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Schizophrenia is a major mental disorder with a wide range of psychiatric symptoms. This study explored the structure of psychiatric symptoms of schizophrenia using network analysis in a large representative Asian sample based on a survey of clinical features and treatment used in schizophrenia patients across 15 countries/territories in Asia.Data on the demographic characteristics and psychiatric symptoms in schizophrenia patients were extracted from the dataset of the fourth Research on Asia Psychotropic Prescription for Antipsychotics (REAP-AP) project. The presence of the following psychiatric symptoms including delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms, social/occupational dysfunction, verbal aggression, physical aggression, and affective symptoms were analyzed.A total of 3681 patients were included. The network analysis revealed that verbal aggression, hallucinations, and social/occupational dysfunction were the most central symptoms, while the connections between social/occupational dysfunction and verbal aggression, and between hallucinations and disorganized speech were the two strongest edges. There were significant gender differences in the network structure based on the network structure invariance test (M=0.74, P = 0.03) and invariant edge strength test. The positive correlation between verbal aggression and hallucinations was significantly stronger in the female network than that in the male network (P = 0.03), while a negative correlation between affective symptoms and negative symptoms was found in the female, but not the male network (P 0.01).Central symptoms including verbal aggression, hallucinations, and socio-occupational dysfunction should be addressed in developing targeted treatment strategy for schizophrenia patients.

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.

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.

Highlights • The reproduction number had three peaks that came several days before the surge in COVID-19 cases. • There was a strong negative correlation between the kinematic viscosity of atmospheric air and the reproduction number. • One influencing factor is air temperature, which means the winter season could have an effect on viral transmission., Background The large number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into fear in recent times. In Japan, 18,769 novel coronavirus disease 2019 (COVID-19) cases have been reported as of June 30, 2020. This study aimed to assess whether cluster infection prevention is possible by evaluating the association between viral transmission and meteorological factors. Methods This study included 1263 people who were successively diagnosed with COVID-19 in Hokkaido, Japan between January 24, 2020 and June 30, 2020. After obtaining the values from the Japanese Meteorological Agency, the average scores of air temperature and humidity were calculated and compared with COVID-19 reproduction numbers, and the association between COVID-19 incidence or reproduction number and meteorological factors was assessed. Results The COVID-19 reproduction number in Hokkaido had three peaks that came several days before the surge in COVID-19 cases. The peaks are indicative of cluster infections. There was a strong negative correlation between the kinematic viscosity of atmospheric air and the reproduction number. Discussion and Conclusion Analysis of the reproduction number is important for predicting or suppressing COVID-19 infection clusters. The authors found a strong association between meteorological factors, such as kinematic viscosity of atmospheric air and the incidence of COVID-19 infection. Meteorological forecasts could provide foreknowledge about COVID-19 infection clusters in the future.

Purpose/Background: Clozapine clearance is influenced by sex, smoking status, ethnicity, co-prescription of inducers or inhibitors, obesity and inflammation. In 126 Beijing inpatients, we measured repeated trough steady-state serum concentrations and identified 4% (5/126) who were phenotypical poor metabolizers (PMs); none were ultrarapid metabolizers (UMs). They were defined as being 2 standard deviations beyond the means of total clozapine concentration/dose ratios stratified by sex and smoking. Using this definition, this study explores the prevalences of PMs and UMs using data from 4 already-published Asian samples. Three samples were East Asian (Beijing 2, Taipei and Seoul); one was from South India (Vallore). Findings/Results: The prevalence of phenotypical PMs ranged from 2-13%, but inflammation was not excluded. The prevalence was 7.3% (14/191) for Beijing 2, 11% (8/70) for Taipei, 13% (9/67) for Seoul, and 2% (2/101) for the Vellore sample. Five phenotypical PMs appeared to be associated with extreme obesity. Phenotypic UM prevalence ranged from 0-1.6%, but may be partly explained by lack of adherence. A Vellore phenotypic UM appeared to be associated with induction through high coffee intake. Implications/Conclusions: Around 10% of Asians may be clozapine PMs and may only need 50-150 mg/day to get therapeutic concentrations. Future studies combining gene sequencing for new alleles with repeated concentrations and careful control of confounders including inhibitors, inflammation and obesity should provide better estimations of the prevalence of phenotypic clozapine PMs across races. Clozapine UM studies require excluding potent inducers, careful supervision of compliance in inpatient settings and multiple serum concentrations.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

Objective Regular surveys are important to monitor the use of psychotropic medications in clinical practice. This study examined the psychotropic prescription patterns in adult Asian schizophrenia patients based on the data of the Research on Asian Psychotropic Prescription (REAP) 2016 survey. Methods : This cross-sectional survey across 15 Asian countries/territories collected socio-demographic and clinical data with standardized procedures between March and May 2016. The socio-demographic and clinical characteristics of the patients were recorded with a standardized questionnaire. Results Altogether 3,537 adult patients with schizophrenia were consecutively screened and enrolled in the survey. The mean age was 38.66 ± 11.55 years and 59.7% of the sample were male. The mean dose of antipsychotics in chlorpromazine equivalents (CPZeq) was 424 ± 376 mg/day; 31.3% and 80.8% received first- and second- generation antipsychotics, respectively and 42.6% had antipsychotic polypharmacy, 11.7% had antidepressants, 13.7% had mood stabilizers, 27.8% had benzodiazepines, and 45.6% had anticholinergics. Conclusions Psychotropic prescription patterns in Asian adult patients with schizophrenia varied across countries. Regular surveys on psychotropic medications for schizophrenia are important to monitor pharmacotherapy practice in Asia.

Ketamine has emerged as a major substance of abuse worldwide. Evidence suggests a role of orexin system in reward processing, withdrawal, and stress response. It also interacts with the stress mechanisms of hypothalamic–pituitary–adrenal (HPA) axis to regulate drug-taking behavior. The study aimed to explore the relevance of orexin and stress hormones to chronic ketamine abuse. We enrolled 67 ketamine-dependent (KD) patients and 64 controls. The levels of orexin-A, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline, 1 week, and 2 weeks after ketamine discontinuation. KD patients were assessed by Beck Depression Inventory, Beck Anxiety Inventory, and Visual Analogue Scale for ketamine craving at baseline. Compared with the controls, KD patients had significantly lower orexin-A (0.65 ± 0.12 vs. 0.74 ± 0.10 ng/mL, p

Background: Although cannabis use has been linked with schizophrenia in a dose–response pattern, to our knowledge, the relationship between cannabis and schizophrenia has rarely been report...

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.

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.

