[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"major-depressive-disorder\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:major-depressive-disorder":626},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,212,0,25,[9,49,77,109,122,144,186,212,246,270,289,314,334,354,380,404,422,441,464,491,512,533,562,581,603],{"id":10,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":15,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":38,"startDateStruct":41,"completionDateStruct":43,"leadSponsor":45,"locationsCount":48},"100053248",false,"NCT05437588","Neural-Derived Plasma Exosomal MicroRNAs As Promising Novel Biomarkers for Suicidality and Treatment Outcome in Adolescents","Inclusion Criteria:\n\nAll participants:\n\n1. Physically healthy\n2. willing and able to provide informed consent (if under 18 also parent or guardian consent)\n\nMDD participants:\n\n1. A definite diagnosis of DSM-5\n2. a Children's Depression Rating Scale-Revised (CDRS-R) score \\>=30. Suicidal ideation participants: Columbia Suicide Severity Rating Scale (C-SSRS) score \\>=4 rated over the last two weeks.\n\nSuicide attempt group:\n\n1\\. Participants will have had an attempt in the previous two weeks that is serious enough to require medical attention and shows evidence of at least a medium level of intent on the Suicide Intent Scale.\n\nNon-psychiatric controls:\n\n1\\. No history of any major mental illness (excluding specific phobia) or substance use disorder.\n\nExclusion Criteria:\n\n* Exclusion criteria:\n\n  1. Pregnancy or lactation\n  2. post-partum state (being within 2 months of delivery or miscarriage);\n  3. homicide risk as determined by clinical interview\n  4. any of the following DSM-V diagnoses or categories: a) a lifetime history of psychotic disorder; b) alcohol or drug use disorder (except nicotine\u002Fcaffeine) within the last month; the use of any hallucinogen (except cannabis), including phencyclidine in the last month; c) bipolar disorder; d) pervasive developmental disorder; e) cognitive disorder; f) DSM-5 paranoid, schizoid, or schizotypal personality disorders (PDs) (participants with other PDs will be allowed as long as MDD criteria are met); g) anorexia nervosa.\n  5. recent myocardial infarction or unstable angina, active neoplasm in the past 6 months, immunosuppressive or corticosteroid therapy within the last month, chemotherapy, and head injury or loss of consciousness in the past 6 months\n  6. use of hallucinogens (except for cannabis), methamphetamine, or cocaine in the last 2 weeks.",true,"ALL","10 Years","24 Years",{"count":20,"type":21},240,"ESTIMATED","INTERVENTIONAL",[24],"NA","This study is dedicated to help identify biomarkers for depression and suicide. The purpose of the study is to better understand these links to improve medical and psychiatric care in the future. This research is also to test the effects of standard treatment of depression on improvement in depressive and suicidal behavior and on biomarkers (e.g. miRNA) for these disorders.",[27,28,29,30,31,32,33,34,35],"Major Depressive Disorder","Suicidal Ideas","Suicide, Attempted","MDD","Depression","Depression, Teen","Depression and Suicide","Depression in Adolescence","Suicide","RECRUITING","2026-07-10",{"date":39,"type":40},"2026-07-13","ACTUAL",{"date":42,"type":40},"2022-10-01",{"date":44,"type":21},"2027-06-30",{"name":46,"class":47},"University of Alabama at Birmingham","OTHER",2,{"id":50,"slug":4,"hasResults":11,"nctId":51,"briefTitle":52,"officialTitle":52,"acronym":4,"eligibilityCriteria":53,"healthyVolunteers":15,"sex":16,"minAge":54,"maxAge":55,"enrollmentInfo":56,"targetDuration":4,"studyType":22,"phases":58,"briefSummary":60,"conditions":61,"keywords":63,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":69,"startDateStruct":70,"completionDateStruct":72,"leadSponsor":74,"locationsCount":48},"100054265","NCT00018057","Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders","* INCLUSION CRITERIA:\n\nALL JUVENILE SUBJECTS\n\n* Age: 8-17 (subjects who consent as 17-year-olds but turn 18 during the course of the study will be eligible to complete all procedures completed by other subjects who consent as 17-year-olds but do not turn 18).\n* Consent: can give consent\u002Fassent (Parents will provide consent; minors will provide assent)\n* IQ: all subjects will have IQ\\>70 (Assessment relies on either a WASI or assessment by trained clinical staff during the subject s screening visit. Completion of required activities during the screening visit requires an IQ above 70.)\n* Language: all subjects will speak English (Tasks in this protocol have not been validated in languages other than English)\n\nALL ADULT SUBJECTS\n\n* Age: 18-65\n* Consent: can give consent\n* IQ: all subjects will have IQ\\>70 (Assessment relies on either a WASI or assessment by trained clinical staff during the subject s screening visit. Completion of required activities during the screening visit requires an IQ above 70.)\n* Language: all subjects will speak English (Tasks in this protocol have not been validated in languages other than English)\n\nALL SUBJECTS WITH AN ANXIETY DISORDER\n\n* Diagnosis: Current Diagnosis of OCD, Social Phobia, Separation Anxiety, Generalized Anxiety Disorder, or Panic Disorder (Based on K-SADS (juveniles) or SCID (adults))\n* Symptom Severity: Clinically significant, ongoing anxiety symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)\n* Clinical Impairment: Clinically significant, ongoing distress or impairment from anxiety (This will be documented by clinician review with patients and their families during at least two visits with families.)\n\nALL PREVIOUSLY ENROLLED ADOLESCENT PATIENTS, CHILD AND ADULT HEALTHY VOLUNTEERS, AND ALL HEALTHY VOLUNTEERS TURNED PATIENTS\n\n* Diagnosis: Current Diagnosis of OCD, Social Phobia, Separation Anxiety, Generalized Anxiety Disorder, or Panic Disorder; No current diagnosis (Based on K-SADS (juveniles) or SCID (adults))\n* Clinical Impairment (as applicable): Clinically significant, ongoing symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)\n* Symptom Severity (as applicable): Clinically significant, ongoing symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)\n\nEXCLUSION CRITERIA:\n\nALL SUBJECTS\n\n* Any serious medical condition or condition that interferes with fMRI or M\u002FEEG scanning, and for patients electing medication, any condition that increases risk of SSRI treatment. (All patients will complete a medical history. Healthy volunteer participants will be medication- free and have no current serious medical conditions, based on a review of their medical history. Subjects only will be excluded from the MRI portions of the study based on this exclusion criterion.)\n* Pregnancy (Subjects only will be excluded from the MRI portions of the study based on this exclusion criterion.)\n* Current use of any psychoactive substance; current suicidal ideation as indicated by the presence of intent for engaging in suicidal behaviors; current diagnosis of attention deficit hyperactivity disorder (ADHD) of sufficient severity to require pharmacotherapy. (These factors could complicate treatment with an SSRI. No subject on medication will be accepted into the trial. Subjects will not be taken off of medications to enter the trial.)\n* Current diagnoses, major depressive disorder (MDD), post-traumatic distress disorder, conduct disorder. (These factors may be affected by SSRI treatment, influencing ability to detect effects on anxiety\u002Fsymptoms of depression. Of note, subjects who present with a diagnosis of MDD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop MDD when followed over time. Subjects will be allowed to remain in the study if they develop these diagnoses after enrollment.)\n* Past or current history of mania, psychosis, or severe pervasive developmental disorder. (These factors may be affected by SSRI treatment, influencing ability to detect effects on anxiety\u002Fsymptoms of depression. Of note, subjects who present with a diagnosis of MDD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop MDD when followed over time. Subjects will be allowed to remain in the study if they develop these diagnoses after enrollment.)\n* Recent use of an SSRI with failure to respond or tolerate SSRI treatment at an adequate dose and duration. (This is designed to exclude subjects who have failed a trial of an SSRI for their current problem with anxiety. For previously enrolled participants, including patients and healthy volunteers, current use of an SSRI does not exclude participation from follow-up research tasks.)\n* History of any (excepting nicotine-related and cannabis-related) DSM5-defined moderate to severe substance use disorder (or DSM-IV-defined substance dependence).\n\nHEALTHY ADULT SUBJECTS\n\n-Any current psychiatric diagnosis (Assessment relies on SCID)","8 Years","65 Years",{"count":57,"type":21},3500,[59],"PHASE2","Study Description:\n\nThis study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neuro-cognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M\u002FEEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points.