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288 active trials for Major Depressive Disorder

Fixed Order, Open-Label, Dose-Escalation Study of DMT in Humans

The goal of this fixed order, open-label, dose-escalation study is to investigate the safety and efficacy of specific doses of dimethyltryptamine (DMT) in humans.

Start: March 2021

Combination of Novel Therapies for CKD Comorbid Depression

The overall goal of the study is to determine if treatment of a Major Depressive Disorder (MDD) improves the outcomes of patients with chronic kidney disease (CKD). We showed that MDD is present in 25% of CKD patients and independently associated with progression to End-Stage Kidney Disease, hospitalization, and death. Depression is also associated with lower quality of life (QOL), fatigue, poor sleep, and non-adherence to diet and medications. However, evidence for efficacy and tolerability of commonly-used antidepressant medications or nonpharmacologic treatments are limited in CKD patients. Our group was the first to conduct a double-blind randomized controlled trial for MDD treatment in 201 patients with non-dialysis CKD, and showed that sertraline, a commonly used selective serotonin reuptake inhibitor (SSRI), was no more efficacious than placebo for improving depressive symptoms. It becomes imperative to test novel strategies to treat MDD in CKD. We propose to compare with a control group, the efficacy and tolerability of two novel treatment strategies - (1) Behavioral Activation Teletherapy (BAT) for 16 weeks, with the addition of bupropion, a non-SSRI antidepressant, at 8 weeks for patients whose depression has not remitted (non-remitters); and (2) bupropion for 16 weeks, with the addition of BAT at 8 weeks for non-remitters. In Aim 1, we will investigate the efficacy and tolerability of these 2 strategies vs. control for improvement in a primary endpoint of depressive symptoms in 201 patients (67 per group) with non-dialysis CKD stages 3b-5 and MDD at 2 sites, randomized 1:1:1 to either strategy or a control group of Clinical Management plus placebo. We hypothesize that either approach vs. control will result in a minimal clinically important difference of 2 points improvement in depressive symptoms, as ascertained blindly by the Quick Inventory of Depressive Symptomatology. In Aim 2 we will investigate the efficacy and tolerability of 8 weeks of (1) single-blind BAT plus placebo or (2) double-blind bupropion plus Clinical Management vs. control for improvement in depressive symptoms. In Aim 3, we will compare the efficacy of these 2 treatments strategies vs. control for improvement in CKD patient-centered outcomes including a. adherence to medications and healthcare visits; b. fatigue; c. sleep; and d. overall functioning. A clinical trial is urgently needed to address the evidence gap that exists for MDD treatment in CKD patients.

Start: September 2020

SSIPP vs. PST vs. WLC

The COVID-19 pandemic and continued lockdown measures have led to social isolation that is likely disproportionately affecting community-dwelling seniors. This social isolation of seniors is expected to cause detrimental health effects especially in those who have an ongoing or new onset late life depressive episode. The COVID-19 pandemic has also made accessing formal psychotherapy services increasingly difficult due to an increased demand for these services and a limited number of trained professionals available to deliver these interventions. We plan to conduct a single blind, pilot, randomized controlled trial (RCT), comparing a virtually delivered (telephone) student led mental health supportive initiative, Student Senior Isolation Prevention Partnership (SSIPP) (n=15) compared to a telephone delivered standard psychotherapy intervention, problem-solving therapy (PST) (n=15) versus a wait list control (n=15) in community-dwelling seniors suffering from late life depression. Participants in this study will be blinded to the hypothesis, while those performing data analysis will be blinded to treatment allocation. Both SSIPP and PST will be delivered via telephone as a weekly session for 12-weeks. Feasibility measures of recruitment, retention and costs will be collected as primary outcome measures. Self-rated measures of depression, anxiety, and resilience will comprise secondary exploratory outcomes. We anticipate that it will be feasible to conduct an RCT of these telephone interventions, SSIPP and PST, in socially isolated community-dwelling seniors. Data from this study will be critical to plan a subsequent confirmatory large-scale RCT. It could be that telephone delivered medical student led supportive intervention, SSIPP and/or a telephone delivered psychotherapy initiative, PST, can be feasibly applied in the current pandemic to a high-risk population, isolated seniors suffering from depression.

Start: June 2021

Social Reward and Its Effect on Brain Functions in Psychotherapies for Mid- and Late-Life Depression

Abnormalities in the Positive Valence System (PVS) are associated with depressive symptoms and reduced behavioral activation in mid- and late-life. This study will investigate the engagement of the PVS during exposure to social rewards, part of a novel streamlined psychotherapy for mid- and late-life depression. Use of computational modeling will enable identification of neuroimaging and behavioral profiles associated with greater treatment response, and may guide future personalization of psychotherapy.