Background and Objective: Antipsychotic polypharmacy (APP) is a controversial topic in the treatment of older adults with schizophrenia. The objective of this study was to examine the use of APP in older adult Asian patients with schizophrenia and its associated demographic and clinical factors. Methods: This study was based on the fourth survey of the consortium known as the Research on Asian Psychotropic Prescription Pattern for Antipsychotics. Fifteen Asian countries/territories participated in this survey, including Bangladesh, Mainland China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, Thailand, and Vietnam. Basic demographic and clinical characteristics were collected using a standardized data collection form. Results: Among the 879 older adults with schizophrenia included in the survey, the rate of APP was 40.5%. Multiple logistic regression analysis revealed that higher antipsychotic doses ( P < .001, odds ratio [OR] = 1.003, 95% confidence interval [CI]: 1.002-1.003), longer duration of illness ( P = .02, OR = 1.845, 95% CI: 1.087-3.132), and the prescription of anticholinergics ( P < .001, OR = 1.871, 95% CI: 1.329-2.635), second-generation antipsychotics ( P = .001, OR = 2.264, 95% CI: 1.453-3.529), and first-generation antipsychotics ( P < .001, OR = 3.344, 95% CI: 2.307-4.847) were significantly associated with APP. Conclusion: Antipsychotic polypharmacy was common in older adult Asian patients with schizophrenia. Compared to the results of previous surveys, the use of APP showed a declining trend over time. Considering the general poor health status of older patients with schizophrenia and their increased risk of drug-induced adverse events, the use of APP in this population needs careful consideration.

Clozapine is an effective antipsychotic medication for treatment resistant schizophrenia and is widely used in Asian countries. This study investigated clozapine prescription patterns and their associated factors in Asian countries and territories based on the database of the Research on Asian Psychotropic prescription study (REAP) conducted in 2016. Demographic and clinical information of 3744 schizophrenia patients in 15 Asian countries and territories was collected with a standardized data collection form. In total, 18.4% of the sample received clozapine, ranging from 2.6% in Japan to 32.3% in Hong Kong. Binary logistic regression analysis revealed that higher antipsychotic dose (OR = 1.002, P

OBJECTIVE Long-term follow-up data regarding the association between methamphetamine use and cardiovascular and cerebrovascular complications are scarce. We investigated the risk of complications in methamphetamine users over a decade. METHODS A total of 1,315 inpatients treated for methamphetamine use were recruited from the Psychiatric Inpatient Medical Claims database in Taiwan between January 1, 1997, and December 31, 2000, and matched with a population proxy comparison group at a ratio of 1:4 through propensity score matching. All patients were monitored for any incident complication until December 31, 2010. Cox proportional hazards model was used to estimate the risk of ICD-9-CM cardiovascular diseases and stroke events. RESULTS The patients were mostly male, and approximately half were younger than 30 years. The methamphetamine cohort had higher incidences of cardiovascular diseases and stroke events than the comparison cohort (87.5/10,000 vs 55.3/10,000 person-years, P < .001) and was significantly associated with an increased risk of the complications (hazard ratio [HR] = 1.55, P < .001), particularly arrhythmia (HR = 1.92, P = .014) and hemorrhagic stroke (HR = 2.09, P = .001). The risk of cardiovascular sequelae was more significant in younger patients (< 30 y) (HR = 2.22, P = .001), whereas the risk of stroke events was higher among the older patients (≥ 30 y) (HR = 1.86, P = .001). CONCLUSIONS Methamphetamine use is significantly associated with a risk of subsequent cardiovascular and cerebrovascular complications. Age appears to be an effect modifier for the risk estimation.

Methamphetamine (MAMP) and ketamine are neurotoxic drugs whose chronic use has been linked with a cognitive decline in some users. This paper aims to assess the possible effect of concomitant ketamine use on the neurocognitive performance of MAMP users.This study divides 42 MAMP users into MAMP users who use ketamine (MAMP+K, n = 16) and MAMP users who do not use ketamine (MAMP-K, n = 26). The performance of these two groups was compared using the Brief Assessment of Cognition in Schizophrenia (BACS), Conners' Continuous Performance Tests (CPT), the Wisconsin Card Sorting Test (WCST), the Iowa Gambling Task (IGT), and the Barratt Impulsiveness Scale (BIS).In comparison to the MAMP-K group, the MAMP+K group showed worse performances in verbal fluency, executive function and composite score in BACS; worse performances in total errors, perseverative errors, nonperseverative errors and conceptual level response in WCST; and greater levels of total scores and novelty-seeking in BIS. Neither the attention function evaluated with CPT nor the decision-making behavior evaluated with IGT was associated with previous ketamine use.This study detected worse executive function and higher impulsivity level among MAMP users with additional ketamine use versus their counterparts without ketamine use. Further studies with a longitudinal design and a large sample size are necessary to clarify the connection between cognitive deficits and concomitant use of MAMP and ketamine.

Acute and adverse effects of ketamine on cognitive functioning have been documented. No longitudinal study has examined whether cognitive deficits can be reversed following ketamine abstinence although it has been suggested in some cross-sectional studies. This study aimed to investigate the changes in cognitive functioning among ketamine users following a 12-week abstinence from ketamine.In this longitudinal study, 114 ketamine users completed clinical and cognitive assessments at both baseline and 12-week follow-up with the following instruments: Severity of Dependence Scale, Beck Depression Inventory (BDI), Anxiety Subscale of the Hospital Anxiety Depression Scale (HADSA), and a cognitive battery.BDI (p0.001) and HADSA (p = 0.044) scores were significantly reduced at the 12-week follow-up. Significant improvements were found in Wechsler Adult Intelligence Scale (Third edition) immediate recall (p0.001) and delayed recall (p0.001) on the Rey-Osterrieth Complex Figure Test, and in delayed recall (p0.001), and immediate recall (p = 0.001) on the Logical Memory component of the Wechsler Memory Scale (Third Edition) at the 12-week follow-up. Participants completed the Stroop Inference Test significantly faster (p0.001); and required fewer number of attempts (p0.001) and produced fewer perseverative errors (p0.001) on the Wisconsin Card Sorting Test at the 12-week follow-up.Chronic ketamine users' verbal and visual memory and executive functions improved after 12 weeks of ketamine abstinence.

Introduction To evaluate efficacy and safety of lurasidone for the treatment of Asian patients with schizophrenia. Methods Patients with schizophrenia from Japan, South Korea, Malaysia, and Taiwan were randomly assigned to 6 weeks of double-blind treatment with 40 or 80 mg/d of lurasidone or placebo. The primary efficacy measure was change from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) total score. Efficacy was evaluated using a mixed-model repeated-measures (MMRM) analysis in the modified intention-to-treat (mITT) population. Results On the basis of the analysis for the mITT population, the estimated difference score for lurasidone 40 and 80 mg/d vs placebo was -4.8 (P = 0.050) and -4.2 (P = 0.080). For the full intention-to-treat (ITT) population, the difference score for lurasidone 40 and 80 mg/d vs placebo was -5.8 (P = 0.017) and -4.2 (P = 0.043). The most frequent adverse events in the lurasidone 40 and 80 mg/d and placebo groups, respectively, were akathisia (7.3%, 10.4%, 3.3%), somnolence (6.0%, 2.6%, 0.7%), and vomiting (6.0%, 5.8%, 2.0%). The proportion of patients experiencing clinically significant weight gain (≥7%) was 5.3% for lurasidone 40 mg/d, 1.3% for 80 mg/d, and 1.4% for placebo. End point changes in metabolic parameters and prolactin were comparable for both lurasidone groups and placebo. Conclusions In the ITT (but not the mITT) population, treatment with lurasidone was associated with significant improvement in the PANSS total score in patients with schizophrenia. Lurasidone was generally well tolerated with minimal impact on weight and metabolic parameters.

