Dataset Information

Outcomes reported in randomised clinical trials of major depressive disorder treatments in adolescents: a systematic scoping review protocol.

ABSTRACT:

Introduction

Major depressive disorder (MDD) is a common mental health condition in adolescents. Randomised clinical trials (RCTs) are the gold standard for assessing the safety and efficacy of interventions in this population. Heterogeneity in the outcomes measured and reported between RCTs limits the ability to compare, contrast, and combine trial results in a clinically meaningful way. There is currently no core outcome set (COS) available for use in RCTs evaluating interventions in adolescents with MDD. We will conduct a systematic scoping review of outcomes reported in adolescent depression RCTs to assess the variability of trial outcomes and to inform the development of a COS for adolescent MDD.

Methods and analysis

We will apply methods based on the Joanna Briggs Institute scoping review methods manual. RCTs evaluating any treatment intervention for adolescent MDD published in the last 10 years will be located using an electronic bibliographic database search (MEDLINE, PsycINFO and Cochrane Central Register of Controlled Trials). Title and abstract screening, full-text screening, and data charting of eligible studies will be performed in duplicate. Outcomes identified will be mapped to an outcome-domain framework. Data analysis will include summary statistics of the characteristics of the included trials and outcomes.

Ethics and dissemination

The results of this review will inform the development of a COS for adolescent MDD. The development and implementation of a COS for RCTs evaluating interventions in adolescents with MDD promise to help reduce variability in trial outcome selection, definition, measurement and reporting, ultimately facilitating evidence synthesis that will help to identify the best treatment practices for adolescents with MDD.

SUBMITTER: Monsour A

PROVIDER: S-EPMC6340428 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Outcomes reported in randomised clinical trials of major depressive disorder treatments in adolescents: a systematic scoping review protocol.

Monsour Andrea A Mew Emma J EJ Szatmari Peter P Patel Sagar S Saeed Leena L Offringa Martin M Butcher Nancy J NJ

BMJ open 20190115 1

<h4>Introduction</h4>Major depressive disorder (MDD) is a common mental health condition in adolescents. Randomised clinical trials (RCTs) are the gold standard for assessing the safety and efficacy of interventions in this population. Heterogeneity in the outcomes measured and reported between RCTs limits the ability to compare, contrast, and combine trial results in a clinically meaningful way. There is currently no core outcome set (COS) available for use in RCTs evaluating interventions in a ...[more]

PMID: 30782729

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Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:BackgroundSelective serotonin reuptake inhibitors (SSRIs) are amongst the most prescribed antidepressants for adolescents with depressive symptoms and major depressive disorder. However, SSRIs have significant shortcomings as a first-line treatment considering that not all patients respond to these antidepressants. Amongst paediatric populations, meta-analyses indicate that up to approximately 40% of patients do not respond, and for those who do show benefit, there is substantial heterogeneity in response onset. The neurotransmitter serotonin (5-HT) plays a role in the clinical effectiveness and mechanisms of action of SSRIs. However, the exact and complete mechanism of action and reasons for the low response rate to SSRIs in some adolescent populations remains unknown.MethodsTo examine SSRI response and the role of 5-HT, this study will employ a randomised double-blind within subject, repeated measures design, recruiting adolescent patients with major depressive disorder. Participants will be subjected to acute tryptophan depletion (ATD) and the balanced control condition on two separate study days within a first study phase (Phase A), and the order in which these conditions (ATD/balanced control condition) occur will be random. This phase will be followed by Phase B, where participants will receive open label pharmacological treatment as usual with the SSRI fluoxetine and followed-up over a 12-week period.DiscussionATD is a neurodietary method typically used to investigate the impact of lowered brain 5-HT synthesis on mood and behaviour. The major hypothesis of this study is that ATD will be negatively associated with mood and cognitive functioning, therefore reflecting individual serotonergic sensitivity and related depressive symptoms. Additionally, we expect the aforementioned effects of ATD administration on mood to predict clinical improvement with regard to overall depressive symptomatology 12 weeks into SSRI treatment.Trial registrationAustralian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001561471 . Registered on 11 November 2016.