\n\nPrimary Objectives:\n\nTo compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli.\n\nSecondary Objectives:\n\n1. To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale.\n2. To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine.\n3. To document relations among broad arrays of clinical, cognitive, and neural measures\n\nPrimary Endpoints:\n\nIndices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm.\n\nSecondary Endpoints:\n\n1. Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score.\n2. Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli.",[62,27],"Anxiety Disorders",[64,65,66,67,68],"fMRI","Emotion","Normal Volunteers","Magnetic Resonance Imaging","CBT",{"date":39,"type":40},{"date":71,"type":40},"2001-10-02",{"date":73,"type":21},"2029-01-01",{"name":75,"class":76},"National Institute of Mental Health (NIMH)","NIH",{"id":78,"slug":4,"hasResults":11,"nctId":79,"briefTitle":80,"officialTitle":81,"acronym":82,"eligibilityCriteria":83,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":85,"enrollmentInfo":86,"targetDuration":4,"studyType":22,"phases":88,"briefSummary":90,"conditions":91,"keywords":92,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":98,"lastUpdatePostDateStruct":99,"startDateStruct":101,"completionDateStruct":103,"leadSponsor":105,"locationsCount":108},"100559491","NCT06564818","\"A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder\"","A Phase III, Placebo-Controlled, Randomized, Double-Blind Trial of Oral Doses of CYB003 to Assess Combined Safety and Efficacy in Humans With Major Depressive Disorder","APPROACH","Inclusion Criteria:\n\nParticipants must meet all the following criteria to be included in the trial:\n\n* Aged 18 to 85 years inclusive, at Screening\n* Participant has a diagnosis of MDD (single or recurrent episode as defined by DSM-5 TR \\[if single episode, duration of ≥4 weeks and ≤24 months\\] and established as per evaluation by the Investigator. The first MDD episode must have occurred prior to age 60.\n* Depression is of moderate to severe degree at Screening and Baseline, independently confirmed by additional clinical assessments\n* Participant has been on a stable dose of a single antidepressant medication at an adequate dose (label specified) for an adequate duration in the last month prior to Screening and has had an inadequate response (less than 50% improvement), as judged by the Investigator.\n* Participant has a body mass index (BMI) of 40 kg\u002Fm2 or less (BMI ≤ 40 kg\u002Fm2), inclusive, at Screening.\n* Participant is able to refrain from nicotine use during the dosing session (up to 8 hours)\n* Registered with a healthcare professional who can confirm the diagnosis and previous treatments received by the participant.\n* Participants capable of producing sperm must use a condom plus spermicide during the trial and for 12 weeks after their final dose of trial medication, if their partner is a person of childbearing potential.\n* Participants of childbearing potential who have a partner capable of producing sperm must agree to use a highly effective method of contraception (i.e., failure rate less than 1% when used consistently and correctly) in combination with the use of a condom plus spermicide during the trial and for 12 weeks after their final dose of trial medication. Such participants must have a negative pregnancy test at Screening and Day 1 prior to dosing.\n* Female participants who were capable of producing eggs (ova) must agree that the only exclusion from the requirement for contraception during the trial is to be postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy, or bilateral oophorectomy. Postmenopausal is defined as spontaneous amenorrhea for at least 12 months, and a serum follicle-stimulating hormone level in the menopausal range, unless the participant is taking hormone replacement therapy or is using hormonal contraception.\n* Participant has provided written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.\n\nExclusion Criteria:\n\nParticipants with any of the following characteristics\u002Fconditions will be excluded from trial participation:\n\n* Current or previously diagnosed schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder, brief psychotic disorder, current or previous history of bipolar disorder, or current borderline personality disorder.\n* Participants with a medical diagnosis of attention deficit hyperactivity disorder (ADHD) will be excluded if currently taking medication for ADHD\n* Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type 1 (first degree relatives).\n* Significant suicide risk within the past 6 months, during the Screening Period, or at Baseline; or (b) suicidal behaviors within 12 months of Screening; or (c) clinical assessment of significant suicidal risk during clinical interview; or (d) non-suicidal self-injury within 12 months of Screening.\n* Current or previous diagnosis of treatment-resistant MDD, defined as failure to respond to 2 or more antidepressant treatments of 2 different classes given at an adequate dose (label specified) for an adequate duration as judged by the Investigator and clinical interview.\n* Has had electroconvulsive treatment, transcranial magnetic stimulation, deep brain stimulation, or vagal nerve stimulation for any episode of MDD in the last 6 months.\n* Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressant, mirtazapine, trazodone, moclobemide, buspirone, ketamine or S-ketamine, or an antipsychotic or mood stabilizer for MDD. Note: if receiving these medications for another indication, they must be discontinued ≥ 14 days or 5 half-lives, whichever is longer, prior to Day 1.\n* Participant report of (or if available in medical record) exposure to psilocin, or 5-HT2a receptor agonists, or any other psychedelics, such as ayahuasca, mescaline, lysergic acid diethylamide, peyote, or 3,4-methylenedioxymethamphetamine, more than 10 times over the participant's lifetime or any psychedelic use within 12 months prior to Screening.\n* Participant report of (or if available in medical record) treatment with ketamine or S-ketamine use within 6 months prior to Screening.\n* Clinically relevant history of abnormal physical health interfering with the trial as determined by medical history and physical examinations obtained during Screening as judged by the Investigator (including but not limited to, neurological, cardiovascular, respiratory, gastrointestinal \\[including dyspepsia or gastroesophageal reflux disease\\], hepatic, or renal disorder).\n* Participants with renal insufficiency.\n* Has hypothyroidism or hyperthyroidism, unless controlled on appropriate medication.\n* Current diagnosis of uncontrolled hypertension or an arrhythmia, or clinically relevant abnormal results for heart rate or blood pressure\n* History or clinical evidence of any disease and\u002For existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the trial medication.\n* Participant has a presence or relevant history of organic brain disorders (e.g., epilepsy, seizure, intracranial hypertension, intracranial bleed and aneurysmal disease, brain tumor or other medical conditions associated with seizures or convulsions).\n* Known sensitivity to psilocin and\u002For any excipients present in the formulation.\n* Participant is taking or has taken OTC doses of 5-HTP or St John's Wort within 14 days prior to trial medication administration.\n* The participant has participated in a clinical trial and has received a medication or a new chemical entity within 12 weeks prior to dosing with the current trial medication. Participants who have completed observational or non-interventional studies will be allowed.\n* Participants capable of producing sperm who will not abstain from sperm donation between first dosing and 12 weeks after final dosing.\n* Participants of childbearing potential who are pregnant, breastfeeding, planning to conceive or unwilling to abstain from egg (ova) donation between first dosing and 12 weeks after final dosing.\n* History of serotonin syndrome.\n* Unwilling to consent to audio and video recording of psychological support and dosing sessions.\n* Staff and family members of Cybin IRL Limited, investigator sites, contract research organization or other vendors.","18 Years","85 Years",{"count":87,"type":21},220,[89],"PHASE3","The purpose of this study is to examine the efficacy, safety, and tolerability of CYB003 compared to matching placebo as adjunctive treatment in participants with MDD.",[27],[27,30,93,94,95,96,97,31],"Psilocybin","Psychedelic","Psilocin","CYB003","CYB003-001","2026-07-01",{"date":100,"type":40},"2026-07-02",{"date":102,"type":40},"2024-12-17",{"date":104,"type":21},"2026-09",{"name":106,"class":107},"Cybin IRL Limited","INDUSTRY",47,{"id":110,"slug":4,"hasResults":11,"nctId":51,"briefTitle":52,"officialTitle":52,"acronym":4,"eligibilityCriteria":111,"healthyVolunteers":15,"sex":16,"minAge":54,"maxAge":55,"enrollmentInfo":112,"targetDuration":4,"studyType":22,"phases":113,"briefSummary":60,"conditions":114,"keywords":115,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":116,"lastUpdatePostDateStruct":117,"startDateStruct":119,"completionDateStruct":120,"leadSponsor":121,"locationsCount":48},"100059514","* INCLUSION CRITERIA:\n\nALL JUVENILE SUBJECTS\n\n* Age: 8-17 (subjects who consent as 17-year-olds but turn 18 during the course of the study will be eligible to complete all procedures completed by other subjects who consent as 17-year-olds but do not turn 18).