Obesity-related genetic variants, including TMEM18 (rs6548238), SH2B1 (rs7498665), and GNPDA2 (rs10938397), have been shown to be associated with obesity in the general population. Our study aimed to test whether these genetic variants are associated with metabolic profiles and metformin treatment response in clozapine-treated schizophrenic patients. We recruited 107 clozapine-treated patients who were genotyped and measured their metabolic profiles. Fifty-five subjects, who had at least 1 metabolic abnormality in a range of measures, were subsequently randomized to a 24-week trial of metformin (n = 28) or placebo (n = 27). We examined the associations between TMEM18, SH2B1, GNPDA2 genetic variants and metabolic profiles at baseline in all patients and metabolic changes in the trial groups. We found a significant association between SH2B1 and blood pressure at baseline in all patients. In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04). A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups. In the placebo group, no association between genetic variants and changes in metabolic profiles was found. In conclusion, the study results suggest that these genes might be associated with metabolic abnormalities and response to metformin in clozapine-treated patients with schizophrenia.

Aim The aim of the present study was to survey the prevalence of antipsychotic polypharmacy and combined medication use across 15 Asian countries and areas in 2016. Methods By using the results from the fourth survey of Research on Asian Prescription Patterns on antipsychotics, the rates of polypharmacy and combined medication use in each country were analyzed. Daily medications prescribed for the treatment of inpatients or outpatients with schizophrenia, including antipsychotics, mood stabilizers, anxiolytics, hypnotics, and antiparkinson agents, were collected. Fifteen countries from Asia participated in this study. Results A total of 3744 patients' prescription forms were examined. The prescription patterns differed across these Asian countries, with the highest rate of polypharmacy noted in Vietnam (59.1%) and the lowest in Myanmar (22.0%). Furthermore, the combined use of other medications, expressed as highest and lowest rate, respectively, was as follows: mood stabilizers, China (35.0%) and Bangladesh (1.0%); antidepressants, South Korea (36.6%) and Bangladesh (0%); anxiolytics, Pakistan (55.7%) and Myanmar (8.5%); hypnotics, Japan (61.1%) and, equally, Myanmar (0%) and Sri Lanka (0%); and antiparkinson agents, Bangladesh (87.9%) and Vietnam (10.9%). The average psychotropic drug loading of all patients was 2.01 ± 1.64, with the highest and lowest loadings noted in Japan (4.13 ± 3.13) and Indonesia (1.16 ± 0.68), respectively. Conclusion Differences in psychiatrist training as well as the civil culture and health insurance system of each country may have contributed to the differences in these rates. The concept of drug loading can be applied to other medical fields.

Reactive oxygen species (ROS) are thought to play a role in the adverse physical and mental consequences of methamphetamine usage. The oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a well-known biomarker of ROS-induced DNA damage. Currently, there is insufficient clinical information about methamphetamine-induced oxidative DNA damage.This study examined differences in blood levels of 8-OHdG between methamphetamine users and non-users as well as alterations in 8-OHdG levels after 2 weeks of methamphetamine abstinence.We recruited 182 methamphetamine users (78.6% of male) and 71 healthy controls (95.8% of male). Baseline serum 8-OHdG levels were measured in both groups using a competitive enzyme-linked immunosorbent assay. In methamphetamine users, 8-OHdG levels were measured again 2 weeks after baseline measurement.The results showed that methamphetamine users had significantly higher 8-OHdG levels (0.34 ± 0.13 ng/mL) than healthy controls (0.30 ± 0.08 ng/mL) (p 0.001). The 8-OHdG levels did not alter after 2 weeks of methamphetamine abstinence (0.32 ± 0.12 ng/mL, p = 0.051 compared to baseline measurement; p = 0.12 compared to healthy controls). No significant correlations were observed between baseline 8-OHdG levels in methamphetamine users and post-abstinence interval, age of the first methamphetamine use, duration of methamphetamine use, or history of frequent methamphetamine use.Our findings suggest that methamphetamine users had an enhanced level of oxidative damage, which did not normalize during early abstinence. Future studies are required to determine the effects of long-term methamphetamine abstinence and potential confounders on 8-OHdG levels in methamphetamine users.

The change in psychiatric diagnoses in clinical practice is not an unusual phenomenon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders is a major clinical issue because of the differences in treatment regimens and long-term prognoses. In this study, we used a nationwide population-based sample to compare the diagnostic consistency and interchange rate between schizophrenic disorders and bipolar disorders.In total, 25 711 and 11 261 patients newly diagnosed as having schizophrenic disorder and bipolar disorder, respectively, were retrospectively enrolled from the Psychiatric Inpatient Medical Claims database between 2001 and 2005. We followed these two cohorts for 7 years to determine whether their diagnoses were consistent throughout subsequent hospitalizations. The interchange between the two diagnoses was analyzed.In the schizophrenic disorder cohort, the overall diagnostic consistency rate was 87.3% and the rate of change to bipolar disorder was 3.0% during the 7-year follow-up. Additional analyses of subtypes revealed that the change rate from schizoaffective disorder to bipolar disorder was 12.0%. In the bipolar disorder cohort, the overall diagnostic consistency rate was 71.9% and the rate of change to schizophrenic disorder was 8.3%.Changes in the diagnosis of a major psychosis are not uncommon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders might be attributed to the evolution of clinical symptoms and the observation of preserved social functions that contradict the original diagnosis. While making a psychotic diagnosis, clinicians should be aware of the possibility of the change in diagnosis in the future.

Ketamine has emerged as a major substance of abuse worldwide and has been listed with methamphetamine (METH) as two of the most widely available illicit substances in Taiwan. Only a few studies have examined the long-term consequences of chronic and heavy ketamine abuse. We compared the cognitive function of ketamine-dependent patients with that of METH-dependent patients and healthy controls. We recruited 165 participants (58 ketamine-dependent and 49 METH-dependent patients who sought treatment and 58 healthy controls) and evaluated them by using a cognitive test battery, the Brief Assessment of Cognition in Schizophrenia, with scores being estimated in reference to normative data in general population. The ketamine-dependent patients had significantly poorer performance than did the controls in many cognitive tests, including verbal memory, motor speed, verbal fluency, and attention and processing speed, and the battery as a whole. METH-dependent patients exhibited poorer function in motor speed, verbal fluency, and attention and processing speed. The ketamine group performed poorer than did METH group in the domains of verbal memory, working memory, and attention and processing speed and the composite battery scores. A previous experience of ketamine-induced psychotomimetic symptoms, using higher doses of ketamine, and longer abstinence appeared to be associated with performance in some tests; however, the significance disappeared after multiple comparison correction. The ketamine-dependent patients had impaired cognitive function, and METH-dependent patients exhibited intermediate performance between ketamine-dependent patients and healthy controls. Given the growing population of ketamine abusers, public education on the cognitive consequences should be provided.

