Major Depressive Disorder Clinical Trials

The main purpose of this study is to investigate the effects of ketamine on decision-making and emotion processing in a sample of individuals diagnosed with Major Depressive Disorder (MDD). Read Less

The goal of this proposal is to examine the influence of feedback timing on learning and brain function in individuals with moderate-to-severe traumatic brain injury (TBI), with and without depression. Read Less

This study is being completed to see if participants activity levels may have an impact as a treatment for depression, or depressive symptoms. Eligible participants will be enrolled and have an 8-week running intervention three times each week. The study hypothesizes that adolescents with Psychiatric disorders that are experiencing depressive symptoms will participate in a supported running intervention. Read Less

HYPOTHESIS: Pregnenolone administration will be associated with greater reduction in depressive symptom severity than placebo in women with current mMDD. STUDY AIMS: Primary Aim: Determine if pregnenolone is associated with greater reduction in depressive symptom severity than placebo in women with mMDD, as measured by MADRS. Secondary Aims: Determine if pregnenolone is associated with greater reduction in anxiety symptom severity than placebo in women with mMDD. Determine if pregnenolone is associated with greater improvement in cognition than placebo in women with mMDD. Determine if pregnenolone is associated with greater improvement in quality of life than placebo in women with mMDD. Determine if pregnenolone is associated with greater improvement in vasomotor symptoms of menopause than placebo. Mechanistic Aims: Determine whether changes in neurosteroid levels with pregnenolone mediate clinical response. Determine if baseline neurosteroid levels predict pregnenolone response. Determine whether depressive symptoms, anxiety, sleep or vasomotor symptoms improve first. A crossed-lagged panel model will explore serial correlations between changes in outcome measures. Read Less

Targeted and individualized treatments for mental health disorders are critically needed. Repetitive transcranial magnetic stimulation (rTMS) represents the front-line of new and innovative approaches to normalizing dysfunctional brain networks in those with mental illness. rTMS is FDA-approved for depression and obsessive-compulsive disorder with clinical trials underway for PTSD and addiction, among others. However, remission rates are suboptimal and ideal stimulation parameters are unknown. We recently completed a randomized, double blind clinical trial and a depression severity biomarker that predicts clinical outcome. The overarching goal of this study is to develop the first broadly generalizable platform for real-time biomarker monitoring and personalized rTMS treatment. We plan to recruit patients with medication-resistant depression and in perform a four-phase, cross-over, double-blind, placebo-controlled trial to 1) identify how standard and optimized rTMS patterns engage the depression severity biomarker, and 2) determine the dose-response of these rTMS patterns. Findings from this study will provide the basis for a double-blind, randomized clinical trial comparing rTMS optimized to the individual against standard rTMS. Read Less

Depression is a highly prevalent condition characterized by persistent low mood, energy, and activity that can affect one's thoughts, mood, behavior, and sense of well-being. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulatory technique, is an effective treatment for depression when targeting the dorsolateral prefrontal cortex (dlPFC) of the central executive network (CEN). However, remission rates are suboptimal and individual methods to target the dlPFC are lacking. In this study, we will enroll 50 patients with major depression and in a single rTMS 'dose,' prospective, randomized, double-blind, cross-over design will assess whether rTMS targeted to an individual's central executive network (CEN) assessed by single pulse TMS can enhance network modulation. If successful, this work will lead to a clinical rTMS trial comparing this personalized targeting approach against standard rTMS. Read Less

The purpose of this study is to determine whether psilocybin, a hallucinogenic drug, is effective in reducing depressive symptoms and amount of drinking in patients with co-occurring Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). Read Less

The primary purpose of this study is to evaluate the pharmacokinetics and safety of Zuranolone in adolescents (ages 12 to 17 years) with MDD. Read Less

The goal of this study is to evaluate the use of ecological-momentary-assessment (EMA) as a method for scheduling maintenance treatments for patients with Major Depressive Disorder (MDD) who responded to an initial acute course of Transcranial Magnetic Stimulation (TMS). To assess symptom re-emergence and severity over time, the Patient Health Questionnaire-9 item (PHQ-9) will be administered weekly via a prompt with a link send to a participants' smart phones. Adaptive algorithm software will monitor each participant's PHQ-9 scores over time and determine when a threshold increase in symptoms has occured and maintenance TMS sessions should be offered. Participants in this study will be randomized to either receive weekly EMA (monitoring only) or weekly EMA with maintenance TMS sessions (scheduled as indicated by the EMA algorithm). Participation for each subject will last for one year, with maintenance TMS offered as an adjunct to ongoing treatment as usual (TAU) for depression, i.e., ongoing pharmacotherapy, psychotherapy. Read Less

