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.

Home-Based Contingency Management Delivered by Community Health Workers to Improve Alcohol Abstinence: A Randomized Control Trial.

AIM: To evaluate the effectiveness of home-based contingency management (CM) in improving abstinence in an incentive-dependent manner among alcoholic individuals. METHODS: A 12-week, home-visit (HV) only controlled, randomized incentive-ranging trial of 161 adults with current alcohol dependence was recruited using social network theory techniques. Participants randomly received HV, low- (CM-L) or higher-magnitude CM (CM-H). Community health workers made regular home visits, monitored drinking behavior and delivered CM as appropriate. Two follow-up visits at weeks 13 and 16 were conducted to assess whether abstinence would still be maintained after the interventions discontinued. Rates of continuous reported abstinence (primary), numbers of positive breath samples (secondary) over the intervention period and rates of prolonged reported abstinence (secondary) were evaluated. RESULTS: CM did not significantly improve the rates of continuous reported abstinence across the 12-week intervention period (odds ratio (OR) for trend 1.2, 95% confidence interval (CI) 0.7-2.1, P = 0.601). There was a significant reduction, however, in the average number of positive breath samples submitted by the CM-H group (generalized linear model, ß -0.5, 95% CI -0.9 to -0.2, P = 0.005). The CM-H arm also had a significantly higher abstinence rate during the follow-up period (OR 3.4, 95% CI 1.3-8.8, P = 0.013). Event history model suggested that the CM-H condition had significantly higher chances of achieving renewed abstinence across the study period (OR 2.0, 95% CI 1.3-3.2, P = 0.003). CONCLUSIONS: Home-based CM with sufficient incentive is promising in reducing alcohol use and in improving rates of abstinence over time. Allowing for a certain grace period may better capture the delayed treatment effect of home-based CM.

Estimating Impact Based on Stages of Mental Illness on Employment and Earnings in Bangkok Metropolitan Region.

BACKGROUND: Evidence suggests mental disorders are associated with substantial economic burden. However, as the status of mental illness tends to change over time, estimating the burden based on cross-sectional presence or severity of illness may be problematic. An approach based on illness staging may provide a more stable estimate. AIMS OF THE STUDY: We aim to explore whether three predefined stages of mental illness (i.e. early active, remitted, chronic) have differential impact on employment and earnings. METHODS: A community survey of household population aged 18 and over in a university hospital's catchment area within Bangkok Metropolitan Region (BMR) was conducted (N=3877). The third version of the World Health Organization-Composite International Diagnostic Interview (WHO-CIDI) was administered to assess lifetime and 12-month common major mental disorders and the Kessler Psychological Distress Scale (K6) to assess current psychological distress. Multivariate approaches were used to estimate the observed and expected annual earnings and employment for persons with mental illness at each stage, controlling for sociodemographic variables. RESULTS: Increasing level of chronicity, from the early active to the remitted and then to the chronic stage, was associated with increasing reduction in earnings (beta --0.14 95% CI -0.15 to --0.13, p = 0.004). All stages of illness were significantly associated with reduced earnings, with individuals at chronic stage having 12-month earnings averaging 78,522 Thai baht (USD 2,356) less than those without a history of mental illness, followed by those at remitted (38,703 baht or USD 1,161) and early active stages (25,870 baht or USD 776), with the same values for control variables. Remitted and chronic stages, but not early active one, were associated with reduced odds of paid employment. The estimated societal-level loss in earnings was 26.9 billion baht (USD 808.2 million) in the total BMR population. DISCUSSION: The findings suggest that all stages of mental disorders, particularly chronic one, are associated with substantial individual- and societal-level burden, and highlight differences in employment and earnings gaps among individuals at each stage of illness. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Mental health service should be provided in close coordination with vocational and welfare services in order to alleviate financial and work difficulties faced by mentally ill people at various stages of illness. IMPLICATIONS FOR HEALTH POLICIES: There is a need to tailor disability benefits and employment promotion schemes to the needs of mentally ill people at each stage in order to maximize their productivity and quality of life. IMPLICATIONS FOR FURTHER RESEARCH: Direct and other indirect costs of mental illness should be further investigated. Longitudinal studies would help to clarify how much of the reported association is due to mental illness causing unemployment and reduced earnings or vice versa.

Chicken Essence and Cognitive Function: A Systematic Review and Meta-Analysis.