Background Ketamine abuse causes cognitive impairments, which negatively impact on users’ abstinence, prognosis, and quality of life. Results of cognitive impairments in chronic ketamine users have been inconsistent across studies, possibly due to the small sample sizes and the confounding effects of concomitant use of other illicit drugs. This study investigated the cognitive impairment and its related factors in chronic ketamine users with a large sample size and explored the impact of another drug use on cognitive functions. Methods Cognitive functions, including working, verbal and visual memory and executive functions were assessed in ketamine users: 286 non-heavy other drug users and 279 heavy other drug users, and 261 healthy controls. Correlations between cognitive impairment and patterns of ketamine use were analysed. Results Verbal and visual memory were impaired, but working memory and executive functions were intact for all ketamine users. No significant cognitive differences were found between the two ketamine groups. Greater number of days of ketamine use in the past month was associated with worse visual memory performance in non-heavy other drug users. Higher dose of ketamine use was associated with worse short-term verbal memory in heavy other drug users. Conclusion Verbal and visual memory are impaired in chronic ketamine users. Other drug use appears to have no impact on ketamine users’ cognitive performance.

Objective The aim of this paper was to analyze medical utilization patterns of female patients with anorexia nervosa before their first inpatient care visit for anorexia nervosa using the National Health Insurance Research Database (NHIRD) of Taiwan. Method We selected female anorexia nervosa patients (n = 239) and control participants hospitalized for peptic ulcers (n = 478) or appendectomy (n = 478) who were matched by age and incident year from two subsets of the NHIRD. The number of visits, specialists, diagnosis distribution, and selected procedures used in ambulatory services during the 2-year period before the index admission were identified and compared. Healthcare service expenditures were also analyzed. Results Compared to the control groups, the female anorexia nervosa patients used more outpatient services (anorexia nervosa, 58.6 ± 45.0 visits; peptic ulcers, 45.3 ± 37.3 visits; appendectomy, 32.5 ± 26.0 visits), mainly due to psychiatric visits. Anorexia nervosa patients were more likely to have received a diagnosis of digestive, endocrine/metabolic, and mental disorders than patients in the control groups. Although nearly equal percentages of patients in the three groups had obtained a diagnosis of a digestive disease, anorexia nervosa patients received digestive disease diagnoses with greater frequency. Conclusions We posit that the various physical symptoms of anorexia nervosa patients and physicians' low level of suspicion of anorexia nervosa led to delayed diagnoses and greater medical utilization than that of the controls groups. Education to raise awareness of anorexia nervosa and other eating disorders among physicians is warranted.

To investigate the involvement of COMT Val158Met and DAT1 3'-UTR VNTR genotypes in the pathogenesis of illicit drug use and drug-induced psychotic disorders (DIP), 187 substance users and 386 normal controls were recruited from Northern Taiwan. Substance users and normal controls significantly differed in allele frequencies of COMT Val158Met (p = 0.039) but not in allele frequencies of DAT1 3'-UTR VNTR (p = 0.879). However, neither allele frequencies of COMT Val158Met nor allele frequencies of DAT1 3'-UTR VNTR were associated with DIP. The findings should be confirmed in further studies of a larger sample size and a more homogenous patient group.

Due to the needs of medical care, the probability of using health care service from heroin users is high. This cross-sectional study investigated the frequency and correlates of health service utilization among heroin users. From June to September 2006, 124 heroin users (110 males and 14 females, mean age: 34.2 ± 8.3 years) who entered two psychiatric hospitals (N = 83) and a detention center (N = 41) in northern Taiwan received a face-to-face interview. Therefore, socio-demographic characteristics, patterns of drug use, psychiatric comorbidities, blood-borne infectious diseases and health service utilization were recorded. The behaviors of health service utilization were classified into the frequency of out-patient department visit and hospitalization, as well as the purchase of over-the-counter drugs. During 12 months prior to interview, 79.8% of the participants attended health care service at least once. The rate of having any event in out-patients service visit, hospitalization, and over-the-counter drugs were 66.1%, 29.8% and 25.8% respectively. The frequency of health service utilization was associated with numerous factors. Among these factors, patients who were recruited from hospital and having a mood disorder were conjoint predictors of out-patient department visit, hospitalization and purchase of over-the-counter drugs. According to the results of this study, social education and routine screening for mood disorders can help heroin users to obtain adequate health care service. The findings of this study are useful references for targeting the heroin users for whom a successful intervention represents the greatest cost benefit.

Background: This study aimed to identify susceptible loci and enriched pathways for bipolar disorder subtype II. Methods: We conducted a genome-wide association scan in discovery samples with 189 bipolar disorder subtype II patients and 1773 controls, and replication samples with 283 bipolar disorder subtype II patients and 500 controls in a Taiwanese Han population using Affymetrix Axiom Genome-Wide CHB1 Array. We performed single-marker and gene-based association analyses, as well as calculated polygeneic risk scores for bipolar disorder subtype II. Pathway enrichment analyses were employed to reveal significant biological pathways. Results: Seven markers were found to be associated with bipolar disorder subtype II in meta-analysis combining both discovery and replication samples (P

A 2-week, randomized, parallel-group open trial was designed to evaluate the safety and tolerability of a rapid initiation regimen with a higher dose of quetiapine (up to 800 mg/d by Day 4) than that used in the conventional initiation regimen of quetiapine (up to 400 mg/d by Day 5) in patients with schizophrenia or schizoaffective disorders. Forty patients were recruited and randomly (3:1) assigned to either the group with rapid initiation of quetiapine or the group with conventional initiation. At the end of the investigation, the difference between the groups in the incidence of adverse events was not significant; a significant drop in the Barnes Akathisia Rating Scale and Simpson-Angus Scale scores was observed only in the group with the rapid initiation regimen. The groups did not differ in terms of improvement on the Clinical Global Impression—Severity of Illness and Positive and Negative Syndrome Scale at the end of the study. The results of our 2-week study suggest that rapid initiation with a higher dose of quetiapine (up to 800 mg/d by Day 4) is well tolerated in patients with schizophrenia or schizoaffective disorders and does not compromise efficacy relative to the conventional initiation.

Methamphetamine as a recreational drug has undergone cycles of popularity, with a recent surge worldwide since the 1990s. This study aimed to identify clinical characteristics associated with suicide mortality in patients with methamphetamine dependence by means of a nested case-control design.In a consecutive series of 1,480 inpatients with methamphetamine dependence (diagnosed according to DSM-III-R and DSM-IV criteria) admitted to a psychiatric center in northern Taiwan from January 1, 1990, through December 31, 2006, 38 deaths due to suicide were identified as cases via record linkage, and 76 controls were randomly selected using risk-set density sampling in a 2:1 ratio, matched for age, sex, and the year of index admission. A standardized chart review process was adopted to collate sociodemographic and clinical information for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of suicide among these patients.For the sociodemographic and symptom profiles at the latest admission, financial independence lowered the risk for suicide (adjusted risk ratio [ARR] = 0.33, P.05), whereas visual hallucinations elevated the risk (ARR = 2.57, P.05) for suicide. For the profiles during the postdischarge period, financial independence (ARR = 0.11, P.05) remained associated with reduced risk for suicide, whereas suicide attempt (ARR = 8.78, P.05) and depressive syndrome (ARR = 3.28, P = .059) were associated with increased risk of suicide.Both protective and risk factors for suicide mortality were found among inpatients with methamphetamine dependence, and the findings have implications for clinical intervention and prevention.