\n* Consent: can give consent\u002Fassent (Parents will provide consent; minors will provide assent)\n* IQ: all subjects will have IQ\\>70 (Assessment relies on either a WASI or assessment by trained clinical staff during the subject s screening visit. Completion of required activities during the screening visit requires an IQ above 70.)\n* Language: all subjects will speak English (Tasks in this protocol have not been validated in languages other than English)\n\nALL ADULT SUBJECTS\n\n* Age: 18-65\n* Consent: can give consent\n* IQ: all subjects will have IQ\\>70 (Assessment relies on either a WASI or assessment by trained clinical staff during the subject s screening visit. Completion of required activities during the screening visit requires an IQ above 70.)\n* Language: all subjects will speak English (Tasks in this protocol have not been validated in languages other than English)\n\nALL SUBJECTS WITH AN ANXIETY DISORDER\n\n* Diagnosis: Current Diagnosis of OCD, Social Phobia, Separation Anxiety, Generalized Anxiety Disorder, or Panic Disorder (Based on K-SADS (juveniles) or SCID (adults))\n* Symptom Severity: Clinically significant, ongoing anxiety symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)\n* Clinical Impairment: Clinically significant, ongoing distress or impairment from anxiety (This will be documented by clinician review with patients and their families during at least two visits with families.)\n\nALL PREVIOUSLY ENROLLED ADOLESCENT PATIENTS, CHILD AND ADULT HEALTHY VOLUNTEERS, AND ALL HEALTHY VOLUNTEERS TURNED PATIENTS\n\n* Diagnosis: Current Diagnosis of OCD, Social Phobia, Separation Anxiety, Generalized Anxiety Disorder, or Panic Disorder; No current diagnosis (Based on K-SADS (juveniles) or SCID (adults))\n* Clinical Impairment (as applicable): Clinically significant, ongoing symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)\n* Symptom Severity (as applicable): Clinically significant, ongoing symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)\n\nEXCLUSION CRITERIA:\n\nALL SUBJECTS\n\n* Any serious medical condition or condition that interferes with fMRI or M\u002FEEG scanning, and for patients electing medication, any condition that increases risk of SSRI treatment. (All patients will complete a medical history. Healthy volunteer participants will be medication- free and have no current serious medical conditions, based on a review of their medical history. Subjects only will be excluded from the MRI portions of the study based on this exclusion criterion.)\n* Pregnancy (Subjects only will be excluded from the MRI portions of the study based on this exclusion criterion.)\n* Current use of any psychoactive substance; current suicidal ideation; current diagnosis of attention deficit hyperactivity disorder (ADHD) of sufficient severity to require pharmacotherapy. (These factors could complicate treatment with an SSRI. No subject on medication will be accepted into the trial. Subjects will not be taken off of medications to enter the trial.)\n* Current diagnoses, major depressive disorder (MDD), post-traumatic distress disorder, conduct disorder. (These factors may be affected by SSRI treatment, influencing ability to detect effects on anxiety\u002Fsymptoms of depression. Of note, subjects who present with a diagnosis of MDD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop MDD when followed over time. Subjects will be allowed to remain in the study if they develop these diagnoses after enrollment.)\n* Past or current history of mania, psychosis, or severe pervasive developmental disorder. (These factors may be affected by SSRI treatment, influencing ability to detect effects on anxiety\u002Fsymptoms of depression. Of note, subjects who present with a diagnosis of MDD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop MDD when followed over time. Subjects will be allowed to remain in the study if they develop these diagnoses after enrollment.)\n* Recent use of an SSRI with failure to respond or tolerate SSRI treatment at an adequate dose and duration. (This is designed to exclude subjects who have failed a trial of an SSRI for their current problem with anxiety. For previously enrolled participants, including patients and healthy volunteers, current use of an SSRI does not exclude participation from follow-up research tasks.)\n* History of any (excepting nicotine-related and cannabis-related) DSM5-defined moderate to severe substance use disorder (or DSM-IV-defined substance dependence).\n\nHEALTHY ADULT SUBJECTS\n\n-Any current psychiatric diagnosis (Assessment relies on SCID)",{"count":57,"type":21},[59],[62,27],[64,65,66,67,68],"2026-06-27",{"date":118,"type":40},"2026-06-30",{"date":71,"type":40},{"date":73,"type":21},{"name":75,"class":76},{"id":123,"slug":4,"hasResults":11,"nctId":124,"briefTitle":125,"officialTitle":126,"acronym":4,"eligibilityCriteria":127,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":128,"enrollmentInfo":129,"targetDuration":4,"studyType":22,"phases":131,"briefSummary":132,"conditions":133,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":134,"lastUpdatePostDateStruct":135,"startDateStruct":137,"completionDateStruct":139,"leadSponsor":141,"locationsCount":143},"100641561","NCT07592689","A Phase 3 Trial of DT120 for Major Depressive Disorder (Ascend)","A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled, 12-Week Study (Part A) With a 40-Week Open-label Extension (Part B) Evaluating the Efficacy and Safety of Oral DT120 Compared to Placebo in the Treatment of Adults With Major Depressive Disorder - Ascend","Inclusion Criteria:\n\n1. Diagnosis of MDD per DSM-5\n2. Male or female aged 18 to 74\n3. Currently experiencing a major depressive episode (MDE) of ≥8 weeks and ≤24 months duration\n4. MADRS Total Score ≥26\n5. CGI-S Score ≥4\n\nExclusion Criteria:\n\n1. Certain psychiatric disorders (other than major depressive disorder)\n2. First degree relative with or lifetime history of a psychotic disorder or bipolar disorder\n3. Current diagnosis of alcohol or substance use disorder (excluding nicotine and caffeine\n4. Any clinically significant unstable illness","74 Years",{"count":130,"type":21},165,[89],"A Phase 3 Double-blind, Placebo-controlled Study (Part A) with an Open-label Extension (Part B) Evaluating DT120 Compared to Placebo in Major Depressive Disorder - Ascend",[27],"2026-06-26",{"date":136,"type":40},"2026-06-29",{"date":138,"type":40},"2026-05-10",{"date":140,"type":21},"2028-06",{"name":142,"class":107},"Definium Therapeutics US, Inc.",27,{"id":145,"slug":4,"hasResults":11,"nctId":146,"briefTitle":147,"officialTitle":147,"acronym":4,"eligibilityCriteria":148,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":149,"enrollmentInfo":150,"targetDuration":4,"studyType":152,"phases":4,"briefSummary":153,"conditions":154,"keywords":174,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":134,"lastUpdatePostDateStruct":179,"startDateStruct":180,"completionDateStruct":182,"leadSponsor":184,"locationsCount":185},"100551600","NCT06462196","Natural History of Depression, Bipolar Disorder and Suicide Risk","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n* Signed consent for Protocol 01-M-0254: The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers\n* Age 18 years or older\n* Able to provide informed consent\n* Able to read and write English\n\nEXCLUSION CRITERIA:\n\n* Unstable medical conditions in the opinion of the investigator that would preclude participation in outpatient or inpatient treatment.\n* Pregnancy\n* Participation in the Protocol 01-M-0254: The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers, as a healthy volunteer.\n* Participants with a history of DSM-IV substance or alcohol abuse or dependence, or DSM-5 substance use disorder (except for caffeine, nicotine, or cannabis), or moderate to severe alcohol use disorder, within the preceding three months. In addition, participants who are currently using drugs (except for caffeine, nicotine, or cannabis) must not have used illicit substances or known drugs of abuse in the two weeks prior to consent and must have a negative drug urine test (except for prescribed benzodiazepines or stimulants) prior to enrolling in the study. Cannabis use is exclusionary if the use is daily, or if participants are unable to abstain during the study, or if function of daily life is impaired by use as determined by a clinician.","120 Years",{"count":151,"type":21},500,"OBSERVATIONAL","Mood disorders, such as depression and bipolar disorder, are difficult to treat. One reason is that there are no objective ways to measure how these disorders affect the body and respond to different treatments. In this study, researchers want to perform tests on people undergoing clinical care for mood disorders. The purpose is to understand the experience of receiving treatment for depression, bipolar disorder, and suicide risk. We also hope that this study will help us to predict which medications will improve thoughts of suicide.