A randomized controlled pilot study of daily intravenous ketamine over three days for treatment-resistant depression.

BACKGROUND: Studies have confirmed the rapid antidepressant action of ketamine in depressive episodes. Nevertheless, a standardized procedure for the delivery of ketamine infusion in individuals suffering from treatment-resistant depression, particularly in terms of infusion frequency and total dosage, remains undetermined. In addition, an efficacious ketamine regimen for persistent pain management involved a continuous 10-day infusion period with no notable adverse effects. Consequently, the primary objective of this study was to evaluate the antidepressant capacity of consecutive ketamine infusions spanning over three successive days, the duration of therapeutic response, and the overall safety profile of the treatment. METHODS: In this randomized controlled trial, participants aged 18-64 with treatment-resistant depression were randomized to receive either intravenous ketamine or midazolam (used as an active placebo) for 40 min daily over three consecutive days. Statistical analysis using repeated measures ANOVA was employed to assess the changes in the total score of the Montgomery-Åsberg Depression Rating Scale (MADRS) and the clinical global impression-Severity from the initial assessment to 10 and 31 days post-infusion. Additionally, the duration of response and remission was evaluated using Kaplan-Meier survival analysis. RESULTS: Out of 33 randomized participants, 20 underwent the treatment as planned. By day 10th, the ketamine group had a mean reduction in MADRS score of 12.55 (95% CI = 6.70-18.09), whereas the midazolam group had a decrease of 17.22 (95% CI = 11.09-23.36). This pattern continued to day 31, with ketamine showing a mean score decrease of 13.73 (95% CI = 7.54-19.91) and midazolam a fall of 12.44 (95% CI = 5.61-19.28). Both treatments were well tolerated, with dissociative symptoms in the ketamine group being temporary and ceasing by the end of each infusion. CONCLUSION: Intravenous ketamine given for three consecutive days did not show a notable antidepressant advantage when compared to the active placebo midazolam, highlighting the need for further research into effective treatments schedules for treatment-resistant depression. TRIAL REGISTRATION: NCT05026203, ClinicalTrials.gov, registered on 24/08/2021.

Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling. RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not. CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

Burnout study during the COVID-19 pandemic in Thailand: psychometric evaluation of the Maslach Burnout Inventory-Human Services Survey for Medical Personnel.

Objectives: This study aimed (1) to determine the psychometric properties of a Thai version of the Maslach Burnout Inventory-Human Services Survey for Medical Personnel (MBI-HSS [MP]) and (2) to examine the mean scores of burnout and associated factors during the COVID-19 pandemic. Methods: Forward and back translations of the MBI-HSS (MP) questionnaire were performed. The Thai version was subsequently completed by 682 Thai physicians and nurses who worked during the COVID-19 pandemic. Exploratory factor analysis was performed on the first subsample (n = 341) by conducting Kaiser Mayer-Olkin sampling adequacy measurement and Bartlett's test of sphericity whereas confirmatory factor analysis (CFA) was performed on the second subsample (n = 341) using fit indices of the normed chi-square (χ2/df), the comparative fit index, the Tucker-Lewis index, and the root mean square error of approximation. This version's internal consistency was investigated using Cronbach's alpha coefficient. Demographic profiles were evaluated with descriptive and analytical statistics. Results: The Thai version of the MBI-HSS (MP) displayed good psychometric characteristics, as the Cronbach's alpha values of the 3 burnout factors ranged from 0.843 to 0.945. The CFA also showed good fit indices (χ2/df = 4.473; P < 0.001; RMSEA = 0.075 (95%CI = 0.055-0.079); CFI = 0.946; and TLI = 0.936). The physicians' mean EE, DP, and PA scores were 25.28 ± 13.27, 7.15 ± 6.11, and 36.83 ± 8.13, respectively, whereas The nurses' mean EE, DP, and PA scores were 23.10 ± 14.14, 4.43 ± 5.06, and 35.67 ± 10.24, respectively. Healthcare professionals who were younger, single, had fewer years of practice, and had more working hours per week tended to express more burnout scores. Conclusions: The Thai version of the MBI-HSS (MP) demonstrates good psychometric properties in assessing burnout among healthcare professionals. Several factors may be pivotal in intensifying burnout.

Clinical use of mood stabilizers beyond treatment for bipolar disorder: The REAP-MS study.

OBJECTIVE: Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar. METHODS: Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection. RESULTS: In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication. CONCLUSIONS: Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation.

Clozapine Use for Bipolar Disorder: An Asian Psychotropic Prescription Patterns Consortium Study.