Long-term use of methamphetamine could induce psychosis, but consequences with regards to intelligence have seldom been investigated. Long-term use of alcohol could also result in intellectual deterioration.The IQ of 34 methamphetamine-induced psychosis (MIP) patients (age, 28.7 +/- 6.1 years) and 34 alcohol-dependent (AD) patients (age, 40.7 +/- 7.3 years) was compared using the Chinese version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III).The average full-scale IQ, verbal IQ, performance IQ, verbal comprehension index, working memory index, perceptual organization index, and processing speed index was 82.3 +/- 10.8, 84.3 +/- 11.9, 81.9 +/- 12.1, 85.5 +/- 11.9, 84.7 +/- 12.5, 85.4 +/- 13.6, and 78.5 +/- 12.7 in MIP patients and 90.5 +/- 12.0, 95.2 +/- 11.3, 86.0 +/- 13.7, 95.5 +/- 11.0, 87.1 +/- 14.5, 96.2 +/- 13.1, and 84.5 +/- 15.0 in AD patients, respectively. There were six MIP patients (17.6%) whose full-scale IQ was70 and 13 (38.2%) whose full-scale IQ was85 and70, while one AD patient had a full-scale IQ70 (2.9%) and 10 (22%) had full-scale IQ85 and70.Long-term use of methamphetamine can result not only in psychosis, but also in mentality deterioration. Intelligence deterioration is more severe in clinical MIP patients than AD patients. Assessment of the mentality of MIP patients is suggested to help with the implementation of rehabilitative programs for these patients.

Substance use disorders are familial, and genetic factors explain a substantial degree of their familial aggregation. Methamphetamine (MAP) abusers are commonly noted as having psychosis, depression and suicidal behavior. The goals of the present study were (i) to investigate relations of clinical correlates, such as gender, drug use behavior, psychiatric comorbidity and psychiatry family history, with suicidal behavior among Chinese MAP abusers; and (ii) to investigate whether there is an association between a polymorphism in the promotor region of the serotonin transporter gene (5-HTTLPR) and suicidal behavior among Chinese MAP abusers. A total of 439 MAP abusers from a hospital and detention center in Taipei were interviewed with the Diagnostic Interview for Genetic Study and the Family Interview for Genetic Study. The 5-HTTLPR polymorphism was compared between 94 MAP abusers with suicide attempts and 294 MAP abusers without suicide attempts, for whom DNA data were available. The results of the present study indicate that among MAP abusers in Taiwan, suicide attempts were significantly related to female gender, history of MAP-induced psychotic disorder, history of MAP-induced depressive disorder, and family history of psychotic disorders. Among suicide attempters, the attempters with moderate to severe lethality used higher MAP doses than those with minimal to mild lethality. In the present sample the triallelic 5-HTTLPR polymorphism (S, LG, LA) was not associated with MAP-induced depressive disorder, MAP-induced psychotic disorder or suicidal behavior, but studies with larger sample sizes are warranted before excluding the role of the 5-HTTLPR polymorphisms in suicidal behavior among MAP abusers.

OBJECTIVE: Asian populations may differ from other races in response to antipsychotics. Studies of aripiprazole in Asian populations are scarce. This study aimed to investigate the efficacy, safety, and tolerability of aripiprazole in Chinese patients with acute schizophrenia or schizoaffective disorder. METHOD: This 4-week, double-blind, randomized, parallel study was conducted in 5 medical centers in Taiwan between March 2004 and January 2005. A total of 83 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomly assigned (with a randomization ratio of 3:2) to 15 mg/day of aripiprazole (N = 49) or 6 mg/day of risperidone (N = 34). Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement scale scores. Extrapyramidal symptoms (EPS), weight gain, serum prolactin level, QTc interval, and self-reported adverse events were assessed as measures of safety and tolerability. RESULTS: Both the aripiprazole and risperidone groups showed statistical improvement from baseline in PANSS total, PANSS positive, PANSS negative, and CGI-S scores at study endpoint (all p < .001). Significant improvement was noted in the first week of treatment for both treatment groups. There were no significant differences in efficacy measures between treatment groups. Aripiprazole showed significantly less EPS liability as assessed by the Simpson-Angus Scale (p < .005) and less serum prolactin level elevation (p < .001) than risperidone. Both groups showed mild weight gain. No patients showed clinically significant QTc interval prolongation in this study. CONCLUSION: Compared with risperidone 6 mg/day, aripiprazole 15 mg/day has comparable efficacy and favorable safety and tolerability profiles in the short-term treatment of Chinese patients with acute schizophrenia. In this group of Chinese patients, the overall response to aripiprazole did not differ from that of white patients. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00283179.

Several lines of evidence have suggested that substance abuse is mediated by the dopaminergic rewarding system, primarily through the activity of the dopamine receptor D1 (DRD1). The purpose of the present study was to evaluate the association of DRD1 A-48G polymorphism with methamphetamine (MAP) abusers and MAP-induced psychosis patients. A total of 363 MAP abusers and 425 healthy normal controls were enrolled. The structural Diagnostic Interview for Genetic Study was used to evaluate all MAP abusers. The MAP abusers were classified into psychosis (n = 135) and non-psychosis (n = 228) groups. A-48G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. The results show that male sex and a higher frequency of MAP abuse were the predisposing factors in the development of MAP psychosis. The DRD1 -48G allele frequency in the MAP psychosis group, non-psychosis group and the healthy normal controls was 0.14, 0.18 and 0.16, respectively. No association was found between DRD1 A-48G polymorphism and MAP abuse and MAP psychosis. However, the data provided additional evidence of ethnicity-related differences in the distribution of polymorphism in comparison to previous studies.

Methamphetamine (MAP) abuse has been common in Taiwan for the past decade. The purpose of the present study was to investigate MAP abuse in Taiwan, with specific attention to psychiatric comorbidity and gender differences. A total of 325 MAP abuse subjects (180 male, 145 female) from a detention center in Taipei were assessed with the Diagnostic Interview for Genetic Studies. The following were studied: drug use behavior, treatment-seeking behavior, lifetime prevalence of mood disorders, MAP psychosis, alcohol use disorders, pathological gambling and antisocial personality. The MAP-abuse subjects in Taiwan had high psychiatric morbidity and low access to mental health services. There also exist certain differences in the prevalence of psychiatric illnesses and treatment-seeking behavior between male and female subjects. Compared with their male counterparts, more female subjects reported experience of mental disturbance and experience of psychiatric treatment. The female subjects more commonly reported suicidal behaviors than the male subjects.