\n\nPeople 18 years or older who are receiving treatment for depression, bipolar disorder, or suicide risk may take part in this study. Participants must have also been enrolled in protocol 01-M-0254.\n\nThis study will be conducted at the NIH Clinical Center in Bethesda, MD. The study typically lasts up to 12 weeks, but may last longer if a participant s treatment continues past that time.\n\nParticipants will have weekly interviews and questionnaires while they are being treated for their mood disorder. Other tests are optional and include psychological testing, blood draws, sleep tests, and imaging scans. These will be done at the start and the end of research participation.",[155,35,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,27,173],"Behavioral Symptoms","Self-Injurious Behavior","Sensory System Agents","Analgesics","Peripheral Nervous System Agents","Physiological Effects of Drugs","Anesthetics, Dissociative","Anesthetics, General","Anesthetics","Central Nervous System Depressants","Excitatory Amino Acid Antagonists","Excitatory Amino Acid Agents","Neurotransmitter Agents","Molecular Mechanisms of Pharmacological Action","Ketamine","Depression, Unipolar","Depressive Symptoms","Treatment Resistant Depression","Depression, Bipolar",[175,35,27,176,177,178,172],"Neurobiology","Bipolar Disorder","Biomarkers","Suicide Risk",{"date":136,"type":40},{"date":181,"type":40},"2024-09-09",{"date":183,"type":21},"2030-06-01",{"name":75,"class":76},1,{"id":187,"slug":4,"hasResults":11,"nctId":188,"briefTitle":189,"officialTitle":190,"acronym":4,"eligibilityCriteria":191,"healthyVolunteers":11,"sex":16,"minAge":18,"maxAge":55,"enrollmentInfo":192,"targetDuration":4,"studyType":22,"phases":194,"briefSummary":195,"conditions":196,"keywords":198,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":204,"lastUpdatePostDateStruct":205,"startDateStruct":206,"completionDateStruct":208,"leadSponsor":210,"locationsCount":185},"100601507","NCT07111390","Feasibility of Home-Based Intermittent 60Hz Light Therapy for Major Depressive Disorder (MDD)","A Feasibility Pilot Study of Home-Based Intermittent 60Hz Light Therapy for the Treatment of Depression","Inclusion Criteria:\n\n* Age between 24 and 65 years (inclusive)\\*.\n* Confirmed diagnosis of Major Depressive Disorder (MDD), based on MINI interview.\n* Hamilton Depression Rating Scale (HDRS-17) score ≥17 at screening.\n* On a stable dose of antidepressant medication for at least 30 days prior to HDRS-17 screening.\n* No evidence of premorbid cognitive impairment, as demonstrated by a standard score \\>85 on the WRAT-5 Reading Recognition Subtest.\n* Confirmed access to a local provider that has primary responsibility for the subjects' clinical care, and who is available for contact in case of increased subject risk due to depressive symptoms.\n* Able to provide informed consent and comply with study procedures.\n* Access to a quiet space suitable for home-based light stimulation sessions.\n* English speaking: All study materials and assessments are only validated in English\n\nExclusion Criteria:\n\n* Presence of primary neurological or autoimmune disorders.\n* Presence of psychiatric comorbidities as determined by the MINI interview (e.g., anxiety disorders, OCD, PTSD, bipolar disorder, psychotic disorder).\n* Current or recent diagnosis of alcohol or substance use disorder.\n* History of bipolar disorder or any psychotic disorder.\n* Clinically significant suicidal ideation or behavior, based on clinician judgment and the Columbia-Suicide Severity Rating Scale (C-SSRS).\n* History of seizure disorder or epilepsy.\n* History of migraine, tinnitus, or photosensitivity.\n* Diagnosis of retinal disease, cataract, or other visual impairments that may interfere with light exposure.\n* Regular use of anti-inflammatory drugs or anticoagulants (e.g., clopidogrel).\n* Pregnancy and Breastfeeding: Currently pregnant, planning pregnancy during the study period, or breastfeeding",{"count":193,"type":21},40,[24],"This pilot study evaluates the feasibility, safety, and preliminary efficacy of home-based 60Hz intermittent light therapy in adults with a major depressive episode (MDE). Participants will be randomized in a 2:1 ratio to receive either active or sham 60Hz intermittent light stimulation for 30 minutes daily (Monday through Friday) over three weeks. The light is delivered through a wearable headset. Clinical assessments will be conducted remotely at baseline, mid-point, post-treatment, and follow-up to measure changes in depressive symptoms.",[31,30,27,197],"Major Depressive Episode",[199,30,31,200,201,202,203],"Brain stimulation","Light therapy","Wearable","Neuromodulation","Telehealth","2026-06-25",{"date":136,"type":40},{"date":207,"type":40},"2025-08-18",{"date":209,"type":21},"2027-02-01",{"name":211,"class":47},"NYU Langone Health",{"id":213,"slug":4,"hasResults":11,"nctId":214,"briefTitle":215,"officialTitle":216,"acronym":217,"eligibilityCriteria":218,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":219,"enrollmentInfo":220,"targetDuration":4,"studyType":22,"phases":222,"briefSummary":223,"conditions":224,"keywords":225,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":238,"lastUpdatePostDateStruct":239,"startDateStruct":240,"completionDateStruct":242,"leadSponsor":244,"locationsCount":185},"100631952","NCT07507370","CARED : A Novel Rapid Treatment Paradigm for Depression","The Carolina Recovery From Depression Protocol (CARED) : A Novel Rapid Treatment Paradigm for Depression","CARED","Inclusion Criteria:\n\n* Any gender, aged 18 - 70\n* Provision of signed and dated informed consent form\n* Stated willingness to comply with all study procedures and availability for the duration of the study\n* DSM-5 diagnosis of unipolar, non-psychotic MDD as evidenced by the Diagnostic Interview for Anxiety, Mood, and Obsessive-Compulsive and Related Neuropsychiatric Disorders (DIAMOND)\n* HDRS-17 score ≥14\n* Low suicide risk (defined for this study as no active suicidal ideation in the past month and no suicide attempts, preparatory actions, or significant non-suicidal self-harm in the previous 2 years). Risk will be assessed utilizing the Columbia-Suicide Severity Rating Scale (C-SSRS) screen and triage version with further exploration of positive responses.\n* Capacity to understand all relevant risks and potential benefits of the study (informed consent).\n* For people of childbearing potential: use of highly effective contraception as determined by the Investigator for at least 1 month prior to screening and agreement to use such a method during study participation\n* History of treatment resistance as indicated by previously or currently not achieving clinically significant symptom reduction on at least one antidepressant medication. This will be evaluated using the Maudsley Treatment Inventory (MTI). Participants with scores greater than or equal to 3 on the MTI will be included.\n\nExclusion Criteria:\n\n* DSM-5 diagnosis of severe alcohol use disorder (AUD) within the last 12 months, as evidenced by the DIAMOND\n* DSM-5 diagnosis of moderate to severe substance use disorder (excluding tobacco) within the last 12 months, as evidenced by the DIAMOND\n* Lifetime history of bipolar disorder, as evidenced by DIAMOND\n* Schizophrenia spectrum and other psychotic disorders, as evidenced by DIAMOND\n* History of autism spectrum disorder (self-reported by participants)\n* Initiated any new psychotropic medication in the 6 weeks prior to screening or had a dose change in the preceding 6 weeks\n* Initiated a new course of psychotherapy in the 6 weeks preceding screening\n* Received any neurostimulation treatment in the 6 weeks preceding screening\n* History of seizures (excluding febrile seizures in childhood or Electroconvulsive Therapy (ECT) induced seizures)\n* Neurological disorders that would increase risk of participation or present a significant confounder in the opinion of the investigator (for example, dementia, history of stroke, Parkinson's disease, multiple sclerosis, history of traumatic brain injury with prolonged loss of consciousness, ruptured cerebral aneurysm, previous CNS radiation)\n* Previously failed to respond to ECT or transcranial magnetic stimulation (TMS)\n* Prior brain surgery and\u002For brain implants\n* Personal or familia history of epilepsy\n* Previous fainting spells or syncope\n* Metal in the brain, skull or elsewhere in the body\n* Implanted medical device that uses electricity and any implanted devices in other areas of the head or neck, or implants located \\\u003C 30cm from the position of the TMS coil\n* Current pregnancy or lactation\n* Currently enrolled in another clinical trial for depression\n* Unstable medical disorder or anything that would place the participant at increased risk or preclude the