Prescribing Pattern of Antidepressants in Children and Adolescents: Findings from the Research on Asia Psychotropic Prescription Pattern.

OBJECTIVE: Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia. METHODS: The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed. RESULTS: A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults. CONCLUSION: Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.

Trends in the access to and the use of antipsychotic medications and psychotropic co-treatments in Asian patients with schizophrenia.

To date, antipsychotics remain the mainstay of treatment for schizophrenia and related disorders although other psychotropic medications and non-pharmaceutical interventions have been used adjunctively in some patients and settings. Regular surveys on access to and prescription patterns of psychotropic medications in clinical practice are an important and efficient way of examining the use and time trends of treatments in a given population and region. Unlike developed Western countries, Asian countries have not fully undergone deinstitutionalisation of the severely and chronically mentally ill, and community-based mental health services are still under-developed. As a result, a large number of psychiatric patients still receive treatments in psychiatric hospitals. Moreover, there have been very limited studies examining access to and prescription patterns of psychotropic medications for schizophrenia patients in Asian countries. In this paper, we focus on the only international project on the use of psychotropic medications in schizophrenia patients in selected East and Southeast Asian countries/territories summarising its major findings. Most of the first- and second-generation antipsychotics (FGAs and SGAs) are available in Asian countries, but the access to psychotropic medications is largely affected by socio-cultural and historical contexts, health insurance schemes, health care policy, medication cost and consumers' preference across different countries/territories. Overall, the proportional use of FGAs, high dose antipsychotic treatment and antipsychotic polypharmacy have decreased, while the use of SGAs and antidepressants have increased and the utilisation of benzodiazepines and mood stabilisers has remained relatively stable over time. However, within these general trends, there is great inter-country variation regarding the psychotropic prescribing patterns and trends in Asian schizophrenia patients that also seems to differ from data in many Western countries.

Antidepressant Prescription Pattern in the Presence of Medical Co-morbidity: REAP-AD 2013 Study.

OBJECTIVE: To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia. METHODS: The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort. RESULTS: Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries. CONCLUSION: Although selective serotonin reuptake inhibitors formed the bulk of antidepressant prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.

Clozapine prescription and quality of life in Chinese patients with schizophrenia treated in primary care.

OBJECTIVE: Clozapine is frequently used to treat schizophrenia in China. Maintenance treatment for clinically stable patients with schizophrenia is usually provided by Chinese primary care physicians, but no study has investigated the frequency of its use prescribed by primary care physicians. This study described the frequency, demographic and clinical characteristics of clozapine treatment and its impact on insight and quality of life (QOL) of patients with schizophrenia treated in primary care in China. METHOD: A total of 623 patients with schizophrenia treated in 22 primary care services in Guangzhou, China in 2013 formed the study sample. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects and QOL were recorded using a standardized protocol and data collection. RESULTS: The frequency of clozapine prescription was 35.6% with a mean daily dose of 127.7±88.2 mg. There were no significant differences between the patients with and without clozapine in either of the QOL domains after controlling the confounding factors. Multiple logistic regression analyses revealed that patients on clozapine had younger age of onset, more hospitalizations, more severe extrapyramidal side effects, but better insight and fewer prescriptions of first generation antipsychotics. CONCLUSIONS: Clozapine use was found to be common and associated with better insight in patients with schizophrenia treated in primary care in China. Further examination of the rationale and appropriateness of clozapine in primary care in China is warranted.

Adjunctive mood stabilizer and benzodiazepine use in older Asian patients with schizophrenia, 2001-2009.

