50 Clinical Trials for Depression (Treatment-Resistant)
The goal of this clinical trial is to learn if Transcranial Magnetic Stimulation (TMS) to part of the brain called the ventromedial prefrontal cortex (VMPFC) can treat a symptom called rumination in adults with major depression that has not responded to at least one medication trial. The main question it aims to answer are: Does TMS to the VMPFC change brain activity on functional magnetic resonance imaging (fMRI) during a negative self-referential processing task in adults with depression? Does TMS to the VMPFC affect rumination in adults with depression? Researchers will compare brain scans and rumination scores before, during, and immediately after TMS. Participants will: Undergo three functional MRI scans Undergo a course of 20 TMS treatments Respond to clinical questionnaires and complete a computer behavioral task
The purpose of this study is to to evaluate the relationships between peak (% change from baseline) central GABA and Glu levels during a 40-min IV ketamine or normal saline infusion utilizing fMRS, and change in peripheral GABA and Glu levels from baseline to 24-hr postinfusion utilizing LCMS, with baseline to 24-hr post-infusion change in depression (MADRS) in 30 TRD adults.
Background: Major depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD. Objective: To test a study drug (HNK) in people with MDD. Eligibility: People aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254. Design: Participants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity. HNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule: They will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study. They will receive no drugs for 2 to 3 weeks. They will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study. One set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo. ...
Late-Life Depression (LLD), or depression in older adults, often presents with motivational deficits, deficits in performance in cognitive domains including processing speed and executive dysfunction, and mobility impairments. This triad of findings implicate dopaminergic dysfunction as a core pathophysiologic feature in depression, and may contribute to cognitive decline and motor disability. Normal aging results in brain-wide dopamine declines, decreased D1/D2 receptor density, and loss of dopamine transporters. Although brain changes associated with depression and aging converge on dopamine circuits, the specific disturbances in LLD and how responsive the system is to modulation remain unclear. In this study, investigators are testing integrative model that aging, in concert with pro-inflammatory shifts, decreases dopamine signaling. These signally changes affects behaviors supported by these circuits, in the context of age-associated cortical atrophy and ischemic microvascular changes, resulting in variable LLD phenotypes. Investigators propose a primary pathway where dopaminergic dysfunction in depressed elders contributes to slowed processing speed and mobility impairments that increase the effort cost associated with voluntary behavior. The central hypothesis of this study is that late-life depression is characterized by dysfunction in the dopamine system and, by enhancing dopamine functioning in the brain. By improving cognitive and motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms.
This Phase 2 study (protocol number VLS-01-203) will determine the efficacy, safety, and tolerability of short-term treatment with a VLS-01 transmucosal buccal film (VLS-01-BU) in patients with treatment resistant Major Depressive disorder (TRD) and will characterize the onset and durability of antidepressant effects of VLS-01-BU versus placebo.
Severe depression is devastating for those affected and is often associated with significant risk of suicide. Electroconvulsive therapy (ECT) is a highly effective acute treatment for severe depression, but its use and acceptability are limited by cognitive side effects. Of these, retrograde memory loss is most concerning, and can be long-term. The introduction of ultrabrief right unilateral (UBRUL) ECT into clinical practice has been an important step in reducing the risk of memory impairment, but significant deficits still occur. A new form of UBRUL ECT which utilises a Frontoparietal electrode placement represents a further development. Preliminary data suggest that Frontoparietal UBRUL has good efficacy and less cognitive side effects than UBRUL given using the conventional Temporoparietal electrode placement. Designed as a pivotal trial, this protocol will be the first RCT comparing these two forms of ECT, producing the rigorous efficacy and safety data required to change clinical practice/policy. This is a multicentre, parallel group RCT with 1:1 allocation ratio between Frontoparietal (intervention) and Temporoparietal (comparator) forms of UBRUL ECT. Participation will involve receiving randomised acute ECT under blinded conditions during the randomised acute treatment period (typically around 4 weeks), then completion of a 24-week follow-up period which commences after the cessation of all acute ECT. The study protocol aims to provide 12 randomised acute ECT treatments, though the number of treatments (and hence the length of the randomised acute treatment period) can be adjusted by the participant's own treating/admitting psychiatrist according to their clinical judgement.