Start: October 2020

A Closed-loop Assessment and Treatment Platform for Unipolar Depression and Anxiety

Specific Aim 1: Finalize development of the closed-loop strategy in the MMT application. Specific Aim 2: Evaluate the acceptability and feasibility of the MMT application with the target population to prepare for a large-scale efficacy trial.

Start: October 2017

A Study of the Safety and Efficacy of SP-624 in the Treatment of Adults With Major Depressive Disorder

This is a Phase 2 clinical study evaluating the safety and effectiveness of SP-624 as compared to placebo in the treatment of adults with Major Depressive Disorder.

Start: September 2020

Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans

Co-occurring post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) is the most common response to trauma; it is associated with poor clinical outcomes and substantial human disability. Veterans with both PTSD and MDD (PTSD+MDD) have been shown to be at much greater suicidal risk than individuals with only one of these disorders. Ketamine given as repeated infusions has been shown to be effective in rapidly reducing PTSD and MDD symptoms in treatment resistant PTSD+MDD individuals. However, knowledge about the mechanisms underlying comorbid PTSD and MDD remain limited. The purpose of this study is to use repeated ketamine infusions as a probe to validate a model of PTSD+MDD that focuses on neuroanatomy and executive functioning.

Start: September 2019

Efficacy of Two Internet Delivered Intervention Programs for Depression: Behavioral Activation vs Physical Activity

To compare the clinical and cost-effectiveness of Behavioral Activation (BA) and Physical Activity (PA) for adults with major depressive disorder (MDD) or adjustment disorder with depressive symptomatology with a wait list control group (WL) in Spanish population.

Start: November 2021

Comparing Individual Therapies for Veterans With Depression, PTSD, and Panic Disorder

Cognitive behavioral therapy (CBT) is a brief, efficient, and effective treatment for individuals with depressive/anxiety disorders. However, CBT is largely underutilized within the Department of Veterans Affairs due to the cost and burden of trainings necessary to deliver all of the related disorder-specific treatments (DSTs). Transdiagnostic Behavior Therapy (TBT), in contrast, is specifically designed to address numerous distinct disorders within a single protocol in Veterans with depressive/anxiety disorders, including posttraumatic stress disorder. The proposed research seeks to evaluate the efficacy of TBT by assessing psychiatric symptomatology and related impairment outcomes in Veterans with depressive/anxiety disorders via a randomized controlled trial of TBT and existing DSTs in Veterans with major depressive disorder, posttraumatic stress disorder, and panic disorder. Assessments will be completed at pre-, mid-, and post-treatment, and at 6-month follow-up. Process variables also will be investigated.

Start: October 2020

Positive Processes and Transition to Health

The R61 will be an open trial to determine if Positive Processes and Transition to Health (PATH) engages the proposed targets: unproductive processing, avoidance, and reward deficits in a sample of 45 adults who have experienced a destabilizing life event involving profound loss or threat, report persistent stressor-related symptoms of PTSD and/or depression, and are elevated on symptoms related to 2 of the 3 therapeutic targets. Additionally, will examine whether patients perceive PATH as helpful and complete/adhere to treatment, and therapist fidelity. Patients will receive 6 sessions of PATH (with 2 boosters, if partial responders). Primary targets will be assessed at pre-treatment, week 3, post-treatment, and at 1- and 3-month follow-up; secondary targets at pre-treatment, weekly during treatment, post-treatment, and at 1- and 3-month follow-ups.

Start: October 2021

Ketamine Treatment Effects on Synaptic Plasticity in Depression

Depression is the leading cause of disability globally (1, 2). One-third to one-half of patients suffering from major depressive disorder (MDD) do not achieve remission even after multiple antidepressant trials (3). Ketamine is a commonly-used FDA-approved anesthetic medication that at subanesthetic doses leads to rapid antidepressant and anti-suicidal ideation effects in hours, rather than weeks, following administration. Despite these promising findings, a key limitation of ketamine treatment is that it only yields an antidepressant response in approximately 50% of those treated. The goal of this project is to A) elucidate ketamine's mechanism of action and B) identify biomarkers predicting treatment outcome to ketamine which could be used to match patients to treatment based on the likelihood of effectiveness at the individual level. Data from animal models suggests that ketamine acts by enhancing the connections between neurons through a process known as synaptic plasticity (4-7), and that these biological changes are responsible for the sustained behavioral effects of ketamine (8). A newly available tool allows us to image the density of these synaptic connections in the living brain using PET (positron emission tomography) imaging with a radiotracer called [11C]UCB-J, which is a marker of synaptic density. We propose to directly quantify synaptic density in depressed patients before and after a course of ketamine, to examine changes in density following treatment. In exploratory analyses, we will examine synaptic density as a mediator of the sustained antidepressant effects of ketamine and as a predictor of treatment outcome. To study these questions, we will quantify synaptic density using PET imaging before and after a course of 4 sequential intravenous infusions of ketamine administered over a two week period. Study participation involves an inpatient stay of approximately three weeks at the New York State Psychiatric Institute at no cost.

