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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., (© 2020 John Wiley & Sons Australia, Ltd.)

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., (© 2020 John Wiley & Sons Ltd.)

Adolescence is a critical neurodevelopmental period for both excitatory and inhibitory (E/I) neurotransmission and often witnesses the typical onsets of schizophrenia. One possibility is that disruptions in adolescent neurodevelopmental processes may produce schizophrenia-like behavioral and neurobiological abnormalities. We previously reported that subchronic treatment of adolescent animals with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 induced cognitive deficits and reduced interneuron densities in rat medial prefrontal cortex, and these changes persisted one week after MK-801 exposure. However, it remains unclear how this treatment may affect E/I balance in hippocampus, which has long been associated with the pathophysiology of schizophrenia. Here, we examined hippocampal E/I biomarkers in adolescent rats treated with MK-801 (0.2 mg/kg, i.p., 14 days) and found increases in the ratio of the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular gamma-aminobutyric acid (GABA) transporter (VGAT) 24 h and 7 days after MK-801 exposure. Interestingly, the increased VGluT1/VGAT ratio at the two time points was driven by upregulated VGluT1 expression and downregulated VGAT expression, respectively. The decrease in VGAT expression persisted 14 days after MK-801 exposure and recovered two weeks later. No alterations in hippocampal interneuron densities were observed. Behaviorally, the treatment decreased prepulse inhibition at 24 h but not 14 days, after MK-801 exposure. Taken together, these results demonstrate that subchronic NMDA receptor blockade during adolescence induces long-term, but not permanent, E/I imbalance in the rat hippocampus, which could be attributed to the dysregulation of glutamatergic transmission in the short term and of GABAergic transmission in the long term., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Both symptom control and functional improvement are important goals in schizophrenia treatment. A post hoc analysis of an 8-week, open-label, single-arm, multi-center study of paliperidone-extended release formulation was conducted to evaluate the correlation between personal/social functioning and symptom control in the acute phase, and to identify factors associated with psychosocial functioning, in patients with acute schizophrenia. Of 608 enrolled patients, 602 (99%) were included in the full analysis set. Correlation and regression analyses were applied to identify the association of Personal and Social Performance (PSP) total scores with Positive and Negative Syndrome Scale (PANSS) total scores and other factors. A significant negative correlation was observed between PSP and PANSS at all visits (week 1: r = -0.55; week 2: r = -0.79, p < 0.0001). Patients with PSP score improvement (≥10 point) showed a higher possibility of symptom improvement (PANSS reduction ≥30%). Duration of illness, PANSS Marder factors, and satisfaction with prior treatment, sleep quality, and daytime drowsiness influenced change in PSP total score at endpoint. These results suggest symptom outcome as an important factor to predict functional improvement in acute schizophrenia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A new self-rating functional scale (SRFS) was developed to assess the functionality of patients with schizophrenia, referred to the structure of Personal and Social Performance Scale (PSP). The main aim of this study was to evaluate the reliability and validity of the SRFS. A total of 210 patients with schizophrenia were recruited from outpatient clinics in six sites in China. Demographic information, SRFS, PSP, World Health Organization Disability Assessment Schedule II, and Positive and Negative Syndrome Scale were assessed. Spearman's correlation coefficient and path analysis were used to assess the reliability and validity of the SRFS. Cronbach's α coefficient was used to assess the internal consistency reliability. Cronbach's α was 0.83, and ranged from 0.80 to 0.82 stably, indicating that the scale was reliable in internal consistency. Spearman's correlation coefficient between split two parts was 0.68 (P<0.01), suggesting a moderate to strong split-half reliability. The standardized regression coefficients ranged from 0.48 to 0.79, indicating moderate construct validity. Spearman's correlation coefficients between SRFS and PSP, World Health Organization Disability Assessment Schedule II, and Positive and Negative Syndrome Scale are 0.59, 0.65, and 0.47 (all P<0.01), respectively, indicating moderate criteria validities. The SRFS is a reliable and valid instrument for assessing personal and social functionality in patients with schizophrenia.