Project description:Conventional antidepressants require 2-8 weeks for a full clinical response. In contrast, two rapidly acting antidepressant interventions, low-dose ketamine and sleep deprivation (SD) therapy, act within hours to robustly decrease depressive symptoms in a subgroup of major depressive disorder (MDD) patients. Evidence that MDD may be a circadian-related illness is based, in part, on a large set of clinical data showing that diurnal rhythmicity (sleep, temperature, mood and hormone secretion) is altered during depressive episodes. In a microarray study, we observed widespread changes in cyclic gene expression in six regions of postmortem brain tissue of depressed patients matched with controls for time-of-death (TOD). We screened 12 000 transcripts and observed that the core clock genes, essential for controlling virtually all rhythms in the body, showed robust 24-h sinusoidal expression patterns in six brain regions in control subjects. In MDD patients matched for TOD with controls, the expression patterns of the clock genes in brain were significantly dysregulated. Some of the most robust changes were seen in anterior cingulate (ACC). These findings suggest that in addition to structural abnormalities, lesion studies, and the large body of functional brain imaging studies reporting increased activation in the ACC of depressed patients who respond to a wide range of therapies, there may be a circadian dysregulation in clock gene expression in a subgroup of MDDs. Here, we review human, animal and neuronal cell culture data suggesting that both low-dose ketamine and SD can modulate circadian rhythms. We hypothesize that the rapid antidepressant actions of ketamine and SD may act, in part, to reset abnormal clock genes in MDD to restore and stabilize circadian rhythmicity. Conversely, clinical relapse may reflect a desynchronization of the clock, indicative of a reactivation of abnormal clock gene function. Future work could involve identifying specific small molecules capable of resetting and stabilizing clock genes to evaluate if they can rapidly relieve symptoms and sustain improvement.

Project description:ObjectiveOur goal was to review current peer-reviewed articles in which the BDI (Beck Depression Inventory), PHQ-9 (Patient Health Questionnaire), or QIDS-SR16 (16-Item Quick Inventory of Depressive Symptomatology) was used as the primary or secondary outcome measure and to evaluate the quality of PRO (Patient-Reported Outcome) reporting in RCTs (Randomized Controlled Trials) according to the 2013 PRO-specific CONSORT (Consolidated Standards of Reporting Trials) extension.MethodsWe systematically searched in electronic databases. A study would be included if it included patients diagnosed with major depressive disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases, version 10 (ICD-10) as participants, was a randomized controlled trial, included the BDI, PHQ-9, or QIDS-SR16 as the primary or secondary outcome measure, published between 1990 and 2013, and was in English. Two of the authors evaluated the quality of PRO reporting according to the 2013 CONSORT-PRO. Logistic regression were used to evaluate the association between reporting completeness and trial characteristics.ResultsA total of 116 studies were included. These studies were conducted in 25 countries. Sample sizes ranged from 12 to 750. The CONSORT-PRO was not cited in any one of the included studies. Among the 116 studies, 2 (1.72%) studies introduced the rationale for PRO assessment, 60 (51.72%) studies explicitly stated statistical approaches for dealing with missing data, 87 (75.00%) studies reported PRO outcome data at baseline and at subsequent time points. The mean score of reporting completeness was 66.24%. Significantly higher reporting completeness was found for RCTs published after 2013 (OR, 95%CI: 3.81, 1.32-10.99). Studies with a higher sample size were more completely reported than studies with a lower sample size (OR, 95%CI: 1.01, 1.00-1.02).ConclusionThe CONSORT-PRO guidance was rarely cited. The quality of PRO reporting in depression studies requires improvement. This result may be meaningful for the promotion of PRO reporting in RCTs.

Dataset Information

Outcomes reported in randomised clinical trials of major depressive disorder treatments in adolescents: a systematic scoping review protocol.

Introduction

Methods and analysis

Ethics and dissemination

Publications

Outcomes reported in randomised clinical trials of major depressive disorder treatments in adolescents: a systematic scoping review protocol.

Similar Datasets

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