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

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

Second-generation antipsychotics activate platelets in antipsychotic-naive and antipsychotic-free patients with schizophrenia: A retrospective study.

Objective: Among the risk factors for cerebrovascular/cardiovascular disease or thromboembolic events caused by the administration of second-generation antipsychotics, clinicians have mainly focused on metabolic side effects, with little interest in the effects on platelet activity. Because excessive platelet activity can increase the risk for cerebrovascular/cardiovascular disease, the aim of this study was to investigate the effect of second-generation antipsychotics on platelet activity in patients with schizophrenia. Methods: The medical records of patients with schizophrenia who were treated with second-generation antipsychotics were retrospectively reviewed. The degree of platelet activation was assessed by measuring the mean platelet component. Results: Wilcoxon signed-rank test revealed that mean platelet component levels were significantly decreased by the administration of second-generation antipsychotics (V = 20; p < 0.05), suggesting that the administration of second-generation antipsychotics may increase platelet activation. Conclusion: Because platelet activation is an additional risk factor for the occurrence of cerebrovascular/cardiovascular disease, results of this study suggest that clinicians should carefully monitor the degree of platelet activation after the administration of second-generation antipsychotics.

Cannabis use correlates with aggressive behavior and long-acting injectable antipsychotic treatment in Asian patients with schizophrenia.

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 reported in Asian population. Aim: We compared the clinical characteristics and psychotropic prescription patterns between cannabis users and non-users among Asian patients with schizophrenia. Moreover, we aimed to identify the independent correlates of cannabis use in these subjects. Methods: We performed the analysis of the data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), a collaborative consortium survey used to collate the prescription patterns for antipsychotic and other psychotropic medications in patients with schizophrenia in Asia. We included 132 schizophrenia patients in the group of lifetime cannabis use and 1756 in the group that had never used cannabis. A binary logistic model was fitted to detect the clinical correlates of lifetime cannabis use. Results: Adjusting for the effects of age, sex, geographical region, income group, duration of untreated psychosis, and Charlson comordity index level, a binary logistic regression model revealed that lifetime cannabis use was independently associated with aggressive behavior [adjusted odds ratio (aOR) = 1.582, 95% confidence interval (CI) = 1.006-2.490, p = .047] and with long-acting injectable antipsychotic treatment (aOR = 1.796, 95% CI = 1.444-2.820, p = .001). Conclusion: Our findings indicate a close link between lifetime cannabis use and aggressive behavior. The use of long-acting, injectable antipsychotics preferentially treats the aggressive behavior cannabis users among patients with schizophrenia in Asia, especially, the South or Southeast Asia.

Examining Patterns of Polypharmacy in Bipolar Disorder: Findings from the REAP-BD, Korea.

Based on Korean data from the Research on Asian Psychotropic Prescription Pattern for Bipolar Disorder, this study tried to present prescription patterns in biopolar disorder (BD) and its associated clinical features. Based on the information obtained from the study with structured questions, the tendency of prescription pattern was studied and analyzed. Polypharmacy was predominant, including simple polypharmacy in 51.1% and complex polypharmacy in 34.2% of patients. Subjects associated with simple or complex polypharmacy were significantly younger, had higher inpatient settings, a larger portion of onset with manic episode, a shorter duration of untreated illness, a shorter duration of current episode, were more overweight, used less antidepressants and used more anxiolytics. These findings can suggest higher polypharmacy rate in more severe BD and highlight the necessity of monitoring the weight of subjects with polypharmacy.

Prevalence of Metabolic Syndrome in Patients with Schizophrenia in Korea: A Multicenter Nationwide Cross-Sectional Study.

OBJECTIVE: We designed a nationwide study with limited exclusion criteria to investigate the prevalence of metabolic syndrome (MetS) in Korea and its relationship with antipsychotic medications. METHODS: This multicenter, cross-sectional, and observational study included patients diagnosed with schizophrenia or schizoaffective disorder. Sixteen hospitals enrolled 845 patients aged 18 to 65 years prescribed any antipsychotic medication between August 2011 and August 2013. MetS was diagnosed using the criteria of the modified Adult Treatment Panel III of the National Cholesterol Education Program with the Korean abdominal obesity definition (waist circumference ≥85 cm in women, ≥90 cm in men). RESULTS: The prevalence of MetS in all patients was 36.5% and was significantly higher in men than women (men, 40.8%; women, 32.2%) and was significantly correlated with age [odds ratio (OR) 1.02] and duration of illness (OR 1.03). The prevalence of MetS across antipsychotic drugs in the major monotherapy group was as follows: 18.8% for quetiapine, 22.0% for aripiprazole, 33.3% for both amisulpride and paliperidone, 34.0% for olanzapine, 35% for risperidone, 39.4% for haloperidol, and 44.7% for clozapine. CONCLUSION: The prevalence of MetS is very high in patients with schizophrenia or schizoaffective disorder. Screening and monitoring of MetS is also strongly recommended.

Hazardous drinking-related characteristics of depressive disorders in Korea: the CRESCEND study.