Objective: This post hoc analysis of an open-label, single-arm, multicenter study was designed to assess the efficacy, safety, and tolerability of paliperidone extended release (ER) in Chinese patients with non-acute schizophrenia, after switching from olanzapine., Methods: Patients with schizophrenia who were dissatisfied with prior olanzapine treatment switched to flexible paliperidone ER (3-12 mg/day) based on clinical judgment. Change from baseline to week 12 in Positive and Negative Syndrome Scale (PANSS) total scores (primary endpoint), PANSS subscale scores, response rate, Clinical Global Impression-Severity (CGI-S) score, personal and social performance (PSP) scores, patient satisfaction with treatment score, change in sleep quality, level of daytime sleepiness and safety were evaluated., Results: Out of 118 enrolled patients, 95 (81%) completed the study. Mean duration of study was 76.9 (23.85) days. The primary endpoint, mean (SD) PANSS total score changed significantly from baseline to endpoint (-19.6 [18.71], P <.0001). Secondary endpoints including PANSS subscale score, PSP, patient satisfaction and daytime drowsiness also significantly improved (P <.001). Most commonly reported (≥1%) treatment-emergent adverse events were akathisia (n = 14 [12%]) and insomnia (n = 9 [8%])., Conclusions: Switching to flexible-dosed paliperidone ER in patients dissatisfied with prior olanzapine treatment achieved good efficacy and tolerability consistently over 12 weeks.

Genome-wide association study results have linked ADCK1 genetic variation with paliperidone efficacy in a European cohort. However, the generalizability of this locus to non-European populations is unknown. Han Chinese schizophrenia patients (n = 159) were treated with paliperidone palmitate and symptom severity was assessed over 3 months. Examination of 13 ADCK1 genetic variants revealed two single nucleotide polymorphisms (rs12590199, rs11159291) and one haplotype (rs2364747-rs12590199) associated with paliperidone palmitate response. Future work into ADCK1's function and its potential interaction with paliperidone is warranted.

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., (© 2018 Japanese Psychogeriatric Society.)

Introduction: To date no study has compared the treatment patterns for schizophrenia specifically between China and Japan. This study examined the cross-national differences in the use of psychotropic drugs and electroconvulsive therapy (ECT) in schizophrenia., Method: Data on 3248 schizophrenia inpatients (n = 1524 in China and n = 1724 in Japan) were collected by either chart review or interviews during the designated 3 study periods between 2001 and 2009. Patients' socio-demographic and clinical characteristics, prescriptions of psychotropic drugs, and ECT use were recorded using a standardized protocol and data collection procedure., Results: Multivariate analyses revealed that compared to their Japanese counterparts, Chinese inpatients had a shorter length of current hospitalization, were significantly less frequently prescribed second-generation antipsychotics (except clozapine), antipsychotic polypharmacy, benzodiazepines, and mood stabilizers, and more likely to receive clozapine, antidepressants, and ECT., Discussion: Substantial variations in inpatient treatment patterns for schizophrenia were found between China and Japan. The common use of ECT and clozapine in Chinese inpatients and the frequent use of antipsychotic polypharmacy and high antipsychotic doses in Japanese inpatients need to be addressed., (© 2017 John Wiley & Sons Australia, Ltd.)

Our previous study demonstrated that there have been changes in the patterns of prescription antipsychotic use in China over the period from 2002 to 2012. The aim of this study was to evaluate whether time trends were present for the prescription of anticholinergic medications (ACMs) during the observation period. A total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were surveyed in 2002, 2006 and 2012. Basic socio-demographic and clinical characteristics and the prescription of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The frequency of ACM prescription was 25.9% in the whole sample (29.5%, 21.6%, and 27.4% in 2002, 2006 and 2012, respectively). In addition, different temporal trends were observed across age groups. Multiple logistic regression analysis of the entire sample showed that ACM prescriptions were predicted by females, outpatients, patients receiving high doses of antipsychotic medication, select study years, benzodiazepine users, patients displaying extrapyramidal side effects, as well as antipsychotic prescription patterns. Although there was more widespread use of second-generation antipsychotics over the past decade, the frequency of ACM use only slightly decreased. How to use ACM appropriately is still a therapeutic issue that needs to foster evidence-based prescription practice., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Little is known about electroconvulsive therapy (ECT) use in the treatment of schizophrenia in China. This study examined the frequency of ECT use, its trend between 2006 and 2012, and its independent demographic and clinical correlates in a nationwide survey in China., Methods: A total of 5162 inpatients in 45 Chinese psychiatric hospitals/centers were interviewed (2696 in 2006 and 2466 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure., Results: Electroconvulsive therapy was used in 6.1% of the whole sample; 4.7% in 2006 and 7.7% in 2012 (P < 0.001) with wide interprovince variations. Multiple logistic regression analyses of the whole sample revealed that patients receiving ECT were more likely to be women, receive second-generation antipsychotics, treated in tertiary referral centers (level III hospitals), had a shorter illness duration, and more positive and depressive symptoms (R = 0.181; P < 0.001)., Conclusions: Electroconvulsive therapy for schizophrenia has increased between 2006 and 2012 in China. Its percentage was higher than the figures reported in most other countries. Reasons for the substantial variations in the frequency of ECT across different provinces in China require further investigations.

