Stigma towards mental illness in Asian nations and low-and-middle-income countries, and comparison with high-income countries: A literature review and practice implications.

Background: Stigma related to mental illness (and its treatment) is prevalent worldwide. This stigma could be at the structural or organizational level, societal level (interpersonal stigma), and the individual level (internalized stigma). Vulnerable populations, for example, gender minorities, children, adolescents, and geriatric populations, are more prone to stigma. The magnitude of stigma and its negative influence is determined by socio-cultural factors and macro (mental health policies, programs) or micro-level factors (societal views, health sectors, or individuals' attitudes towards mentally ill persons). Mental health stigma is associated with more serious psychological problems among the victims, reduced access to mental health care, poor adherence to treatment, and unfavorable outcomes. Although various nationwide and well-established anti-stigma interventions/campaigns exist in high-income countries (HICs) with favorable outcomes, a comprehensive synthesis of literature from the Low- and Middle-Income Countries (LMICs), more so from the Asian continent is lacking. The lack of such literature impedes growth in stigma-related research, including developing anti-stigma interventions. Aim: To synthesize the available mental health stigma literature from Asia and LMICs and compare them on the mental health stigma, anti-stigma interventions, and the effectiveness of such interventions from HICs. Materials and Methods: PubMed and Google Scholar databases were screened using the following search terms: stigma, prejudice, discrimination, stereotype, perceived stigma, associate stigma (for Stigma), mental health, mental illness, mental disorder psychiatric* (for mental health), and low-and-middle-income countries, LMICs, High-income countries, and Asia, South Asian Association for Regional Cooperation/SAARC (for countries of interest). Bibliographic and grey literature were also performed to obtain the relevant records. Results: The anti-stigma interventions in Asia nations and LMICs are generalized (vs. disorder specific), population-based (vs. specific groups, such as patients, caregivers, and health professionals), mostly educative (vs. contact-based or attitude and behavioral-based programs), and lacking in long-term effectiveness data. Government, international/national bodies, professional organizations, and mental health professionals can play a crucial in addressing mental health stigma. Conclusion: There is a need for a multi-modal intervention and multi-sectoral coordination to mitigate the mental health stigma. Greater research (nationwide surveys, cultural determinants of stigma, culture-specific anti-stigma interventions) in this area is required.

A Machine-Learning-Algorithm-Based Prediction Model for Psychotic Symptoms in Patients with Depressive Disorder.

Psychotic symptoms are rarely concurrent with the clinical manifestations of depression. Additionally, whether psychotic major depression is a subtype of major depression or a clinical syndrome distinct from non-psychotic major depression remains controversial. Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, we developed a machine-learning-algorithm-based prediction model for concurrent psychotic symptoms in patients with depressive disorders. The advantages of machine learning algorithms include the easy identification of trends and patterns, handling of multi-dimensional and multi-faceted data, and wide application. Among 1171 patients with depressive disorders, those with psychotic symptoms were characterized by significantly higher rates of depressed mood, loss of interest and enjoyment, reduced energy and diminished activity, reduced self-esteem and self-confidence, ideas of guilt and unworthiness, psychomotor agitation or retardation, disturbed sleep, diminished appetite, and greater proportions of moderate and severe degrees of depression compared to patients without psychotic symptoms. The area under the curve was 0.823. The overall accuracy was 0.931 (95% confidence interval: 0.897-0.956). Severe depression (degree of depression) was the most important variable in the prediction model, followed by diminished appetite, subthreshold (degree of depression), ideas or acts of self-harm or suicide, outpatient status, age, psychomotor retardation or agitation, and others. In conclusion, the machine-learning-based model predicted concurrent psychotic symptoms in patients with major depression in connection with the "severity psychosis" hypothesis.

Machine Learning Algorithm-Based Prediction Model for the Augmented Use of Clozapine with Electroconvulsive Therapy in Patients with Schizophrenia.