participant's full compliance with or completion of the study, in the opinion of the Investigator\n* Non-English speaking individuals are excluded because the ability to accurately and completely communicate study information, answer questions about the study, and obtain consent in the English language are necessary, and due to resource constraints it is not feasible to engage an interpreter for language services.","70 Years",{"count":221,"type":21},30,[24],"The purpose of this study is to primarily assess the feasibility and secondarily assess the efficacy of a single session intervention (SSI) that combines non-invasive brain stimulation and psychotherapy for Major Depressive Disorder (MDD). investigators will recruit 30 people with MDD, with at least mild to moderate symptoms, who are resistant to typical treatments for Major Depressive Disorder. In this trial, participants will receive psychotherapy, Intermittent Theta Burst Stimulation Transcranial Magnetic Stimulation (iTBS), and either active or sham (placebo) Transcranial Alternating Current Stimulation (tACS).",[27],[226,227,228,229,230,231,31,232,233,234,235,236,237],"Non-invasive Brain Stimulation","Psychotherapy","Transcranial Magnetic Stimulation","Single Session Intervention","tACS","Behavioral Activation","Transcranial Alternating Current Stimulation","Acceptance and Commitment Therapy","Mood Disorders","Brief Intervention","TMS","Neurostimulation","2026-06-23",{"date":204,"type":40},{"date":241,"type":40},"2026-04-14",{"date":243,"type":21},"2028-07-01",{"name":245,"class":47},"University of North Carolina, Chapel Hill",{"id":247,"slug":4,"hasResults":11,"nctId":248,"briefTitle":249,"officialTitle":250,"acronym":4,"eligibilityCriteria":251,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":4,"enrollmentInfo":252,"targetDuration":4,"studyType":22,"phases":254,"briefSummary":255,"conditions":256,"keywords":257,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":261,"lastUpdatePostDateStruct":262,"startDateStruct":263,"completionDateStruct":265,"leadSponsor":267,"locationsCount":269},"100590100","NCT06963021","NBI-1065845-MDD3026: Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)","A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NBI-1065845 as Adjunctive Treatment in Subjects With Major Depressive Disorder (MDD)","Key Inclusion Criteria:\n\n* Participant has a primary diagnosis of recurrent MDD (moderate or severe) or persistent depressive disorder.\n* Participant has had an inadequate response to oral antidepressant treatments in the current episode of depression.\n* Participant must have been taking oral antidepressants for at least 8 weeks and is willing to continue the same oral antidepressants at the same dose and frequency of administration throughout participation in the study.\n* Total Hamilton Depression Rating Scale-17 Item (HAM-D17) score ≥22 at screening and at study baseline (Day 1).\n* Willing and able to comply with all study procedures and restrictions in the opinion of the investigator.\n\nKey Exclusion Criteria:\n\n* A current or prior psychiatric disorder diagnosis in the last 1 year that was the primary focus of treatment other than MDD.\n* Are considered by the investigator to be at imminent risk of suicide or injury to self or others.\n* Participants depressive symptoms have previously demonstrated nonresponse to electroconvulsive therapy (ECT) in the current major depressive episode.",{"count":253,"type":21},200,[89],"The study will evaluate the efficacy of NBI-1065845 compared with placebo as an adjunctive treatment in participants with MDD on improving symptoms of depression.",[27],[30,31,27,258,259,260],"NBI-1065845","TAK-653","MADRS","2026-06-22",{"date":238,"type":40},{"date":264,"type":40},"2025-05-30",{"date":266,"type":21},"2027-07",{"name":268,"class":107},"Neurocrine Biosciences",34,{"id":271,"slug":4,"hasResults":11,"nctId":272,"briefTitle":273,"officialTitle":274,"acronym":4,"eligibilityCriteria":275,"healthyVolunteers":15,"sex":16,"minAge":84,"maxAge":4,"enrollmentInfo":276,"targetDuration":4,"studyType":22,"phases":278,"briefSummary":279,"conditions":280,"keywords":4,"overallStatus":281,"whyStopped":4,"lastUpdateSubmitDate":261,"lastUpdatePostDateStruct":282,"startDateStruct":283,"completionDateStruct":284,"leadSponsor":286,"locationsCount":185},"100558207","NCT06548113","Sensory Synchronized Imaging and Neuromodulation","Investigation of Sensory Synchronized Human Brain Imaging and Neuromodulation","Inclusion Criteria:\n\n* Men and women, ages 18 years and up\n* English speaking\n* Military Veterans\n\nExclusion Criteria:\n\n* Those with a contraindication for MRIs (e.g. implanted metal)\n* History of head trauma with loss of consciousness\n* History of seizures or on medications that substantially reduce seizure threshold\n* Neurological or uncontrolled medical disease\n* Active substance abuse\n* Currently pregnant or breastfeeding",{"count":277,"type":21},250,[24],"The purpose of this research study is to better understand the relationship between the type of brain stimulation used and how it changes brain activity in adult military Veterans. The goal is to use this understanding to develop new, personalized brain stimulation. The investigators evaluate brain changes from different types of transcranial magnetic brain stimulation (TMS).",[27],"NOT_YET_RECRUITING",{"date":204,"type":40},{"date":39,"type":21},{"date":285,"type":21},"2030-12-31",{"name":287,"class":288},"VA Office of Research and Development","FED",{"id":290,"slug":4,"hasResults":11,"nctId":291,"briefTitle":292,"officialTitle":292,"acronym":4,"eligibilityCriteria":293,"healthyVolunteers":15,"sex":16,"minAge":84,"maxAge":294,"enrollmentInfo":295,"targetDuration":4,"studyType":22,"phases":297,"briefSummary":298,"conditions":299,"keywords":302,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":306,"lastUpdatePostDateStruct":307,"startDateStruct":308,"completionDateStruct":310,"leadSponsor":312,"locationsCount":185},"100480663","NCT05538910","Defining Neurobiological Links Between Substance Use and Mental Illness","* INCLUSION CRITERIA:\n\nTo be eligible for this study, an individual must meet all the following criteria assessed under the currently approved NIDA IRP screening protocol for the evaluation of potential research subjects (here referred to as the NIDA screening protocol). This is a protocol led by the Office of the Clinical Director (OCD) at the National Institute on Drug Abuse Intramural Research Program (NIDA IRP) to assess potential research participants eligibility for entering clinical protocols at the NIDA\u002FIRP. Additional details can be found in the NIDA screening protocol documents. As routinely done at the NIDA IRP, the screening procedures and data collected under the NIDA\n\nscreening protocol will capture information above and beyond what is necessary to determine eligibility for this protocol but allows the Investigators to assess the eligibility criteria for this protocol.\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\nAll Participants:\n\n1. Able and willing to provide written informed consent.\n2. Both sexes and all ethnic origins, age between 18 and 60 at the time of consent. Justification: Many neural processes change with age, and these changes could introduce unwanted variability in both behavioral and MRI signals.\n3. Be generally healthy\n4. Absence of pregnancy and breastfeeding. Justification: study procedures and drugs used in the current protocol may complicate pregnancy or be transferred to nursing children. Assessment tool(s): Urine and\u002For serum pregnancy tests, and clinical interview. Urine pregnancy tests will also be conducted at the beginning of each imaging visit.\n5. Have a Breath Alcohol Value of 0 on all study visit days involving scanning. Participant may be rescheduled if this value is greater than 0.\n\nMDD Subjects:\n\n1. Meet DSM-5 diagnostic criteria for current MDD at screening Clinical judgement will be used to interpret criteria.\n2. Have a baseline (Hamilton Depression) HAM-D score indicative of current depression as evaluated by clinical staff.\n3. Current stable serotonin modulating drug (e.g. SSRI\u002FSNRI\u002Fserotonin modulator) treatment is allowed (no changes in the last 2 months). Specific medications will be evaluated by the MAI\n\nRemitted MDD Subjects:\n\n1. Meet DSM-5 diagnostic criteria for remitted MDD (full remission or partial remission or past depression) Clinical judgement will be used to interpret criteria.\n2. HAM-D score indicating no clinically relevant depression as evaluated by clinical staff.\n3. Current stable serotonin modulating drug (e.g. SSRI\u002FSNRI\u002Fserotonin modulator) treatment is allowed (no changes in the last 2 months). Specific medications will be evaluated by the MAI.\n\nControl Subjects (without MDD):\n\n1. In addition to the absence of medical, neurological, and psychiatric illness listed above, control participants must not have current\u002Flifetime MDD. Clinical judgement will be used to interpret criteria.\n2. HAM-D score indicating no clinically-relevant depression as evaluated by clinical staff.