114 Original Paper Use of Anticholinergic Drugs in Patients with Schizophrenia in Asia from 2001 to 2009 Authors Y.-T. Xiang 1 , 2 , C.-Y. Wang 2 , T.-M. Si 3 , E. H. M. Lee 1 , Y.-L. He 4 , G. S. Ungvari 5 , H. F. K. Chiu1 , S.-Y. Yang 6 , M.-Y. Chong 7 , C.-H. Tan 8 , E.-H. Kua 8 , S. Fujii 9 , K. Sim 10 , K. H. Yong 10 , J. K. Trivedi 11 , E.-K. Chung 12 , P. Udomratn 13 , K.-Y. Chee 14 , N. Sartorius 15 , N. Shinfuku 16 Affi liations A ffi liation addresses are listed at the end of the article Abstract variations at each time period. Multiple logistic ▼ regression analysis of the whole sample showed Objective: The aim of this study was to survey that patients taking ACM presented with more the use of anticholinergic medication (ACM) in severe positive, negative, and extrapyramidal Asia between 2001 and 2009 and examine its symptoms. They were also more likely to receive demographic and clinical correlates. fi rst-generation and depot antipsychotics and Method: A total of 6 761 hospitalized schizo- antipsychotic polypharmacy, and less likely to phrenia patients in 9 Asian countries and terri- receive second-generation ones. tories were examined between 2001 and 2009. Conclusions: The wide variation in ACM pre- The patients ’ socio-demographic and clinical scription across Asia suggests that a combination received 24.12.2010 characteristics and the prescriptions of psycho- of clinical, social, economic and cultural fac- revised 04.03.2011 tropic drugs were recorded using a standardized tors play a role in determining the use of these accepted 09.03.2011 protocol and data collection procedure. drugs. Regular reviews of ACM use are desirable Results: The frequency of ACM prescription to reveal the discrepancy between treatment Bibliography decreased from 66.3 % in 2001, to 52.8 % in 2004 guidelines and clinical practice. DOI http://dx.doi.org/ and 54.6 % in 2009, with wide inter-country 10.1055/s-0031-1275658 Published online ahead of print: 13 April 2011 Pharmacopsychiatry 2011; Introduction 2001 were taking ACM. Since the 2001 survey, 44: 114 – 118 ▼ economic factors, health-care policies, and health © Georg Thieme Verlag KG The use of anticholinergic drugs (ACM) in the insurance in Asia have changed considerably, Stuttgart · New York treatment of drug-induced extrapyramidal side accompanied by the widespread use of second- Downloaded by: Head, Collection Management. Copyrighted material. ISSN 0176-3679 eff ects (EPS) has been a controversial issue, par- generation antipsychotic drugs (SGAs) and inten- ticularly their continuous prescription in chronic sive continuing medical education programs Correspondence schizophrenia [1 – 3] . Side eff ects related to ACM organized by professional associations and drug Dr. Y.-T. Xiang Department of Psychiatry are cognitive impairment [4, 5] , the potential for companies. To determine the current trend in Chinese University of abuse [6] , central anticholinergic syndrome at prescribing patterns of ACM in this region, the Hong Kong higher doses [7] , worsening of positive symptoms survey was repeated in 2004 and 2009 with the Ground Floor, Multicentre [8] , and elevated risk for tardive dyskinesia (TD) same design and instruments. Tai Po Hospital [9] . Nevertheless, ACM can improve patients ’ This study set out (i) to examine the prescription Tai Po, N.T. treatment adherence [2, 10] and have no eupho- pattern of ACM and its trend over time in schizo- Hong Kong riant eff ects at therapeutic doses [11] . phrenia inpatients in Asia; and (ii) to explore the People ’ s Republic of China Tel.: + 852 / 2607/ 6041 Preliminary evidence suggests that Asian patients demographic and clinical correlates of ACM use Fax: + 852 / 2647/ 5321 require lower doses of antipsychotics and that in the pooled sample with an increase in power [email protected] they are more sensitive to EPS compared with compared with the baseline survey conducted in their Western counterparts [12, 13] . Repeated 2001 [14] . Dr. Tian-Mei Si surveys in the same region are more useful than Peking University Institute of a single survey because longitudinal studies can Mental Health reveal important trends in pharmacotherapy Patients and Methods Beijing People ’ s Republic of China over time and help to evaluate the eff ectiveness ▼ Tel.: + 8610 / 8280/1948 of education and training of clinicians. Sim et al. Settings, study design, and subjects Fax: + 8610 / 6235/ 2880 [14] found that 34.7 – 82 % of 2 399 schizophrenia The study was part of the Research on Asian Psy- [email protected] inpatients in 6 Asian countries and territories in chotropic Prescription Pattern (REAP) project, Xiang Y-T et al. Use of Anticholinergic Drugs … Pharmacopsychiatry 2011; 44: 114 – 118 Original Paper 115 which is an ongoing pharmaco-epidemiological survey designed to refl ect the prescription trends of psychotropic drugs in hospi- talized schizophrenia patients in 6 Asian countries and territo- 2009 ries, including mainland China (in the following: China), Hong