Start: October 2020

Using Voice Biomarkers to Predict the Likelihood of Major Depressive Disorder

Major Depressive Disorder (MDD) is the leading cause of disability worldwide. Depression and anxiety disorders are among the most prevalent of all mental disorders, with an estimated annual prevalence of 9.7% and 18.1% respectively. It has been known for the last 100 years that depression and anxiety both likely affect vocal acoustic properties. In 1921, Emil Kraepelin, characterized depressed patient's voices as having a lower pitch, lower volume, lower rate of speech, more monotony of prosody as well as more hesitations, stuttering, and whispering. Mechanistically, it is possible that the neural circuitry involved in the pathophysiology of mood and anxiety disorders impinge upon the neural circuit involved in speech production, affecting qualities that include rate, prosody, speech latency and other paralinguistic features. Thus, acoustic features of speech may be one of the more readily accessible biomarkers for these conditions. Given this understanding, the investigators sought to develop a passive vocal biomarker instrument for depression and anxiety screening that could markedly expand access as well as standardize the quality of screening in primary care settings.

Start: April 2021

Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

The purpose of this research study is to assess which antidepressants work the best in older adults who have treatment-resistant depression (TRD).

Start: February 2017

The Phosphodiesterase 3 Inhibitor Cilostazol as an Adjunct to Antidepressants in Major Depressive Disorder Patients

Cilostazol is a PDE 3 inhibitor, which showed as decrease in HAM-D scores in post-stroke depression through inhibition of neurodegeneration in the primary lesion and secondary extrafocal sites and through promotion of neurogenesis. These beneficial effects on post-stroke depression may be involved in activation of CREB/BDNF signaling.The aim of the current study is to evaluate the potential adjunct antidepressant effect of cilostazol in adult patients with MDD. Furthermore, we will assess the relationship between HAM-D score and BDNF as well as their role as a therapeutic targets of MDD.

Start: August 2019

Biomarker-guided rTMS for Treatment Resistant Depression

Repetitive transcranial magnetic stimulation (rTMS) is a treatment for depression. The investigators are continuing to learn how to optimize outcomes from rTMS treatment. The purpose of this research project is to use brain network connectivity patterns as measured by resting state functional magnetic resonance imaging (fMRI) to confirm a way to optimize the use of rTMS to treat depression. In addition, the study aims to gain a better understanding of how rTMS influences brain networks.

Start: August 2021

Concurrent fMRI-guided rTMS and Cognitive Therapy for the Treatment of Major Depressive Episodes

Background: Repetitive transcranial magnetic stimulation (rTMS) is a treatment for depression. It stimulates the brain. Researchers want to see if using magnetic resonance imaging (MRI) scans helps locate the best area for rTMS in each person. They also want to find other ways to make it more effective. Objective: To study the effects of combining MRI- guided transcranial magnetic stimulation (TMS) and talk therapy on the brain in people with depression. Eligibility: Adults ages 18-65 with a major depressive disorder and current depression. If taking an antidepressant, should have been doing so for at least 4 weeks. Design: Participants will be screened with medical and psychiatric history, psychiatric evaluation, physical exam, and blood and urine tests. Phase 1 is 1-4 visits in 1 week. Participants will have: Brain MRI. Participants will lie on a table in a scanner. Questions about their medical history and psychology symptoms Tests of mood and thinking Tests of brain activity. Participants may do tasks during these tests: A cone with magnetic detectors is put on the head. A cap with electrodes is put on the scalp. TMS. A brief electrical current passes through a wire coil on the scalp. A metal disk will be placed on the arm. A nerve will be stimulated with a small electrical shock. Phase 2 is about 6 to 7 weeks. There will be 30 daily sessions of combined therapy and repetitive TMS (rTMS) for 6 weeks. Participants will receive rTMS and another therapy by computer. For rTMS, repeated pulses will pass through the coil. This is followed by up to 3 additional visits, when: Participants will repeat Phase 1 tests Participants will rate their depression symptoms. Phase 3 is 3 visits over 3 months. Participants will rate their depression symptoms and repeat some of the previous questionnaires and tests of mood and thinking.

