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Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease. We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer's disease. Patients concomitantly using other medicines for Alzheimer's disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer's disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and the Alzheimer's Disease Co-operative Study–Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov (NCT01689246) and the European Union Clinical Trials Registry (2012-002866-11). Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control [n=354, 6·32, 95% CI 5·31−7·34]: 75 mg LMTM twice a day [n=257] −0·02, −1·60 to 1·56, p=0·9834, 125 mg LMTM twice a day [n=250] −0·43, −2·06 to 1·20, p=0·9323; change in ADCS-ADL score compared with control [−8·22, 95% CI −9·63 to −6·82]: 75 mg LMTM twice a day −0·93, −3·12 to 1·26, p=0·8659; 125 mg LMTM twice a day −0·34, −2·61 to 1·93, p=0·9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants. The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer's disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer's disease will be reported soon. TauRx Therapeutics.

Background Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine's acute effects on explicit suicidal cognition and a performance‐based index of implicit suicidal cognition (Implicit Association Test; IAT) previously linked to suicidal behavior. Method Symptomatic patients with treatment‐resistant unipolar major depression (inadequate response to ≥3 antidepressants) were assessed using a composite index of explicit suicidal ideation (Beck Scale for Suicidal Ideation, Montgomery‐Asberg Rating Scale suicide item, Quick Inventory of Depressive Symptoms suicide item) and the IAT to assess suicidality implicitly. Measures were taken at baseline and 24 hr following a single subanesthetic dose of ketamine (n = 36) or midazolam (n = 21), a psychoactive placebo agent selected for its similar, rapid anesthetic effects. Twenty four hours postinfusion, explicit suicidal cognition was significantly reduced in the ketamine but not the midazolam group. Results Fifty three percent of ketamine‐treated patients scored zero on all three explicit suicide measures at 24 hr, compared with 24% of the midazolam group (χ2 = 4.6; P = .03). Implicit associations between self‐ and escape‐related words were reduced following ketamine (P = .01; d = .58) but not midazolam (P = .68; d = .09). Ketamine‐specific decreases in explicit suicidal cognition were largest in patients with elevated suicidal cognition at baseline, and were mediated by decreases in nonsuicide‐related depressive symptoms. Conclusions Intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo. Further study is warranted to test ketamine's antisuicidal effects in higher‐risk samples.

Background Mental health is increasingly viewed as the presence of various aspects of well-being rather than just the absence of mental illness. The Mental Health Continuum-Short Form (MHC-SF) is a 14-item instrument that assesses mental health, focusing on emotional, psychological, and social well-being. The present study examined for the first time the psychometric properties of the Dutch version of the MHC-SF among adolescents, focusing on its factor structure, internal consistency, construct validity, and gender and age factorial invariance. Methods Data were collected from a school-based sample of 1175 adolescents (53.4% girls) aged 11–17 years (M = 13.7; SD = 1.1). Participants completed an online questionnaire in the classroom during regular school hours. Statistical analyses to evaluate the factor structure, internal consistency, construct validity, and gender and age factorial invariance were performed in SPSS and R. Results Using confirmatory factor analyses, a satisfactory-to-good fit was obtained for the three-factor model (emotional, psychological, and social well-being). The MHC-SF scores showed good internal consistency (Cronbach’s alpha = .91) and results supported convergent and divergent validity. Finally, the MHC-SF showed gender and age factorial invariance. Conclusion The current psychometric evaluation indicates the MHC-SF is a reliable and valid instrument to assess multiple dimensions of well-being among Dutch adolescents. The instrument can be applied for research purposes and in clinical practice.

Background Youth mental health has emerged as a pressing global issue. However, to advance research gaps in low-income settings, we need valid measures of common mental health disorders. Using primary data collected in five countries (Kenya, Malawi, Tanzania, Zambia, and Zimbabwe), this study aims to assess the psychometric properties of the commonly used 10-item Center for Epidemiological Studies Depression (CES-D 10) scale among poor, disadvantaged youth populations in sub-Saharan African (SSA). Methods Youth samples from each country (sample sizes ranging from 651 to 2098) come from large household surveys with youth modules, collected for impact evaluations of cash transfer programs targeted to poor families. For each sample, we assessed internal consistency (alpha), conducted factor analysis, and then examined construct validity and measurement invariance. We performed both exploratory (EFA) and confirmatory factor analysis (CFA) to examine and confirm the structure of the CES-D 10 for each country and then used multigroup CFA to assess measurement invariance across gender and age. Multivariate analyses were conducted to assess construct validity via test of the relationship between CES-D 10 and background characteristics. Results Results show the CES-D 10 had strong psychometric properties and was a reliable measure of depressive symptoms among disadvantaged youth in SSA. Across countries, there was high internal consistency (Cronbach alphas = 0.70–0.76) and the traditional two-factor solution showed good model fit. Full measurement invariance of the CES-D 10 was supported across gender. Consistent with previous literature on risk factors for depressive symptoms, the CES-D 10 was associated with increasing age, and female gender and being out of school in some locations. Conclusions Results from this study support broad use of the CES-D 10 among poor youth populations in SSA. Between one-third and two-thirds of our samples demonstrated depressive symptoms as classified by recommended cut-offs for the CES-D 10, indicating a high burden of mental illness in disadvantaged youth populations. This tool can be used in future efforts to study prevalence and dynamics of depressive symptoms in this population, as well as effectiveness of policies and interventions to improve the mental health of youth in SSA.