Objective: This study examined the pattern of adjunctive antidepressant use in schizophrenia patients and its demographic and clinical correlates in a nationwide survey in China., Methods: Fourteen thousand and thirteen patients in 45 Chinese psychiatric hospitals or centers were interviewed (4,486 in 2002, 5,288 in 2006, and 4,239 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Chi-square test, independent-samples t test, Mann-Whitney U test, and multiple logistic regression analysis were used in data analyses., Results: Antidepressant use was found in 5.2% of the study population with 4.6% in 2002, 4.3% in 2006, and 6.9% in 2012, respectively. A significant increase in use from 2006 to 2012 was found (p < .001). Multiple logistic regression analyses in the whole population revealed that patients receiving adjunctive antidepressants were more likely to be outpatients in tertiary referral centers (level-III hospitals) and who had an earlier age of onset, less severe global illness, but more depressive symptoms. They were less likely to receive first-generation antipsychotics but more likely to receive benzodiazepines (R 2  = 0.255, p < .001)., Conclusions: Despite an increasing trend, the frequency of antidepressant use in schizophrenia in China was considerably lower than in Western countries. The benefits and risks associated with concomitant use of antidepressants in schizophrenia need to be studied further., (Copyright © 2017 John Wiley & Sons, Ltd.)

This study was designed to examine the validity and reliability of the Chinese version of the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX) in patients with schizophrenia taking antipsychotics. It was conducted in a sample of 135 patients aged between 18 and 50 years old and diagnosed with schizophrenia. Demographic data and clinical features were assessed with PRSexDQ, the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI), and the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale. The internal consistency of the Chinese version of PRSexDQ using Cronbach's α was 0.902. The test-retest and inter rater reliability was both high with p<0.001. PRSexDQ was correlated with corresponding items in the UKU Side Effects Rating Scale (Items 4.12-4.16), and showed good sensitivity, specificity, positive and negative predictive value. It could also clearly detect differences in SD rates of three monotherapy groups: patients treated with risperidone had the highest scores, followed by patients treated with olanzapine, whereas patients treated with aripiprazole had the lowest scores. The Chinese version of PRSexDQ is a reliable and valid instrument to assess patients with schizophrenia. Assessed by PRSexDQ, 53.2% of total subjects in our study reported symptoms of SD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: We examined the time trends and correlates of clozapine use in schizophrenia patients in China., Method: A total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were interviewed in 2002, 2006 and 2012. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects, satisfaction with treatment and quality of life (QOL) were recorded in a standardized fashion., Results: Clozapine was used in 32.9% of the whole sample; with corresponding figures of 39.7%, 32.5% and 26.4% in 2002, 2006 and 2012 (p<0.001). Families of clozapine users had lower satisfaction with treatment than those of the non-clozapine group, without significant differences with respect to patients' treatment satisfaction and mental or physical QOL. In multiple logistic regression analyses, compared to the non-clozapine group, patients on clozapine had an earlier age of onset, longer illness duration, more global illness severity and drug-induced central nervous system, gastrointestinal and other side effects, lower antipsychotic doses, less delusions and hallucinations, more negative symptoms, were more likely male, inpatients, to have a family history of psychiatric disorders, receive treatments in regional centers and receive antipsychotic polypharmacy, but less likely to have health insurance and receive first-generation antipsychotics and benzodiazepines (R(2)=0.498, p<0.001)., Conclusions: Clozapine was used in one-third of schizophrenia patients in China, with decreasing frequency since 2002. Patients prescribed clozapine had multiple markers of greater global illness severity/chronicity and decreased satisfaction with treatment by the families, but similar QOL and less delusions and hallucinations than patients not prescribed clozapine., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aims: Little is known about electroconvulsive therapy (ECT) use in Asian inpatients with schizophrenia. This study examined trends of ECT use for schizophrenia patients in Asia between 2001 and 2009 and its independent demographic and clinical correlates., Methods: Data on 6761 hospitalized schizophrenia patients (2001 = 2399, 2004 = 2136, and 2009 = 2226) in nine Asian countries and territories were collected by either chart review or interviews during a 1-month period. Patients' sociodemographic and clinical characteristics, prescriptions of psychotropic drugs and ECT use were recorded using a standardized protocol and data-collection procedure., Results: The frequency of ECT was 3.3% in the whole sample; rising from 1.8% in 2001 to 3.3% in 2004 and 4.9% in 2009 (P < 0.0001). However, this increased trend was driven solely by increased ECT use in China (P < 0.0001), and the inclusion of India in the 2009 survey. There were wide inter-country variations: 2001, 0% (Hong Kong, Korea) to 5.9% (China); 2004, 0% (Singapore) to 11.1% (China); 2009, 0% (Hong Kong) to 13.8% (India) and 15.2% (China). Multiple logistic regression analysis of the whole sample revealed that patients receiving ECT were less likely in the 35-64-year age group, had shorter length of current hospitalization and fewer negative symptoms, and were more likely to receive second-generation antipsychotic medications compared to those who were not treated with ECT (R(2)  = 0.264, P < 0.001)., Conclusions: ECT use for schizophrenia has increased over the past decade in China, being low/relatively stable in other Asian countries/regions. Reasons for substantial variations in ECT frequency in Asia require further study., (© 2015 The Authors. Psychiatry and Clinical Neurosciences © 2015 Japanese Society of Psychiatry and Neurology.)

