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Common Use of High Doses of Antipsychotic Medications in Older Asian Patients with Schizophrenia (2001–2009)

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Common Use of High Doses of Antipsychotic Medications in Older Asian Patients with Schizophrenia (2001–2009) RESEARCH ARTICLE Common use of high doses of antipsychotic medications in older Asian patients with schizophrenia (2001–2009) † Yu-Tao Xiang1,2, , Yan Li1, Christoph U. Correll3, Gabor S. Ungvari4,5, Helen F.K. Chiu1, Kelly Y. C. Lai1, † Quan-Sheng Tang6,7, , Wei Hao6, Tian-Mei Si8, Chuan-Yue Wang2, Edwin H. M Lee9, Yan-Ling He10, Shu-Yu Yang11, Mian-Yoon Chong12, Ee-Heok Kua13, Senta Fujii14, Kang Sim15, Michael K.H. Yong16, Jitendra K. Trivedi17, Eun-Kee Chung18, Pichet Udomratn19, Kok-Yoon Chee20, Norman Sartorius21, Chay-Hoon Tan22 and Naotaka Shinfuku23 1Department of Psychiatry, Chinese University of Hong Kong, Hong Kong, China 2Beijing Anding Hospital, Capital Medical University, Beijing, China 3Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA 4School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia 5The University of Notre Dame Australia/Marian Centre, Perth, Australia 6Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China 7Nanning Red Cross Hospital, Nanning, Guangxi Province, China 8The Key Laboratory of Mental Health, Ministry of Mental Health and Peking University Institute of Mental Health, Beijing, China 9Department of Psychiatry, University of Hong Kong, Hong Kong, China 10Department of Psychiatric Epidemiology, Shanghai Mental Health Center, Shanghai, China 11Department of Pharmacy, Taipei City Hospital, Taipei, Taiwan 12Kaohsiung Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Kaohsiung, Taiwan 13Department of Psychological Medicine, National University of Singapore, Singapore, Singapore 14Hyogo Institute for Traumatic Stress (HITS), Kobe, Japan 15Department of General Psychiatry, Institute of Mental Health, Buangkok View, Singapore, Singapore 16Department of Medicine, Alexandra Hospital/Jurong Health Services, Singapore 17Department of Psychiatry, C.S.M. Medical University UP, Lucknow, Uttar Pradesh India 18Department of Psychiatry, National Seoul Hospital, Seoul, Korea 19Department of Psychiatry, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand 20Department of Psychiatry and Mental Health, Tunku Abdul Rahman Institute of Neuroscience, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia 21Association for the Improvement of Mental Health Programs, Geneva, Switzerland 22Department of Pharmacology, National University of Singapore, Singapore, Singapore 23Department of Social Welfare, School of Human Sciences, Seinan Gakuin University, Fukuoka, Japan Correspondence to: Y-T. Xiang, E-mail: [email protected]; W. Hao, E-mail: [email protected] † Yu-Tao Xiang and Quan-Sheng Tang contributed equally to the paper. Objective: This study aimed to examine the use of high doses of antipsychotic medications (≥600 mg/day chlorpromazine equivalent) in older Asian patients with schizophrenia and its demographic and clinical correlates. Method: Information on hospitalized patients with schizophrenia aged ≥50 years was extracted from the database of the Research on Asian Psychotropic Prescription Patterns study (2001–2009). Data on 2203 patients in six Asian countries and territories, including China, Hong Kong, Japan, Korea, Singapore and Taiwan, were analyzed. Socio-demographic and clinical characteristics and antipsychotic prescriptions were recorded. Results: The frequency for high-dose antipsychotic medications was 36.0% overall, with 38.4% in 2001, 33.3% in 2004 and 36.0% in 2009. Multiple logistic regression analysis of the whole sample showed that compared to patients receiving low-medium antipsychotic doses, those on high doses had a longer illness duration (odds ratio (OR): 2.0, 95% confidence interval (CI):1.2–3.3, p = 0.008), were more likely in the 50–59-year group (OR: 0.95, 95% CI: 0.94–0.97, p < 0.001), more often had current positive (OR: 1.5, 95% CI: 1.2–1.8, p < 0.001) or negative symptoms (OR: 1.3, 95% CI: 1.03–1.6, p = 0.03), and more com- monly received antipsychotic polypharmacy (OR: 5.3, 95% CI: 4.1–6.7, p < 0.001). Extrapyramidal symp- toms (p = 0.25) and tardive dyskinesia (p = 0.92) were not more frequent in the high-dose group. Copyright # 2013 John Wiley & Sons, Ltd. Int J Geriatr Psychiatry 2014; 29: 359–366 360 Y.