Total Total 6.6 3.8 6.6 Kong, Taiwan, Singapore, Japan, and Korea using a standardized 2004 2 136 2 226 protocol and data collection procedure. Centers in India, Malay- 57.8 48.3 3.6 71.5 74.7 sia, and Thailand joined the survey in 2009. The 3 REAP surveys 2001 were conducted in July 2001, July 2004, and October 2008 – March 2009. Details of the REAP project methodology have been described elsewhere [15, 16] . Participating patients needed to Malaysia 2009 satisfy the following study criteria: (i) ICD-10 or DSM-IV schizo- phrenia; (ii) be able to comprehend the aims of the study; and 37.2 43.6 43.1 43.9 (iii) be willing to provide written or oral consent according to the Thailand requirements of the clinical research ethics committees in the 2009 7 30.8 23.0 45.5 64.7 73.7 .4 7.7 .9 82.1 28.0 .9 74.4 78.0 29.0 28.0 37.0 67.8 26.9 51.9 66.3 41.7 52.8 54.6 respective study sites. Patients suff ering from major medical .4 69.2 72.0 55.9 57.3 60.6 India 10.8 10.2 10.7 13.5 14.2 13.7 conditions were excluded. The study was approved by the Insti- 2009 tutional Review Boards of the respective centers. Eligible patients were recruited consecutively, and their socio- 2009 demographic and clinical variables including age, sex, the type and dose of antipsychotics, signifi cant symptoms (both positive 2004 Taiwan rst-generation antipsychotics; SGA = second-generation antipsychotics; and negative) within the past month, and extrapyramidal side fi eff ects, tardive dyskinesia (TD), and use of antipsychotic medi- 2001 cations at the study time were collected by a review of medical records in 2001, and by either a review of medical records or 2009 patient interview in both 2004 and 2009 using a questionnaire designed for the study. Only a review of medical records was 2004 used in some participating centers due to logistic reasons. The Singapore data were collected by the attending psychiatrist of the patient at the time of study or by members of the research team (expe- 2001 rienced psychiatrists) with the agreement of the psychiatrist in charge of the patient. Doses of antipsychotic drugs were con- 2009 verted into chlorpromazine equivalent milligrams (CPZeq) [17 – Korea 19] . TD is treated separately from other forms of EPS because of 2004 its special characteristics and treatment strategy compared with other extrapyramidal symptoms. Consensus meetings on data 2001 collection and the uniformity of data entry were held before each survey. In REAP surveys, psychotropic drugs were catego- 2009 rized according to the World Health Organization Anatomic ects; TD = tardive dyskinesia; CPZeq = chlorpromazine equivalents; FGA = Therapeutic Chemical (WHO-ATC) system [20, 21] , and ACMs ff Japan include trihexyphenidyl, biperiden, benztropine, promethazine, 2004 procyclidine, amantadine, piroheptine and mazaticol. Downloaded by: Head, Collection Management. Copyrighted material. 2001 Statistical analysis The data were analyzed using SPSS 13.0 for Windows. Compari- 2009 sons among the 3 cohorts with respect to the proportion of indi- viduals prescribed ACM in each study site were conducted using 2004 chi-square ( χ 2 ) tests. The comparisons between ACM and non- Hong Kong ACM groups with respect to socio-demographic and clinical 2001 characteristics were performed by independent samples t-test, Mann-Whitney U-test, and chi-square test, as appropriate. Mul- tiple logistic regression analysis was used to determine the inde- 2009 pendent contribution of demographic and clinical variables to China ACM use. The level of signifi cance was set at 0.05 (2-tailed). 2004 49.1 72.4 70.7 71.3 75.0 9.0 74.3 66.2 59.3 45.0 36.4 45.8 29.3 37.4 9.0 41.2 50.4 47.1 47.0 12.8 8.0 52.4 60.9 65.3 52.1 68.5 84.0 63.0 63.2 71.5 80.7 71.3 77.2 79.9 47.0 84.6 80.0 73.3 67.7 76.8 93.4 94.9 75.0 6 2001 Results ▼ Altogether, 6 761 patients were involved in the investigations; 2 399, 2 136, and 2 226 patients in 2001, 2004, and 2009, respect Socio-demographic and clinical characteristics and anticholinergic drug prescription in 2001, 2004, and 2009. drug prescription characteristics and anticholinergic and clinical Socio-demographic i v e l y . ● ▶ Table 1 displays the socio-demographic and clinical characteristics of the whole sample and separately by study site ACM ACM = anticholinergic drugs Centers in India, Malaysia and Thailand joined the survey in 2009; EPS = extrapyramidal side e extrapyramidal = and Thailand joined the survey in India, Malaysia Centers in 2009; EPS negative negative symptoms ( % ) EPS ( % ) TD ( % ) FGA ( % ) SGA ( % ) ACM ( % ) 18.8 11.5 3.1 47.3 20.0 1.4 64.0 35.1 71.3 34.7 75.6 24.2 2.7 73.0 44.4 83.9 49.1 19.0 22.2 36.4 26.0 46.3 28.7 20.0 50.0 68.0 24.0 32.9 2.0 46.0 50.0 87.4 24.3 40.0 6.7 50.4 66.6 37.1 87.1 75.6 52.9 7.7 27.2 70.2 85.0 72.9 23.9 4.9 64.4 66.3 37.1 12.3 76.0 45.9 46.1 27.5 3.8 33.5 84.3 75.0 13.0 4.4 68.0 81.3 6.7 39.5 82.0 2.1 49.0 30.9 16.5 73.6 52.1 2.7 41.1 50.0 67.0 38.3 30 48.6 4.4 63.3 37.7 64.6 54.7 2.0 30 73.5 53.3 1.3 80.