Active clinical trials for "Depressive Disorder"

The investigators will conduct a randomized controlled trial (RCT), comparing SSM (n=96) versus HEP (n=96) in 192 LLD participants stratified by site and presence of treatment resistant late life depression (TR-LLD). Participants will be blinded to the treatment hypothesis while investigators, raters and treating clinicians will be additionally blinded to the intervention. Both SSM and HEP will be taught over 4 consecutive days in similar sized groups (4-10 participants) followed by weekly reinforcement sessions for subsequent 11 weeks. Trained raters will collect data on depression symptoms (HAM-D 17 scale) and cognition at baseline, 12-week and 26-week follow-up as the primary and secondary outcome measures respectively.

To evaluate effects of mantra meditation on depressive symptoms if applied as adjunctive therapy to psychotherapy and/or antidepressant drugs and to explore if meditation leads to increased spirituality as a potential mediating factor of positive mental health.

Most clinical major depression responds to standard treatments (medication and psychotherapy); however, a significant subset of depressed patients (15-20%) do not respond to these treatments and are referred to as treatment-resistant major depression (TRMD). New treatments for TRMD are needed, and one promising line of research are drugs known as N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. In a recent pilot study, our group demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD. This application proposes to take the next important step in understanding how nitrous oxide exerts its effects in the human brain by using state-of-the-art brain neuroimaging (functional connectivity magnetic resonance imaging) in a group of non-depressed, healthy volunteers and comparing the results to a group of TRMD patients. This study involves exposing 20 non-depressed healthy participants and 20 TRMD participants to nitrous oxide and a placebo gas, to compare their brain images before and after each of the inhalation sessions. Sessions will be separated by at least one month to prevent treatment effects from carrying over into the following session. All willing and eligible subjects will undergo up to six functional connectivity MRI scans, and two inhalation sessions. Functional imaging in the brain will allow us to trace the interconnections between various parts of the brain, including those involved with emotion and depression. Other procedures will involve screening materials to ensure safety of the participants before beginning the study (i.e. no MRI scan contraindications) and that subjects meet eligibility criteria to being in the targeted age range, depression/non-depressed state, neurological disorder history, and no medication exclusions.

For a number of reasons women with major depressive disorder often discontinue conventional antidepressants when they become pregnant and prefer not to take them when depressive illness develops in the course of pregnancy. There is now considerable evidence that the administration of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), as monotherapy has antidepressant effects. If it could be clearly established as effective such an approach would offer a valuable alternative for woman who are at risk for, or who develop, depressive disorder during pregnancy. Strongly positive placebo-controlled trials of EPA supplementation, though, co-exist with entirely negative ones. No clear reasons for these discrepancies have emerged but one possibility is that the samples studied have differed in the proportion of individuals likely to benefit from EPA supplementation. As there has been no effort to identify such individuals we propose to explore two groups of measures, both relevant to EPA's likely mechanisms of action, as potential tools for identifying individuals likely to benefit this treatment. Hypothesis: Among women who experience major depressive episodes during their first two trimesters of pregnancy, baseline measures of cytokine activity and erythrocyte PUFA concentrations will be associated, in an additive or interactive fashion, with subsequent improvement in depressive symptoms among women taking omega-3 PUFA supplementation.

Among people with HIV, the severity of depressive symptoms has repeatedly been associated with the presence of self-reported cognitive difficulties, even in the absence of impairment on neuropsychological testing. There is uncertainty about the clinical importance of these self-reports, especially when neuropsychological testing is normal. However, there is growing evidence that these self-reports are clinically important. For example, among patients with major depressive disorder (MDD), evidence suggests that functional impairments is mediated by self-reported cognitive dysfunction, rather than objective cognitive dysfunction. Treatment of depression with Cognitive-Behaviour Therapy (CBT) has been shown to improve depressive symptoms and psychosocial functioning in patients with recurrent major depressive disorder, but there are few studies of the impact of psychotherapy on self-reported cognition and cognitive performance. Good Days Ahead (GDA) is a computerized treatment program developed to address symptoms of depression and anxiety. It teaches the basic principles of computerized behavioral therapy (CBT) in nine therapy sessions, each typically taking 30 minutes to complete. GDA has been found to be as effective as face-to-face CBT in decreasing symptoms of depression and anxiety. The hypothesis is that people whose depressive symptoms are reduced following treatment with cCBT will also report fewer cognitive difficulties than before treatment. A second hypothesis is that changes in self-reported cognition will be concordant with changes in cognitive performance, such that people who make no improvement in self-report cognition will also show no improvement in cognitive performance and those who do improve on self-report will improve on cognitive performance.

