Antipsychotic Prescription Pattern among Child and Adolescent Patients with Psychiatric Illnesses in Taiwan

Transcription

1 222 Taiwanese Journal of Psychiatry (Taipei) Vol. 31 No Original Article Antipsychotic Prescription Pattern among Child and Adolescent Patients with Psychiatric Illnesses in Taiwan Shu-Wen Cheng, M.S. 1, Hung-Yu Chan, M.D., Ph.D. 2,3* Objectives: The prevalence of antipsychotic prescription for child and adolescent patients with psychiatric illnesses is increasing over the world. No studies exist to focus on the prescription pattern and trend of antipsychotic use for child and adolescent patients in psychiatric hospitals of Taiwan. Methods: In this retrospective study for all outpatients equal or below 18 years of age in a psychiatric hospital, we collected related study variables from the study hospital from 2004 to Reviewing the electronic medical information system, we extracted both patients demographic data (information for sex, age, psychiatric diagnosis, and prescriptions of antipsychotic drugs). Results: During the study period, the proportion of participants received antipsychotics was increased significantly (from 13.63% in 2004, to 15.02% in 2013, p < 0.001). The proportion of participants received second generation antipsychotics (SGAs) was increased (from 5.84% in 2004, to 10.59% in 2013, p < 0.001), but first-generation antipsychotics (FGAs) was decreased (from 8.05% to 4.97%, p < 0.001). The age group of years of age showed that the highest increase (from 7.53% to 9.11%, p < 0.001). The male gender was found to be significantly increased (from 7.89% to 9.51%, p < 0.001). Conclusion: The results are in line with the trend of the world about the increasing SGA use for psychiatric patients below 18 years of age. In spite of the potential benefits of SGAs on treating illnesses or symptoms, we need caution the potential side effects of long-term SGA use. We expect the appropriate use of antipsychotics for psychiatric patients of children and adolescents, to improve the care quality for this population. Key words: children and adolescents, psychiatric illnesses, antipsychotic drugs, prescription patterns (Taiwanese Journal of Psychiatry [Taipei] 2017; 31: ) 1 Department of Pharmacy, Taoyuan Psychiatric Center, Taoyuan, Taiwan 2 Department of General Psychiatry, Taoyuan Psychiatric Center, Taoyuan, Taiwan 3 Department of Psychiatry, National Taiwan University Hospital and School of Medicine, National Taiwan University, Taipei, Taiwan Received: January 3, 2017; revised: February 3, 2017; accepted: March 1, * Corresponding author. No. 71, Long-Show Street, Taoyuan 330, Taiwan Hung-Yu Chan < jan30@seed.net.tw>