The augmentation of clozapine with electroconvulsive therapy (ECT) has been an optimal treatment option for patients with treatment- or clozapine-resistant schizophrenia. Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics survey, which was the largest international psychiatry research collaboration in Asia, our study aimed to develop a machine learning algorithm-based substantial prediction model for the augmented use of clozapine with ECT in patients with schizophrenia in terms of precision medicine. A random forest model and least absolute shrinkage and selection operator (LASSO) model were used to develop a substantial prediction model for the augmented use of clozapine with ECT. Among the 3744 Asian patients with schizophrenia, those treated with a combination of clozapine and ECT were characterized by significantly greater proportions of females and inpatients, a longer duration of illness, and a greater prevalence of negative symptoms and social or occupational dysfunction than those not treated. In the random forest model, the area under the curve (AUC), which was the most preferred indicator of the prediction model, was 0.774. The overall accuracy was 0.817 (95% confidence interval, 0.793−0.839). Inpatient status was the most important variable in the substantial prediction model, followed by BMI, age, social or occupational dysfunction, persistent symptoms, illness duration > 20 years, and others. Furthermore, the AUC and overall accuracy of the LASSO model were 0.831 and 0.644 (95% CI, 0.615−0.672), respectively. Despite the subtle differences in both AUC and overall accuracy of the random forest model and LASSO model, the important variables were commonly shared by the two models. Using the machine learning algorithm, our findings allow the development of a substantial prediction model for the augmented use of clozapine with ECT in Asian patients with schizophrenia. This substantial prediction model can support further studies to develop a substantial prediction model for the augmented use of clozapine with ECT in patients with schizophrenia in a strict epidemiological context.

Relationship Between Body Mass Index and Extrapyramidal Symptoms in Asian Patients with Schizophrenia: The Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP).

BACKGROUND: Although an inverse relationship between body mass index (BMI) and Parkinson disease (PD) has been repeatedly reported, to our knowledge, the relationship between BMI and antipsychotic-induced extrapyramidal symptoms (EPS) has rarely been studied in patients with schizophrenia. Our study aimed to evaluate the relationship between BMI and EPS in patients with schizophrenia. SUBJECTS AND METHODS: Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP) study, we compared the prevalence of EPS in 1448 schizophrenia patients stratified as underweight, normal range, overweight pre-obese, overweight obese I, overweight obese II, and overweight obese III according to the World Health Organization (WHO) classification system for body weight status, and with underweight, normal range, overweight at risk, overweight obese I, and overweight obese II according to the Asia-Pacific obesity classification. RESULTS: In the first step of the WHO classification system for body weight status, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with greater rates of bradykinesia and muscle rigidity, and a lower rate of gait disturbance. In the second step of the Asia-Pacific obesity classification, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with a higher rate of muscle rigidity. CONCLUSION: Findings of the present study consistently revealed that underweight was associated with a greater rate of muscle rigidity in a stepwise pattern among Asian patients with schizophrenia. Although the mechanism underlying the inverse relationship between BMI and muscle rigidity cannot be sufficiently explained, it is speculated that low BMI may contribute to the development of muscle rigidity regardless of antipsychotic "typicality" and dose in patients with schizophrenia.

QT interval prolongation noted in one percent of 2553 Asian patients with schizophrenia: Findings from the REAP-AP survey.

Although the association between antipsychotic use and corrected QT interval (QTc) prolongation has been repeatedly confirmed, the relationship has been rarely studied in a practical setting. Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP) survey, our study aimed to investigate the prevalence and clinical correlates of QTc prolongation in 2553 Asian patients with schizophrenia. After adjusting for the potential effect of confounding factors, the baseline and clinical characteristics of the schizophrenia patients with and without QTc prolongation were compared using analyses of covariance and binary logistic analyses. In addition, a binary logistic analysis model with a forward selection method was used to identify the distinctive clinical correlates of QTc prolongation. QTc prolongation was noted in 1.1% of Asian patients with schizophrenia. Schizophrenia patients were characterized by lower proportions of disorganized speech and negative symptoms; higher use of amisulpride and clozapine; and higher proportions of rigidity, hypercholesterolemia, and sedation than those without QTc prolongation. Finally, a binary logistic mode showed that amisulpride, clozapine, rigidity, and hypercholesterolemia might be the distinctive clinical correlates of QTc prolongation in Asian patients with schizophrenia. These findings indicate the clinical implications that the uses of amisulpride and clozapine and the occurrences of rigidity and hypercholesterolemia may be potential risk factors for QTc prolongation of schizophrenia patients.

Coprescription of mood stabilizers in schizophrenia, dosing, and clinical correlates: An international study.

