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.

A review of schizophrenia research in malaysia.

Research in schizophrenia has advanced tremendously. One hundred and seventy five articles related to Schizophrenia were found from a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. This project aims to examine published research articles, in local and international journals in order to provide a glimpse of the research interest in Malaysia with regards to schizophrenia. Single case study, case series report, reviews and registry reports were not included in this review. Medication trial, unless it concerned a wider scope of psychopharmacology was also excluded from this review. A total of 105 articles were included in this review. Despite numerous genetics studies conducted and published, a definitive conclusion on the aetiology or mechanism underlying schizophrenia remains elusive. The National Mental Health - Schizophrenia Registry (NMHR) proved to be an important platform for many studies and publications. Studies stemmed from NMHR have provided significant insight into the baseline characteristic of patients with schizophrenia, pathway to care, and outcomes of the illness. International and regional collaborations have also encouraged important work involving stigma and discrimination in schizophrenia. Ministry of Health's hospitals (MOH) are the main research sites in the country with regards to schizophrenia research. Numbers of schizophrenia research are still low in relation to the number of universities and hospitals in the country. Some of the weaknesses include duplication of studies, over-emphasising clinical trials and ignoring basic clinical research, and the lack of publications in international and regional journals.

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.

Determinants of subjective quality of life in first-episode schizophrenia: perspective from Malaysia.

AIM: This study sought to examine the determinants of subjective quality of life among patients with first-episode schizophrenia in a developing country. METHOD: One-hundred and twenty patients registered with National Mental Health Registry for Schizophrenia from 1 January 2003 to 31 August 2005 were included. They were diagnosed with first-episode schizophrenia, schizoaffective and schizophreniform disorders and had been compliant to treatment. Sociodemographic data were obtained and the Brief Psychiatric Rating Scale-Anchored Version, Health of The Nation Outcome Scales, Simpson-Angus Extrapyramidal Side Effects Scale, Barnes Akathisia Scale and the World Health Organization Quality of Life were used to assess psychopathology, side effects from antipsychotics and subjective quality of life. RESULTS: Gender, positive and disorganized symptoms of schizophrenia, and cognitive and physical impairments appeared to be the most important predictors of subjective quality of life among the patients from this centre in Malaysia. CONCLUSION: Different domains of self-rated quality of life correlated with different sociodemographic and clinical characteristics. Some of the characteristics were malleable and a better understanding of these could lead to improvements in the management of patients with schizophrenia.

The National Mental Health Registry (NMHR).

The National Mental Health Registry (NMHR) collects information about patients with mental disorder in Malaysia. This information allows us to estimate the incidence of selected mental disorders, and to evaluate risk factors and treatment in the country. The National Mental Health Registry (NMHR) presented its first report in 2004, a year after its establishment. The report focused on schizophrenia as a pioneer project for the National Mental Health Registry. The development of the registry has progressed with data collected from government-based facilities, the academia and the private sector. The 2003-2005 report was recently published and distributed. Since then the registry has progressed to include suicides and other mental illnesses such as depression. The NMHR Report 2003-2005 provides detailed information about the profile of persons with Schizophrenia who presented for the first time to various psychiatry and mental health providers throughout Malaysia. More detailed description regarding pharmacotherapy is reported and few cross tabulations done in an effort to provide better understanding and more clinically meaningful reports.

Molecular genetic analysis of para-Bombay phenotypes in Chinese: a novel non-functional FUT1 allele is identified.

BACKGROUND AND OBJECTIVES: The para-Bombay phenotype (also known as H-deficient secretor) is characterized by a lack of ABH antigens on red cells, but ABH substances are found in saliva. Molecular genetic analysis was performed for five Chinese individuals serologically typed as para-Bombay. MATERIALS AND METHODS: ABO genotyping and mutational analysis of both FUT1 (or H) and FUT2 (or Se) loci were performed for these individuals using the polymerase chain reaction, single-strand conformation polymorphism analysis and direct DNA sequencing. RESULTS: The ABO genotypes of these para-Bombay individuals correlated with the types of ABH substances found in the saliva. Their FUT1 genotypes were h1h2 (three individuals), h2h2 (one individual) and h2h6 (one individual). Alleles h1 (547-552delAG) and h2 (880-882delTT) were known frameshift mutations, while h6 (522C > A) was a missense mutation (Phe174Leu) not previously reported. These three mutations were rare sequence variations, each with an allele frequency of less than 0.005. Phe174 might be functionally important because this residue is conserved from mouse to human. Their FUT2 genotypes were Se357se357,385 for the h2h6 individual and Se357Se357) for the others. Both FUT2 alleles were known: one functional (Se357) and one weakly functional (se357,385). That they carried at least one copy of a functional FUT2 allele was consistent with their secretor status. As FUT1 and FUT2 are adjacent on 19q13.3, there are three possible haplotypes in these para-Bombay individuals: h1-Se357; h2-Se357; and h6-se357,385. CONCLUSIONS: A novel non-functional FUT1 allele (522C > A, or Phe174Leu) was identified in a para-Bombay individual and on a se357,385 haplotype background.