-T. Xiang et al. Conclusions: High doses of antipsychotic medications were used in more than one third of older Asian patients with schizophrenia. The reasons for the frequent use of high antipsychotic doses in older Asian patients warrant further investigation. Copyright # 2013 John Wiley & Sons, Ltd. Key words: schizophrenia; prescription patterns; high dose; older patients; Asia History: Received 27 January 2013; Accepted 17 July 2013; Published online 13 August 2013 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/gps.4011 Introduction large-scale, pharmaco-epidemiological surveys on high antipsychotic doses in older patients with schizophrenia. In the past several decades, the use of high antipsychotic We conducted a secondary analysis of the data from doses has been a continuously controversial topic in the Research on Asian Psychotropic Prescription (REAP) both clinical practice and research (Sim et al., 2009). project. This study set out to (i) examine the prescribing Although most of the studies and treatment recommen- patterns of high doses of antipsychotics (defined as dations do not support this practice, antipsychotic 600 mg/day chlorpromazine equivalent [CPZeq] or drugs are still widely prescribed in high doses in the more)inolderAsianpatients with schizophrenia during – treatment of schizophrenia. For example, 15.4 41% of the period between 2001 and 2009, and (ii) explore the schizophrenia inpatients in the USA (Buchanan et al., demographic and clinical correlates of high-dose 2010; Kreyenbuhl et al., 2010) and in Europe (Webb antipsychotic use in this population. Because of the and Agnew, 1975; Gottlieb et al., 2006) receive high- poorer general health status of older patients and dose antipsychotics. There have been only a few studies heightened vulnerability to psychotropic-induced that examined the prescription patterns of high-dose side effects (Uchida et al., 2009b; Meyers and Jeste, antipsychotics in treatment-refractory schizophrenia 2010), we hypothesized that first, only a small propor- (Kinon et al., 2008; Lindenmayer et al., 2011; Honer tion of Asian older patients would receive high-dose et al., 2012). So far, there has been no convincing antipsychotics, and second, that the proportion of evidence for the improved efficacy of high doses, but high-dose antipsychotic use would significantly the risk of extrapyramidal side effects (Pierre, 2005) decrease over time. and hyperprolactinemia (Byerly et al., 2007) was dose related. In recent years, mortality of schizophrenia has shown Methods a decreasing trend following the general improvement of psychiatric and medical care, enabling many patients Settings, study design and subjects with schizophrenia to live into older adulthood (Kohen et al., 2010). Compared with their younger counter- The REAP project is an ongoing pharmaco-epidemiological parts, older schizophrenia patients are more likely to study of psychotropic drug prescription trends in have drug-induced side effects and poor general health schizophrenia inpatients in Asia. The first REAP study (Uchida et al., 2009b; Meyers and Jeste, 2010); was conducted in July 2001, followed by two waves of therefore, treatment guidelines for younger adult pa- studies in July 2004 and October 2008–March 2009 tients are not entirely applicable to this population. using the same design and standardized protocol. The Age-related pharmacokinetic changes influence drug participating countries and territories included main- absorption and excretion, which may increase the land China (China hereafter), Hong Kong, Japan, susceptibility for antipsychotic-induced adverse effects Korea, Singapore and Taiwan. Centers in India, (Masand, 2000). In contrast to the several treatment Malaysia and Thailand joined the REAP study in guidelines published for adult schizophrenia patients, 2009. Consensus meetings on data collection and uni- we could locate only one set of guidelines for older formity of data entry were held prior to each survey. patients. Alexopoulos et al. (2004) surveyed expert Data of patients who met the following criteria were opinions for recommendations on indications for anti- analyzed in this report: (i) Diagnosis of schizophrenia psychotic use in patients aged 65 years and older. The according to ICD-10 (categories F20) or DSM-IV authors advocated for the use of lower antipsychotic (categories 295.30–295.60) based on a review of medical doses in older patients, for example, 1.25–3.5 mg of records. (ii) Age of 50 years or older. The age cut-off of risperidone, whereas the therapeutic dose of risperidone older patients varied from 50 to 65 years across is 4–8 mg for adult patients. We could not locate any participating institutions according to local cultural Copyright # 2013 John Wiley & Sons, Ltd. Int J Geriatr Psychiatry 2014; 29: 359–366 High antipsychotic doses in schizophrenia 361 and professional traditions. In order to make the popu- analysis with the “Enter” method was used to determine lation homogeneous, those aged ≥50 years in the dataset the demographic and clinical variables independently of the REAP project were defined as “older patients” in influencing high antipsychotic doses. Cross-sectional this study. The same age cut-off
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