Objective: Little is known about the pattern of QT interval (QTc) prolongation in Asian patients with schizophrenia. This study examined trends of QTc prolongation in schizophrenia inpatients in six Asian countries and territories between 2004 and 2008/2009 and its independent demographic and clinical correlates., Method: Data on 3482 hospitalized schizophrenia patients (2004 = 1826 and 2008/2009 = 1656) in six Asian countries and territories were collected by either chart review or interviews during a 1-month period. Patients' sociodemographic and clinical characteristics, prescriptions of psychotropic drugs, and QTc interval were recorded using a standardized protocol and data collection procedure., Results: The frequency of QTc prolongation (>456 ms) was 2.4% in the whole sample, decreasing from 3.1% in 2004 to 1.6% in 2008/2009 (p = 0.004) with wide intercountry variations. However, this decreased trend was driven by decreased QTc prolongation detected in China and Hong Kong (both p-values < 0.05). Multiple logistic regression analysis of the whole sample revealed that patients having more likely to have an illness lasting longer than 5 years and received antipsychotics classified as list-1 drugs according to the Arizona Centre for Education and Research on Therapeutics. Compared with 2004, patients in 2008/2009 were less likely to have QTc prolongation. Thioridazine caused QTc prolongation most frequently (odds ratio (OR) 4.4; 95% confidence interval (CI) 1.2-15.2), followed by sulpiride (OR 2.4; 95% CI 1.3-4.5), clozapine (OR 2.4; 95% CI 1.4-4.2), and chlorpromazine (OR 1.9; 95% CI 1.07-3.5)., Conclusions: Frequency of QTc prolongation was low in Asian patients with schizophrenia. QTc prolongation in schizophrenia decreased in China and Hong Kong between 2004 and 2008/2009 but increased in Taiwan over the same period, remaining low in the other countries., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: This study examined the use, demographic and clinical correlates of antipsychotic polypharmacy (APP) and its associations with treatment satisfaction and quality of life (QOL) in schizophrenia patients in China., Method: A total of 4239 patients in 45 nationwide Chinese psychiatric hospitals/centers were interviewed in 2012 in the third cross-sectional study, with the first two having been conducted in 2002 and 2006. Patients' socio-demographic and clinical characteristics, including psychopathology, side effects, satisfaction with treatment and QOL, were recorded using a standardized protocol and data collection procedure., Results: The proportion of APP prescriptions in 2012 was 34.2%, which was significantly higher than the frequency of APP in 2002 (26.1%) and 2006 (26.4%) (p<0.001). Of patients on APP, 91.1% received two antipsychotics, 8.6% received three and 0.3% received four or more antipsychotics. Multiple logistic regression analyses revealed that compared to those on antipsychotic monotherapy, patients on APP and their families had lower satisfaction with treatment, had higher QOL in the mental domain, younger age of onset, more side effects, higher doses of antipsychotics and were more likely to receive first-generation antipsychotics and less likely to receive benzodiazepines (total R (2)=0.31, p<0.001)., Conclusions: APP was found in about one in three schizophrenia patients. The prevalence of APP seems to have been increasing since 2002. Considering the increased frequency of drug-induced side effects and the patients' and their relatives' dissatisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of APP and its alternatives is warranted., (© The Royal Australian and New Zealand College of Psychiatrists 2014.)