2 Cheng SW, Chan HY 223 Introduction Antipsychotic drugs are the most important medications in treating patients with psychotic disorders [1]. The development of second-generation antipsychotics (SGAs) has improved in the treatment of psychotic disorders [2]. SGAs might have better efficacy in negative or cognitive or affective symptoms, and less EPS side effects [3, 4]. But SGAs still have problems, such as somnolence, obesity, hyperglycemia, hyperlipidemia, and QTc prolongation, influencing clinicians prescribing habits and patients drug adherence [5]. Different SGAs have been suggested with different frequencies to receive metabolic syndrome monitoring. The consensus of the metabolic syndrome monitoring protocol for SGAs has been convened by the American Diabetes Association (ADA), the American Psychiatric Association, the American Association of Clinical Endocrinologists, and the North American Association [6, 7]. They focused mostly on the diabetes risk, advised baseline, plasma glucose level in four months, and glycosylated hemoglobin test after initiating or changing an antipsychotic medication. Prescriptions of antipsychotic medications among children and adolescents are increasing greatly in recent years [8, 9]. The safety issues of antipsychotics in children and adolescents are especially a major concern. Previous studies showed that children and adolescents are more sensitive to antipsychotic side effects extrapyramidal symptoms (EPS), sedation, body weight gain, and hyperprolactinemia than adults [10]. Furthermore, most of antipsychotic studies are focused on adult population, and only few studies on investigating the efficacy and safety of antipsychotics in children and adolescents. Therefore, antipsychotic off-labeled use is common for children and adolescents with various psychiatric illnesses or symptoms. Only few antipsychotics haloperidol, thioridazine, pimozide, risperidone, olanzapine and aripiprazole are approved by the Food and Drug Administration (FDA) of the USA in treating some psychiatric illnesses in children and adolescents [11-16]. To our best knowledge, published studies on patients characteristics and the trend of antipsychotic use are lacking in Taiwan in the children and adolescents with psychiatric illnesses. In this study, we intended to investigate patients characteristics and the trend of antipsychotic use in the child and adolescent patients with psychiatric illnesses, and to examine the associated factors for the prescription trend. Methods Study setting This study was conducted at the Taoyuan Psychiatric Center (TYPC), a public, regional teaching hospital in the northern Taiwan, providing service of 282 acute beds, 380 chronic beds, and 300 day-care beds. The hospital has one of the biggest child psychiatric services in Taiwan. TYPC provides various treatments for child and adolescent psychiatric patients including (A) outpatient treatment more than 1,700 patient visits per month, (B) 50 day-care beds for adolescents, (C) 50 day-care beds for children, and (D) 12 acute beds for child and adolescent patients. The study proposal was approved by our hospital institutional review board, without the need to obtain the informal consent from the study patients. Study design, study variables and data extraction This is a retrospective study for all outpatients equal or below 18 years old. We collected

3 224 Antipsychotic Prescription for Children related study variables from the electronic medical information system from 2004 to 2013 at TYPC, where was established an electronic medical information system in January Data from this system are transformed into related database, referred to as the data warehouse. We extracted study data from the warehouse and created our analytic data set with Statistical Package for Social Science software version 18.0 for Windows (SPSS, Inc., Chicago, Illinois, USA), and Statistical Analytic System software version 9.3 (SAS institute Inc, Cary, North Carolina, USA). Reviewing the electronic medical information system, we extracted both patients demographic and clinical data including information of sex, age, psychiatric diagnosis and prescriptions of antipsychotics. Antipsychotics are classified with Anatomical Therapeutic Chemical (ATC) system of the World Health Organization (WHO). A study pharmacist with a more than 20-year experience in psychiatric research extracted the data. The corresponding author (HYC), a board-certificated psychiatrist, regularly supervised and discussed with the pharmacist (SWC) on the extraction study results. Statistical analysis Categorical variables were compared using Chi-square and Fisher s exact test, and continuous variables were compared using independent t test. Cochrane-Armitage trend test were used for examining the time trend of antipsychotic prescriptions. Whether receiving antipsychotic prescription was chosen as the outcome variable for logistic regression. All results were expressed as means and standard deviations. We used SPSS and SAS for all statistical analysis in this study. The differences between the groups were considered significant if p-values were smaller than Results Table 1 lists and compares patients demographic data and baseline clinical characteristics of the participants who received and not received antipsychotic drugs. Table 2 shows the distribution of antipsychotics prescription. Figure 1 shows the proportion of participants received antipsychotics increased over the 10 years study period from 2004 to Figure 2 depicts the proportion of participants received FGAs and SGAs. Figure 3 describes the proportion of participants received antipsychotics in different age group over the study period. Figure 4 illustrates the proportion of participants received antipsychotics in different gender over the study period. Discussion To our best knowledge, this is the first study focusing on the antipsychotic prescription for psychiatric outpatients of children and adolescents in psychiatric hospitals of Taiwan. In this study, we found that the proportion of antipsychotic prescription was increased around 10% (from 13.63% in 2004 to 15.02% in 2013) (Figure 1), and that the age group of years and male gender were the most important contributors (Table 1). We also found that the proportion of SGAs was increased, but FGAs were decreased over the 10- year study period (Figure 2). The results of this study are valuable with important clinical implications in antipsychotic prescriptions for children and adolescents. Published papers on the increasing trend of antipsychotic prescription for psychiatric patients of children and adolescents have similar results with this study. For example, Zito et al. in a study have shown the magnitude of increase from 1.6 to