Start: May 2018

Transcranial Direct Current Stimulation (tDCS) Therapy in Major Depression

Noninvasive transcranial direct current stimulation (tDCS) is a low-intensity neuromodulation technique of minimal risk that has been used as an experimental procedure for reducing depressive symptoms and symptoms of other brain disorders. Though tDCS applied to prefrontal brain areas is shown to reduce symptoms in some people with major depressive disorder (MDD), the extent of antidepressant response often differs. Methods that map current flow directly in the brain while a person is receiving tDCS and that determine how functional neuroimaging signal changes after a series of tDCS sessions may help us understand how tDCS works, how it can be optimized, and if it can be used as an effective antidepressant. Investigators will address these questions in a two-part randomized double blind exploratory clinical trial. For this part of the study, investigators will determine relationships between target engagement and clinical outcomes (mood) and functional sub-constructs of cognitive control and emotion negativity bias, and whether imaging markers at baseline predict changes in antidepressant response. One hundred people with depression (50 in each group) will be randomized to receive either HD-tDCS or sham-tDCS for a total of 12 sessions each lasting 20 minutes occurring on consecutive weekdays. At the first and last session, subjects will receive 20-30 minutes of active or sham HD-tDCS in the MRI scanner, which will allow investigators to map tDCS currents, and track changes in regional cerebral blood flow (rCBF) pre-to- post treatment using completely non-invasive methods. At the first and last session and mid-way through the trial, participants will also complete a series of clinical ratings and neurocognitive tests.

Start: December 2020

Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder

Background: Most medications that treat depression take weeks or months to work. Researchers want to develop fast-acting treatments. One dose of ketamine has a rapid antidepressant effect. For most people, this lasts a week or less. Repeated doses of ketamine may help maintain this effect. Objective: Main Study: To study the effects of ketamine in treating depression. Ketamine Metabolites Substudy: To study how ketamine effects brain chemistry. To study how ketamine effects the brain. This is done by looking at metabolites, which are created when a drug is broken down. Eligibility: Main Study: People ages 18-65 with major depressive disorder and healthy volunteers Ketamine Metabolites Substudy: Healthy volunteers ages 18-65 Design: Main Study: Participants will be screened in another study, with: Medical and psychiatric history Psychiatric and physical exam Blood, urine, and heart tests Participants will be inpatients at NIH for 4 phases totaling 14-20 weeks. Phase I (2-7 weeks): Gradually stop current medications MRI: Participants lie and perform tasks in a machine that takes pictures of the body. Mood and thinking tests Blood and urine tests Sleep test: Monitors on the skin record brain waves, breathing, heart rate, and movement during sleep. Transcranial magnetic stimulation: A coil on the scalp gives an electrical current that affects brain activity. Stress tests: Electrodes on the skin measure reactions to loud noises or electric shocks. Phase I tests are repeated in Phases II and III and in the final visit. Phase II (4-5 weeks): 4 weekly IV infusions of ketamine or a placebo during an MRI or MEG. For the MEG, a cone over the head records brain activity. Phase III (optional): 8 infusions of ketamine over 4 weeks Phase IV (optional): Symptoms monitoring for 4 weeks Participants will have a final visit. They will be offered standard treatment at NIH for up to 2 months. Ketamine Metabolites Substudy: Participants will be screened in another study, with: Medical and psychiatric history Psychiatric and physical exam Blood, urine, and heart tests Participants will be inpatients at NIH for 4 days. Study Procedures: Mood and thinking tests Blood and urine tests 1 infusion of ketamine Spinal tap and spinal catheter: Used to get samples of cerebrospinal fluid (CSF). This is a fluid that moves around and within the brain and spinal cord. Studying CSF will help us learn how ketamine effects brain chemistry

Start: May 2017

Improving Attentional and Cognitive Control in the Psychological Treatment of Intrusive Thoughts

The investigators are conducting this study to learn more about the cognitive and attentional processes among individuals with three types of repetitive negative thinking (RNT): mental rituals (as seen in obsessive compulsive disorder, OCD), worries (as seen in generalized anxiety disorder, GAD), and ruminations (as seen in major depressive disorder, MDD). Specifically, the investigators are studying whether psychological treatment can help people with RNT who have trouble stopping unwanted thoughts and shifting their attention.

Start: April 2021

Electroconvulsive Therapy Amplitude Titration

This study is focused on advancing ECT treatment for older adults with depressive disorders by refining neuromodulation stimulus parameters to improve efficacy and cognitive safety.

Start: March 2021