Background and Objective: The extended-release formulation of quetiapine (quetiapine XR), which was developed to provide more convenient once-daily administration, has been widely studied to characterize its pharmacokinetics in Caucasian populations but has rarely been studied in an Asia population. This study was conducted to evaluate the pharmacokinetics and tolerability of quetiapine XR administered as a single dose (300 mg) and multiple doses (300, 600, and 800 mg) in Han Chinese patients with schizophrenia., Methods: This was a single-center, open-label, single-dose and multiple-dose randomized study. Among the 55 randomized subjects, a total of 40 female or male patients in 300 mg (n = 13), 600 mg (n = 13), or 800 mg (n = 14) groups completed the study of quetiapine fumarate XR. The treatment phase consisted of 5 consecutive days and was preceded by a 1- to 2-day titration period for the 600 and 800 mg groups. Pharmacokinetic parameters for both quetiapine and N-desalkyl quetiapine (norquetiapine) were determined. The tolerability evaluation included adverse events (AEs) noted by monitoring, physical examinations, vital signs, and clinical laboratory tests., Results: N-desalkyl quetiapine was formed from quetiapine with an approximate metabolite to parent ratio of 0.5 across the three dose groups. The geometric mean elimination half-life (t ½) of both quetiapine and N-desalkyl quetiapine was consistent for the three dosing groups (approximately 7 h for quetiapine and approximately 18 h for N-desalkyl quetiapine). The geometric mean maximum plasma concentrations (C max) at steady state (C max,ss) of quetiapine for the three groups were 467, 740, and 1,126 ng/mL, respectively, and for N-desalkyl quetiapine were 138, 262, and 426 ng/mL, respectively. The values for the geometric mean area under the plasma concentration-time curve over a dosing interval at the steady-state (AUCss) of quetiapine were 5,094, 7,685, and 13,237 ng·h/mL, respectively, and for N-desalkyl quetiapine were 2,284, 4,341, and 7,216 ng·h/mL, respectively. The apparent oral clearance (CL/F) of quetiapine at steady state appeared to be comparable across the three dose groups. The pharmacokinetics of quetiapine XR were dose-proportional across the dosage range employed. The most common AE was somnolence, but all of the reported AEs were mild. There were no serious AEs or other significant AEs., Conclusion: Quetiapine fumarate XR has a dose-proportional pharmacokinetic profile at doses ranging from 300 to 800 mg once daily, and a slower time to reach C max and steady state after 3 days of sequential dosing. Therefore, it offers a simple and rapid dose-escalation option and more convenient once-daily administration. The three dosages of quetiapine fumarate XR were generally well-tolerated in this pharmacokinetic study of Han Chinese patients with schizophrenia.

