Shu-Yu Yang

Antipsychotic drug prescription for schizophrenia in East Asia: rationale for change

Abstract  The purpose of this international collaborative study was to investigate the prescription patterns of antipsychotic drugs for schizophrenia in East Asia and to analyze factors that affect these patterns. Prescription patterns for patients admitted for treatment of schizophrenia were surveyed using a standardized protocol from six East‐Asian region/countries: China, Hong Kong, Japan, Korea, Singapore and Taiwan. Patients’ social and clinical characteristics, psychiatric symptoms, course of illness, and adverse effects of medications were systematically assessed and recorded. Prescriptions of the first‐ and second‐generation antipsychotic drugs were compared. A total of 2399 patients were recruited. The second‐generation drugs comprised 28.1% of all prescribed antipsychotics, and 46% of the antipsychotic prescriptions were in the context of polypharmacy. The mean dosage of antipsychotics for the whole sample was 675.3 + 645.1 mg chlorpromazine equivalents. Japan had a high frequency of prescribing high doses and polypharmacy; Singapore had a high utilization of depot injections while China had a higher prescription of clozapine. Using multiple logistic regression analysis, distinctions in the prescription patterns of antipsychotic drugs were found: first‐generation drugs were mainly for controlling aggressive behavior, while second‐generation drugs were targeted at the alleviation of positive, negative psychotic symptoms as well as disruptive behavior in schizophrenia. The present collaborative study highlighted differences in the prescription patterns, especially the under‐utilization of second‐generation antipsychotic drugs in East Asia. The pattern of antipsychotic medication use varied from country to country and is likely to be influenced by the prevailing health‐care system, the availability and cost of the drugs.

Antipsychotic polypharmacy in inpatients with schizophrenia in Asia (2001−2009)

OBJECTIVE This study aimed to identify trends in the use of antipsychotic polypharmacy (APP) and their demographic and clinical correlates in the treatment of schizophrenia in Asia between 2001 and 2009. METHOD A total of 6,761 schizophrenia inpatients in 9 Asian countries and territories were examined; 2,399 in 2001, 2,136 in 2004, and 2,226 in 2009. Patients’ socio-demographic and clinical characteristics and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. RESULTS The proportion of APP prescription decreased from 46.8 % in 2001, to 38.3 % in 2004, and increased to 43.4 % in 2009, with wide intercountry variations at each survey. Multiple logistic regression analysis of the whole sample revealed that patients on APP were younger, had a higher dose of antipsychotics in chlorpromazine equivalents, and more severe positive and negative symptoms. They were also more likely to receive depot and fi rst-generation antipsychotic drugs. CONCLUSIONS The frequency of APP prescription varied between countries and territories, suggesting that a host of clinical and socio-cultural factors played a role in determining APP use in Asia. To resolve the discrepancy between treatment recommendation and clinical practice, regular reviews of prescription patterns are needed.

High‐dose antipsychotic use in schizophrenia: a comparison between the 2001 and 2004 Research on East Asia Psychotropic Prescription (REAP) studies

AIMS We aimed to examine the frequency of high-dose (defined as mean chlorpromazine mg equivalent doses above 1000) antipsychotic prescriptions in schizophrenia and their clinical correlates in the context of a comparison between studies in 2001 and 2004 within six East Asian countries and territories. METHODS Prescriptions of high-dose antipsychotic for a sample of 2136 patients with schizophrenia from six countries and territories (mainland China, Hong Kong, Korea, Japan, Taiwan and Singapore) were evaluated in 2004 and compared with data obtained for 2399 patients in 2001. RESULTS Overall, the comparison between 2001 and 2004 showed a significant decrease in high-dose antipsychotic use from 17.9 to 6.5% [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.26, 0.39, P < 0.001]. Patients who received high-dose antipsychotics were significantly more likely to have multiple admissions (OR 1.96, 95% CI 1.16, 3.33, P = 0.009), more positive psychotic symptoms such as delusions (OR 2.05, 95% CI 1.38, 3.05, P < 0.001) and hallucinations (OR 1.85, 95% CI 1.30, 2.64, P = 0.001), but less likely to have negative symptoms (OR 0.58, 95% CI 0.40, 0.82, P = 0.002). Multivariate regression analyses revealed that prescription of high-dose antipsychotics was also predicted by younger age (P < 0.001), time period of study (2001; P < 0.001), use of first-generation antipsychotic (P < 0.001) and depot antipsychotics (P < 0.001) as well as antipsychotic polytherapy (P < 0.001). CONCLUSIONS We identified the clinical profile and treatment characteristics of patients who are at risk of receiving high antipsychotic doses. These findings should provide impetus for clinicians to constantly monitor the drug regimes and to foster rational, evidence-based prescribing practices.