OBJECTIVES: To determine the efficacy of chicken essence for improving cognitive performance. Material and Method: English language database including Embase, Medline, PsychINFO and Global Health (up to May 2014) were searched. Inclusion criteria were randomized double-blind controlled studies (RCT) or cross-over studies comparing chicken essence with placebo. Results: Four trials were included. Three studies measured cognitive performance, while the remaining study assessed cognitive performance after fatigue-inducing tasks. When compared to placebo, chicken essence improved arithmetic (SMD -1.23, 95% CI -2.51 to -0.31) and memory (SMD -3.94, 95% CI -4.59 to -3.29). There were no ascertainable positive effects on attention/concentration (SMD -1.55, 95% CI -4.77 to 1.67), anti-fatigue (SMD 1.20, 95% CI 0.53 to 1.88), and recovery from mental fatigue (SMD -0.38, 95% CI -1.0 to 0.25). However, the levels of evidence with respect to each cognitive domain was rated as 'very low' using the GRADE system because of low sample size, inconsistency and high risk of bias. Conclusion: There are few trials examining the efficacy of chicken essence to cognitive performance. Furthermore, the level of evidence was very low. Using it for this indication is not suggested at present. Additional high quality RCT designs are needed to arrive at a stronger conclusion.

A Case Report of Ketamine-induced Hypoglycemia in Treatment Resistance Depression.

Ketamine therapy can reduce the risk of suicide and depression in the treatment resistant patient. Adverse effects of ketamine infusion include blurred vision, nausea and vomiting, hepatotoxicity, headache, and cystitis. However, the effect of ketamine infusion on blood glucose remains unclear. This report describes several episodes of hypoglycemia in a 36-year-old man with type 1 diabetes mellitus after ketamine infusion for treatment-resistance depression. He has been receiving subcutaneous insulin injection and denied any severe hypoglycemia events in the prior 20 years. He had unsuccessful treatment for depression. His depressive conditions were subsequently improved due to ketamine therapy, however, he had recurrent hypoglycemia episodes. Clinicians should be aware of this potential adverse effect on initiating ketamine infusion with patients who had type 1 diabetes.

Efficacy and acceptability of vitamin D supplements for depressed patients: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This systematic review and meta-analysis synthesized the evidence from randomized controlled trials comparing vitamin D and placebo in reducing depressive symptoms and contributing to all-cause dropout rates. METHODS: Inclusion criteria were randomized controlled trials comparing reduced depression between depressed patients receiving vitamin D and those receiving placebo. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through January 2022. RESULTS: Eighteen trials (1980 participants, median age 39 y) were included in the meta-analysis. Vitamin D supplements were significantly superior to placebo in reducing depression (standardized mean difference = -0.49; 95% confidence interval [CI], -0.75 to -0.23; I2 = 81%). Depressed adults (standardized mean difference = -0.70; 95% CI, -1.09 to -0.31) responded to vitamin D significantly better than children and adolescents (standardized mean difference = 0.10; 95% CI -0.27 to 0.47). Vitamin D administered as bolus doses (oral intermittent high doses or intramuscular single high dose) appeared to be more effective than that taken daily by the oral route (P < 0.01). Patients with more severe depression tended to respond better than those with less severity (P = 0.053). We found no moderating effect of concurrent antidepressant use, presence of major depressive disorder diagnosis, physical comorbidity, sex, duration and doses of vitamin D supplement, serum 25-hydroxyvitamin D levels at baseline, and changes in serum 25-hydroxyvitamin D levels in the vitamin D group. Dropout rates were indifferent between the groups (17 trials; risk ratio = 0.84; 95% CI, 0.6-1.16; I2 = 0). CONCLUSIONS: Heterogeneous data suggested that vitamin D supplements are effective and safe for depressed patients.

Classification and analysis of text transcription from Thai depression assessment tasks among patients with depression.

Depression is a serious mental health disorder that poses a major public health concern in Thailand and have a profound impact on individuals' physical and mental health. In addition, the lack of number to mental health services and limited number of psychiatrists in Thailand make depression particularly challenging to diagnose and treat, leaving many individuals with the condition untreated. Recent studies have explored the use of natural language processing to enable access to the classification of depression, particularly with a trend toward transfer learning from pre-trained language model. In this study, we attempted to evaluate the effectiveness of using XLM-RoBERTa, a pre-trained multi-lingual language model supporting the Thai language, for the classification of depression from a limited set of text transcripts from speech responses. Twelve Thai depression assessment questions were developed to collect text transcripts of speech responses to be used with XLM-RoBERTa in transfer learning. The results of transfer learning with text transcription from speech responses of 80 participants (40 with depression and 40 normal control) showed that when only one question (Q1) of "How are you these days?" was used, the recall, precision, specificity, and accuracy were 82.5%, 84.65, 85.00, and 83.75%, respectively. When utilizing the first three questions from Thai depression assessment tasks (Q1 - Q3), the values increased to 87.50%, 92.11%, 92.50%, and 90.00%, respectively. The local interpretable model explanations were analyzed to determine which words contributed the most to the model's word cloud visualization. Our findings were consistent with previously published literature and provide similar explanation for clinical settings. It was discovered that the classification model for individuals with depression relied heavily on negative terms such as 'not,' 'sad,', 'mood', 'suicide', 'bad', and 'bore' whereas normal control participants used neutral to positive terms such as 'recently,' 'fine,', 'normally', 'work', and 'working'. The findings of the study suggest that screening for depression can be facilitated by eliciting just three questions from patients with depression, making the process more accessible and less time-consuming while reducing the already huge burden on healthcare workers.