Objective: This study aimed to examine the use of high doses of antipsychotic medications (≥600 mg/day chlorpromazine equivalent) in older Asian patients with schizophrenia and its demographic and clinical correlates., Method: Information on hospitalized patients with schizophrenia aged ≥50 years was extracted from the database of the Research on Asian Psychotropic Prescription Patterns study (2001-2009). Data on 2203 patients in six Asian countries and territories, including China, Hong Kong, Japan, Korea, Singapore and Taiwan, were analyzed. Socio-demographic and clinical characteristics and antipsychotic prescriptions were recorded., Results: The frequency for high-dose antipsychotic medications was 36.0% overall, with 38.4% in 2001, 33.3% in 2004 and 36.0% in 2009. Multiple logistic regression analysis of the whole sample showed that compared to patients receiving low-medium antipsychotic doses, those on high doses had a longer illness duration (odds ratio (OR): 2.0, 95% confidence interval (CI):1.2-3.3, p = 0.008), were more likely in the 50-59-year group (OR: 0.95, 95% CI: 0.94-0.97, p < 0.001), more often had current positive (OR: 1.5, 95% CI: 1.2-1.8, p < 0.001) or negative symptoms (OR: 1.3, 95% CI: 1.03-1.6, p = 0.03), and more commonly received antipsychotic polypharmacy (OR: 5.3, 95% CI: 4.1-6.7, p < 0.001). Extrapyramidal symptoms (p = 0.25) and tardive dyskinesia (p = 0.92) were not more frequent in the high-dose group., Conclusions: High doses of antipsychotic medications were used in more than one third of older Asian patients with schizophrenia. The reasons for the frequent use of high antipsychotic doses in older Asian patients warrant further investigation., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: To date there has been no large-scale international study that examined the use of clozapine in older patients with schizophrenia. This study examined the use of clozapine and its demographic and clinical correlates in older patients with schizophrenia in East Asia during the period between 2001 and 2009., Method: Information on 1,157 hospitalized patients with schizophrenia aged 50 or older in five East Asian countries and territories (China, Hong Kong, Korea, Singapore and Taiwan) was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) project. Socio-demographic and clinical characteristics and prescription of psychotropic medications were recorded., Results: Clozapine was prescribed for 20.6% of the pooled sample; 19.0% in 2001, 19.4% in 2004 and 22.9% in 2009. Multiple logistic regression analysis of the whole sample revealed that patients taking clozapine had a longer duration of illness, more negative symptoms and were less likely to receive first generation antipsychotic and anticholinergic drugs, but more likely to report weight gain compared to those not receiving clozapine. Compared to those in other sites, older patients in China were more likely to receive clozapine., Conclusions: The prescription of clozapine for older Asian schizophrenia inpatients has remained at a stable level during the past decade. The appropriateness of use of clozapine in China needs to be further explored.

Introduction: Little is known about the prescription patterns of adjunctive antidepressants in Asian schizophrenia patients. This study aimed to examine trends in the use of antidepressants and their demographic and clinical correlates in the treatment of schizophrenia in Asia between 2001 and 2009., Methods: A total of 6,761 hospitalized schizophrenia patients in nine 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 antidepressant prescription was 6.8% in the whole sample; 5.3% in 2001, 6.5% in 2004 and 8.7% in 2009. There were wide inter-country variations at each survey ranging from 0.9% in Hong Kong to 15.3% in Singapore in 2001; from 1.9% in Korea to 15.4% in Singapore in 2004; and from 2.7% in Japan to 22.0% in Singapore in 2009. Multiple logistic regression analysis of the whole sample revealed that patients on antidepressants were younger, more likely to receive benzodiazepines and have significant extrapyramidal side-effects and less likely to have significant positive symptoms., Discussion: Unlike findings in Western countries, adjunctive antidepressant prescription for schizophrenia was not common in Asia. The frequency of antidepressant prescription varied among countries and territories, suggesting that a host of clinical and socio-cultural factors played a role in determining antidepressant use in Asia., (Copyright © 2012 Wiley Publishing Asia Pty Ltd.)

Objective: This study surveyed the use of anticholinergic medications (ACMs) in older Asian patients with schizophrenia and examined its demographic and clinical correlates., Method: A total of 1452 hospitalized patients with schizophrenia aged 55 years or older in nine Asian countries and territories were surveyed between 2001 and 2009. The cross-sectional data of patients' socio-demographic and clinical characteristics and the prescriptions of antipsychotic drugs and ACM were recorded using a standardized protocol and data collection procedure., Results: The frequency of ACM prescription was 64.6% in the pooled sample, with 72.4%, 61.9%, and 59.5% in 2001, 2004, and 2009, respectively. Multiple logistic regression analysis of the whole sample revealed that patients on ACM had a higher dose of antipsychotic medications, and were more likely to have extrapyramidal side effects and receive first-generation antipsychotic medications., Conclusions: Anticholinergic medications were frequently used in older Asian patients with schizophrenia. Considering the potential side effects of ACM, the rationale for their widespread use in this patient population should be revisited., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: The aim of this study was to survey the use of antipsychotic polypharmacy (APP) in older Asian patients with schizophrenia and examine its demographic and clinical correlates., Methods: Information on hospitalized patients with schizophrenia aged 55 or older was extracted from the database of the Research on Asian Psychotropic Prescription Patterns study. Data on 1439 patients in 6 Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, and Taiwan were analyzed. Sociodemographic and clinical characteristics and antipsychotic prescriptions were recorded using a standardized protocol and data collection procedure., Results: The frequency of APP prescription was 51.6% in the pooled sample with wide intercountry variations. Multiple logistic regression analysis of the whole sample showed that patients on APP had higher antipsychotic doses and also were more likely to receive first-generation antipsychotics., Conclusions: Use of APP was common in older Asian patients with schizophrenia. Given the limited evidence supporting its efficacy, the potentially severe side effects and high costs, APP should be used with caution in this population. The reasons for and outcomes of the use of APP in this patient population merit further exploration.