Background: People with TRD are often helped by electroconvulsive therapy (ECT). But ECT can affect memory and thinking. Researchers want to study a treatment called TEST that uses less electricity. Objective: To study the safety and feasibility of TEST and assess its antidepressant effects. Eligibility: Adults aged 25-64 with major depression that has not been relieved by current treatments. Design: Participants will be admitted to the NIH Clinical Center for 5 18 weeks over 2 3 treatment phases. Their medications may be adjusted. Participants will be interviewed about their depression, side effects, and other treatments they are receiving. They will complete questionnaires. They will give blood and urine samples. Their brain waves and heart rhythm will be recorded. They will take tests of memory, attention, mental functioning, and thinking. Participants will have magnetic resonance imaging (MRI) scans of the head and brain. They will lie on a table that slides in and out of the scanner. Pictures of brain chemicals will also be taken. They may complete tasks during the MRI. Participants will receive TEST and/or sham treatments. They may receive optional ECT. An intravenous catheter will be placed in an arm vein to receive general anesthesia. Two electrodes will be placed on the front of their head. An electric current will be passed from the ECT machine through the electrodes. For sham treatments, they will not receive the electric current. Their breathing, heart rate, brain function, blood pressure, and body movements will be measured. Participants will have 7 follow-up visits over 6 months. Visits can be done via telehealth. Participation will last for up to 42 weeks. Read Less

To explore whether intravenous ketamine followed by buprenorphine produces more rapid and sustained anti-suicidal effects than ketamine followed by placebo, investigators will conduct a single study that will take approximately 2.5 years to complete. 60 subjects (60 infusions) or approximately 24 infusions per year. Read Less

Major depressive disorder (MDD) affects an estimated 350 million people worldwide and is a leading contributor to global disease burden. Commonly used monoamine reuptake-inhibiting treatments for depression are suboptimal, resulting in only 30% of patients achieving remission. This may be because monoamine dysfunction is not the primary pathophysiology in all MDD patients. One avenue for the development of novel MDD treatments is through anti-inflammatory drugs; MDD is linked to a pro-inflammatory phenotype characterized by microglial activation, leading to the release of pro-inflammatory cytokines and upregulation of cellular markers including cyclooxygenase-2 (COX-2) and translocator protein (TSPO; a protein located on the outer membrane of microglia). Relevant to this proposal, TSPO can serve as an in vivo marker of neuroinflammation using the newly developed positron emission tomography (PET) tracer for TSPO, [18F]FEPPA. In support of this, a recent [18F]FEPPA PET study found that MDD patients in a current major depressive episode (MDE) had significantly higher TSPO binding in the prefrontal cortex (PFC), anterior cingulate cortex (ACC) and insula, relative to healthy controls. The prefrontal cortex and ACC are both implicated in mood regulation whereas the insula is involved in interoceptive signaling, which is known to be abnormal in MDD. Celecoxib, a selective COX-2 nonsteroidal anti-inflammatory drug (NSAID), is a promising new treatment for neuroinflammation in MDD. Clinical studies have observed that, in a subset of depressed patients, celecoxib treatment reduced depression severity as assessed by the Hamilton Depression Rating Scale (HDRS). While these findings demonstrate that celecoxib reduces symptom severity, PET imaging technology is critical for understanding how celecoxib affects the underlying pathophysiology of depression. Here, the team will investigate neuroinflammation as an underlying pathology in depression and test whether neuroinflammation is reduced by celecoxib in MDD patients. Specifically, in the proposed pilot study, MDD patients in a current MDE will receive [18F]FEPPA PET scans prior to and following 8 weeks of treatment with 400mg/day of celecoxib, with HDRS scores obtained at each time point. The investigators hypothesize that following celecoxib treatment, patients will show a significant reduction in neuroinflammation in the PFC, ACC and insula, which will correlate positively with the reduction in depressive symptoms, as measured by the HDRS. The proposed study will use novel imaging technology, [18F]FEPPA PET, to measure the effects of celecoxib on neuroinflammation in MDD patients. Our results will help to 1) identify neuroinflammation as an underlying pathology in MDD and 2) test whether reduction of inflammation is the mechanism of action of celecoxib. As such, the results of this study will aid in the development of targeted clinical treatments to improve remission rates in MDD patients. Read Less