A functional neuroanatomy of tics in Tourette syndrome.

BACKGROUND: Tics are involuntary, brief, stereotyped motor and vocal behaviors often associated with irresistible urges. They are a defining symptom of the classic neuropsychiatric disorder, Tourette syndrome (TS), and constitute an example of disordered human volition. The neural correlates of tics are not well understood and have not been imaged selectively. METHODS: Event-related [(15)O]H(2)O positron emission tomography techniques combined with time-synchronized audio and videotaping were used to determine the duration of, frequency of, and radiotracer input during tics in each of 72 scans from 6 patients with TS. This permitted a voxel-by-voxel correlational analysis within Statistical Parametric Mapping of patterns of neural activity associated with the tics. RESULTS: Brain regions in which activity was significantly correlated with tic occurrence in the group included medial and lateral premotor cortices, anterior cingulate cortex, dorsolateral-rostral prefrontal cortex, inferior parietal cortex, putamen, and caudate, as well as primary motor cortex, the Broca's area, superior temporal gyrus, insula, and claustrum. In an individual patient with prominent coprolalia, such vocal tics were associated with activity in prerolandic and postrolandic language regions, insula, caudate, thalamus, and cerebellum, while activity in sensorimotor cortex was noted with motor tics. CONCLUSIONS: Aberrant activity in the interrelated sensorimotor, language, executive, and paralimbic circuits identified in this study may account for the initiation and execution of diverse motor and vocal behaviors that characterize tics in TS, as well as for the urges that often accompany them. Arch Gen Psychiatry. 2000;57:741-748

The audiogenic startle reflex in Tourette's syndrome.

The motor response pattern of the audiogenic startle reflex was studied in 15 Tourette's syndrome (TS) patients and 15 normal, age-matched control subjects, using auditory stimuli at 88 and 114 dB. The louder stimuli readily elicited responses in the orbicularis oculi (in all subjects), masseter, sternomastoid, trapezius, deltoid, and biceps (in most subjects) muscles, with a few subjects having responses in the forearm flexors and quadriceps. The TS subjects did not differ from controls in the onset latency, amplitude, and first peak latency of the reflex response in any of the muscles. Rates of habituation in the orbicularis oculi muscle were widely variable across the subjects, and the two groups did not differ overall in the habituation rates. Our study does not support the reports of an abnormal audiogenic startle reflex in TS.

Outcome of neonates with electrographically identified seizures, or at risk of seizures.

A prospective study was conducted to investigate survival at 1 month and survival and developmental outcome at 1 year in a cohort of 53 neonates either suspected of or at risk of having seizures. For all patients, presence of seizures, diagnoses, and structural abnormalities were identified. If seizures were present, seizure variables were quantified. Correlations between neonatal parameters and subsequent outcome were investigated. Forty-three patients survived the first month of life. Background EEG was the only significant predictor of survival at 1 month. Three patients died after 1 month, and 2 of the three had extremely depressed interictal EEGs. Development outcome at 1 year was determined for all available surviving patients. Abnormal findings from brain imaging studies and number of independent electrographic seizure foci were correlated with some aspects of outcome at 1 year. No other correlations were identified between neonatal parameters and outcome.

A controlled study of sensory tics in Gilles de 1a Tourette syndrome and obsessive-compulsive disorder using a structured interview.

OBJECTIVE: To determine the prevalence and characteristics of sensory tics in the Gilles de la Tourette syndrome (GTS), and a matched population of patients with obsessive-compulsive disorder (OCD) using a structured assessment. METHODS: 50 subjects each of GTS, OCD, and healthy controls were studied to determine the prevalence and phenomenology of sensory tics, and diagnose tic disorders, OCD, and affective disorders according to DSM-III-R criteria. The severity of tics and obsessive-compulsive symptoms were quantified using the Tourette syndrome global scale (TSGS) and Yale-Brown obsessive-compulsive scale (Y-BOCS) respectively. RESULTS: The GTS group (28%) had significantly-greater life-time prevalence of sensory tics than the OCD (10%) and healthy (8%) groups (P < 0.05). The sensory tics in both the GTS and OCD groups were predominantly located in rostral anatomical sites. Multiple sensory tics occurred in some patients with GTS or OCD, but not in healthy subjects. Within the OCD group, those who had sensory tics had significantly higher TSGS scores (P < 0.0001), and a higher prevalence of GTS (P < 0.005). CONCLUSIONS: Sensory tics seem to be a common and distinctive feature of GTS and that subpopulation of patients with OCD predisposed to tic disorders. Neurophysiologically, a possible explanation for sensory tics is that they represent the subjectively experienced component of neural dysfunction below the threshold for motor and vocal tic production.