4 Cheng SW, Chan HY 225 Table 1. Demographic data and baseline clinical characteristics of the participants (N = 173,209) Variables Not received n (%) Antipsychotics Received n (%) Patients received antipsychotics 150,002 (86.60) 23,207 (13.40) Age-mean SD, years*** Age group*** 1-6 y/o 16,138 (10.76) 110 (0.47) 7-9 y/o 36,999 (24.67) 651 (2.81) y/o 37,547 (25.03) 2,624 (11.30) y/o 36,199 (24.13) 6,975 (30.06) y/o 23,119 (15.41) 12,847 (55.36) Gender*** Male 113,319 (75.55) 14,293 (61.59) Female 36,683 (24.45) 8,914 (38.41) ICD-9-CM diagnosis*** Affective psychosis (296) 2,539 (1.69) 2,528 (10.89) Schizophrenia (295) 705 (0.47) 4,472 (19.27) Neurotic disorder ( , ) 14,071 (9.38) 2,121 (9.14) Childhood hyperkinetic syndrome (314) 75,400 (50.27) 3,245 (13.98) Organic/non-organic psychosis (293, 294, 298) 726 (0.48) 2,341 (10.09) Autistic spectrum disorder (299) 33,121 (22.08) 6,526 (28.12) Mental retardation ( ) 10,957 (7.30) 1,150 (4.96) Others (8.32) 824 (3.55) * p < 0.05, ** p < 0.01, *** p < SD, standard deviation 5.5 times in different areas during the period of [17]. Another study has illustrated the proportion of people below 18 years old received antipsychotics rose from 3.2% in 1997 to 5.0% in 2000 [18]. The study of Nick et al. has demonstrated that the increasing trend for antipsychotics prescription in children and adolescents is due to the more and more popular SGA use [19]. The magnitude of antipsychotic prescription increase in this study was around 10% (Figure 1) which is lower than that in previous studies but is similar in the increasing SGA use. The increasing SGA for psychiatric child and adolescent patients may be related with their broader therapeutic indications in psychiatric illnesses. In addition to schizophrenia, schizoaffective disorder, bipolar disorder, depressive disorder, autistic disorder with aggressive behaviors, and Tourette syndrome are all the therapeutic indications of SGAs [20]. Furthermore, most SGAs, except risperidone, have less EPS and hyperprolactinemia-related side effects than FGAs [3]. But some SGAs have higher propensity to develop metabolic syndrome than FGAs, especially in child and adolescent population [21, 22]. Clinicians still need caution the long-term side effects of SGAs and use them appropriately.

