Protocol and rationale-the efficacy of minocycline as an adjunctive treatment for major depressive disorder: a double blind, randomised, placebo controlled trial

While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of \u27antidepressant\u27 but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression

The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): study protocol for a randomised control trial.

The aim of the Youth Depression Alleviation-Combined Treatment (YoDA-C) study is to determine whether antidepressant medication should be started as a first-line treatment for youth depression delivered concurrently with psychotherapy. Doubts about the use of medication have been raised by meta-analyses in which the efficacy and safety of antidepressants in young people have been questioned, and subsequent treatment guidelines for youth depression have provided only qualified support

The College News, 1918-05-23, Vol. 04, No. 27

Bryn Mawr College student newspaper. Merged with The Haverford News in 1968 to form the Bi-college News (with various titles from 1968 on). Published weekly (except holidays) during the academic year

A novel way to quantify schizophrenia symptoms in clinical trials

Background: A major problem in quantifying symptoms of schizophrenia is establishing a reliable distinction between enduring and dynamic aspects of psychopathology. This is critical for accurate diagnosis, monitoring and evaluating treatment effects in both clinical practice and trials. Materials and methods: We applied Generalizability Theory, a robust novel method to distinguish between dynamic and stable aspects of schizophrenia symptoms in the widely used Positive and Negative Symptom Scale (PANSS) using a longitudinal measurement design. The sample included 107 patients with chronic schizophrenia assessed using the PANSS at five time points over a 24‐week period during a multi‐site clinical trial of N‐Acetylcysteine as an add‐on to maintenance medication for the treatment of chronic schizophrenia. Results: The original PANSS and its three subscales demonstrated good reliability and generalizability of scores (G = 0.77‐0.93) across sample population and occasions making them suitable for assessment of psychosis risks and long‐lasting change following a treatment, while subscales of the five‐factor models appeared less reliable. The most enduring symptoms represented by the PANSS were poor attention, delusions, blunted affect and poor rapport. More dynamic symptoms with 40%‐50% of variance explained by patient transient state including grandiosity, preoccupation, somatic concerns, guilt feeling and hallucinatory behaviour. Conclusions: Identified dynamic symptoms are more amendable to change and should be the primary target of interventions aiming at effectively treating schizophrenia. Separating out the dynamic symptoms would increase assay sensitivity in trials, reduce the signal to noise ratio and increase the potential to detect the effects of novel therapies in clinical trials

Maintenance N-acetyl cysteine treatment for bipolar disorder : a double-blind randomised placebo controlled trial

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493)

A full Bayesian hierarchical mixture model for the variance of gene differential expression

<p>Abstract</p> <p>Background</p> <p>In many laboratory-based high throughput microarray experiments, there are very few replicates of gene expression levels. Thus, estimates of gene variances are inaccurate. Visual inspection of graphical summaries of these data usually reveals that heteroscedasticity is present, and the standard approach to address this is to take a log₂transformation. In such circumstances, it is then common to assume that gene variability is constant when an analysis of these data is undertaken. However, this is perhaps too stringent an assumption. More careful inspection reveals that the simple log₂transformation does not remove the problem of heteroscedasticity. An alternative strategy is to assume independent gene-specific variances; although again this is problematic as variance estimates based on few replications are highly unstable. More meaningful and reliable comparisons of gene expression might be achieved, for different conditions or different tissue samples, where the test statistics are based on accurate estimates of gene variability; a crucial step in the identification of differentially expressed genes.</p> <p>Results</p> <p>We propose a Bayesian mixture model, which classifies genes according to similarity in their variance. The result is that genes in the same latent class share the similar variance, estimated from a larger number of replicates than purely those per gene, i.e. the total of all replicates of all genes in the same latent class. An example dataset, consisting of 9216 genes with four replicates per condition, resulted in four latent classes based on their similarity of the variance.</p> <p>Conclusion</p> <p>The mixture variance model provides a realistic and flexible estimate for the variance of gene expression data under limited replicates. We believe that in using the latent class variances, estimated from a larger number of genes in each derived latent group, the <it>p</it>-values obtained are more robust than either using a constant gene or gene-specific variance estimate.</p

The SMILES trial: An important first step

The SMILES trial was the first intervention study to test dietary improvement as a treatment strategy for depression. Molendijk et al. propose that expectation bias and difficulties with blinding might account for the large effect size. While we acknowledge the issue of expectation bias in lifestyle intervention trials and indeed discuss this as a key limitation in our paper, we observed a strong correlation between dietary change and change in depression scores, which we argue is consistent with a causal effect and we believe unlikely to be an artefact of inadequate blinding. Since its publication, our results have been largely replicated and our recent economic evaluation of SMILES suggests that the benefits of our approach extend beyond depression. We argue that the SMILES trial should be considered an important, albeit preliminary, first step in the field of nutritional psychiatry research

A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial)

Correction to this article published: Jacka, FN, O'Neil, Adrienne, Opie, Rachelle, Itsiopoulos, Catherine, Cotton, SM, Mohebbi, M, Castle, David J, Dash, Sarah (external link), Mihalopoulos, Cathrine, Chatterton, Mary Lou, Brazionis, Laima, Dean, OM, Hodge, A. M and Berk, Michael (2018) Correction to: A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial). BMC Medicine, 16 (1). ISSN 1741-701

Correction to: A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial)

The original version of this paper [1] did not specify that a website was used in the final year of recruitment, in addition to the other stated recruitment methods. Corrigendum to: Jacka, FN, O'Neil, Adrienne, Opie, Rachelle, Itsiopoulos, Catherine, Cotton, Sue, Mohebbi, M, Castle, David, Dash, Sarah , Mihalopoulos, Cathrine, Chatterton, Mary Lou, Brazionis, Laima, Dean, OM, Hodge, Allison M and Berk, Michael (2017) A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial). BMC Medicine, 15. ISSN 1741-701