The clinical outcome for methamphetamine (MAP) abusers is variable. MAP exerts its biological activity through rapid conversion to amphetamine (AP) and MAP itself. The dopamine transporter (DAT) is the main modulator of MAP/AP-induced dopamine release and dopamine neurotoxicity, and is also the major regulator of dopamine level in the brain. We tested for an association between a DAT-gene polymorphism and clinical variations in MAP abusers. A total of 146 MAP abusers were enrolled in the study and classified into three clinically distinct groups: MAP dependence (n = 30), MAP psychosis (n = 88) and chronic MAP psychosis (n = 28). Patients with schizophrenia (n = 79) and healthy controls (n = 72) were also recruited for the study. The 40 base pair variable number tandem repeat polymorphism in the 3'-untranslated region of the DAT was the focus of the investigation. The subjects were all Chinese residents of Taiwan. The respective allelic frequencies for DAT repeats 11, 10 and 9 were 0.067, 0.833 and 0.083 for the MAP-dependence group, 0.006, 0.864 and 0.119 for the MAP psychosis group, 0.018, 0.893 and 0.089 for the chronic MAP psychosis group, 0.019, 0.911 and 0.07 for the schizophrenic controls, and 0.021, 0.889 and 0.083 for the healthy controls. No significant associations were demonstrated between this DAT polymorphism in genotype and allele frequency and the clinical outcome of MAP abusers. The biological relevance of the variable number tandem repeat polymorphism in the 3'-untranslated region of DAT in MAP abusers was not demonstrated in this study.

We analyzed two polymorphisms in genes encoding proteins of the dopamine system, the Val158Met polymorphism in the catechol-O-methyltransferase gene and the 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene for association with methamphetamine abuse. We used a case/control design with 416 methamphetamine abusing subjects and 435 normal controls. All subjects were Han Chinese from Taiwan. We found an excess of the high activity Val158 allele in the methamphetamine abuser group, consistent with several previous reports of association of this allele with drug abuse. The 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene itself did not show significant association with methamphetamine abuse. However, analysis of the 120-bp VNTR polymorphism and the exon 3 VNTR in the dopamine D4 receptor as a haplotype showed significant association with methamphetamine abuse, which gave an empirical P value 0.0034 for a heterogeneity model. Moreover, there were significant interactive effects between polymorphisms in the catechol-O-methyltransferase and dopamine D4 genes. The evidence of interaction between COMT 158 Val/Met and DRD4 48-bp VNTR polymorphisms (P = 0.0003, OR = 1.45, 95% CI: 1.148-1.77), and between COMT 158 Val/Met and DRD4 120 bp promoter polymorphisms (P = 0.01, OR = 1.10, 95% CI: 1.10-1.18) were significant but the latter was weak. We conclude that genetic variation in the dopamine system may encode an additive effect on risk of becoming a methamphetamine abuser.

Background Recent substance abuse research indicates gender differences in the substance-related epidemiology, biological responses, progression to dependence, medical consequences and treatments. Studies exploring human sex-different responses to ketamine are rare and there has been no systemic survey of gender differences in ketamine use. Determining whether females are more susceptible than males to ketamine withdrawal symptoms and adverse effects is important, because it associated with treatment retention and outcome in drug users. Methods The Taiwanese juridical system has implemented a new regulation on ketamine in the year 2009. Ketamine users who are caught by the police, are mandated to attend an educational program. We recruited ketamine offenders from February 2010 to May 2012 at the Kunming branch of the Taipei City Hospital, where the educational classes are held. A designed questionnaire was performed to gather information about demographic characteristics, discontinuation symptoms, concomitant use of other substances, and subjective experience of memory impairment or urinary discomforts, and to compare the gender differences. Results A total of 1,614 ketamine users were surveyed and most of them were males (83.8%), with an average age of 26.3 ± 5.4 years. Female ketamine users presented significantly more discontinuation symptoms such as anxiety, dysphoria, and tremors compared with male users. 72.4% of total ketamine users smoked cigarettes concomitantly. Male ketamine users had a higher rate of concomitant betel nut use, while female ketamine users had a higher rate of concomitant hypnotic and alcohol use. 76% of total ketamine users reported cognitive impairment and 51.6% mentioned urinary symptoms. Furthermore, female ketamine users self-reported significantly greater levels of severity in cognitive impairment and urinary discomforts compared with male users. Less than 10% of total ketamine users in our study reported the desire to transfer for medical intervention or treatment, despite the high rates of discontinuation symptoms and negative physical side effects. Conclusions Gender differences were noted in the subjective experience of discontinuation symptoms, concomitant substance use, and severity of impairment related to ketamine use. However, the probable cause of the gender differences found in this study requires further investigation. We hoped our study will stimulate further research in this field.

BACKGROUND: The mortality risk is high among individuals dependent on heroin, and suicide is a severe consequence of long-term heroin use. We estimated the incidence of suicide mortality and its risk factors in a large Asian cohort with heroin dependence. METHODS: A consecutive series of 2750 inpatients dependent on heroin admitted to a psychiatric center in northern Taiwan between 1990 and 2010 were retrospectively enrolled as the study cohort. These patients were linked to the Taiwan National Mortality Database to obtain each mortality event. We determined the Standardized Mortality Ratio (SMR) for each cause of death. Among the deceased, 69 deaths were due to suicide (cases); 138 controls were randomly selected using risk-set density sampling based on a nested case-control design. We collected clinical information from subjects' medical records. Multivariate conditional logistic regression was employed to explore the correlates of suicide mortality. RESULTS: The findings showed a 7.9-fold SMR for all-cause mortality among heroin users compared to the general population while the SMR for suicide mortality was 16.2. Multivariate analysis showed that suicide attempt as the reason for the index admission (adjusted risk ratio [RR]=4.29, p=0.035) and depressive syndrome anytime during life (adjusted RR=2.61, p=0.019) were associated with the risk of suicide mortality. CONCLUSIONS: Individuals dependent on heroin are more likely to die of suicide compared to the general population. We recommend that clinical psychiatric staff carefully gather information related to the identified risk factors to prevent suicide among heroin users. Language: en

Background Prolonged exposure to methamphetamine (meth) has neurotoxic effects and impairs neurocognitive functions. This study aims to ascertain whether meth users who experience persistent psychosis suffer more severe cognitive impairment than those not experiencing persistent psychosis. Methods This cross-sectional study includes 252 participants: 25 meth users without psychosis (METH − P), 50 with brief psychosis (METH + BP), and 56 with persistent psychosis (METH + PP), as well as 54 patients with schizophrenia and 67 healthy controls. The neurocognitive function and clinical psychopathology of each patient were evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS) and the Brief Psychiatric Rating Scale (BPRS), respectively. Results All cognitive domains evaluated with BACS (verbal memory, working memory, motor speed, verbal fluency, attention and processing speed, executive function, and composite scores) in METH + PP patients were similar to those in the schizophrenia patients and were worse than those in METH − P, METH + BP, and the healthy control subjects. Furthermore, cognitive functioning in meth users that did not experience persistent psychosis showed no statistically significant difference compared with the healthy control subjects. Among the meth users in this study, the negative symptom scores in the BPRS correlated to cognitive performance on the BACS, with the exception of motor speed. Conclusions Meth users display heterogeneity in their psychotic symptoms and cognitive profiles. Therefore, persistent psychotic symptoms may denote a risk for cognitive decline among meth users. Further longitudinal studies should be performed in the future to clarify the causal relationship between cognitive deficits and the development of persistent psychosis.