\n\nDaily Nicotine Users (Study Arm 2):\n\n1. Uses nicotine daily for at least six months\n2. Positive urine screen for cotinine\n\nEXCLUSION CRITERIA (STUDY ARM 1):\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n1. Subjects with suicidal ideation where outpatient treatment is determined unsafe.\n2. Lifetime history or current diagnosis of any of the following psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features. The MAI and\u002For PI\u002FLI will reserve the right to exclude based psychiatric history not explicitly described in this criterion\n\n   a. Within the control group, Current\u002Flifetime MDD will be exclusionary for controls. Those currently using antidepressants to treat anxiety disorders typically co-morbid with MDD such as general anxiety disorder and panic disorder will be excluded. The MAI will reserve the right to exclude on the basis of psychiatric history not explicitly described in this criterion.\n3. Are cognitively impaired or have a learning disability severe enough to have required intervention throughout most or all of K-12 education. The MAI will reserve the right to evaluate if a participant s history of educational placement is likely to represent a learning disability that could significantly impact the data gathered in this study based on the severity and type of learning disability. Justification: Cognitive impairment and learning disabilities may be associated with altered brain functioning in regions recruited during laboratory task performance.\n4. Heavy caffeine users (consume greater than 500 mg on a regular or daily basis. This is approximately five 8 fl oz cups of coffee). Participants will be asked to not deviate from their typical caffeine use on all scanning days.\n5. May not have regularly used any nicotine product in the past year; must never have been daily nicotine users for more than 1 month.\n6. Must have an expired carbon monoxide level of less than or equal to 5 ppm and cotinine levels consistent with a non-smoker. Depending on the commercially available test used, a level equivalent to a non-smoker status will be used, ideally indicative of a urine cotinine level of around 10 ng\u002Fml. However, given the known limitations of rapid tests to return specific quantifications of cotinine levels, if the present test is unable to quantify cotinine at this level, the lowest level of detection will be used as a cut off and MAI \u002F PI discretion may be used to determine whether this cut off coupled with participant history and environmental factors indicates personal nicotine use versus secondhand smoke environment.\n7. History of moderate or severe substance use disorder in the past 6 months (other than caffeine)\n8. Current pharmacological treatment for opioid use disorder (i.e., use of methadone)\n9. Current use of illegal drugs other than marijuana as measured by urine drug screen Marijuana will not be allowed in the 24 hours prior to scanning based on self-report. Study day can be rescheduled to accommodate.\n10. Participants may not use anticholinergic drugs (i.e., scopolamine), dopamine enhancing drugs (i.e. methylphenidate), or other medications that may impact MRI measures (i.e. benzodiazepines) prior to any scanning visit within a timeframe that is likely to directly\n\n    impact the study questions. MAI discretion regarding timeframe of allowed use will be based on half-life, pharmacology of the drug in question, and pattern of use by the participant. Scanning visit timing can be adjusted to accommodate.\n11. May not use drugs that directly enhance dopamine (i.e., methylphenidate) in the week prior to any scanning visit. Scanning visit timing can be adjusted to accommodate.\n12. Any past or present significant cardiovascular, cerebrovascular, or respiratory conditions, including arrhythmias, acute coronary syndrome, ischemic heart disease, or, uncontrolled hypertension\n13. Body mass index (BMI) lower than 18.5 kg\u002Fm\\^2\n14. Contraindications to MRI as determined by MRI Safety Screening form and mock scanner trial (when available).\n15. Abnormal structural MRI, significant head trauma, current neurological illness including but not limited to frequent migraines, multiple sclerosis, movement disorder\n16. Lifetime history of significant seizure disorder\n17. Any other serious or unstable medical illness as defined by self-report, the evaluation of vital signs or other observation that in the view of the investigators would compromise the safety of an individual during participation\n\n    All data collected will be evaluated by members of the study team to decide if there is an existing medical illness that would compromise participation in this research\n18. Subjects that cannot speak English. Justification: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify, given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI procedures. The inability to effectively communicate MRI safety procedures in a language other than English could compromise the safety of non-English speaking participants\n\nExclusion Criteria (Study Arm 2)\n\n1. Subjects with active suicidal ideation where outpatient treatment is determined unsafe.\n2. Current psychiatric symptoms in which the ability to adhere to study protocol is determined to be impaired by clinical staff\u002FMAI (e.g., difficulty understanding or answering questions, difficulty remaining still in the fMRI scanner)\n3. Are cognitively impaired or have a learning disability severe enough to have required intervention throughout most or all of K-12 education. The MAI will reserve the right to evaluate if a participant s history of educational placement is likely to represent a learning disability that could significantly impact the data gathered in this study based on the severity and type of learning disability.\n\n   Justification: Cognitive impairment and learning disabilities may be associated with altered brain functioning in regions recruited\n\n   during laboratory task performance.\n4. Heavy caffeine users (consume greater than 500 mg on a regular or daily basis. This is approximately five 8 fl oz cups of coffee). Participants will be asked to not deviate from their typical caffeine use on all scanning days.\n5. Active severe substance use disorder in the past 6 months (other than caffeine and nicotine)\n6. Contraindications to MRI as determined by MRI Safety Screening form and mock scanner trial (when available).\n7. Abnormal structural MRI, significant head trauma, current neurological illness likely to impact fMRI signal or ability to comply with study requirements (e.g., staying still in scanner)\n8. Any serious or unstable medical illness as defined by self-report, the evaluation of vital signs or other observation that in the view of the investigators, would compromise the safety of an individual during participation. All data collected will be evaluated by members of the study team to decide if there is an existing medical illness that would compromise participation in this research\n9. Subjects that cannot speak English. Justification: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify, given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI procedures. The inability to effectively communicate MRI safety procedures in a language other than English could compromise the safety of non-English speaking participants","60 Years",{"count":296,"type":21},620,[24],"Background:\n\nNicotine dependence leads to about 480,000 deaths every year in the United States. People with major depressive disorder (MDD) are twice as likely to use nicotine compared to the general population. They have greater withdrawal symptoms and are more likely to relapse after quitting compared with smokers without MDD. More research is needed on how nicotine affects brain function in those with MDD.\n\nObjective:\n\nTo understand how nicotine affects symptoms of depression and related brain function.\n\nEligibility:\n\nPeople aged 18 to 60 years, at the time of consent, with and without MDD who do not smoke cigarettes or use other nicotine products.\n\nDesign:\n\nParticipants will have 2 or 3 study visits over 1 year.\n\nParticipants will have 2 MRI scans no less than 4 days apart. Each scan visit will last 5 to 7 hours. At each scan, they will have urine and breath tests to screen for recent use of alcohol, nicotine, and illegal drugs.\n\nBefore each scan, they will take 1 of 2 medications: nicotine or placebo. Participants will receive each medication once. They will not know which medication they are receiving at each scan.\n\nFor each MRI scan, they will lie on a table that slides into a cylinder. Sometimes they will be asked to lie still. Sometimes they will complete tasks on a computer. Tasks may include identifying colors or playing games to win money. Each scan will take about 2 hours.\n\nParticipants will answer questions about their thoughts, feelings, and behaviors before and after each scan.