OBJECTIVE: Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses). METHODS: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates. RESULTS: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses. CONCLUSIONS: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.

Patterns of long acting injectable antipsychotic use and associated clinical factors in schizophrenia among 15 Asian countries and region.

INTRODUCTION: Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established. METHODS: Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region. RESULTS: Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications. DISCUSSION: These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.

Network analysis of the depressive symptom profiles in Asian patients with depressive disorders: Findings from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD).

AIM: We aimed to estimate the network structures of depressive symptoms using network analysis and evaluated the geographic regional differences in theses network structures among Asian patients with depressive disorders. METHODS: Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD), the network of the ICD-10 diagnostic criteria for depressive episode was estimated from 1174 Asian patients with depressive disorders. The node strength centrality of all ICD-10 diagnostic criteria for a depressive episode was estimated using a community-detection algorithm. In addition, networks of depressive symptoms were estimated separately among East Asian patients and South or Southeast Asian patients. Moreover, networks were estimated separately among Asian patients from high-income countries and those from middle-income countries. RESULTS: Persistent sadness, fatigue, and loss of interest were the most centrally situated within the network of depressive symptoms in Asian patients with depressive disorders overall. A community-detection algorithm estimated that when excluding psychomotor disturbance as an outlier, the other nine symptoms formed the largest clinically meaningful cluster. Geographic and economic variations in networks of depressive symptoms were evaluated. CONCLUSION: Our findings demonstrated that the typical symptoms of the ICD-10 diagnostic criteria for depressive episode are the most centrally situated within the network of depressive symptoms. Furthermore, our findings suggested that cultural influences related to geographic and economic distributions of participants could influence the estimated depressive symptom network in Asian patients with depressive disorders.

Predicting Symptomatic and Functional Improvements over 1 Year in Patients with First-Episode Psychosis Using Resting-State Electroencephalography.

OBJECTIVE: Although early intervention from the beginning of a psychotic episode is essential for a better prognosis, biomarkers predictive of symptomatic and functional improvement in early psychotic disorders are lacking. This study aimed to investigate whether the spectral power of resting-state electroencephalography (EEG) can be used as a predictive marker of the 1-year prognosis in patients with first-episode psychosis (FEP). METHODS: Twenty-four patients with FEP and matched healthy control (HC) subjects were examined with resting-state EEG at baseline. The symptomatic severity and functional status of FEP patients were assessed at baseline and reassessed after 1 year of usual treatment. Repeated measures analysis of variance was conducted to compare EEG spectral powers across the groups. Multiple regression analysis revealed EEG spectral powers predictive of symptomatic and functional improvement in FEP patients at the 1-year follow-up. RESULTS: Delta band power in the frontal and posterior regions was significantly higher in patients with FEP than in HCs. Higher delta band power in the posterior region predicted later improvement of positive symptoms and general functional status. Lower delta band power in the frontal region predicted improvement of negative symptoms and general functioning after 1 year. CONCLUSION: These results suggest that increased delta absolute power is observed from the beginning of psychotic disorders. Furthermore, decreased delta power in the frontal region and increased delta power in the posterior region might be used as a predictive marker of a better prognosis of FEP, which would aid early intervention in clinical practice.

Electroconvulsive shock restores the decreased coverage of brain blood vessels by astrocytic endfeet and ameliorates depressive-like behavior.

BACKGROUND: Although growing evidence indicates that ECT affects astrocytes, the exact mechanisms of the therapeutic effect of ECT are still unknown. Astrocytic endfeet express the water channel aquaporin (AQP) 4 abundantly and ensheath brain blood vessels to form gliovascular units. It has been shown that the coverage of blood vessels by AQP4-immunostained endfeet is decreased in the prefrontal cortex (PFC) of patients with major depression. This study was made to determine whether ECT restores the astrocytic coverage of blood vessels with amelioration of depressive symptoms. METHODS: After electroconvulsive shock (ECS) administration to rats, the forced swimming test (FST) and Y-maze test were performed. Subsequently, immunofluorescence analysis was conducted to measure the coverage of blood vessels by astrocytic endfeet in the PFC and hippocampus by using the endothelial cell marker lectin and anti-AQP4 antibody. We also performed Western blot to examine the effects of ECS on the hippocampal expression of AQP4 and the tight junction molecule claudin-5. RESULTS: Gunn rats showed learned helplessness and impaired spatial working memory, compared to normal control Wistar rats. ECS significantly improved the depressive-like behavior. Gunn rats showed a decrease in astrocytic coverage of blood vessels, that was significantly increased by ECS. ECS significantly increased expression of AQP4 and claudin-5 in Gunn rats. CONCLUSIONS: ECS increased the reduced coverage of blood vessels by astrocytic endfeet in the mPFC and hippocampus with amelioration of depressive-like behavior. Therefore, therapeutic mechanism of ECT may involve restoration of the impaired gliovascular units by increasing the astrocytic-endfoot coverage of blood vessels.