BackgroundCancer is a serious public health problem worldwide, and its relationship with affective disorders is not clear.AimsTo investigate alcohol- and tobacco-related cancer risk among patients with affective disorders in a large Taiwanese cohort.MethodRecords of newly admitted patients with affective disorders from January 1997 through December 2002 were retrieved from the Psychiatric Inpatient Medical Claims database in Taiwan. Cancers were stratified by site and grouped into tobacco- or alcohol-related cancers. Standardised incidence ratios (SIRs) were calculated to compare the risk of cancer between those with affective disorders and the general population.ResultsSome 10 207 patients with bipolar disorder and 9826 with major depression were included. The risk of cancer was higher in patients with major depression (SIR = 2.01, 95% CI 1.85–2.19) than in those with bipolar disorder (SIR 1.39, 95% CI 1.26–1.53). The elevated cancer risk among individuals ever admitted to hospital for affective disorders was more pronounced in tobacco- and/or alcohol-related cancers.ConclusionsElevated cancer risk was found in patients who had received in-patient care for affective disorders. They require holistic approaches to lifestyle behaviours and associated cancer risks.

Dextromethorphan has been reported to ameliorate opioid withdrawal symptoms in both animal and human subjects. In the present study, we investigated the efficacy of dextromethorphan as an add-on medication in heroin detoxification treatment in a double-blind, placebo-controlled design. Sixty-five heroin-dependent patients (male, 63; female, 2) participated in this inpatient detoxification trial after giving informed consent. Clonidine 0.075 mg 4 times a day was given as an antiwithdrawal medication at baseline. Each patient was then randomly assigned to treatment with either dextromethorphan 60 mg or placebo 4 times a day as additional medication. Flurazepam 30 mg was given before bedtime for insomnia. Other medications that were allowed included loperamide for diarrhea and lorazepam for agitation. Participants were monitored using the Objective Opioid Withdrawal Scale 3 times a day as the primary outcome to compare drug efficacy between groups. Generalized estimating equation model analysis revealed that the Objective Opioid Withdrawal Scale had no group difference between dextromethorphan and placebo group overall (P = 0.29), whereas a significant difference between groups was found during day 3 to day 6 (P = 0.04) by post hoc analysis. There was no difference in the Clinical Global Impression Scale, patient's impression of treatment, and use of ancillary medications between groups. No severe adverse effects were noticed. We suggest that dextromethorphan has some beneficial effect in attenuating the severity of opioid withdrawal symptoms and can be used as an adjunction medication in the treatment of opioid withdrawal, whereas the exact efficacy needs further investigation.

Psychotropic polypharmacy in the treatment of bipolar disorder has proliferated. Yet evidence about the prevalence and predictors of different combinations of polypharmacy in inpatient settings is scarce.The Nationwide Psychiatric Inpatient Medical Claims (2000-2007) in Taiwan were used to examine prescriptions for mood stabilizers, antipsychotics, and antidepressants among recently discharged patients with bipolar disorder (N=5,449; 51% women, mean±SD age=36.8±12.4).A total of 71% of prescriptions involved between-class polypharmacy, and 17% involved within-class polypharmacy. Patients older than 50 and patients at medical centers (500 beds) were less likely to receive polypharmacy. Lower prescribed doses predicted polypharmacy. Receiving polypharmacy was not associated with a higher rate of readmission within one year.There was substantial use of various forms of polypharmacy in the treatment of inpatients with bipolar disorder. Randomized studies should be used to compare the cost-effectiveness of common psychotropic combinations and monotherapy to treat bipolar disorder.

Background Metformin has been used for alleviating metabolic abnormalities in patients with schizophrenia. The lowest dose of metformin to treat metabolic abnormalities in clozapine-treated patients is 1000 mg/d. This study was designed to determine whether metformin at 500 mg/d and 1000 mg/d is effective in improving the metabolic profiles of clozapine-treated patients with pre-existing metabolic abnormalities, and whether its effectiveness depends on metformin dosage. Methods In this 12-week, randomized, double-blind, placebo-controlled trial, metformin at 500 mg/d or 1000 mg/d was prescribed to clozapine-treated patients with schizophrenia who had pre-existing metabolic abnormalities. The recruited patients underwent physical and laboratory evaluations at weeks 4, 8, and 12. The outcomes were any changes in metabolic traits. Results Among the 96 clozapine-treated patients with schizophrenia screened for the trial, 55 patients with pre-existing metabolic abnormalities were randomly assigned to placebo (n = 18), metformin dosage at 500 mg/d (n = 18), and metformin dosage at 1000 mg/d (n = 19) groups. The body weight (BW) of patients in the metformin 1000 mg/d group significantly decreased, by a mean of 0.97 kg over the 12 week trial period. Moreover, patients in the metformin at 500 mg/d and 1000 mg/d groups had a significant decrease in body mass index (BMI) after 12 weeks, with the mean decrease being 0.70 and 0.50 kg/m2, respectively. No significant changes were observed in the other metabolic parameters of patients in the three groups. Conclusions Our results demonstrated that a low metformin dosage of either 500 mg/d or 1000 mg/d for 12 weeks slightly reduced the BW and BMI of clozapine-treated patients with pre-existing metabolic abnormalities. A longer period of treatment with a larger sample is warranted to determine the factors that influence the metformin treatment response. Trial Registration ClinicalTrials.gov NCT02751307

Dependence on benzodiazepines (BZDs) or Z-drugs (zolpidem, zopicline and zaleplon) is a common clinical phenomenon. Traditional detoxification of BZDs dependence includes tapering used dose gradually and using equivalent doses of long-acting BZDs as substitutes. This kind of regimen tends to take a long time (up to 4weeks) and may require hospitalization. Acetylcholinesterase inhibitors have been shown to reverse BZDs induced sedation. We propose that oral form acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) also posses the effect of inhibiting GABA receptors, and act as indirect antagonist, to be applied in the rapid detoxification treatment of BZDs and Z-drug dependence.

