Active clinical trials for "Depressive Disorder, Major"

The study will investigate whether a nociceptin receptor antagonist will normalize neural and behavioral processes of approach/avoidance decision-making in unmedicated individuals with major depressive disorder (MDD) and anxiety disorders. More specifically, the study aims to investigate dysregulation within (1) corticostriatal-midbrain circuitry and (2) nociceptin/orphanin FQ peptide and the nociceptin receptor (NOPR).

The aim of this pilot project proposal is to test the hypothesis that decreased sleep slow-wave activity (SWA) observed in individuals with major depressive disorder (MDD) is related to mood dysfunction, and that manipulating SWA may serve to improve mood by normalizing SWA regulation. The investigators propose to enhance SWA during nighttime sleep in a group of 20 antidepressant-free males and females age 25-50 with varying degrees of impairment in mood. Each participant will undergo one baseline night of sleep in the laboratory and then will sleep with the SmartSleep Headband nightly for two weeks in their own home. For one week, slow-wave sleep will be enhanced. On the alternate week, sleep will not be changed. Following the two weeks of sleeping with the device, participants will then spend another night in the sleep laboratory to assess changes in sleep. Mood will be assessed by self-report and clinician-administered scales following the baseline night of sleep, virtually after the first experimental week, and at the conclusion of the study.

The goal of this study is to collect biologically based data for defining predictors and correlates of the effects of ALTO-100.

Background: Depression is a highly recurrent disorder, which often requires lifelong treatment. Psychotherapy has an important role in the treatment of depression, both in the treatment of the acute phase and in prevention of relapses. Mindfulness-based therapies have become popular in the last decade. Mindfulness-based Cognitive Therapy (MBCT) is an established treatment for relapse prevention in Major Depressive Disorder (MDD) and there is preliminary evidence of its efficacy in treating acute symptoms. Several studies have highlighted the benefits of MBCT in reducing the severity of depressive symptoms in patients diagnosed with a current Major Depressive Episode, as indicated by some meta-analyses showing that MBCT is more effective than treatment as usual in decreasing depressive symptoms and equivalent to active treatments. However, the results at follow-up were less conclusive, due to the limited number of studies and moderate-to-large heterogeneity within the subgroups. A number of studies have examined the effects of MBCT on a larger spectrum of factors that can affect the severity of depression. In patients with MDD, MBCT was more effective than treatment as usual in decreasing rumination, worry, negative affect and dysfunctional attitudes, increasing mindfulness skills and positive affect and improving sleep and quality of life. However, data comparing the specific effect of MBCT with other active treatments (for example Cognitive Behavioural Therapy, CBT) are lacking. Most trials exploring the efficacy of MBCT have been conducted with group MBCT, but there is less evidence about the use of individual MBCT (I-MBCT). Individual MBCT may have some advantages, compared with group therapy, such as better attendance and higher efficacy in major depression, when compared with group therapy. Furthermore, the individual format can often be better tailored to a specific patient, with a slower progression and a longer number of sessions, if needed. Objective: The primary objective of this pilot trial was to test the feasibility of a larger randomized trial examining the changes in depressive and anxiety symptoms, rumination, mindfulness, emotion regulation, behavioral activation and negative automatic thoughts during I-MBCT and cognitive behavioural therapy (CBT). Further objectives were: (a) replicating studies evaluating the efficacy of I-MBCT to improve depression, in particularly in patients diagnosed with a major depressive disorder; (b) assessing the persistence of benefits of I-MBCT after the end of treatment; (c) comparing the effects of I-MBCT with CBT, not only on depressive symptoms, but also on factors which are specifically targeted by MBCT, such as rumination and mindfulness; explore possible predictors of outcome of MBCT. Hypotheses: We make the following hypotheses: a) a larger trial comparing I-MBCT with CBT examining the changes of depressive and anxiety symptoms, rumination, mindfulness, emotion regulation, behavioral activation and negative automatic thoughts is feasible, with recruitment rates and drop-off rates consistent with those usually observed among participants with current major depression; b) the levels of depressive and anxiety symptoms, rumination, emotion dysregulation, and negative automatic thoughts will decrease during I-MBCT, while the levels of mindfulness and behavioral activation will increase, with effect sizes similar to those observed in CBT; c) the changes in depressive and anxiety symptoms, rumination, emotion dysregulation, negative automatic thoughts, mindfulness and behavioral activation will be maintained at follow-up; d) the changes in mindfulness and rumination dimensions are expected to be larger during MBCT than CBT; these analyses will be exploratory, given the state of knowledge; d) we will explore the role of predictors of clinical variables, such as earlier age at onset of the mood disorder; longer and more severe current episode; presence of current comorbidity with anxiety disorders, initial levels of anxiety, behavioral activation, emotion dysregulation and of the history of severe childhood maltreatment in predicting the outcome to MBCT and CBT.

Objective: The aim of this randomized controlled trial was to compare the efficacy and safety of sertraline and escitalopram in participants with moderate to severe major depressive disorder (MDD). Methods: A total of 744 participants with moderate to severe MDD were randomly assigned to receive either sertraline or escitalopram for 8 weeks. Drug dosages and titration schedules were based on the recommendations of the prescribing information for each product and according to the judgment of the clinicians involved in the study. The primary outcome measures were changes from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) scale as well as frequency of adverse events in both groups.

