TREATMENT RESISTANT DEPRESSION

This early-phase study tests whether deep brain stimulation (DBS) is safe and effective for people with severe depression that hasn't responded to other treatments. Twenty adults aged 18-65 with major depression or bipolar disorder will receive a DBS implant and be monitored for …

This study tests whether repeated sessions of a brain stimulation treatment called rTMS can help people with hard-to-treat depression maintain their improvement. 75 adults who already responded to an initial rTMS course will receive either standard, clustered, or fake (sham) main…

This study tests if electrical stimulation on the brain's surface can help people with severe depression that hasn't improved with other treatments. Participants get a surgically placed device that sends mild pulses to the front of the brain. The goal is to see if this reduces de…

This study is observing 500 people with treatment-resistant depression who receive Vagus Nerve Stimulation (VNS) therapy. The goal is to see how well the device works over months and years in everyday medical practice. Researchers will measure changes in depression severity using…

This study tests a device that stimulates a nerve in the neck to help people with depression that hasn't improved with standard treatments. About 6,800 adults will either receive active stimulation or no stimulation, and researchers will track their depression symptoms over a yea…

This study tests a device that sends mild electrical pulses to a specific area of the brain in adults with severe depression that hasn't improved with multiple treatments. The goal is to see if this approach can safely reduce depression symptoms and improve daily life. Participan…

This study tests whether a 6-week intensified medication plan works better than usual care for people with major depression whose first antidepressant failed. About 418 adults aged 18–65 will receive either the intensified treatment (including esketamine nasal spray or IV ketamin…

This study tests whether using brain scans to guide magnetic stimulation (rTMS) can improve depression treatment for people who haven't gotten better with medication. About 348 adults with major depression will receive rTMS, with the stimulation targeted based on their individual…

This study tests a type of talk therapy called schema therapy for people with chronic or treatment-resistant depression. Researchers will compare it to standard psychotherapy in 129 adults across six psychiatric centers in Denmark. The goal is to see if schema therapy works bette…

This phase 3 trial tests whether adding intravenous ketamine to electroconvulsive therapy (ECT) can better treat severe depression that hasn't responded to other medications. Thirty adults with treatment-resistant major depressive disorder will receive either ketamine or a placeb…

This study is testing whether combining psilocybin (a psychedelic drug) with a type of brain stimulation called aiTBS is safe and can help people with depression that hasn't improved with other treatments. About 100 adults aged 22-65 with treatment-resistant major depression will…

This study tests two types of ketamine—Spravato® and standard racemic ketamine—in 162 adults whose depression hasn't improved with at least two other antidepressants. Participants are randomly assigned to one treatment and complete questionnaires about mood, side effects, and qua…

This study is for people with depression that hasn't improved with medication. It combines a type of brain stimulation called iTBS with digital mindfulness training. The goal is to see if this combination can improve brain function and reduce depression symptoms. About 120 adults…

This study tests whether adding ketamine to internet-based cognitive behavioral therapy (i-CBT) can rapidly reduce suicidal thoughts and behaviors in people with treatment-resistant depression. About 110 adults aged 21-65 will receive weekly i-CBT for 13 weeks, with half also get…

This study tests a non-invasive brain stimulation technique called accelerated theta burst stimulation (aTBS) to see if it can reduce suicidal thoughts in people with treatment-resistant depression. 76 adults will receive either bilateral (both sides) or unilateral (one side) sti…

This study tests whether a 40 Hz flickering light, used at home for one hour daily, can reduce depression symptoms in people with major depressive disorder. Sixty adults with treatment-resistant depression will receive either the active light or a placebo light for six weeks. The…

This study tests whether very small, repeated doses of psilocybin (the active ingredient in magic mushrooms) combined with short-term talk therapy can safely reduce depression in people who haven't gotten better with standard treatments. Twenty adults aged 18-65 with treatment-re…

This early study tests if a precise type of radiation, called stereotactic radiotherapy, can safely help people with severe depression that hasn't improved with standard treatments. Nine adults aged 18 to 50 with treatment-resistant depression will receive the radiation and be mo…

This study compares two types of talk therapy—CBASP and Behavioral Activation—for people with persistent depression that hasn't improved with prior treatments. About 396 inpatients will receive one of the therapies for 16 weeks. Researchers will measure changes in depression seve…

This study tests a new medicine called VLS-01, given as a film placed inside the cheek, for people whose depression hasn't improved with other treatments. About 142 adults aged 18 to 65 with treatment-resistant depression will receive either the study drug or a placebo. The goal …

This study tests a new, quick brain stimulation treatment for people with depression that hasn't improved with standard medications. 78 adults will receive either real or fake stimulation over five days to see if it safely eases symptoms. The treatment uses MRI scans to target ea…

This early-stage study tests whether psilocybin (the active ingredient in magic mushrooms) combined with talk therapy is safe and tolerable for autistic adults with depression that hasn't improved with other treatments. Twenty intellectually able adults will receive two doses (10…

This study tests an experimental nasal spray called BPL-003, given with psychological support, for people with depression that hasn't improved with at least two prior treatments. About 64 adults with major depressive disorder will receive one or two doses to see if it is safe and…

This study looks at how the brain handles negative beliefs in people with treatment-resistant depression. Researchers will use brain scans (fMRI) to see how beliefs change before and after a single dose of ketamine. The goal is to understand why some depressed patients hold onto …

This study looks at how electroconvulsive therapy (ECT) changes sleep patterns and brain communication in people with depression that hasn't improved with other treatments. Researchers will measure brain activity during sleep and wakefulness in 50 participants. The goal is to und…

This study looks at how low-intensity focused ultrasound can temporarily change brain activity in people with treatment-resistant depression. Researchers want to understand which brain circuits cause symptoms like loss of pleasure and repetitive negative thinking. 140 adults aged…

This study aims to learn more about how depression, bipolar disorder, and suicide risk affect people and how treatments work. Researchers will observe 500 adults already receiving care at the NIH Clinical Center. Participants will complete weekly interviews and questionnaires, an…

This study aims to understand how the brain processes social and emotional information in people with treatment-resistant depression or epilepsy. Researchers will use electrodes placed inside the skull to record brain activity while participants perform tasks involving emotions. …

This study aims to understand why about 30% of people with depression do not respond to standard antidepressants. Researchers will use brain scans to compare dopamine receptors in three groups: people with treatment-resistant depression, those whose depression responds to medicat…

This study follows 1,000 adults aged 18–99 with treatment-resistant depression or OCD who receive advanced therapies like ECT, TMS, or ketamine. Researchers collect brain scans, cognitive tests, and other data before, during, and after treatment to find markers that predict who w…

This study looks at how deep brain stimulation (DBS) affects electrical signals in the brain for people with severe depression that hasn't improved with other treatments. Ten participants will have electrodes implanted in a brain region called the subcallosal cingulate to record …