Objective: This study examined the prescribing patterns of several first- (FGAs) and second-generation antipsychotic (SGAs) medications administered to older Asian patients with schizophrenia during the period between 2001 and 2009., Method: Information on hospitalized patients with schizophrenia aged 65 or older was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001-2009). There were no older patients in Thailand, therefore data on 467 patients in eight Asian countries and territories including China, Hong Kong SAR, India, Japan, Korea, Malaysia, Singapore, and Taiwan were analysed. Cross-sectional socio-demographic data, clinical characteristics and antipsychotic prescriptions were assessed using a standardized protocol and data collection procedure., Results: Of the 467 patients, 192 patients (41.1%) received FGAs only, 166 (35.5%) received SGAs only and 109 (23.3%) received a combination of FGAs and SGAs. Of the FGAs, haloperidol was the most commonly used (31.3%; mean 9.4 ± 6.7 mg/day), followed by chlorpromazine (15.4%; mean 126.4 ± 156.4 mg/day) and sulpiride (6.6%; mean 375.0 ± 287.0 mg/day). Of the SGAs, risperidone was the most commonly used (31.5%; mean 4.5 ± 2.7 mg/day), followed by olanzapine (13.1%; mean 13.6 ± 6.5 mg/day), quetiapine (7.3%; mean 325.0 ± 237.3 mg/day) and aripiprazole (1.9%; mean 17.6 ± 7.7 mg/day)., Conclusions: FGAs and higher doses of certain SGAs (risperidone, olanzapine and quetiapine) were still commonly dispensed to older Asian patients with schizophrenia. Considering older patients' reduced tolerability of potentially severe side effects associated with FGAs and higher doses of certain SGAs, continuing education and training addressing the rational use of antipsychotics in this population is clearly needed.

Objective: This study surveyed the prescribing patterns of antipsychotic medications in Asian older schizophrenia patients with extrapyramidal side effects (EPS) during the period between 2001 and 2009., Method: Information on 848 hospitalized patients with schizophrenia aged 60 or older was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001 - 2009). Data from those patients with reported EPS from 8 Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, Taiwan, India and Malaysia were analyzed. The cross-sectional data of sociodemographic and clinical characteristics and antipsychotic prescriptions were collected using a standardized protocol and data collection procedure., Results: Of the 309/848 (36%) patients suffering from EPS, 210 patients (210/309; 68.0%) received at least one type of first generation antipsychotic (FGA), and 99 (99/309; 32.0%) received second generation antipsychotics (SGAs) only. Of SGAs prescribed in patients with EPS, risperidone was the most commonly used (100/309; 32.4%) followed by olanzapine (33/309; 10.7%) and quetiapine (25/309; 8.1%)., Conclusions: FGAs were frequently used in Asian older schizophrenia patients with EPS. Considering the potential adverse effects of FGAs on existing EPS, the reasons for the frequent use of FGAs need to be urgently identified.

Background: This study examined the use of low doses of antipsychotic medications (300 mg/day CPZeq or less) in older Asian patients with schizophrenia and its demographic and clinical correlates., Methods: Information on hospitalized patients with schizophrenia, aged 55 years or older, was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001-2009). Data on 1,452 patients in eight Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, Taiwan, India, and Malaysia were analyzed. Sociodemographic and clinical characteristics and antipsychotic prescriptions were recorded using a standardized protocol and data collection procedure., Results: The prescription frequency for low doses of antipsychotic medications was 40.9% in the pooled sample. Multiple logistic regression analysis of the whole sample showed that patients on low doses of antipsychotic medications were more likely to be female, have an older age, a shorter length of illness, and less positive symptoms. Of patients in the six countries and territories that participated in all the surveys between 2001 and 2009, those in Japan were less likely to receive low doses of antipsychotics., Conclusion: Low doses of antipsychotic medications were only applied in less than half of older Asian patients with schizophrenia.