This study is a multicenter, randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of brexpiprazole as adjunctive therapy in the treatment of Major Depressive Disorder. A total of approximately 1100 subjects will be enrolled into the single-blind treatment for 6 weeks, and 480 incomplete responders will be randomized to brexpiprazole (2~3 mg) or placebo in a 1:1 ratio (approximately 240 subjects in each group), for treatment of 6 weeks.

The investigators propose to determine if 8 weeks of dietary augmentation with oral 5g creatine monohydrate daily and 100 mg of 5-hydroxytryptophan (5-HTP) twice daily reduces hypoxia-related depressive symptoms measured by the 17-item Hamilton Depression Rating Scale (HAM-D) in women with SSRI- or SNRI-resistant depression, combined with the examination of changes in functional connectivity based on resting-state fMRI and changes in brain metabolism inferred from phosphorus-31 magnetic resonance spectroscopy.

The investigators hypothesize that personalizing the rTMS targets using functional MRI will increase its efficacy. The most dysfunctional regions or the most dysfunctional network will be stimulated homogeneously. Individualized rTMS will be compared to traditional rTMS procedure and to trans-cranial direct current stimulation (tDCS) in a randomized cross-over trial. In this pilot study the primary outcome measure will be the correction of the MRI anomalies. Symptoms reduction and the proportion of remitters will be secondary outcome measurements.

The goal of this proposal is to conduct the first pilot study of whether consuming flavanol supplements will augment the cognitive and mood benefits of antidepressant medication in older adults with Late LifeDepression (LLD). Flavanols represent a specific group of plant derived nutrients that are found in cocoa beans, grapes, tea, berries and various other fruits and vegetables. The specific flavanols investigated in this study come from cocoa. Currently available treatments for LLD (i.e., antidepressant medication) are limited in efficacy, especially in individuals who also suffer from cognitive impairment. Recent studies performed at Columbia and elsewhere suggest that flavanols may induce beneficial brain changes that support cognitive functioning and elevate mood, but their precise clinical effects in older adults with combined depression and cognitive impairment remain to be evaluated. For this study, the investigators plan to recruit 50 adults aged ≥60 years who have Major Depressive Disorder, meet a minimum depressive symptom threshold despite currently receiving an adequate trial of an antidepressant, and have a significant cognitive complaints without a diagnosis of dementia. Subjects will be randomized to receive 8 weeks of augmentation treatment with flavanol capsules (in addition to continuing their antidepressant) vs. capsules not containing flavanols. Pre- and post-treatment MRI scanning of the brain will be conducted, and comprehensive pre- and post-treatment neuropsychological assessment will be performed. Results from this project will allow the investigators to evaluate a novel therapeutic approach to LLD, which could have large public health ramifications given the prevalence, frequent treatment resistance, and chronicity characteristic of LLD.

In the Investigator's ongoing studies of Posttraumatic Stress Disorder (PTSD) in older adults, it has been found that older adults with PTSD frequently meet the criteria for comorbid Major Depressive Disorder (MDD). Moreover, relative to trauma-exposed healthy controls (TEHCs), elders with PTSD manifest executive function deficits, fatigability, and mobility and physical function deficits that are consistent with what the investigator has observed in depressed older adults. Yet, the investigator has found that very few older adults with combined PTSD/MDD have received appropriate antidepressant treatment for their condition. These findings give rise to the questions of (1) how effective is antidepressant treatment for depressive symptoms in the context of PTSD/MDD and (2) are cognitive and physical function deficits in PTSD/MDD patients reversible with effective antidepressant treatment?