5 226 Antipsychotic Prescription for Children Table 2. The distribution of antipsychotics prescription (N = 24,068) Drug name Prescriptions n (%) First generation antipsychotics 8,850 (36.77) Chlorpromazine 404 (1.68) Cis-Clopenthixol 4 (0.02) Clopenthixol depot injection 3 (0.01) Clotiapine 250 (1.04) Flupentixol 208 (0.86) Fluphenazine depot injection 39 (0.16) Haloperidol 1,288 (5.35) Haloperidol depot injection 43 (0.18) Loxapine 11 (0.06) Sulpiride 5,919 (24.59) Thioridazine 612 (2.54) Trifluoperazine 69 (0.29) Second generation antipsychotics 15,218 (63.23) Amisulpride 281 (1.17) Aripiprazole 2,954 (12.27) Clozapine 255 (1.06) Olanzapine 527 (2.19) Paliperidone 85 (0.35) Quetiapine 1,233 (5.12) Risperidone 9,156 (38.04) Risperidone LA injection 125 (0.52) Ziprasidone 293 (1.22) Zotepine 309 (1.28) Previous studies showed that the top three psychiatric diagnoses of children and adolescents which received antipsychotics are disruptive behavior disorders, depressive disorders, and bipolar disorders [20, 23]. In this study, autistic spectrum disorder, schizophrenia and hyperkinetic syndrome were the top three diagnoses treated with antipsychotics. In most situations, antipsychotics are used to treat disruptive or aggressive behaviors of autistic spectrum disorder and hyperkinetic syndrome [24]. Therefore, the results of this study are in line with those in previous studies in some aspects. But in our study (Table 1), we found that schizophrenia was the second diagnosis treated with antipsychotics (19.27%). The finding is different from that found from previous studies. This may be due to different population and diagnosis composite among different studies. As shown in Table 1, our study showed male psychiatric child and adolescent patients (61.59%) had higher proportion to receive antipsychotics than female ones (38.41%). The results are similar to those in several previous studies [25, 26]. This finding may be due to the higher prevalence of autistic spectrum disorder and hyperkinetic syndrome in male child and adolescent patients [25,

6 Cheng SW, Chan HY 227 Figure 1. The proportion of participants received ( ) and not received ( ) antipsychotics from 2004 to *** p < tested by Cochran-Armitage test for trend. Figure 2. The proportion of participants received first generation antipsychotics (FGAs, ) and second generation antipsychotics (SGAs, ) from 2004 to *** p < tested by Cochran-Armitage test for trend.

7 228 Antipsychotic Prescription for Children Figure 3. The proportion of participants received antipsychotics in different age group ( 1-6, 7-9***, 10-12***, 13-15**, 16-18***) from 2004 to * p < 0.05, ** p < 0.01, *** p < tested by Cochran- Armitage test for trend. 26]. Another possible reason is higher risk of disruptive and aggressive behaviors in male child and adolescent patients than female patients. This study showed that adolescent was the major population to receive antipsychotic treatment for the patients equal or below 18 years of age (Table 1). Over 85% of the participants of this study received antipsychotics were no less than 12 years of age (16-18 years 55.36%, and years 30.06%), and the average age when receiving antipsychotics was years old (Table 1). Furthermore, the age group of years of age was the highest increased population over the study period (Figure 3). The results are compatible with those from several previous studies [27]. It may reflect the safety concerns of antipsychotics for patients below 12 years old, and the therapeutic concept of using psychological approach and behavioral modification methods for this young population. Children and adolescents treated with antipsychotic medications are at greater risk than adults for experiencing adverse events such as EPS, elevated prolactin concentrations, sedation, significant weight gain, elevated triglyceride concentrations, and insulin resistance [28]. Study limitations The readers are cautioned against over-interpret the study results because it has four limitations: In this study, we included the data of patients of only one single psychiatric center. The findings from this study may not be generalized to other studies because of differences in local practice patterns.

8 Cheng SW, Chan HY 229 Figure 4. The proportion of participants received antipsychotics in different gender ( female, male***) from 2004 to *** p < tested by Cochran-Armitage test for trend. The psychiatric diagnoses from the electronic database might be incorrect in some patients and different from those in real clinical circumstances. Some variables are related to antipsychotic treatment for child and adolescent studies but are difficult to retrieve from a retrospective study. The information includes the profiles and severity of psychotic/mood/disruptive symptoms, family support, doctors and patients attitude toward a specific medication, previous history and treatment responses of antipsychotics, and the policy changes of the Bureau of National Health Insurance of Taiwan during the study period. To further investigate probable mechanisms explaining the proportion and trend changes over the study period was difficult in this study. Laboratory data were not available in this study. Therefore, we did not know the effects of those antipsychotics on metabolic syndrome and other related profiles which need the data of laboratory examinations. Summary The study showed that the proportion of antipsychotic prescription was increased around 10%, that and the age group of years of age and male gender were the most important contributors, and that the proportion of SGAs was increased but FGAs decreased over the 10 years study period. The results are in line with the trend of the world in increasing SGA use for psychiatric patients below 18 years of age. In spite of the potential benefits of SGAs on those illnesses or