OBJECTIVE: This study surveyed the use of adjunctive mood stabilizers (MS) and benzodiazepines (BZD) in older Asian schizophrenia patients and examined their demographic and clinical correlates. METHOD: Information on hospitalized schizophrenia patients aged 55 years or more were extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study. A total of 1,452 patients from 9 Asian countries and territories was included in the study. The patients' sociodemographic and clinical characteristics and the prescriptions of antipsychotics, MS and BZD were recorded using a standardized protocol and data collection procedure. RESULTS: The frequency of MS prescription was 26.7% in the pooled sample, with 25.5% in 2001, 26.9% in 2004 and 27.7% in 2009. The corresponding figures for BZD were 20.7%, 20.2%, 18.4% and 23.1%, respectively. Multiple logistic regression analysis of the whole sample revealed that patients on MS were younger and more likely to be men and to have extrapyramidal side effects (EPS) and a longer duration of illness. Compared to patients in China, those in Japan were more likely to receive MS, while Korean patents were prescribed less MS. In contrast, there were no significant sociodemographic or clinical correlates of BZD use. Compared to patients in China, their Korean and Singaporean counterparts were more likely to be on BZD. CONCLUSIONS: The use of MS and BZD is not uncommon in older Asian patients with schizophrenia. Given the paucity of empirical data on the efficacy of these agents in individuals with schizophrenia of any age and concerns about added side effects in older patients in particular, the rationale for the prescription of these agents in this population warrants further examination.

Antipsychotic polypharmacy in inpatients with schizophrenia in Asia (2001-2009).

OBJECTIVE: This study aimed to identify trends in the use of antipsychotic polypharmacy (APP) and their demographic and clinical correlates in the treatment of schizophrenia in Asia between 2001 and 2009. METHOD: A total of 6,761 schizophrenia inpatients in 9 Asian countries and territories were examined; 2,399 in 2001, 2,136 in 2004, and 2,226 in 2009. Patients' socio-demographic and clinical characteristics and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. RESULTS: The proportion of APP prescription decreased from 46.8 % in 2001, to 38.3 % in 2004, and increased to 43.4 % in 2009, with wide intercountry variations at each survey. Multiple logistic regression analysis of the whole sample revealed that patients on APP were younger, had a higher dose of antipsychotics in chlorpromazine equivalents, and more severe positive and negative symptoms. They were also more likely to receive depot and fi rst-generation antipsychotic drugs. CONCLUSIONS: The frequency of APP prescription varied between countries and territories, suggesting that a host of clinical and socio-cultural factors played a role in determining APP use in Asia. To resolve the discrepancy between treatment recommendation and clinical practice, regular reviews of prescription patterns are needed.

Tardive dyskinesia in the treatment of schizophrenia: the findings of the Research on Asian Psychotropic Prescription Pattern (REAP) survey (2001 - 2009).

OBJECTIVE: The aim of the study was to survey the frequency of tardive dyskinesia (TD) in patients with schizophrenia and its demographic and clinical correlates in selected Asian countries. METHOD: A total of 6,761 hospitalized schizophrenia patients in nine Asian countries and territories were examined from 2001 to 2009. TD was evaluated as "present" or "absent" according to the clinical judgment of experienced psychiatrists. The patients' socio-demographic and clinical characteristics and the prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. RESULTS: The frequency of TD in the whole sample was 5.0% with wide variations between countries (0 - 14.9%). Multiple logistic regression analysis showed that the following variables were independently associated with TD: study time, study site, older age, male gender, more severe negative and extrapyramidal symptoms and less anticholinergic drugs. CONCLUSIONS: A generally low frequency of TD in Asian schizophrenia patients with inter-ethnic variations was recorded. It is unclear whether the low prevalence of TD compared with Western data is real or the result of it being insufficiently recognized.

Use of anticholinergic drugs in patients with schizophrenia in Asia from 2001 to 2009.

OBJECTIVE: The aim of this study was to survey the use of anticholinergic medication (ACM) in Asia between 2001 and 2009 and examine its demographic and clinical correlates. METHOD: A total of 6 761 hospitalized schizophrenia patients in 9 Asian countries and territories were examined between 2001 and 2009. The patients' socio-demographic and clinical characteristics and the prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. RESULTS: The frequency of ACM prescription decreased from 66.3% in 2001, to 52.8% in 2004 and 54.6% in 2009, with wide inter-country variations at each time period. Multiple logistic regression analysis of the whole sample showed that patients taking ACM presented with more severe positive, negative, and extrapyramidal symptoms. They were also more likely to receive first-generation and depot antipsychotics and antipsychotic polypharmacy, and less likely to receive second-generation ones. CONCLUSIONS: The wide variation in ACM prescription across Asia suggests that a combination of clinical, social, economic and cultural factors play a role in determining the use of these drugs. Regular reviews of ACM use are desirable to reveal the discrepancy between treatment guidelines and clinical practice.