Background Previous reports concerning the effects of gender and age on steady-state plasma concentrations of clozapine and its major metabolites, norclozapine and clozapine-N-oxide, have been controversial. Since the frequency distribution of the plasma levels is asymmetrical and skewed to the right, the statistical methods (such as analysis of variance and regression analysis) used earlier are actually inappropriate for analyzing the effects of the variables on the concentrations and might contribute to the inconsistent results. The goal of the present study, with befitting statistics, is to measure the potential effect of dose, gender, age, and body weight on plasma levels of clozapine and its 2 major metabolites. Method We retrospectively analyzed data from a therapeutic drug monitoring study for steady-state plasma clozapine, norclozapine, and clozapine-N-oxide levels that was conducted in a large group of Chinese schizophrenic inpatients (male:female ratio = 83:79; age range, 33.8 +/- 9.3 years). The daily doses of clozapine had ranged from 100 to 900 mg, with a mean +/- SD value of 379.5 +/- 142.2 mg. Plasma concentrations had been measured using high-performance liquid chromatography with ultraviolet detection. Multiple linear regression was adopted to quantify the effects of various factors on the plasma levels. The natural logarithm of the plasma level was used as the dependent variable to overcome the skewness problem. Results After adjusting the effects of gender, age, and body weight by multiple linear regression, each 1-mg increment in the daily dose could raise the clozapine level by 0.31%, norclozapine by 0.27%, and clozapine-N-oxide by 0.16%. Female patients had 34.9% higher clozapine levels and 36.3% higher norclozapine, with other variables being controlled. No sex differences were demonstrated for clozapine-N-oxide levels. Each 1-year increment in age would elevate the clozapine level by 1.1%, norclozapine by 1.0%, and clozapine-N-oxide by 1.0%. Body weight could not influence the levels of these compounds. Conclusion The present results suggest that women possess higher plasma levels (about one third higher) of clozapine and norclozapine, but not the N-oxide metabolite. Each addition of 1 year in age elevated clozapine and either metabolite's levels by about 1%. Furthermore, every 1-mg increase in the daily dose raised clozapine and norclozapine concentrations by approximately 0.3%. These findings could assist clinicians in optimizing clozapine dosing strategies.

Plasma concentrations of clozapine and its metabolites desmethylclozapine and clozapine N-oxide were measured in 61 patients with refractory schizophrenia. Before the initiation of clozapine, each patient was given haloperidol (HL) up to 60 mg/day for at least 4 weeks without improvement. Patients were then given a fixed dose of clozapine 400 mg/day. Patients were assessed with the Brief Psychiatric Rating Scale (BPRS) at baseline before HL therapy, at the end of HL at 6 weeks, before clozapine, and after 6 weeks of clozapine therapy. Clozapine and its metabolites were measured by high-performance liquid chromatography with ultraviolet detection. The mean plasma concentrations of clozapine, desmethylclozapine, and clozapine N-oxide were 598 +/- 314, 281 +/- 140, and 90 +/- 29 ng/ml, respectively. The mean decrease in the total BPRS scores from baseline clozapine to the 6-week treatment period was 11 +/- 4. Clinical improvement was noted to occur in most patients with clozapine plasma levels > 300 ng/ml. Improvement diminished in patients with clozapine plasma levels > 700 ng/ml. The most common adverse effects were sedation and hypersalivation. Significant correlations between plasma clozapine concentrations and adverse side effects were not found.

A total of 125 heroin users were recruited from a detention center and two psychiatric hospitals in northern Taiwan during 2006 in order to investigate the prevalence and correlates of blood-borne infections among heroin users. The seroprevalence rates of the human immunodeficiency virus (HIV), hepatitis C virus (HCV), HBV, HDV, and syphilis were 15.2%, 74.4%, 15.2%, 6.4%, and 8%, respectively. Injection risk behaviors were associated with HIV, HCV, and syphilis infections, but not with HBV infections. Meanwhile, HCV and HBV infections were correlated with the duration of heroin use and age of the subjects, respectively. The results of this study suggest that a comprehensive public health program is needed to prevent transmission of these blood-borne infections. The study's limitations are noted.

Objective: Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia. Whether or not the beneficial effects can be sustained after discontinuation of metformin needs to be evaluated. We conducted a 24-week randomized, double-blind, placebo-controlled study to evaluate the effect of metformin on metabolic features in clozapine-treated patients with schizophrenia and followed their body weight after stopping the intervention for at least 24 weeks. Method: The study was conducted between September 2008 and July 2011. We recruited patients with DSM-IV diagnosis of schizophrenia or schizoaffective disorder who had been taking clozapine for more than 3 months, were overweight or obese, or fulfilled at least 1 criteria of metabolic syndrome. Eligible patients were randomized to receive metformin 1,500 mg/d or placebo. We followed metabolic features at baseline and at weeks 2, 4, 8, 16, and 24 and rechecked body weight when the patients stopped the trial after at least 24 weeks. Results: A total of 55 subjects (28 in the metformin and 27 in the placebo group) were enrolled. There were no significant differences in all baseline characteristics between the 2 groups, except that patients in the metformin group had higher fasting plasma glucose levels (P = .03). After the 24-week intervention, body weight (P < .0001), body mass index (P < .0001), fasting plasma glucose (P < .0001), highdensity lipoprotein cholesterol (P = .03), insulin level (P = .01), and homeostasis model assessment index (P = .02) had significant changes in the metformin group. At the end of the intervention, 8 patients (28.57%) lost more than 7% of their body weight in the metformin group. Mean body weight returned to baseline after patients stopped the intervention in the metformin group. Conclusions: Metformin can significantly reduce body weight and reverse metabolic abnormalities in clozapine-treated patients with schizophrenia and preexisting metabolic abnormalities. However, the beneficial effects of metformin on body weight disappeared after discontinuing this medication. Trial Registration: ClinicalTrials.gov identifier: NCT01300637

Methamphetamine (METH) administration is associated with excessive oxidative stress. It is not known whether the systemic oxidative stress indices would alter during early abstinence in METH abusers with positive urine testing for recent METH exposure.Sixty-four non-treatment-seeking METH abusers enrolled from a controlled environment and 60 healthy controls participated in the study. Fasting serum malondialdehyde (MDA) levels and anti-oxidant indices, including superoxide dismutase (SOD) and catalase (CAT) activity, and glutathione (GSH) levels, were measured at baseline and 2 weeks after the first measurement. We compared the differences of these oxidative stress indices between METH abusers and controls and examined the changes of the indices 2 weeks after baseline in the METH group.At baseline, the recently abstinent METH abusers had significantly higher MDA levels, lower SOD activity, and higher CAT activity and GSH levels compared to healthy controls. CAT and GSH values were positively correlated with MDA but negatively correlated with SOD. These oxidative stress indices did not significantly correlate with age, smoking amount, Alcohol Use Disorder Identification Test scores, or METH use variables. After 2 more weeks of abstinence, the indices did not alter nor normalize.Compared to controls, we found that METH abusers have persistently higher systemic oxidative stress throughout early abstinence. The compromised SOD as well as elevated CAT activity and GSH levels may act together as a compensatory mechanism to counteract excessive oxidative stress induced by METH. Whether the oxidative stress could improve after a longer period of abstinence needs to be examined in future studies.

Illicit drug users, entering a detention center and two psychiatric hospitals in Northern Taiwan, were interviewed for lifetime drug-use-related psychiatric disorders and suicide attempts. Among 197 participants, 17.3%, 16.8%, and 14.2% had a drug-induced psychotic disorder (DIP), a drug-induced mood disorder (DIM), and a history of suicide attempts, respectively. Continuous use of methamphetamine and joblessness were associated with DIP and DIM, accordingly. Polysubstance use was collectively correlated with DIP and DIM. Female gender and history of having any mood disorder were predictors of suicide. These results provide useful clues for detecting drug-related psychiatric disorders and suicide among illicit drug users. The study's limitations are noted.