\n\nThey will have a blood test after each scan.",[27,300,301],"Substance Use Disorder","Normal Physiology",[64,303,304,305],"Reward Function","Affective Processing","Interoceptive Awareness","2026-06-19",{"date":238,"type":40},{"date":309,"type":40},"2023-02-02",{"date":311,"type":21},"2027-12-31",{"name":313,"class":76},"National Institute on Drug Abuse (NIDA)",{"id":315,"slug":4,"hasResults":11,"nctId":316,"briefTitle":317,"officialTitle":318,"acronym":4,"eligibilityCriteria":319,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":4,"enrollmentInfo":320,"targetDuration":4,"studyType":22,"phases":322,"briefSummary":323,"conditions":324,"keywords":325,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":326,"lastUpdatePostDateStruct":327,"startDateStruct":328,"completionDateStruct":330,"leadSponsor":332,"locationsCount":333},"100590360","NCT06966401","Long-Term Study to Assess the Safety and Tolerability of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)","A Long-Term, Open-Label Study to Assess the Safety and Tolerability of NBI-1065845 as Adjunctive Treatment in Subjects With Major Depressive Disorder (MDD)","Key Inclusion Criteria:\n\n* Participant has a primary diagnosis of recurrent MDD (moderate or severe) or persistent depressive disorder.\n* Participant has had an inadequate response to oral antidepressant treatments in the current episode of depression.\n* Participant must have been taking oral antidepressants for at least 8 weeks prior to screening.\n* Willing and able to comply with all study procedures and restrictions in the opinion of the investigator.\n\nKey Exclusion Criteria:\n\n* A current or prior psychiatric disorder diagnosis in the last 1 year that was the primary focus of treatment other than MDD.\n* Are considered by the investigator to be at imminent risk of suicide or injury to self or others.\n\nOther protocol defined inclusion and exclusion criteria apply.",{"count":321,"type":21},850,[89],"This study will evaluate the long-term safety and tolerability of NBI-1065845 as an adjunctive treatment in participants with MDD.",[27],[30,31,27,258,259],"2026-06-18",{"date":261,"type":40},{"date":329,"type":40},"2025-04-16",{"date":331,"type":21},"2030-05",{"name":268,"class":107},98,{"id":335,"slug":4,"hasResults":11,"nctId":336,"briefTitle":337,"officialTitle":338,"acronym":4,"eligibilityCriteria":339,"healthyVolunteers":11,"sex":16,"minAge":340,"maxAge":219,"enrollmentInfo":341,"targetDuration":4,"studyType":22,"phases":343,"briefSummary":344,"conditions":345,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":346,"lastUpdatePostDateStruct":347,"startDateStruct":348,"completionDateStruct":350,"leadSponsor":352,"locationsCount":185},"100498707","NCT05773755","DBS for TRD With the Medtronic Percept PC","Deep Brain Stimulation for Treatment Resistant Depression: Exploration of Local Field Potentials (LFPs) With the Medtronic Percept PC System","Inclusion Criteria:\n\n* Age 25-70 years old.\n* Ability to provide written informed consent.\n* Primary psychiatric diagnosis of Major Depressive Disorder (MDD), either single episode or recurrent type, without psychotic features, currently experiencing a Major Depressive Episode (MDE), as diagnosed by Structured Clinical Interview for DSM IV-TR or DSM-5 (SCID-IV or SCID-5). Two independent psychiatrists will confirm the diagnosis, as well.\n* Current depressive episode of at least two years duration OR a history of more than 3 lifetime depressive episodes.\n* Minimum score at study entry of 20 on the 17-item Hamilton Depression Rating Scale\n* Average pre-operative HDRS-17 score of 20 or greater (averaged over four weekly pre-surgical evaluations during the four weeks prior to surgery)\n* A maximum Global Assessment of Functioning of 50 or less.\n* Confirmed to have treatment-resistant depression (TRD). Treatment-resistance will be defined as failure to respond to at least four adequate antidepressant treatments (assessed with the Antidepressant Treatment History Form \\[ATHF-SF\\] and verified through medical records) during the current episode. Treatments which support study inclusion include antidepressive medications, certain augmentation agents, evidenced-based psychotherapy, and neuromodulation (ECT, transcranial magnetic stimulation (TMS)). For those patients who have not received ECT, patients may be considered eligible for study participation if they have received adequate trials of an SSRI, SNRI, augmentation agent (certain atypical antipsychotic medications, Lithium), and TMS and\u002For ketamine.\n* ability comply with study and device management procedures.\n\nExclusion criteria:\n\n* Other primary Axis I conditions\n* Active suicidal ideation with intent, suicide attempt within the last six months, more than three suicide attempts within the last two years, or serious suicide risk as determined by the study psychiatrists\n* Other primary neurological disorders or unstable medical illness\n* Conditions requiring anticoagulant therapy which cannot be discontinued for the perioperative period, as required\n* Pregnancy or plan to come pregnant during the study\n* Contraindications for general anesthesia, neurosurgery, or an MRI scan\n* Currently implanted with a cardiac pacemaker \u002F defibrillator or other implanted electrical device which may interfere with DBS stimulator or the function of which may be impacted by its implantation.","25 Years",{"count":342,"type":21},20,[24],"Of the estimated 30 million Americans who suffer from Major Depressive Disorder, approximately 10% are considered treatment resistant. Deep brain stimulation (DBS) to a region of the brain called the subcallosal cingulate (SCC) is an emerging strategy for treatment resistant depression (TRD), which involves placement of electrodes in a specific region of the brain and stimulating that area with electricity. This is believed to reset the brain network responsible for symptoms and results in a significant antidepressant response. A series of open-label studies have demonstrated sustained, long-term antidepressant effects in 40-60% of patients who received this treatment. A challenge to the effective dissemination of this fledgling treatment is the absence of biomarkers (objective, measureable indications of the state of the body and brain) to guide device placement and select stimulation parameters during follow-up care.\n\nBy using a DBS device called the Percept PC (Medtronic, Inc) which has the ability to both deliver stimulation to and record electrical signals directly from the brain, this study aims to identify changes in local field potentials (LFPs), specific electrical signals that are thought to represent how the brain communicates information from one region to another, to see how this relates to DBS parameter settings and patient depressive symptomatology. The goal of this study is to study LFPs before and during active DBS stimulation to identify changes that correlate with the antidepressant effects of SCC DBS.\n\nThe study team will recruit 20 patients with TRD and implant them with the Percept PC system. Participants will be asked to complete short questionnaires and collect LFP data twice daily for the first year of the study, as well as have weekly in person research procedures and assessments with the study team for up to one year. These include meetings with the study psychiatrist, psychologist, symptom ratings, and movement, voice, and video recordings. A brief discontinuation experiment will be conducted after 6 months of stimulation, in which the stimulation will be turned off and patterns of LFP changes will be recorded. The entire study is expected to last about 5 years, parcellated into several study phases. All participants are required to live in the New York metropolitan area for the first several months of the study.",[27,172],"2026-06-17",{"date":261,"type":40},{"date":349,"type":40},"2023-03-01",{"date":351,"type":21},"2028-12",{"name":353,"class":47},"Helen Mayberg, MD",{"id":355,"slug":4,"hasResults":11,"nctId":356,"briefTitle":357,"officialTitle":358,"acronym":4,"eligibilityCriteria":359,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":4,"enrollmentInfo":360,"targetDuration":4,"studyType":22,"phases":362,"briefSummary":364,"conditions":365,"keywords":369,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":371,"lastUpdatePostDateStruct":372,"startDateStruct":374,"completionDateStruct":376,"leadSponsor":378,"locationsCount":379},"100601024","NCT07105111","A Study to Evaluate the Effectiveness of Valbenazine in Adult Participants With Tardive Dyskinesia (TD) Who Remain Symptomatic While Receiving or After Stopping a Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor","A Phase 4, Open-Label Study to Evaluate the Efficacy of Valbenazine on Clinician- and Patient-Reported Outcomes in Patients With Tardive Dyskinesia (TD) Who Remain Symptomatic While on Deutetrabenazine or After Discontinuing Prior TD Treatment With a Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor","Key Inclusion Criteria:\n\n* 18 years of age or older\n* Diagnosed with one of the following at least 3 months prior to screening: schizophrenia or schizoaffective disorder, bipolar disorder, or major depressive disorder\n* Diagnosed with at least mild neuroleptic-induced