Ethnic differences in quality of life in adolescents among Chinese, Malay and Indians in Singapore.

BACKGROUND: Health-related quality of life in adolescents and ethnic and cultural differences are not well characterized. We used the Quality of Life Questionnaire for Adolescents (QOLQA) to examine ethnic differences in reported QOL scores among Chinese, Malay and Indian ethnicities in Singapore. METHODS: The 70-item QOLQA measuring five QOL domains (physical, psychological, independence, social and environmental) was administered to a random sample of 1363 school-children aged 10-15 years, representative of the ethnic composition of Singapore adolescents (Chinese 72%, Malays 20% and Indians 8%). RESULTS: Indians reported the highest overall QOL (mean 3.71 +/- SD 0.54) compared to Chinese (3.59 +/- 0.43), p < 0.05, and Malays (3.58 +/- 0.44), p < 0.05. In particular, Indians had significantly higher psychological QOL scores (3.73 +/- 0.61) compared to Chinese (3.55 +/- 0.54), p < 0.01. On the other hand, Chinese scored highest on physical and independence domains (3.97 +/- 0.54), p < 0.01 compared to Malays (3.82 +/- 0.55). There were no statistically significant gender differences in QOL scores. QOL declined significantly from age 10 to 15 for overall score, psychological, physical (p < 0.01) and environmental (p < 0.05). Lower socio-economic status and the self-report of a significant health problem were significantly associated with lower overall QOL and most domains. These ethnic differences persisted after adjusting for differences in socio-economic and health status. Psychometric properties and known group construct validity appeared to be similar across different ethnic groups, but compared to Chinese (r = 0.39) or Malays (r = 0.39), Indians showed a higher correlation of psychological scores with physical score (r = 0.59) and with other domain scores. CONCLUSION: Significant ethnic differences in reported adolescent quality of life among Chinese, Malays and Indians in Singapore that are independent of socioeconomic and health status suggest important cultural differences.

Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin.

BACKGROUND/AIMS: The gastric peptide ghrelin, an endogenous ligand for growth-hormone secretagogue receptor, has two major molecular forms: acylated ghrelin and desacyl ghrelin. Acylated ghrelin induces a positive energy balance, while desacyl ghrelin has been reported to be devoid of any endocrine activities. The authors examined the effects of desacyl ghrelin on energy balance. METHODS: The authors measured food intake, gastric emptying, c-Fos expression in the hypothalamus, and gene expression of hypothalamic neuropeptides in mice after administration of desacyl ghrelin. To explore the effects of long term overexpression of desacyl ghrelin, transgenic mice that overexpressed desacyl ghrelin were created. RESULTS: Administration of desacyl ghrelin decreased food intake and gastric emptying rate through an action on the paraventricular nucleus and the arcuate nucleus in the hypothalamus. Gene expression of anorexigenic cocaine and amphetamine regulated transcript and urocortin in the hypothalamus was increased by desacyl ghrelin. Desacyl ghrelin overexpressing mice exhibited a decrease in body weight, food intake, and fat pad mass weight accompanied by moderately decreased linear growth. Gastric emptying was also decreased in desacyl ghrelin overexpressing mice. CONCLUSIONS: These findings indicate that in contrast to acylated ghrelin, desacyl ghrelin induces a negative energy balance by decreasing food intake and delaying gastric emptying. The effect is mediated via the hypothalamus. Although derived from the same precursor, the inverse effects of these two peptides suggest that the stomach might be involved as an endocrine organ in the regulation of the energy balance.

High dose antipsychotic use in schizophrenia: findings of the REAP (research on east Asia psychotropic prescriptions) study.