Cognitive behaviour therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD) but access to CBT is limited. Internet-based CBT (ICBT) with therapist support is potentially a more accessible treatment. There are no randomized controlled trials testing ICBT for OCD. The aim of this study was to investigate the efficacy of ICBT for OCD in a randomized controlled trial. Participants (n=101) diagnosed with OCD were randomized to either 10 weeks of ICBT or to an attention control condition, consisting of online supportive therapy. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS) administered by blinded assessors. Both treatments lead to significant improvements in OCD symptoms, but ICBT resulted in larger improvements than the control condition on the YBOCS, with a significant between-group effect size (Cohen's d) of 1.12 (95% CI 0.69-1.53) at post-treatment. The proportion of participants showing clinically significant improvement was 60% (95% CI 46-72) in the ICBT group compared to 6% (95% CI 1-17) in the control condition. The results were sustained at follow-up. ICBT is an efficacious treatment for OCD that could substantially increase access to CBT for OCD patients. Replication studies are warranted.

Smartphone-based psychoeducation interventions may be a low-cost, user-friendly alternative to resource-consuming, face-to-face antenatal classes to educate expectant mothers. This study aimed to empirically examine whether such an intervention would lead to reduced postnatal depression, anxiety, or stress and result in a better health-related quality of life. A single-blind randomized controlled trial was conducted in Hong Kong. All first-time expectant mothers with less than 24 weeks of gestation remaining and attending the antenatal clinic at a public hospital were included. Participants were assigned to the intervention group or the control group by drawing lots. The lots, presented in sealed opaque envelopes, were randomly designated as \"intervention\" or \"control\" by stratified randomization. The intervention, a psychoeducational mobile app, was provided in addition to the treatment as usual (TAU) services from the hospital. Follow up with participants took place at 4 weeks postpartum. The primary outcome was the difference in the levels of antenatal and postnatal depression, assessed by the Edinburgh Postnatal Depression Scale (EPDS). The intention-to-treat approach was employed in the analyses. The final sample was 660 expectant mothers (n =330 and n =330). The mean difference in EPDS scores between the two groups was -0.65 (95% CI -1.29 to 0.00; P=.049) after adjusting for confounding factors. Associations were found between participation in the intervention and reduced depression, and attendance in TAU classes and increased stress levels. The smartphone-based intervention plus TAU services was effective in reducing postnatal depression at 4 weeks postpartum compared with a control condition of TAU only, making this a cost-effective alternative to TAU education for expectant mothers. Limitations of the study included the short postpartum period after which the follow-up assessment was conducted and the inclusion of first-time mothers rather than all mothers. HKU Clinical Trials Registry HKUCTR-2024; http://www.hkuctr.com/Study/Show/ 34f62a2f6d594273a290491827206384.

The aim of this study is to examine the efficacy of mindfulness-based cognitive therapy (MBCT) in addition to treatment as usual (TAU) for recurrent depressive patients with and without a current depressive episode. A randomized, controlled trial comparing MBCT+TAU (n=102) with TAU alone (n=103). The study population consisted of patients with three or more previous depressive episodes. Primary outcome measure was post-treatment depressive symptoms according to the Hamilton Rating Scale for Depression. Secondary outcome measures included the Beck Depression Inventory, rumination, worry and mindfulness skills. Group comparisons were carried out with linear mixed modelling, controlling for intra-group correlations. Additional mediation analyses were performed. Comparisons were made between patients with and without a current depressive episode. Patients in the MBCT+TAU group reported less depressive symptoms, worry and rumination and increased levels of mindfulness skills compared with patients receiving TAU alone. MBCT resulted in a comparable reduction of depressive symptoms for patients with and without a current depressive episode. Additional analyses suggest that the reduction of depressive symptoms was mediated by decreased levels of rumination and worry. The study findings suggest that MBCT is as effective for patients with recurrent depression who are currently depressed as for patients who are in remission. Directions towards a better understanding of the mechanisms of action of MBCT are given, although future research is needed to support these hypotheses.

No abstract available Copyright © 2010 S. Karger AG, Basel [PUBLICATION ABSTRACT]