Adjunctive benzodiazepine treatment of hospitalized schizophrenia patients in Asia from 2001 to 2008

Benzodiazepines are commonly prescribed to patients with schizophrenia in many countries, but as little is known about such treatment in Asia, we evaluated their adjunctive use for 6761 in-patients diagnosed with schizophrenia in nine Asian countries using a cross-sectional study design in 2001, 2004 and 2008. Multivariate logistic regression and multivariate linear regression analyses were performed to assess predictors of benzodiazepine use and dose, respectively. Overall, 54% of the patients received adjunctive benzodiazepines at an average daily dose equivalent to 30.3 mg diazepam, with minor changes over the years sampled. Benzodiazepine use was highest in Taiwan and Japan, lowest in Thailand and China, and was associated with fewer years ill, presence of delusions (OR 1.24), hallucinations (OR 1.22), disorganized speech (OR 1.17), social or occupational dysfunction (OR 1.16), and use of mood stabilizers (OR 3.15), antiparkinsonian (OR 1.79) or antidepressant drugs (OR 1.33), and lower doses of antipsychotics (all p=0.016 to <0.001). Benzodiazepine doses were highest in Taiwan and China, lowest in Korea and Singapore; higher doses were associated with being young, male, physically aggressive, receiving mood stabilizers, and having electroconvulsive treatment (all p=0.019 to <0.001). Benzodiazepine use was associated with neurological and systemic adverse effects. In conclusion, benzodiazepine use was common in Asian patients with schizophrenia. Predictors of benzodiazepine use and dose differed in this population. Critical clinical guidelines should be developed specifically for Asian countries to address sound practices in regard to use of benzodiazepines for psychotic disorders.

Antipsychotic Drugs, Mood Stabilizers, and Risk of Pneumonia in Bipolar Disorder: A Nationwide Case-Control Study

OBJECTIVE Like mood stabilizers, most second-generation antipsychotics are widely used to treat patients with bipolar disorder, yet their safety is still a concern. This study explored the association between antipsychotics and mood stabilizers and the risk of pneumonia, and it provides evidence-based information for clinical practice. METHOD In a nationwide cohort of bipolar patients (ICD-9 codes 296.0 to 296.16, 296.4 to 296.81, and 296.89) derived from the National Health Insurance Research Database in Taiwan, who were admitted between July 1, 1998, and December 31, 2006 (N = 9,999), we identified 571 patients who developed pneumonia (ICD-9 codes 480 to 486 and 507) requiring hospitalization defined as cases. On the basis of risk-set sampling in a 1:4 ratio, 2,277 matched controls were selected from the same cohort. We used conditional logistic regression to assess the association between drug exposure and pneumonia and sensitivity analyses to validate the association. RESULTS Current use of several antipsychotics separately, including olanzapine (adjusted risk ratio [RR] = 2.97, P < .001), clozapine (RR = 2.59, P < .01), and haloperidol (RR = 3.68, P < .001), is associated with a dose-dependent increase in the risk of pneumonia. Interestingly, lithium has a dose-dependent protective effect from pneumonia. Among certain drug combinations, olanzapine plus carbamazepine had the highest risk (RR = 11.88, P < .01), followed by clozapine plus valproic acid (RR = 4.80, P < .001). CONCLUSIONS Several antipsychotics, but not mood stabilizers, were associated with the risk of pneumonia, which deserves our concern regarding patient safety. Some of the combinations of therapy resulted in synergy of risk.

Clozapine Use in Schizophrenia: Findings of the Research on Asia Psychotropic Prescription (REAP) Studies from 2001 to 2009:

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.

Prescribing antipsychotic drugs for inpatients with schizophrenia in Asia: Comparison of REAP-2001 and REAP-2004 studies: Prescribing antipsychotics in REAP study

Introduction: This international collaborative study aimed to investigate the trend and change in prescription patterns of antipsychotic drugs for inpatient schizophrenia in Asia by comparing two surveys in 2001 and 2004.

Use of electroconvulsive therapy for Asian patients with schizophrenia (2001–2009): Trends and correlates

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.

Common use of high doses of antipsychotic medications in older Asian patients with schizophrenia (2001-2009)

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.

Adjunctive antidepressant prescriptions for hospitalized patients with schizophrenia in Asia (2001–2009)

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.