BACKGROUND: High-dose antipsychotic regimes (defined as the prescription of more than 1000 chlorpromazine-equivalents milligrams of antipsychotic per day) in the management of patients with schizophrenia are not uncommon, but most reports are from western countries. Recent functional neuroimaging studies have found that the previous notion concerning the use of antipsychotic medication, especially in high doses, was unsupported and untenable. METHODS: This international study examined the use of high dose antipsychotic medication and its clinical correlates in schizophrenia patients within six East Asian countries/territories. RESULTS: Within the study group (n = 2399), 430 patients (17.9%) were prescribed high dose antipsychotics. Antipsychotic use varied significantly between countries, with Japan, Korea, and Singapore using higher doses than the other countries. High dose antipsychotic use was associated with younger age in Japan (p < 0.001), longer duration of admission (p < 0.001), duration of illness (p < 0.001, particularly in Korea and Taiwan), positive psychotic symptoms (p < 0.001, particularly in Japan and Korea), and aggression (p < 0.05, particularly in Japan), and also with a higher likelihood of extrapyramidal and autonomic adverse effects (p < 0.05, particularly in China). Country, younger age, the presence of delusions and disorganized speech, polypharmacy, and receiving depot medication but not atypical antipsychotic drugs were important predictors of high antipsychotic use. CONCLUSIONS: This survey revealed that high antipsychotic dosing is not an uncommon practice in East Asia. It behooves the prescribing clinicians to constantly reevaluate the rationale for such a practice.

Post-earthquake quality of life and psychological well-being: longitudinal evaluation in a rural community sample in northern China.

This study aims to observe longitudinal change of quality of life (QOL) and psychological well-being in a community sample affected by an earthquake and to examine the relationship between QOL and disaster exposure, post-disaster support and other related variables. The subjects, from two villages at different distances from the epicenter, were assessed using the brief version of the World Health Organization Quality of Life Assessment (WHOQOL-BREF) and three subscales of a symptoms checklist at 3 months (n=335) and 9 months (n=253) after the earthquake, respectively. Exposure to the earthquake was associated with multidimensional impairment in QOL, including physical, psychological and environmental domains at 3 months, and psychological and environmental domains at 9 months. The victims also suffered significantly more psychological distress in terms of depression, somatization and anxiety. At both assessment points the group that experienced lower initial exposure but then received less post-disaster help reported poorer QOL and psychological well-being. The two victim groups also differed significantly in changing trend along time. The group that received more support showed a general improvement in post-disaster well-being from 3 months to 9 months. The results confirm that post-disaster variables could be as important to post-disaster psychosocial outcomes as variables of pre-disaster vulnerability and disaster per se. A comprehensive and prospective assessment of disaster effects is imperative for the better organization of disaster relief programs and psychosocial interventions.

[The mental health of school children after the Great Hanshin-Awaji Earthquake: II. Longitudinal analysis].

UNLABELLED: We conducted surveys to investigate the nature of the recovery processes and psychological reactions of children and adolescents affected by the Great Hanshin Awaji Earthquake. The investigations were carried out 4 times at 4 months, 6 months, one year and two years after the disaster. SUBJECTS: About 9000 school children in the 3rd grade, the 5th grade, the 8th grade living in the disaster area. METHOD: The questionnaire consisted of 9-12 items regarding situation and behavior when the earthquake occurred, and 22 items regarding mental health condition, and was filled out in the classroom under supervision by the teacher in charge. The responses were rated from 1 to 4 depending on the frequency of the symptoms, and statistically analyzed. RESULTS: By factor analysis, three factors were elicited. Factor 1 was interpreted as being related to fear and anxiety, factor 2 as related to depression and physical symptoms, and factor 3 as related to pro-social tendencies. These 3 factors were distinct and stable throughout all 4 surveys and each of them showed unique recovery processes. The mean score of factor 1 was highest at 4 months after the earthquake, and decreased as time passed. This factor shows that fear and anxiety seem to be directly related to the experience of the earthquake. According to the severity of the disaster, more severe damage brought about a higher mean score of factor 1. Furthermore, younger children and girls were more strongly affected. Each of the differences in the severity of disaster, in age, and in gender decreased as time passed. The mean score of factor 2 peaked at 6 months, and it slightly recovered after one year. However, the score at the 1st year was still higher than that of the 4th month. At two years the score returned to almost the same level as that of the 4th month. We think that factor 2, involving depressive mood and psychophysical symptoms, may be a secondary phenomenon to fear and anxiety. Other possibilities are that they may be caused by environmental changes after the disaster, inconveniences of daily life, loss of jobs of parents, or masked by hypomanic mood which covered over the disaster area soon after the earthquake (so-called heroic phase). Older children have a greater tolerance for depressive mood and psychophysical symptoms, but those symptoms occurring in older children have a tendency to continue for a longer time. Girls are more heavily affected and need more time to recover from trauma than boys. The mean score of factor 3 showed a gradual decrease as time passed. There was no difference in the way of decrease according to the severity of disaster, age and gender. It may be natural that, since the interest in the earthquake decreased as time passed, consideration for the victims decreased. CONCLUSIONS: The problems of mental health of children and adolescents after the disaster may consist of at least 2 different components; "fear and anxiety," which appeared just after the disaster and decreased earlier; "depressive and psychophysical symptoms" appeared later and stayed longer.