Depression and suicidal ideation/attempt/death are major causes of morbidity and mortality from psychiatric illnesses. In 2009, the World Health Organization listed depression as the leading cause of years lost due to disability worldwide. Suicide is the 9th most common cause of death in Canada with 1.6% of Canadians ultimately dying from suicide (Statistics Canada, 2012) and the 2nd most common cause of death in young people after accidental deaths. This information highlights the importance of finding treatments to prevent suicidal deaths. Ketamine has been shown to provide rapid treatment response for major depressive episodes both in major depressive disorder (MDD) and bipolar disorder (BD), via a single intravenous infusion which persists for at least 72 hours. The purpose of this study is to conduct a pilot trial of IV ketamine + treatment as usual (TAU) vs. midazolam (an active placebo) + TAU to estimate sample size for a full-scale RCT examining these treatments for decreasing suicidal ideation among depressed inpatients with major depressive disorder and bipolar depression. A total of 52 patients will be recruited for this trial. All subjects will be inpatients at Sunnybrook Health Sciences Centre with a diagnosis of either major depressive disorder or bipolar disorder type I or II currently depressed. Suicidal ideation must be present at baseline assessment in order to be included in the study. Thirteen subjects will be randomized to each treatment arm in each treatment stream - that is, 13 will be recruited to ketamine + TAU in the major depressive disorder stream, and 13 will be recruited to the midazolam + TAU in the major depressive stream. Likewise, 26 subjects with bipolar depression will be randomized to these two treatments.

Recent reports have shown that alcohol misuse is a particularly serious problem among the 18 to 25 year old age group. Previous medication trials with SSRI antidepressants among young adults with co-occurring depressive disorders, including our own recent trials with SSRI medications, have produced disappointing results, especially for decreasing the level of alcohol consumption. Mirtazapine is a non-SSRI medication with a unique structure and mechanism of action. Recent study results suggest that mirtazapine is more effective than other antidepressants for treating non-comorbid depression. A few recent studies with mirtazapine have been conducted among subjects with comorbid AUD/MDD, and those studies have demonstrated efficacy for mirtazapine for decreasing the depressive symptoms and the alcohol craving of subjects with comorbid AUD/MDD. However, those studies did not measure level of alcohol consumption, so it is unclear whether mirtazapine decreases the level of alcohol use of that comorbid population. The results of our own very recent open label pilot study suggest robust within-group efficacy for mirtazapine for decreasing both the level of alcohol use and the depressive symptoms of comorbid subjects. However, that pilot study did not include a placebo control group, so the efficacy of mirtazapine versus placebo for decreasing the level of alcohol use among persons with comorbid AUD/MDD remains unclear. This grant submission proposes to conduct a first double-blind, placebo-controlled pilot study to provide a preliminary assessment of the efficacy of mirtazapine versus placebo for decreasing both the alcohol use and depressive symptoms of young adults with comorbid AUD/MDD. If results (effect sizes) from the proposed study are found to be promising concerning outcome differences between the mirtazapine and placebo groups, then we will use those findings to apply for an R01 study to definitively assess the efficacy of mirtazapine for treating young adults with AUD/MDD.

This project aims to evaluate whether a dose-response relationship exists between dose of polyunsaturated fatty acids (PUFA), delivered as eicosapentaenoic acid (EPA), and change in markers of inflammation, and whether these effects differ from placebo. A key secondary aim is to evaluate the antidepressant effectiveness of EPA in overweight adult outpatients with current major depressive disorder (MDD). To address these aims, the project will use a four-arm, randomized, parallel-group, placebo-controlled design comparing placebo versus three doses of EPA (1 gm/day, 2 gm/day, or 4 gm/day) administered over 12 weeks. The study is to be conducted at two sites: Emory University School of Medicine, and Massachusetts General Hospital. Eligible participants will be between the ages of 18-80 who have current MDD, are overweight, and who demonstrate peripheral inflammation, defined as an high sensitivity C-reactive protein (hs-CRP) level ≥ 3 mg/L. The primary outcome will be change in plasma interleukin-6 (IL-6) levels and/or mitogen-stimulated peripheral blood mononuclear cells (PBMC) Tumor Necrosis Factor-alpha (TNF-α) expression levels in EPA- versus placebo-treated participants. The results of this investigation are intended to be used to design and power a larger definitive test of the efficacy and biological effects of EPA in patients with major depressive disorder.

With the dissatisfaction of monoamine-based pharmacotherapy and the high comorbidity of physical illness in depression, the serotonin hypothesis seems to fail in approaching the etiology of depression. Based upon the evidence from epidemiological data, case-control studies of PUFAs compositions, and antidepressant effects in clinical trials, phospholipid polyunsaturated fatty acids (PUFAs) is enlightening a promising path to discover the unsolved of depression.

The purpose of this study is to evaluate the efficacy of a multi-component yoga intervention featuring Sudarshan Kriya Yoga (SKY) as an adjunctive treatment for patients with Major Depressive Disorders with incomplete response to antidepressants.