This study aims to evaluate the feasibility, safety, and tolerability of an innovative approach to treating Major Depressive Disorder (MDD), particularly in cases where patients have not responded well to traditional therapies. Specifically, the objective is to evaluate the antidepressant effects of a Dose-Optimized and Spaced Transcranial Direct Current Stimulation (DOS-tDCS) protocol in participants with treatment-resistant depression (TRD) compared to spaced tDCS only and sham tDCS in a 3-arm randomized controlled trial (RCT). The proposed method involves applying low-intensity electrical currents through the scalp in a manner that is both more intense and more frequently spaced than standard treatments. This approach is hypothesized to lead to a significant reduction in depressive symptoms. Participants in the study will be randomly assigned to one of three groups: the experimental group receiving the DOS-tDCS treatment, a group receiving spaced tDCS only, or a control group receiving a sham (placebo) treatment. Outcomes will be measured over a period of six weeks. The study's goal is to offer a potentially more accessible and effective treatment option for individuals who have not benefited from existing MDD therapies.
Electroconvulsive therapy (ECT) is one of the most efficacious treatments available for treatment-resistant depression (TRD). Although a maintenance ECT protocol exists, multiple barriers limit its use for long-term use. These barriers include procedure tolerability, cognitive side effects, financial burden, and unreliable social support to accompany patients for these treatments. On the other hand, a different modality of noninvasive neuromodulation called transcranial magnetic stimulation (TMS) can be performed in the outpatient setting and does not need anesthesia. The likelihood of cognitive adverse effects with TMS is much lower than with ECT. Our clinical question encompasses piloting a maintenance TMS regimen to maintain remission in treatment-resistant major depressive disorder. This will be a patient-preference clinical trial, with patients offered the choice to initiate maintenance TMS versus maintenance ECT after their index ECT sessions for treatment-resistant depression. There will be no randomization or placebo involved in this study.
The core objective of this study is to enhance the translational potential of this electroencephalogram (EEG) biomarker by using ketamine(KET)-induced gamma potentiation as a prognostic marker of 4-week treatment outcome. Previous research focused exclusively on KET-induced gamma band potentiation (GBP) in the context of a single infusion. Our study design captures the clinical variation associated with real-world treatment resistant depression (TRD) patients and allows us to analyze the relative importance of GBP to antidepressant symptom reduction across the induction phase of treatment. If successful, it provides a compelling rationale for a larger prospective investigation of gamma dynamics as a moderator of outcome to varied TRD therapies which impact the balance of cortical excitation and inhibition.
The goal of this clinical trial is to evaluate the effectiveness and safety of bilateral stimulation of the subcallosal cingulate white matter (SCCwm) using Deep Brain Stimulation (DBS) as an adjunctive treatment of non-psychotic unipolar Major Depressive Disorder (MDD) in adults.
The goal of this clinical trial is to test how well psilocybin-assisted therapy works in treating people with depression. The main questions this study aims to answer are: * Does psilocybin with assisted therapy help improve symptoms for people with depression? * How long do the effects of this treatment last? Participants will: * Take part in a couple of screening and preparation visits. * Be given psilocybin in one or two treatment sessions. * Attend a series of follow-up sessions over the following year. * Complete forms and surveys to test how their symptoms have changed and what they thought of their experience. Researchers will also compare whether one treatment or two treatments help improve symptoms more for participants.
The researchers are trying to test the feasibility and acceptability of using transcranial Direct Current Stimulation (tDCS) in hospitalized adult patients with Treatment Resistant Depression (TRD), assess for any preliminary effect on depressive and cognitive symptoms, and explore the utility of biomarkers to assess response to tDCS.
The purpose of this study is to evaluate the efficacy of psilocybin on the symptom of anhedonia in individuals with treatment-resistant major depressive disorder.