Psychotropic drug-prescribing correlates of disorganized speech in Asians with schizophrenia: The REAP-AP study.

BACKGROUND: Although disorganized speech is seen as one of the nuclear features of schizophrenia, there have been few reports of disorganized speech-associated psychotropic drug-prescribing patterns in large samples of schizophrenia patients. OBJECTIVE: We aimed to examine the prevalence of disorganized speech and its correlates in terms of psychotropic drug prescribing, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. METHOD: A total of 3744 patients with the ICD-10 diagnosis of schizophrenia were enrolled from 71 survey centers in 15 Asian countries/areas. An essential criterion of disorganized speech was that it was "severe enough to impair substantially effective communication" as defined in the DSM-5. A binary logistic model was fitted to identify the psychotropic drug-prescribing correlates of disorganized speech. RESULTS: After adjusting for the potential effects of confounding variables, the binary logistic regression model showed that the presence of disorganized speech was directly associated with adjunctive use of mood stabilizers (P < 0.001) and cumulative diazepam equivalent dose (P < 0.0001), and inversely associated with adjunctive use of anti-Parkinson drugs (P < 0.0001). CONCLUSION: The association between disorganized speech and adjunctive use of mood stabilizers could perhaps be understood in the context of a relationship with impulsiveness/aggressiveness, or in terms of deconstructing the Kraepelinian dualism.

Concurrent antipsychotic use in older adults treated with antidepressants in Asia.

AIM: Depressive disorders are common in old age. Antipsychotics (APs) are often used as an adjunctive treatment with antidepressants (ADs) in this population but its patterns of use in Asia are not known. This study explored the rate of combination of APs and ADs in older adult psychiatric patients in Asia. METHODS: This is a secondary analysis of the database of a multicentre study which recorded participants' basic demographical and clinical data in standardised format in 10 Asian countries and territories. The data were analysed using univariate and multivariate logistic regression analyses. RESULTS: A total of 955 older adult psychiatric in- and outpatients were included in this study. The proportion of concurrent AP and AD use was 32.0%, ranging from 23.3% in Korea to 44.0% in Taiwan. Multivariate logistic regression analysis found that younger age, inpatient status and diagnosis of schizophrenia, anxiety and other mental disorders were significantly related to a higher proportion of concurrent use of APs and ADs. CONCLUSION: Around a third of older adult psychiatric patients had concurrent AP and AD use in the Asian countries/regions surveyed. Considering the uncertain effectiveness and questionable safety of the AP and AD combination in this patient population, such should be cautiously used.

Concurrent benzodiazepine use in older adults treated with antidepressants in Asia.

ABSTRACTBackground:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates. METHODS: The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed. RESULTS: The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants. CONCLUSIONS: Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

Physical comorbidities in older adults receiving antidepressants in Asia.

BACKGROUND: The present study explored the patterns of physical comorbidities and their associated demographic and clinical factors in older psychiatric patients prescribed with antidepressants in Asia. METHODS: Demographic and clinical information of 955 older adults were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Standardized data collection procedure was used to record demographic and clinical data. RESULTS: Proportion of physical comorbidities in this cohort was 44%. Multiple logistic regression analyses showed that older age (OR = 1.7, P < 0.001), higher number of depressive symptoms (OR = 1.09, P = 0.016), being treated in psychiatric hospital (OR = 0.5, P = 0.002), living in high income countries/territories (OR = 2.4, P = 0.002), use of benzodiazepines (OR = 1.4, P = 0.013) and diagnosis of 'other psychiatric disorders' (except mood, anxiety disorders and schizophrenia) (OR = 2.7, P < 0.001) were significantly associated with physical comorbidities. CONCLUSIONS: Physical comorbidities in older patients prescribed with antidepressants were common in Asia. Integrating physical care into the treatment of older psychiatric patients should be urgently considered.