BACKGROUND: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing. METHODS: We examined the prevalence and clinical correlates of clozapine treatment for BD in 13 Asian countries and regions (China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, and Thailand) within an Asian Prescription Patterns Research Consortium. We compared BD patients treated with clozapine or not in initial bivariate comparisons followed by multivariable logistic regression modeling. RESULTS: Clozapine was given to 2.13% of BD patients overall, at a mean daily dose of 275 (confidence interval, 267-282) chlorpromazine-equivalent mg/day. Patients receiving clozapine were older, more likely males, hospitalized, currently manic, and given greater numbers of mood-stabilizing and antipsychotic drugs in addition to clozapine. Logistic regression revealed that older age, male sex, current mania, and greater number of other antipsychotics remained significantly associated with clozapine treatment. Clozapine use was not associated with depressed mood, remission of illness, suicidal risk, or electroconvulsive treatment within the previous 12 months. CONCLUSIONS: The identified associations of clozapine use with particular clinical features call for vigilance in personalized clinical monitoring so as to optimize clinical outcomes of BD patients and to limit risks of adverse effects of polytherapy.

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

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

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

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

Dosing of Mood Stabilizers for Bipolar Disorder Patients in the Research on Asian Psychotropic Prescription Patterns Consortium Study.

BACKGROUND: Because use and dosing of mood stabilizers (MSs) to treat bipolar disorder (BD) patients in Asia are not well documented, we examined prevalence and clinical correlates of treatment of Asian BD patients with relatively high doses of MSs. METHODS: We conducted a pharmacoepidemiological survey across 13 Asian countries and territory in the Research on Asian Psychotropic Prescription Patterns Consortium. Mood stabilizer doses were converted to lithium carbonate equivalents (Li-eq milligrams per day). We compared relatively high (>900 Li-eq mg/day) versus lower MS doses by bivariate comparisons, followed by multivariable linear regression to identify factors associated with higher MS doses. RESULTS: Among 1647 participants, MS dose averaged 584 (confidence interval, 565-603 Li-eq mg/d). Preliminarily, the 13.1% of the subjects given greater than 900 mg/d versus those given lower doses were younger, male, currently hospitalized, not currently depressed, and reported lifetime suicidal ideation; they also received relatively high doses of antipsychotics, received electroconvulsive treatment within the previous 12 months, and had greater ratings of tremors and sedation. By linear regression modeling, the mean proportion given high doses of MS was associated significantly and independently with higher doses of antipsychotics, younger age, male sex, hospitalized, more years of illness, country, higher body mass index, recent electroconvulsive treatment, and being in illness remission. CONCLUSIONS: Relatively high doses of MSs for BD are prevalent, but vary markedly among Asian countries, and are particularly likely among young males, ill for many years, and given high doses of antipsychotics or ECT. These characteristics allow better identification of patient profiles that can guide treatment of BD patients.

Prescription Patterns for Bipolar Disorder in Asian Countries: Findings from Research on Asian Prescription Pattern-Bipolar Disorder.

OBJECTIVE: Pharmacotherapy including mood stabilizers and antipsychotics are frequently used in bipolar disorder (BD); however, the lack of consensus regarding the definition of polypharmacy hinders conducting comparative studies across different settings and countries. Research on Asian Prescription Pattern (REAP) is the largest and the longest lasting international collaborative research in psychiatry in Asia. The objective of REAP BD was to investigate the prescription patterns of psychotropic medications across Asian countries. The rates of polypharmacy and psychotropic drug load were also analyzed. METHODS: The data collection was web-based. Prescription patterns were categorized as (1) mood stabilizer monotherapy: one mood stabilizer; (2) antipsychotic monotherapy: one antipsychotic; (3) simple polypharmacy: one mood stabilizer and one antipsychotic; and (4) complex polypharmacy: ≥ 2 mood stabilizers or/and antipsychotics. The psychotropic drug load in each patient was calculated using the defined daily dose method. RESULTS: Among 2003 patients with BD (52.1% female, 42.4 years) from 12 countries, 1,619 (80.8%) patients received mood stabilizers, 1,644 (82.14%) received antipsychotics, and 424 (21.2%) received antidepressants, with 14.7% mood stabilizer monotherapy, 13.4% antipsychotic monotherapy, 48.9% simple polypharmacy, 20.3% complex polypharmacy, and 2.6% other therapy. The average psychotropic drug load was 2.05 ± 1.40. Results varied widely between countries. CONCLUSION: Over 70% of psychotropic regimens involved polypharmacy, which accords with the high prevalence of polypharmacy in BD under a permissive criterion (2 or more core psychotropic drugs) worldwide. Notably, ≥ 80% of our sample received antipsychotics, which may indicate an increasing trend in antipsychotic use for BD treatment.

Prevalence and Factors Associated with Fear of Falling in Community-Dwelling Thai Elderly.