The purpose of this study is to investigate the effectiveness of accelerated intermittent theta-burst transcranial magnetic stimulation (aiTBS) in inducing anti-depressant responses in individuals with treatment-resistant depression of bipolar II disorder. This is a double-blind, randomized, sham-controlled trial that targets a single location on the left dorsolateral prefrontal cortex (LDLPFC) using the MagPro rTMS system.
The goal of this clinical trial is to determine the impact of omega-3 fatty acids on the production of anti-inflammatory effects and clinical improvement in people with depression who have not responded well to standard antidepressant treatment. The main questions it seeks to answer are: 1. Do omega-3 fatty acids added to ineffective antidepressant treatment increase production of compounds that reduce inflammation? 2. Is the increase in these anti-inflammatory compounds associated with a stronger antidepressant effect? Participants taking antidepressants that have not worked completely will be assigned at random for a 12-week period to one of the following: 1. an omega-3 preparation 2. an inactive placebo During the course of the study, blood tests will be obtained for compounds associated with inflammation, and questionnaires to measure clinical improvement in depressive symptoms will be administered.
This is a prospective clinical trial to confirm the effectiveness of bilateral accelerated theta burst stimulation (aTBS) on suicidal ideation (SI), while exploring cortical inhibition measures in this treatment paradigm. In this proposed study, the investigators will evaluate the anti-suicidal effects of bilateral aTBS over the DLPFC compared to accelerated intermittent theta burst stimulation (aiTBS) over the left DLPFC in participants with TRD and SI. Additionally, the investigators aim to identify neurophysiological targets through which bilateral aTBS induces remission of SI in TRD differentially from aiTBS.
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.
This research study is designed to test if electrical stimulation of the surface of the brain in the frontal region will help treat depressive symptoms. Participants receive intermittent electrical stimulation to the brain, which involves surgically placing electric leads in between the tough fibrous membrane covering the surface of the brain and the surface of the brain itself. This type of stimulation is referred to as bilateral subdural prefrontal cortical stimulation (PCS) because it will specifically target the outer layer of the brain at the midline, right behind the forehead. It uses a pacemaker-like device, the Proclaim Elite SCS System (non-rechargeable) or the Eterna SCS System (rechargeable), both by Abbott Laboratories for stimulation. Although the U.S. Food and Drug Administration (FDA) has approved the Proclaim Elite SCS system for brain stimulation for patients with chronic pain and muscular diseases, such as Parkinson's, its use is still investigational, and the surgery is still experimental for patients who have depression.
The purpose of this study is to compare the efficacy and side effects magnetic seizure therapy (MST) and electroconvulsive therapy (ECT) in Bipolar Depression (MST-BpD) and Treatment Resistant Depression (MST-TRD).
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.
Treatment resistant depression remains a major problem for individuals and society. Surgical procedures may provide relief for some of these patients. The most frequently considered surgical approach is deep brain stimulation (DBS) of a part of the brain called the subcallosal cingulate region. However, the effectiveness and safety is not well established. The investigators will use a novel approach using advanced imaging technique (magnetic resonance tractography) to evaluate the feasibility and safety of this surgical approach. An innovative method for the definition of DBS target will be applied that redefines the concept of targeting as one of targeting a symptomatic network rather than a structural brain region using subject-based brain anatomy to define the target location. The correlation between imaging findings at baseline with the mood score changes at different time points of the study will be investigated.
Objectives of this study are to determine whether active VNS Therapy treatment is superior to a no stimulation control in producing a reduction in baseline depressive symptom severity, based on multiple depression scale assessment tools at 12 months from randomization.
The purpose of this study is to compare the effects on depressive symptoms of subjects who discontinue serotonergic antidepressants (a certain type of antidepressant, such as Prozac, that works on serotonin receptors in the brain) with the effects on depressive symptoms of subjects who continue to take serotonergic antidepressants. During this study, subjects will also be presented with the opportunity to undergo genetic testing for the serotonin gene transporter which has a short or long form. This is being done because it has been demonstrated that genetic testing improves outcome while treating treatment-resistant depression.
