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.

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.

Antidepressant-induced tardive syndrome: a retrospective epidemiological study.

INTRODUCTION: The impact of using antidepressant on the occurrence of tardive syndrome is rarely studied. Here we aimed to investigate the prevalence of various types of antidepressant induced tardive syndrome. METHODS: This study was conducted by means of a retrospective survey. Subjects receiving antidepressant(s) for over 6 months, but no other agents that may cause involuntary movements, were consecutively recruited. Tardive syndrome was evaluated in every included subject. Possible confounding medical conditions were carefully ruled out. RESULTS: Of the 158 included subjects, 22 (14.0 %) were found to have at least one tardive syndrome. The prevalence of subtypes of tardive syndromes was: tardive dystonia: 10.8 %, tardive dykinesia: 3.2 %, tardive tremor: 1.3 %, tardive parkinsonism: 1.3 %, tardive tics: 1.3 %, tardive sensory syndrome: 1.3 %, and tardive myoclonus: 0.6 %. Using serotonin-norepinephrine reuptake inhibitors and previous marital status significantly increase the risk of tardive syndrome. DISCUSSION: This study showed that antidepressants may induce various types of tardive syndrome, of which tardive dystonia is the predominant form. Clinicians should be cautious of this infrequent but distressing adverse effect when using antidepressants.

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.

Genome-wide association study of bipolar I disorder in the Han Chinese population.

We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, ß-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study.

To compare the prevalence of extrapyramidal syndrome (EPS) between the first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), the co-prescribing rate of anti-Parkinson drugs (APDs) of each antipsychotic drug was analyzed using population database. Fourteen antipsychotics had been prescribed during the 5-year study period. Among the SGAs, quetiapine had the lowest crude co-prescribing rate of APDs (27.09%), whereas risperidone had the highest rate (66.50%). Among the FGAs, thioridazine and loxapine had the lowest (60.99%) and highest rates (96.35%), respectively. The rankings of the co-prescribing rate of APDs among antipsychotics, in increasing order, were quetiapine, clozapine, olanzapine, thioridazine, zotepine, chlorpromazine, risperidone, sulpiride, clotiapine, flupentixol, haloperidol, zuclopentixol, trifluoperazine, and loxapine. The results indicate that the risk of EPS appears to be lower in SGAs than in FGAs; however, the considerably high rate of EPS in some of the newer generation of antipsychotics warrants clinical attention.

A 3-year panel study of mental disorders among adolescents in Taiwan.

OBJECTIVE: This study investigated the prevalence and changing trends of mental disorders and the effects of gender and urbanization among adolescents in Taiwan. METHOD: A random sample of seventh-grade students (N=1,070) was recruited from one urban and one rural junior high school in which 1,051 (98.2%) and 1,035 (96.7%) were reassessed in the second and third years, respectively. A two-stage case identification was conducted by mental health professionals with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version, supplemented by information from the Child Behavior Checklist. RESULTS: The weighted 3-month prevalence rates across the 3 consecutive years for overall psychiatric disorders were 20.3%, 22.7%, and 14.8%, respectively. The most prevalent psychiatric condition was attention deficit hyperactivity disorder (ADHD) in the first 2 years and substance use disorders in the third. During the 3 years, the rates for ADHD, specific phobia, and social phobia decreased, and the rates for major depression and substance use disorders, conversely, increased. Although conduct disorder, ADHD, and substance use disorders were more prevalent among boys, the rates for major depression, social phobia, specific phobia, and adjustment disorder were higher among girls. Rural adolescents had higher rates of conduct disorder, oppositional defiant disorder, and substance use disorders than their urban counterparts. CONCLUSIONS: Our findings are similar to those of previous studies among adolescents in prevalence rates, changing trends of most mental disorders, and gender effects. The differential changing trends in various diagnostic groups may imply the importance of specific measures for prevention during adolescence.

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.

Apolipoprotein E polymorphism and Alzheimer's disease.

We aimed to determine the association and related factors of the apolipoprotein E (ApoE) genotype and Alzheimer's disease (AD) in Taiwan. We examined ApoE genotypes in 50 Chinese patients with AD and 50 age- and sex-matched controls. The patients met the criteria of probable AD of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and AD of the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV). There were 28 females and 22 males in the case and control groups. The mean age of onset of AD was 72. 62 years. The average interval between onset and research was 3.85 years. The frequency of ApoE epsilon 4 in the AD group was significantly higher than that in the controls (0.13 versus 0.02, p < 0.05). The odds ratio for AD in individuals with at least one ApoE epsilon 4 allele was 6.0 (95% CI 1.34 to 55.3, p < 0.001). The linear trend for AD in proportion to alleles of ApoE epsilon 4 was significant (chi 2 = 8.3, p = 0.004). The risk of ApoE epsilon 4 allele for the late-onset AD patients, males, or those who received less education was higher than that for the early-onset AD patients, females, or those who had received more education. The sensitivity of the epsilon 4 allele was 24%, the specificity 96%, the positive predictive value 86%, and the negative predictive value 56%. Our results supported that the ApoE epsilon 4 allele is related to AD in Taiwan. In addition, sex and education may play important roles in the presence of ApoE epsilon 4 allele. The epsilon 4 allele seemed helpful as an adjunct for diagnostic testing of AD.

A multidimensional assessment of insights in schizophrenic patients.