BACKGROUND: Falls are common in older people. The fear of falling (FOF) can lead elderly persons to restrict their activities which reduces quality of life. We aimed to estimate the prevalence and factors associated with FOF in community-dwelling Thai elderly to improve screening, treatment and prevention policies and practices. OBJECTIVES: We aimed to estimate the prevalence and factors associated with FOF in suburban-dwelling Thai seniors. METHODS: Seniors aged 60-85 years old from 4 suburban communities near Bangkok, Thailand, were interviewed and examined. Questionnaires were used to collect data on the FOF, symptoms of depression, anxiety and balance tests. T tests, χ2 tests, and logistic regressions were used in statistical analysis. RESULTS: 210 subjects were enrolled. The mean age was 70.3, and 74.3% were female. Fifty-three (25.2%) reported a previous history of falls. The prevalence of FOF was 35.8% in the subjects with previous history of falls and 21.7% in subjects without previous history of falls. FOF was associated with female gender, age ≥80, living alone, impaired balance, and functional impairment but not with previous history of falls. CONCLUSION: FOF is associated with balance impairment, anxiety, depression, and functional impairment of daily routine activities.

Depression, quality of life and coping style among Thai doctors before their first year of residency training.

OBJECTIVES: Depression and suicide often affect young physicians coping with the demands of residency training. To support effective prevention programmes, we aim to assess depression, quality of life (QoL) and coping style of doctors prior to beginning residency training. METHODS: A cross-sectional study of physicians prior to their first year of residency training at the Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand, was conducted. Questionnaires including the Thai versions of the Proactive Coping Inventory, Patient Health Questionnaire and the Pictorial Thai Quality of Life (PTQL) scale were emailed to all first-year residents 1 week before the beginning of residency training in 2015. Descriptive statistics, χ2 test, independent-sample t-test and Pearson's correlation test were analysed. RESULTS: Among 277 doctors, 102 (36.8%) responded to the survey. The average age of respondents was 26.8 (range 25-33; SD=1.2) and 69.6% were women. Nearly all (99.0%) had moderate-to-high overall QoL scores. Depression was found in 10 (9.8%) of respondents. Depression severity was negatively correlated with proactive coping and QoL. Proactive coping (r=0.509, p<0.001), reflective coping (r=0.266, p=0.007), strategic planning (r=0.347, p<0.001), preventive coping (r=0.298, p=0.002) and emotional support seeking (r=0.252, p=0.011) were positively correlated with QoL. Furthermore, proactive was correlated with lower depressive symptoms severity (r=-0.303, p=0.002). CONCLUSIONS: Although nearly all doctors reported moderate-to-high QoL, positive screening for depression was observed in 9.8% of doctors which is much higher than the prevalence in Thais (1.2%). Mental health promotion policies are essential to help residents effectively cope with the stress and demands of training.

Thai psychiatrists and burnout: A national survey.

OBJECTIVES: To explore the prevalence and factors that contribute to burnout among Thai psychiatrists. BACKGROUND: The practice of psychiatry can lead to emotional fatigue. As rates of emotional illness in Thailand continue to climb, increasing demands are placed on a limited number of psychiatrists. This can lead to burnout, and multiple negative physical and mental health outcomes. MATERIALS AND METHODS: Electronic questionnaires were sent to all 882 Thai psychiatrists and residents via a private social media group managed by the Psychiatric Association of Thailand. The questionnaire included demographic data, the Maslach Burnout Inventory (MBI), the Proactive Coping Inventory, and questions about strategies that Thai psychiatrists believed reduce/prevent burnout. RESULTS: Questionnaires were sent and 227 (25.7%) responded. According to MBI, 112 (49.3%) of respondents reported high level of emotional exhaustion, and 60 (26.4%) had a high level of depersonalization. Nearly all respondents (99.6%) maintained a high level of personal accomplishment. Working more than 50 hours per week (p = 0.003) and more patients per day (p = 0.20) were associated with higher levels of burnout. Feeling satisfied with work (p<0.001) and having a good support system from family (p = 0.027) and colleagues (p = 0.033) were associated with lower levels of burnout. The coping mechanisms related to lower levels of burnout included more emotional support seeking (p = 0.005), more proactive coping (p = 0.047), and less avoidance (p = 0.005). CONCLUSIONS: Compared to a previous study on burnout among Thai psychiatrists in 2011, in this study, the prevalence of high levels of burnout had increased dramatically from 17.1% to 49.3%. An intervention to decrease workload, strengthen social support and encourage proactive coping mechanisms may be beneficial for relieving burnout.

Clozapine-induced agranulocytosis and leukopenia: Incidence, associated factors, and rate of hematologic adverse-effects monitoring in psychiatric out-patient services in Thailand.

The present study aimed to investigate the incidence of agranulocytosis and leukopenia and its associated factors in Thai schizophrenia patients treated with clozapine and the rate of hematologic adverse events monitored in clinical practice. Data were collected from the medical records of 641 outpatients at two hospitals. The results showed no cases of agranulocytosis and 20 cases of leukopenia (3.1%), 85% of which were observed after 1 year of prescription. The associated factors were female (p = 0.019) and duration of clozapine prescription (p = 0.026). According to the guideline for safety monitoring, 23.6% of cases had neutrophils count monitoring.