Tics status.

OBJECTIVES: To describe two patients with tics status, propose a definition of this syndrome and draw attention to its clinical significance. METHOD: Two patients suffering from Tourette's Syndrome who had developed episodes of continual motor tics that lasted from minutes to hours, were non-suppressible and intruded into normal functioning, were treated with an increase in the dose of haloperidol, in one case with the addition of clonazepam. RESULTS: The offset of the episodes was gradual and the tic disorder was worse after the episodes. One patient had further spontaneous episodes of tics status. CONCLUSIONS: The recognition of tics status has implications for the management as well as our understanding of the pathobiology of tics and Tourette's Syndrome. The definition of tics status should be standardised.

Survey on developmental-behavioural training experiences of Australian paediatric advanced trainees.

In order to monitor whether paediatric education has adapted to meet modern practice 91 paediatric advanced trainees were surveyed to elicit their satisfaction with developmental-behavioural (DB) training. A response of 69% was obtained to a postal questionnaire. The traditional imbalance persists, with trainees considering themselves significantly better informed in the medical disciplines (P < 0.001). Satisfaction with training in the 14 developmental disciplines surveyed is less (P < 0.001) and significantly more variable compared with 11 traditional medical disciplines (P < 0.01). Formal rotations in DB disciplines had been received by all respondents by the 7th year of training. However, 46-67% consider themselves ill-informed in learning/school problems, attention-deficit hyperactivity disorder, adolescent problems, paediatric rehabilitation and language impairment. Thirty-seven per cent found formal postgraduate instruction unhelpful. Paediatric advanced training gives exposure to, but unsatisfactory formal education, in developmental and behavioural paediatrics. Current initiatives for mandatory DB training have serious implications for achieving adequate resources and standards to meet clinical and training demands.

The clinical features of Tourette's disorder: an Australian study using a structured interview schedule.

The clinical features of an Australian series of patients fulfilling DSM-III-R criteria for Tourette's Syndrome (TS) were examined. Fifty patients, recruited from a hospital-based outpatient clinic and a self-help group, were interviewed using a structured schedule. TS is a complex disorder with wide ranging manifestations. Forty male and ten female TS patients with a mean age of 20.8 years (SD 11.2) were assessed. The mean age of onset of tics was 8.3 years (SD 3.3). Simple motor tics occurring in the rostral body regions were more common (eye 86%, face and head 80%) when compared both to simple tics occurring caudally (leg 52%) and complex motor tics (58%). Simple vocal tics were more common (94%) than complex ones (44%). There was a rostrocaudal pattern in the age of onset and severity of simple motor tics. Rates of comorbidity were 32%, 18% and 30% for Attention-Deficit Hyperactivity Disorder, Major Depression and Generalised Anxiety Disorder respectively and this was reflected in the considerable proportion (32%) of the sample who first presented for reasons other than their tics. There were substantial delays between the age of first presentation and diagnosis of TS owing to the insidious onset of the disorder, misdiagnosis and delays in presentation for help. A comparison of the features of the present patients with those of other published studies revealed similarities with some differences. Better clinical recognition of the symptoms and modes of presentation of TS may improve existing delays in diagnosis and treatment.

A simple collection method for saliva in children: potential for home monitoring of carbamazepine therapy.

We have developed a method of monitoring plasma concentrations of antiepileptic drugs which uses salivary samples, and is suitable for home monitoring in children. To validate the method, paired plasma and saliva samples from 39 children aged between 2 and 15 years were assayed for carbamazepine and its active metabolite, carbamazepine-10,11-epoxide by h.p.l.c. The method uses a gauze-wrapped cotton ball with attached string, to absorb saliva which is then separated using a syringe and plunger. There was no adsorption of CBZ and CBZ-E and they were stable over 1 month in a domestic freezer. Plasma and salivary free CBZ and CBZ-E concentrations were highly correlated (r2 = 0.99 and 0.98, respectively).

Pharmacological characterization of tardive akathisia.

A patient with tardive neuroleptic-induced akathisia was investigated with multiple pharmacological challenges. It was noted that the patient responded positively to benztropine, bromocriptine, and propranolol, and negatively to physostigmine, and showed little or no response to discontinuation of neuroleptics and challenges with metoclopramide, metoprolol, atenolol, and clonidine. The implications of this pharmacological characterization for the understanding of the pathophysiology of tardive akathisia in relation to acute akathisia and tardive dyskinesia are discussed.