Objective: Optimizing treatment and outcomes for people with schizophrenia requires understanding of how evidence-based treatments are utilized. Clozapine is the most effective antipsychotic drug for treatment-refractory schizophrenia, but few studies have investigated trends and patterns of its use over time internationally. This study examined the prescription patterns of clozapine and its demographic and clinical correlates in Asia from 2001 to 2009., Method: Clozapine prescriptions were collected in a sample of 6761 hospitalized schizophrenia patients in nine Asian countries and regions using a standardized protocol and data collection procedure., Results: Overall, the proportion of patients receiving clozapine prescriptions was stable across the three surveys from 2001 to 2009, ranging from 14.5% to 15.9%. However, the rates and patterns observed within different regions and countries at each survey differed considerably. Clozapine use decreased significantly over time in China, while it increased in Korea and Singapore. Multiple logistic regression analysis revealed that patients taking clozapine were significantly younger, had a higher dose of antipsychotic drugs in chlorpromazine equivalents, were more likely to be female, had fewer extrapyramidal symptoms, and had more negative symptoms, admissions and weight gain in the past month than those not receiving clozapine., Conclusion: The variability in overall rates and changes in prescription rates over time in these samples suggest that factors other than psychopharmacological principles play an important role in determining the use of clozapine in schizophrenia in Asia.

Objective: The purpose of the study was to evaluate the frequency of reported sexual dysfunction (SD) in schizophrenia and its associations with sociodemographic and clinical variables in selected Asian countries., Methods: A total of 5877 schizophrenia patients in nine Asian countries and territories were examined between 2001 and 2009. The patients' sociodemographic and clinical characteristics, prescription of psychotropic drugs, and drug-induced side effects were recorded using a standardized protocol and data collection. SD was evaluated as "present" or "absent" according to the clinical judgment of experienced psychiatrists., Results: The frequency of reported SD in the whole sample in women and men was 3.0%, 0.8%, and 4.6%, respectively, with variations across study sites. In the multivariate analyses, male sex, more second-generation antipsychotics, benzodiazepines, and antidepressants were independently associated with higher likelihood of reported SD, whereas negative symptoms had an inverse association with reported SD., Conclusions: The results of this study indicate that SD was seldom recorded as a side effect by Asian psychiatrists while treating patients with schizophrenia. It is unclear whether the low prevalence of reported SD compared with Western data is real or whether the results are being insufficiently recognized., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: The aim of this study was to investigate the sex differences in prescribing patterns of psychotropic drugs and drug-induced side effects in schizophrenia patients in Asia using the data of the Research on Asian Psychotropic Prescription Pattern (REAP) surveys., Method: The prescription patterns of 6,441 schizophrenia inpatients in six Asian countries and regions were investigated during the 2001-2009 period. The patients' socio-demographic and clinical characteristics and their prescriptions for psychotropic drugs were recorded using a standardized protocol and data collection procedure., Results: Univariate analyses found the following factors to be significantly associated with the male sex: a younger age, higher doses of antipsychotics, less prominent delusions and hallucinations, more prominent negative symptoms, less likelihood of a prescription for second-generation antipsychotics (SGAs), greater use of antipsychotic polypharmacy, mood stabilizers and depot antipsychotics, more frequent tardive dyskinesia (TD), and less weight gain. In multivariate analyses, fewer prescriptions for SGAs, greater use of mood stabilizers, anticholinergics, antipsychotic polypharmacy and depot antipsychotics, extrapyramidal side effects (EPS) and TD, and less weight gain were independently associated with the male sex., Conclusions: Sex is one of the independent contributors to psychotropic prescription and side effects in Asian schizophrenia patients. Psychopharmacological treatment guidelines for schizophrenia should consider the sexes separately.

Recent human genetic studies and postmortem brain examinations of schizophrenia patients strongly indicate that dysregulation of NRG1 and ErbB4 may be important pathogenic factors of schizophrenia. However, this hypothesis has not been validated and fully investigated in animal models of schizophrenia. In this study we quantitatively examined NRG1 and ErbB4 protein expressions by immunohistochemistry and Western blot in the brain of a rat schizophrenia model induced by chronic administration of MK-801 (a noncompetitive NMDA receptor antagonist). Our data showed that NRG1beta and ErbB4 expressions were significantly increased in the rat prefrontal cortex and hippocampus but in different subregions. These findings suggest that altered expressions of NRG1 and ErbB4 might be attributed to the schizophrenia. Further study in the role and mechanism of NRG1 and ErbB4 may lead to better understanding of the pathophysiology for this disorder.