Longitudinal study of earthquake-related PTSD in a randomly selected community sample in north China.

OBJECTIVE: This study longitudinally described rates of posttraumatic stress disorder (PTSD) in two groups with different levels of severity of exposure to an earthquake in North China. The effects of diagnostic criteria on the frequency of detected PTSD were also examined. METHOD: Subjects were randomly sampled in two villages at different distances from the earthquake epicenter. A total of 181 and 157 subjects were assessed at 3 months and 9 months after the earthquake, respectively, for PTSD by using both DSM-IV and DSM-III-R criteria. The brief version of the World Health Organization Quality of Life Assessment and three subscales of the SCL-90-R were also administered at both assessment points. RESULTS: The village with a higher level of initial exposure to the earthquake and a higher level of postearthquake support had a lower frequency of PTSD than the village with a lower level of initial exposure and less postearthquake support. The rate of onset of DSM-IV PTSD within 9 months for the two villages was 19.8% and 30.3%, respectively. In both villages, the rate of onset of earthquake-related PTSD within 9 months was 24.2% by using DSM-IV criteria and 41.4% by using DSM-III-R criteria. The introduction in DSM-IV of a criterion requiring clinically significant distress or impairment in functioning for a diagnosis of PTSD was a major contributor to the lower rate of DSM-IV PTSD. CONCLUSIONS: PTSD may be as prevalent and persistent in disaster victims in China as in those elsewhere. Prompt and effective postdisaster intervention could mitigate the impact of initial exposure and reduce the probability of PTSD occurrence. Caution should be used in comparing rates of postdisaster PTSD identified by using different diagnostic criteria.

Comparative study of quality of life between the Chinese and Japanese adolescent populations.

Researchers from Japan, China and Singapore have initiated a collaborative project, with the aim of comparing adolescent quality of life (QOL) internationally. This study presents the primary results of the investigation conducted in Beijing, China, and Kobe, Japan. The 70-item Quality of Life Questionnaire for Adolescents (QOLQA) was developed and evaluated in Japan and China. In total, 1114 Japanese and 613 Chinese junior high school students, aged 12-15 years, completed the questionnaire. Chinese students scored significantly higher than the Japanese students in overall QOL scores and in most domains. For both groups, subjects had highest score in the independence domain and lowest in psychological domain. In terms of overall QOL score, Chinese male students ranked first, followed by Chinese girls, Japanese boys, and Japanese girls. In the Japanese group, a continuing decrease of QOL scores with age was observed without exception, but no such tendency was present in their Chinese counterparts. No parallel relationship was observed between the higher level of economic development and better quality of life. The results also suggest that mental health promotion should be a priority in improving overall quality of life of adolescents both in Japan and China.

Mental health services in Asia: international perspective and challenge for the coming years.

In contrast to European countries and the United States of America, there has been a steady increase in the psychiatric inpatient population in Japan between 1960 and 1993. Japan has the biggest number of psychiatric beds in the world, both in absolute and relative numbers per population. However, Japan now focuses on community based services and the human rights of patients. In other Asian countries, the number of psychiatric beds is relatively small; however, the numbers are increasing each year in China, the Republic of Korea, Philippines, Indonesia and in many other countries in Asia. These countries are still facing the challenge of increasing psychiatric services and to improve the quality of care with scarce mental health resources. Should Asian countries take the similar path to European countries and develop mental health services? This review provides an overview of Asian mental health services and discussing the following issues: how many psychiatric beds do we need in Asia?; public vs private psychiatric services?; financing scheme to promote community based care in Asia; mental health services in primary health care; family education and user involvement in Asia; and the challenge for psychiatrists in Asia.