clinical response may range between 150 mg/day for female non-smokers to 300 mg/day for male smokers. Clozapine levels may help personalize dosing in clozapine poor metabolizers (PMs) and ultrarapid metabolizers (UMs). Asian PMs may need very low doses (50-150 mg/day) to obtain therapeutic concentrations. About 10% (range 2-13%) of Asians are genetic PM cases. Other PMs are patients taking CYP1A2 inhibitors such as fluvoxamine, oral contraceptives, and valproate. Temporary clozapine PM status may occur during severe systemic infections/inflammations with fever and C-reactive protein (CRP) elevations. Asian UMs include patients taking potent inducers such as phenytoin, and rarely, valproate.

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