9 230 Antipsychotic Prescription for Children symptoms, we need to caution the potential side effects, especially metabolic effects in long-term SGA use. We expect the appropriate antipsychotic use for psychiatric child and adolescent patients, to improve the care quality for this population. Acknowledgements This study was supported by a grant from the Taoyuan Psychiatric Center, Ministry of Health and Welfare of Taiwan (TYPC-10403). The funding body played no rôle in study design, analysis, or interpretation of the study data in this paper. Both authors declare no conflicts of interest in writing this paper. References 1. Casey DE: Neuroleptic drug-induced extrapyramidal syndromes and tardive dyskinesia. Schizophr Res 1991; 4: Kupfer DJ, Sartorius N: The usefulness and use of second-generation antipsychotic medications. Curr Opin Psychiatry 2002; 15: Almandil NB, Wong IC: Review on the current use of antipsychotic drugs in children and adolescents. Arch Dis Child Educ Pract Ed 2011; 96: Seida JC, Schouten JR, Boylan K, et al.: Antipsychotics for children and young adults: a comparative effectiveness review. Pediatrics 2012; 129: Argo TR, Carnahan RM, Perry PJ: Aripiprazole, a novel atypical antipsychotic drug. Pharmacotherapy 2004; 24: Merritt RJ: Obesity. Curr Probl Pediatr 1982; 12: Jerrell JM, McIntyre RS: Adverse events in children and adolescents treated with antipsychotic medications. Hum Psychopharmacol 2008; 23: Olfson M, Crystal S, Huang C, et al.: Trends in antipsychotic drug use by very young, privately insured children. J Am Acad Child Adolesc Psychiatry 2010; 49: Olfson M, Blanco C, Liu SM, et al.: National trends in the office-based treatment of children, adolescents, and adults with antipsychotics. Arch Gen Psychiatry 2012; 69: McConville BJ, Sorter MT: Treatment challenges and safety considerations for antipsychotic use in children and adolescents with psychoses. J Clin Psychiatry 2004; 65: Janicak PG, Davis JM, Preskorn SH, et al.: Principles and Practice of Psychopharmacotherapy. Baltimore, Williams & Wilkins Jennifer C. Seida, Janine R, et al.: Antipsychotics for children and young adults: a comparative effectiveness review. Pediatrics 2012; 129: Olfson M, Blanco C, Liu L, et al.: National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. Arch Gen Psychiatry 2006; 63: Vitiello B, Correll C, van Zwieten-Boot B, et al.: Antipsychotics in children and adolescents: increasing use, evidence for efficacy and safety concerns. Eur Neuropsychopharmacol 2009; 19: Bridget M: Studies shed light on risks and trends in pediatric antipsychotic. JAMA 2010; 303: Warren CR, Serrato JJ, Maguire GA: Off-label uses of second-generation antipsychotic drugs: Taiwanese Journal of Psychiatry [Taipei] 2012: 26; Zito JM, Safer DJ, DosReis S, et al.: Psychotropic practice patterns for youth: a 10-year perspective. Arch Pediatr Adolesc Med 2003; 157: Martin A, Leslie D: Trends in psychotropic medication costs for children and adolescents, Arch Pediatr Adolesc Med 2003; 157: Patel NC, Crismon ML, Hoagwood K, et al.: Trends in the use of typical and atypical antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 2005; 44: Patel NC, Crismon ML, Shafer A: Diagnoses and antipsychotic treatment among youths in a public mental health system. Ann Pharmacother 2006; 40: Hert MD, Dobbelaere M, Sheridan EM, et al.:

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