Clinical Characteristics and Psychotropic Prescribing Patterns Associated with impaired Concentration in Asians with Depressive Disorders: The REAP-AD Study.

The Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) study aimed to survey and review antidepressant prescribing patterns in different clinical settings in Asian countries/areas. The REAP-AD study collected comprehensive data for psychiatric patients prescribed antidepressants in 10 Asian countries/areas during the period from March to June 2013. Depressive disorders have been an important issue closely associated with ill-health and disability in the realm of mental health. Impaired concentration was found to be a consistent symptom in depressive disorders regardless of clinical course, and a predictor of poor treatment outcome. In this work we aimed to identify clinical characteristics independently associated with impaired concentration in patients with depressive disorders, using data from the REAP-AD study. A total of 336 depressive disorder patients with impaired concentration and 786 depressive disorder patients without impaired concentration were recruited from 40 centers in 10 Asian countries/areas. A binary logistic regression model was fitted to identify the independent correlates of impaired concentration in patients with depressive disorders. After adjusting the effects of covariates, the binary logistic model showed that impaired concentration was independently associated with higher rates of loss of interest (P < 0.0001), fatigue (P < 0.0001), low self-confidence (P < 0.0001) and appetite disturbance (P < 0.0001) and with a lower rate of adjunctive antipsychotic prescription (P = 0.007). Our findings suggest that impaired concentration and its associated depressive symptom profiles constitute a unitary depressive symptom cluster that is also an intervening variable for poor social function.

A comparison of clinical characteristics of older adults treated with antidepressants in general and psychiatric hospitals in Asia.

AIM: This study compared the demographics, clinical characteristics, and antidepressant prescription patterns between Asian patients aged 50 years and older attending psychiatric hospitals and those attending general hospitals. METHODS: In total, 955 patients (604 in general hospitals, 351 in psychiatric hospitals) aged 50 years or older treated with antidepressants in 10 Asian countries and territories were examined. Patients' demographics, clinical features, and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. RESULTS: Binary logistic regression revealed that high income and diagnosis of schizophrenia were independently associated with psychiatric hospital treatment, whereas outpatient care, diagnosis of anxiety disorders, and multiple major medical conditions were independently associated with general hospital treatment. In addition, tetracyclic and noradrenergic and specific serotonergic antidepressants were more likely to be prescribed in general hospitals. CONCLUSION: Older adults treated with antidepressants showed different demographic and clinical features between general hospitals and psychiatric hospitals in Asia.

Clinical Use of Mood Stabilizers With Antidepressants in Asia: Report From the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) Projects in 2004 and 2013.

OBJECTIVE: As most reports concerning treatment with combinations of mood stabilizer (MS) with antidepressant (AD) drugs are based in the West, we surveyed characteristics of such cotreatment in 42 sites caring for the mentally ill in 10 Asian countries. METHODS: This cross-sectional, pharmacoepidemiologic study used 2004 and 2013 data from the REAP-AD (Research Study on Asian Psychotropic Prescription Patterns for Antidepressants) to evaluate the rates and doses of MSs given with ADs and associated factors in 4164 psychiatric patients, using standard bivariate methods followed by multivariable logistic regression modeling. RESULTS: Use of MS + AD increased by 104% (5.5% to 11.2%) between 2004 and 2013 and was much more associated with diagnosis of bipolar disorder than major depression or anxiety disorder, as well as with hospitalization > outpatient care, psychiatric > general-medical programs, and young age (all P < 0.001), but not with country, sex, or AD dose. CONCLUSIONS: The findings provide a broad picture of contemporary use of MSs with ADs in Asia, support predictions that such treatment increased in recent years, and was associated with diagnosis of bipolar disorder, treatment in inpatient and psychiatric settings, and younger age.

Factors Associated With Antidepressant Dosing in Asia: Findings From the Research on Asian Psychotropic Prescription Study.