This study aims to construct a multidimensional instrument in assessing insight of schizophrenic patients and further to examine its relationships with other factors such as psychiatric symptoms, demographic characteristics, and course of illness. An instrument (the Schedule for assessment of Insight in Psychosis, SIP) with a 4-point rating scale was constructed to assess the insight of schizophrenic patients in five dimensions. One hundred schizophrenic patients were recruited for the study and all of them received a semi-structured interview using the SIP. Their demographic variables, length of illness and severity of psychotic symptoms were analyzed for insight. The reliability and validity of the SIP were satisfactory. Significant factors related to insight were psychotic symptoms, including both positive and negative symptoms. This study showed insight was affected by a multitude of factors, and it could be assessed quantitatively in various dimensions.

Community study of depression in old age in Taiwan: prevalence, life events and socio-demographic correlates.

BACKGROUND: Published studies of prevalence of depression in old age in Taiwan have yielded equivocal results. AIMS: To study the prevalence of depressive disorders among community-dwelling elderly; further, to assess socio-demographic correlates and life events in relation to depression. METHOD: A randomised sample of 1500 subjects aged 65 and over was selected from three communities. Research psychiatrists conducted all assessments using the Geriatric Mental State Schedule. The diagnosis of depression was made with the GMS-AGECAT (Automated Geriatric Examination for Computerised Assisted Taxonomy); data on life events were collected with the Taiwanese version of the Life Events and Difficulties Schedule. RESULTS: One-month prevalence of psychiatric disorders was 37.7%, with 15.3% depressive neurosis and 5.9% major depression. A high risk of depressive disorders was found among widows with a low educational level living in the urban community, and among those with physical illnesses. CONCLUSIONS: Contrary to most previous reports, we found that the prevalence of depressive disorders among the elderly in the community in Taiwan is high and comparable to rates reported in some studies of UK samples.

Retrospective estimation of the birth prevalence for delayed onset disorders: application to cystic fibrosis in Nova Scotia.

Maximum likelihood methods are used to estimate the birth prevalence, the age-at-diagnosis distribution, and the number of infants born with CF in Nova Scotia over a 20 year period. The data were taken from a registry of CF cases, and, because of the delayed onset of symptoms, some CF affected individuals were not diagnosed by the end of the study period. A goodness-of-fit test for assessing whether the age-at-diagnosis distribution is stable over the 20 years is provided. These methods could be applied equally well to data on any genetic disorder with delayed onset.

Validation of the Chinese Health Questionnaire (CHQ-12) in community elders.

There has been no validated screening instrument for use in non-psychotic illness of the elderly in Taiwan. This study aims to test the validity of the 12-item Chinese Health Questionnaire (CHQ-12) among the elderly in a community study. The CHQ-12 was administrated via reading-out to 222 subjects aged 65 and over from three communities. Psychiatrists using the Geriatric Mental Status Schedule (GMS) assessed psychiatric condition while the diagnosis was made according to the computerized program, AGECAT. Validity indices of the CHQ-12 were calculated, using the Relative Operating Characteristic (ROC) analysis for its optimal cut-off point. Variables hypothesized to affect its performance were assessed. Validity of the CHQ-12 at optimal cut-off point 2/3 were estimated with a sensitivity of 79.7%, a specificity of 83.6%, a positive predictive value of 68.9%, a negative predictive value of 90.0% and an overall misclassification rate of 17.6%, and an estimate of the area under the ROC curve of 0.81. The performance of the CHQ-12 was better in males, in those who were literate, and in those without any physical illness. This study demonstrated that the use of CHQ-12 in the elderly community is as valid as in the general population survey. However, it should be read out by the investigator rather than self-administered due to the high proportion of illiteracy among the Taiwanese elderly.

Substance use disorders among adolescents in Taiwan: prevalence, sociodemographic correlates and psychiatric co-morbidity.

BACKGROUND: This paper reports prevalences, sociodemographic correlates and psychiatric co-morbidity of substance use disorders (SUDs) among adolescents in Taiwan. METHODS: A random sample of ninth grade students (N = 774) was selected from an urban, a suburban and a rural community. Two-stage case identification was employed with a brief screening tool and a modified Chinese version of the Kiddie-SADS conducted by child psychiatrists. RESULTS: The overall prevalence of any SUD was 11.0%, with nicotine (96.0%) as the most prevalent substance. The prevalences of SUDs were significantly higher in boys, rural community and classes with poor academic performance. Sixty-two per cent of all SUD cases suffered from other concurrent psychiatric disorders. The most common co-morbid conditions were conduct disorder, attention deficit hyperactivity disorder and mood disorders. CONCLUSIONS: High prevalences of SUDs were found among adolescent school children in Taiwan. Effects of urbanization, selective migration and the availability of substances are possible explanations for the urban-rural difference on the risk for SUDs. Psychiatric co-morbid conditions for SUD among adolescents in Taiwan were similar to those in Western societies.

Schizophrenia: conceptual change in modern psychiatry.

Schizophrenia is perhaps the most devastating mental illness that psychiatrists must treat. Its chronic course with deteriorating consequences has been the focus of study throughout this century. This paper reviews the concept of schizophrenia, from fundamental Kraepelinian theory of 'dementia praecox' to biological correlates and explanation. Its causes, however, remain obscure and there were no appreciable changes in its treatment modality. A 'bio-psycho-social' model of care is emphasized, aiming at the prevention of deterioration of symptoms, functional impairment, disability and social handicap.