Mindfulness-based interventions reducing and preventing stress and burnout in medical students: A systematic review and meta-analysis.

OBJECTIVE: Stress and burnout are serious problems that impair the well-being and academic performance of medical students. Published systematic reviews and meta-analyses on interventions to reduce the stress experienced by medical students did not conclude which interventions are the most effective due to the heterogeneity of the studies. To enhance the hierarchy of evidence, our study selected only randomized controlled studies. The aims were to obtain more reliable outcomes and to precisely summarize the specific interventions which effectively reduce the stress levels and burnout of medical students. METHODS: We performed a systematic review and meta-analysis according to PRISMA guidelines. Medical databases (Embase, Ovid, and CINAHL) were searched for relevant randomized controlled studies published up to December 2019. Two treatment timepoints (postintervention, and the 6-month follow-up) were chosen. Stress measure outcomes were the main outcomes. A random effects model was used. An intention-to-treat analysis was conducted. RESULTS: Six high-quality studies were found. They compared the efficacies of mindfulness-based interventions and clerkship as usual (N = 689). The stress measurement scores of each mindfulness-based intervention at postintervention were significantly better than those of the control groups, with medium effect size and low heterogeneity (95% CI 0.07-0.51; p = 0.01; I-squared index = 45%). At the 6-month follow-up, the mindfulness groups had significantly better results than the control groups, with medium effect size and negligible heterogeneity (95% CI 0.06-0.55; p = 0.02; I-squared index = 0%). DISCUSSION: The results indicate that mindfulness-based interventions are effective in reducing subjective stress in medical students at both the short- and long-term intervention timepoints.

Mental problems and risk factors for depression among medical students during the COVID-19 pandemic: A cross-sectional study.

Prevalence of depression is high among medical students and several mental problems are identified as risk factors. Coronavirus disease 2019 (COVID-19) pandemic causes difficulties that could adversely affect mental health. However, data concerning prevalence of mental problems, and whether or not these problems remain risk factors for depression during the COVID-19 pandemic in medical students are scarce. To investigate the prevalence of depression, social media addiction, game addiction, sleep quality, eating disorder risk, and perceived stress among Thai medical students, risk factors for depression were investigated. Online surveys via our faculty's learning portals were advertized to medical students who engaged online learning and 224 respondents provided complete data. Study-related medical students' data were collected using the Patient Health Questionnaire-9 for depression, the Social-Media Addiction Screening Scale for social media addiction, the Game Addiction Screening Test for game addiction, the Pittsburgh Sleep Quality Index for sleep quality, the Eating Attitudes Test for eating disorder risk, and the Perceived Stress Scale for perceived stress. Depression was reported in 35.7% of medical students, social-media addiction in 22.3%, game addiction in 4.5%, eating disorder risk in 4.9%, poor sleep quality in 80.8%, and moderate-to-high perceived stress in 71.4%. The independent predictors of depression were lower grade point average, social media addiction, and moderate-to-high perceived stress. A high prevalence of depression, stress, and poor sleep was found among medical students during the COVID-19 pandemic. Medical students who are stressed, have lower grades, and/or who are addicted to social media warrant depression screening.

Is lithium monitoring NICE? Lithium monitoring in a UK secondary care setting.

BACKGROUND: Lithium is widely used for the treatment of bipolar disorder. Owing to its narrow therapeutic index and side-effect profile, regular monitoring of serum levels, renal and thyroid function has been recommended by all major guidelines on lithium use. OBJECTIVES: We investigated whether lithium monitoring during maintenance phase treatment in clinical practice meets the latest recommendation by the National Institute for Health and Clinical excellence (i.e. lithium levels between 0.6 and 1.0 mmol/L and lithium level, thyroid and renal function tests every 6 months) in one of the largest mental health organizations in Europe, the South London and Maudsley (SLaM) NHS Foundation Trust. METHODS: Retrospective data were extracted from SLaM's Clinical Record Interactive Search (CRIS) system. Adult patients with a psychiatric disorder who were on lithium at any point during the period January 2012-January 2016 and had at least one lithium level test result in the system were included in the analyses. RESULTS: A total of 2639 lithium level tests results were retrieved for 412 patients. Overall, the serum level was within the recommended range in 50.7% of all tests, below the range in 42.4% and above in 6.9%. Lithium level, renal and thyroid function tests were performed at the recommended frequency of 6 months (or less) in 76.2%, 72.7% and 60.2% of patients, respectively. CONCLUSION: These data demonstrate that there is a gap between the NICE 2014 recommendation and lithium monitoring practice in secondary care, with a high number of lithium level results below the therapeutic minimum. Reminder strategies for secondary care practitioners, shared care agreements or a central registry for lithium users could improve monitoring performance.