In this study, we sought to examine factors associated with dosing of antidepressants (ADs) in Asia. Based on reported data and clinical experience, we hypothesized that doses of ADs would be associated with demographic and clinical factors and would increase over time. This cross-sectional, pharmacoepidemiological study analyzed data collected within the Research Study on Asian Psychotropic Prescription Pattern for Antidepressants from 4164 participants in 10 Asian countries, using univariate and multivariate methods. The AD doses varied by twofold among countries (highest in PR China and RO Korea, lowest in Singapore and Indonesia), and averaged 124 (120-129) mg/d imipramine-equivalents. Average daily doses increased by 12% between 2004 and 2013. Doses were significantly higher among hospitalized patients and ranked by diagnosis: major depression > anxiety disorders > bipolar disorder, but were not associated with private/public or psychiatric/general-medical settings, nor with age, sex, or cotreatment with a mood stabilizer. In multivariate modeling, AD-dose remained significantly associated with major depressive disorder and being hospitalized. Doses of ADs have increased somewhat in Asia and were higher when used for major depression or anxiety disorders than for bipolar depression and for hospitalized psychiatric patients.

Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat.

BACKGROUND: Although electroconvulsive therapy (ECT) is regarded as one of the efficient treatments for intractable psychiatric disorders, the mechanism of therapeutic action remains unclear. Recently, many studies indicate that ECT affects the immune-related cells, such as microglia, astrocytes, and lymphocytes. Moreover, microglial activation and astrocytic activation have been implicated in the postmortem brains of schizophrenia patients. We previously demonstrated that Gunn rats showed schizophrenia-like behavior and microglial activation in their brains. The present study examined the effects of electroconvulsive shock (ECS), an animal counterpart of ECT, on schizophrenia-like behavior, microgliosis, and astrogliosis in the brain of Gunn rats. METHODS: The rats were divided into four groups, i.e., Wistar sham, Wistar ECS, Gunn sham, and Gunn ECS. ECS groups received ECS once daily for six consecutive days. Subsequently, prepulse inhibition (PPI) test was performed, and immunohistochemistry analysis was carried out to determine the activation degree of microglia and astrocytes in the hippocampus by using anti-CD11b and anti-glial fibrillary acidic protein (GFAP) antibody, respectively. RESULTS: We found PPI deficit in Gunn rats compared to Wistar rats, and it was significantly improved by ECS. Immunohistochemistry analysis revealed that immunoreactivity of CD11b and GFAP was significantly increased in Gunn rats compared to Wistar rats. ECS significantly attenuated the immunoreactivity of both CD11b and GFAP in Gunn rats. CONCLUSIONS: ECS ameliorated schizophrenia-like behavior of Gunn rats and attenuated microgliosis and astrogliosis in the hippocampus of Gunn rats. Accordingly, therapeutic effects of ECT may be exerted, at least in part, by inhibition of glial activation. These results may provide crucial information to elucidate the role of activated glia in the pathogenesis of schizophrenia and to determine whether future therapeutic interventions should attempt to up-regulate or down-regulate glial functions.

Country variations in depressive symptoms profile in Asian countries: Findings of the Research on Asia Psychotropic Prescription (REAP) studies.

INTRODUCTION: This study was to assess differences in the symptom profile of depressive illness across various countries/territories in Asia. The study was a part of the Research on Asia Psychotropic Prescription project. The participating countries/territories include China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand. METHODS: The pattern of depressive symptoms in 1,400 subjects with depressive disorder from 42 psychiatric centers in 10 Asian countries/territories was assessed. We collected information on socio-demographic and clinical characteristics with a standardized protocol and data collection procedure. RESULTS: The most common presentations of depressive symptoms were persistent sadness, loss of interest, and insomnia. Similar findings were found regardless of the region, country, or its income level. Patients with depressive disorder from high-income countries presented significantly more with vegetative symptom cluster (P < 0.05), while those from the upper middle-income countries had significantly more with both mood (P < 0.001) and cognitive symptom clusters (P < 0.01). In lower middle-income countries, patients with depressive symptoms had significantly less mood symptom cluster (P < 0.001) but significantly more cognitive symptom cluster (P < 0.05). DISCUSSION: This study demonstrates that in Asia, despite variations in the initial symptom reported by the patients, across different countries/territories, core depressive symptoms remain the same. Variations have been found in presentation of depressive symptoms with regards to the level of income of countries. Physical or vegetative symptoms were reported more by centers in higher income countries, while depressive cognition and suicidal thoughts/acts were more frequently reported from lower income countries.