This study aimed to identify clinical correlates of hazardous drinking in a large cohort of Korean patients with depression. We recruited a total of 402 depressed patients aged > 18 yr from the Clinical Research Center for Depression (CRESCEND) study in Korea. Patients' drinking habits were assessed using the Korean Alcohol Use Disorder Identification Test (AUDIT-K). Psychometric scales, including the HAMD, HAMA, BPRS, CGI-S, SSI-Beck, SOFAS, and WHOQOL-BREF, were used to assess depression, anxiety, overall psychiatric symptoms, global severity, suicidal ideation, social functioning, and quality of life, respectively. We compared demographic and clinical features and psychometric scores between patients with and without hazardous drinking behavior after adjusting for the effects of age and sex. We then performed binary logistic regression analysis to identify independent correlates of hazardous drinking in the study population. Our results revealed that hazardous drinking was associated with current smoking status, history of attempted suicide, greater psychomotor retardation, suicidal ideation, weight loss, and lower hypochondriasis than non-hazardous drinking. The regression model also demonstrated that more frequent smoking, higher levels of suicidal ideation, and lower levels of hypochondriasis were independently correlates for hazardous drinking in depressed patients. In conclusion, depressed patients who are hazardous drinkers experience severer symptoms and a greater burden of illness than non-hazardous drinkers. In Korea, screening depressed patients for signs of hazardous drinking could help identify subjects who may benefit from comprehensive therapeutic approaches.

Evidence-based, non-pharmacological treatment guideline for depression in Korea.

Although pharmacological treatment constitutes the main therapeutic approach for depression, non-pharmacological treatments (self-care or psychotherapeutic approach) are usually regarded as more essential therapeutic approaches in clinical practice. However, there have been few clinical practice guidelines concerning self-care or psychotherapy in the management of depression. This study introduces the 'Evidence-Based, Non-Pharmacological Treatment Guideline for Depression in Korea.' For the first time, a guideline was developed for non-pharmacological treatments for Korean adults with mild-to-moderate depression. The guideline development process consisted of establishing several key questions related to non-pharmacologic treatments of depression, searching the literature for studies which answer these questions, assessing the evidence level of each selected study, drawing up draft recommendation, and peer review. The Scottish Intercollegiate Guidelines Network grading system was used to evaluate the quality of evidence. As a result of this process, the guideline recommends exercise therapy, bibliotherapy, cognitive behavior therapy, short-term psychodynamic supportive psychotherapy, and interpersonal psychotherapy as the non-pharmacological treatments for adult patients with mild-to-moderate depression in Korea. Hence, it is necessary to develop specific methodologies for several non-pharmacological treatment for Korean adults with depression.

Changes in heart rate dynamics of patients with schizophrenia treated with risperidone.

Neurocardiac dysregulation has been reported in schizophrenia. Indices of heart rate variability (HRV) are useful in assessing the status of cardiac autonomic regulation. We explored within-subject changes in HRV indices in acutely ill patients with schizophrenia treated with risperidone. Sixteen medication-naïve or medication-free patients with DSM-IV schizophrenia completed electrocardiogram (ECG) assessments at baseline and after six weeks of treatment with risperidone. Indices of HRV were extracted from 5-min resting ECG recordings and compared to those obtained from control subjects matched for age and gender. Psychiatric and drug-induced extrapyramidal symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). In comparison with matched controls, patients with acute schizophrenia showed lower values of time-domain measures, lower high-frequency power (HF) and a higher ratio of low to high frequency (LF/HF). In the within-subject analyses, a significant decrease in LF/HF was associated with risperidone treatment. In addition, LF/HF, which initially co-clustered with clinical variables, congregated with other HRV measures after the six-week risperidone treatment. These results indicate that, in the therapeutic process, risperidone treatment may exert a beneficial influence on the sympathovagal imbalance in acute schizophrenia.

Differential pattern of heart rate variability in patients with schizophrenia.

The cardiac autonomic dysfunction has been reported in patients with schizophrenia. Heart rate variability (HRV) provides non-invasive indices of cardiac autonomic modulation. This study examined whether patients with schizophrenia may show a distinctive pattern of HRV compared to healthy controls. Nine measures of time, frequency and complexity domains were extracted from 5-min resting evaluation of HRV in 30 unmedicated patients with schizophrenia and 30 age- and gender-matched controls. In addition to inferential statistics, a hierarchical clustering (HC) was used to examine difference in the interrelationships among HRV measures between the two groups. Multivariate analysis of variance revealed a significant group effect. Significantly lower sample entropy (SampEn) and a trend towards a higher ratio of low- to high frequency (LF/HF) were observed in the schizophrenia group. In the results of HC using Ward's method, SampEn co-clustered with LF/HF ratio in patients with schizophrenia compared to the separation of LF/HF ratio in healthy controls. In concert with decreased parasympathetic activity, low complexity of heart rate dynamics may reduce adaptability of cardiovascular system to changes in internal or external environment, thus increasing the risk of cardiovascular events. Diverse HRV measures combined in a multivariate fashion appear to be useful in understanding the pattern of neurocardiac modulation in patients with schizophrenia.