The purpose of this study is to determine the clinical efficacy of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala's response to positive autobiographical memories in patients with depression who are considered treatment-resistant
A single subanesthetic dose infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and robust antidepressant effects in patients with treatment-refractory major depressive disorder (TRD). A family history of an alcohol use disorder (Family History Positive, FHP) is one of the strongest identified predictors of an improved antidepressant response to ketamine. Like ketamine, alcohol is a functional NMDA receptor antagonist. FHP is associated with differential response to ketamine, e.g. blunted psychotomimetic side effects. One of the primary mechanistic hypotheses for ketamine's antidepressant action is the acute intrasynaptic release of glutamate from major output neurons, e.g. cortical pyramidal cells. Preliminary clinical studies have demonstrated this acute glutamate "surge" in response to subanesthetic dose ketamine. Based on these findings, the investigators hypothesize that ketamine's enhanced antidepressant efficacy in FHP TRD subjects is, at least in part, attributable to increased glutamate release relative to TRD subjects without a family history of alcohol use disorder (Family History Negative, FHN). To test this hypothesis, the investigators have designed a now two-site, open-label study of 18-55-year-old medically and neurologically healthy, currently moderately-to-severely depressed TRD patients. In total, the investigators plan to recruit 25 FHP and 25 FHN TRD subjects. All subjects must not have a current substance use disorder (except nicotine or caffeine). The experimental portion consists of two phases. The preliminary first phase is a medication taper (if needed) and psychotropic medication-free period. The experimental second phase comprises one subanesthetic dose (0.5mg/kg x 40 minute) ketamine infusion. The ketamine infusion will occur during 7T-magnetic resonance imaging (MRI), both resting-state functional MRI (rs-fMRI) and magnetic resonance spectroscopy (MRS) to detect glutamate in the ventromedial prefrontal cortex/ventral anterior cingulate cortex (vmPFC/vACC). The primary outcome measure is group mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from pre-ketamine infusion (baseline) to one-week post-infusion, where the investigators observed ketamine's greatest antidepressant effect in FHP TRD. Additional outcome measures are vmPFC/vACC glutamate change in response to ketamine based on family history status. In summary, this study will provide key mechanistic information on ketamine's improved antidepressant efficacy in a biologically-enriched subgroup. This will contribute to the systematic development of more efficacious, personalized treatments for major depression in an effort to reduce its enormous public health burden.
We propose a clinical study of medial forebrain bundle DBS as a treatment in 20 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that DBS at the same site may also reduce symptomatology in these TRD patients (Schaepfer, 2013). Depression affects up to 10% of the US population and of those at least 10-15% do not benefit from therapies hence why we must explore new treatments. The Percept™ PC system manufactured by Medtronic Neurological will be used in this study. Study subjects will be between the ages of 22 and 70 years of age and suffer from TRD, have failed multiple treatment regimens, including ECT, and remain symptomatic. Those identified as TRD patients will then be enrolled in a clinical pilot study investigating DBS, targeting the MFB.
This is a randomized, double-blind, placebo-controlled, multiple-dose study of ALA-3000 designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy in subjects with treatment-resistant depression (TRD).
The goal of this clinical trial is to demonstrate the feasibility and safety of deep brain stimulation in treatment resistant depression. The main questions it aims to answer are: * Is deep brain stimulation effective in treating treatment resistant depression? * Does deep brain stimulation improve overall clinical well-being and functioning? Participants will be implanted with a deep brain stimulation device. They will then be monitored over a 5-year period by using multiple questionnaires to track their depression symptoms. The device will be turned off at certain time points, unbeknown to the participant, to show the efficacy of the device when it is turned on. The device will be ON for 8.5 months and OFF for 3.5 months during the first year. Researchers will compare questionnaire scores when the device is off versus on to see if the device is working in reducing depression.
Electroconvulsive therapy (ECT) alleviates treatment-resistant depression (TRD) through repeated generalized seizures. The goal of this study is to evaluate how ECT impacts sleep-wake regulation and efficiency of information transfer in functional networks in different states of arousal.
Efficacy, Safety, and Tolerability of two administrations of COMP360 in participants with treatment-resistant depression (TRD)