TD for at least 3 months prior to screening\n\nKey Exclusion Criteria:\n\n* Have comorbid Parkinsonism or abnormal involuntary movement(s) that is more prominent than TD\n* Diagnosis of moderate or severe substance use disorder in the last 6 months\n* History of long QT syndrome, cardiac arrythmia, or severe hepatic impairment",{"count":361,"type":21},50,[363],"PHASE4","This study will evaluate the efficacy of valbenazine on clinician- and patient-reported outcomes in participants with TD while receiving or after stopping a VMAT2 inhibitor.",[366,367,176,27,368],"Schizophrenia","Schizoaffective Disorder","Tardive Dyskinesia",[370],"Valbenazine","2026-06-15",{"date":373,"type":40},"2026-06-16",{"date":375,"type":40},"2025-08-29",{"date":377,"type":21},"2027-01",{"name":268,"class":107},22,{"id":381,"slug":4,"hasResults":11,"nctId":382,"briefTitle":383,"officialTitle":384,"acronym":4,"eligibilityCriteria":385,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":219,"enrollmentInfo":386,"targetDuration":4,"studyType":22,"phases":388,"briefSummary":390,"conditions":391,"keywords":393,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":398,"lastUpdatePostDateStruct":399,"startDateStruct":400,"completionDateStruct":402,"leadSponsor":403,"locationsCount":185},"100360448","NCT03973268","Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression","The Mechanism of Action Underlying Ketamine's Antidepressant Effects: An Investigation of the AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression","* INCLUSION CRITERIA:\n\nPhases I-II\n\n1. 18 to 70 years of age.\n2. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.\n3. All subjects must have undergone a screening assessment under protocol 01-M-0254, \"The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers\".\n4. Subjects must fulfill DSM-IV or -5criteria for Major Depression (Major Depressive Disorder) without psychotic features, based on clinical assessment and informed by a structured diagnostic interview (SCID-P).\n5. Subjects must have an initial score on the MADRS greater than or equal to 22 and a YMRS score of \\\u003C12 within one week of study entry and upon entry into Phase II.\n6. Lack of response to two adequate antidepressant trials, with \\[at least\\] one in the current major depressive episode, operationally defined using the Antidepressant Treatment History Form (ATHF); a failed adequate trial of ECT \\[or TMS\\] would count as an adequate antidepressant trial.\n7. Current major depressive episode lasting at least four weeks\n8. Agree to be hospitalized\n\nOpen-Label Ketamine Treatment\n\n1. Participants must have met all inclusion criteria for and completed Study Phase II\n2. Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase III.\n\nEXCLUSION CRITERIA:\n\nPhases I-II\n\n1. Current psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-5.\n2. Subjects with a history of substance abuse or dependence diagnosis (DSM-IV) or substance use disorder (DSM-5 equivalent) (except for caffeine or nicotine dependence) within the preceding 3 months. In addition, subjects who currently are using drugs (except for caffeine or nicotine) must not have used illicit substances or known drugs of abuse in the 2 weeks prior to screening and must have a negative alcohol and drug urine test (except for prescribed benzodiazepines or stimulants) at screening.\n3. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease, coronary artery disease, atherosclerotic ischemic stroke, and atrial fibrillation), endocrinologic, neurologic, immunologic, or hematologic disease.\n4. Pregnant or nursing individuals or those who are physically able to become pregnant. Participants who are physically able to become pregnant or cause a pregnancy must use at least one form of effective birth control or remain completely abstinent from sexual intercourse during the entire period of study participation (or until the last clinical labs and ratings). Participants able to become pregnant must have negative urine pregnancy tests no more than 24 hours prior to receiving the study drugs and undergoing imaging procedures.\n5. Subjects with one or more seizures without a clear and resolved etiology or current use of medication known to lower seizure threshold. History of seizure (regardless of age or etiology), history of epilepsy in self or first-degree relatives, stroke, brain surgery, head injury, or known structural brain lesion will be excluded from the TMS procedures.\n6. Presence of any medical illness likely to alter brain morphology and\u002For physiology (e.g., hypertension, diabetes) even if controlled by medications.\n7. Clinically significant abnormal laboratory tests.\n8. (For imaging procedures) Subjects with hearing loss that has been clinically evaluated and diagnosed and may be worsened through participation in imaging procedures\n9. Positive HIV test\n10. Weight \\> 119 kg\n11. Treatment with any concomitant psychiatric medication prior to entering Phase II. \\[Medications must be tapered during Phase I.\\]\n12. Treatment with any non-psychiatric medication\u002Fs.\n13. Any use of opioid medication in the past 3 months\n14. Treatment with a reversible monoamine oxidase inhibitor (MAOI) prior to entering Phase II. \\[Medications must be tapered during Phase I.\\]\n15. Treatment with fluoxetine or aripiprazole at the time of screening.\n16. Unwilling to stop undergoing structured, individualized psychotherapy. (Such therapy, including CBT, will not be permitted during Phases I and II of the study.)\n17. Presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clip).\n18. Participants who are uncomfortable in small closed spaces (have claustrophobia).\n19. Are unable to lie comfortably supine for up to 90 minutes and would feel uncomfortable in the MRI and MEG machines.\n20. Subjects who, in the investigator s judgment, pose a current serious suicidal or homicidal risk.\n21. Subjects who have a history of aggressive behavior towards others\n22. A current NIMH employee\u002Fstaff or their immediate family member\n\nOpen-Label Ketamine Treatment\n\n1. Intolerable or serious adverse reaction to ketamine during Phase II\n2. Participants with a positive urine for an illicit substance no more than 24 hours prior to ketamine treatment.\n3. Pregnant or nursing individuals or those who plan to become pregnant.",{"count":387,"type":21},70,[389],"PHASE1","Background:\n\nMost drugs that treat mood disorders take a long time to work. Ketamine works within hours. A dose can last for a week or more. Certain receptors in the brain might help ketamine work. A drug that blocks these receptors might affect how it works.\n\nObjective:\n\nTo see if the antidepressant response of ketamine is linked to AMPA receptors.\n\nEligibility:\n\nAdults ages 18-70 with major depression disorder without psychotic features\n\nDesign:\n\nParticipants will be screened under protocol 01-M-0254. They will have blood tests and a physical exam.\n\nParticipants will stay at the NIH Clinical Center for 5 weeks.\n\nPhase 1 lasts 4 weeks. For 2 weeks, participants will taper off their psychiatric medicine. Then they will have the following tests:\n\n* Blood draws\n* Psychological tests\n* MRI: Participants will lie in a machine that takes pictures of their brain.\n* MEG: Participants will lie down and do tasks. A cone lowered on their head will record brain activity.\n* Optional sleep tests: Electrodes on the scalp and body and belts around the body will monitor participants while they sleep.\n* Optional TMS: Participants will do tasks while a wire coil is held on their scalp. An electrical current will pass through the coil that affects brain activity.\n\nFor phase 2, on day 0 participants will take the study drug or a placebo orally. While having a MEG, they will get ketamine infused into a vein in one arm while blood is drawn from a vein in the other arm. On day 1, participants will again take the study drug or a placebo orally. On days 3-7, they will repeat many of the phase 1 tests. Days 8 and 9 are optional and include an open label ketamine treatment and many of the phase 1 tests.",[31,27,392],"Major Depression",[394,395,396,397,175],"Biomarker","AMPA Antagonist","Magnetoencephalography","Neuropharmacology","2026-06-13",{"date":373,"type":40},{"date":401,"type":40},"2020-01-21",{"date":209,"type":21},{"name":75,"class":76},{"id":405,"slug":4,"hasResults":11,"nctId":406,"briefTitle":407,"officialTitle":407,"acronym":4,"eligibilityCriteria":408,"healthyVolunteers":15,"sex":16,"minAge":84,"maxAge":55,"enrollmentInfo":409,"targetDuration":4,"studyType":22,"phases":411,"briefSummary":412,"conditions":413,"keywords":415,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":398,"lastUpdatePostDateStruct":416,"startDateStruct":417,"completionDateStruct":419,"leadSponsor":421,"locationsCount":185},"100290790","NCT03065335","Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder","* INCLUSION CRITERIA:\n\nInclusion Criteria: All Subjects (Main Study)\n\n1. 18 to 65 years of age.\n2. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.\n3. All subjects must have undergone a screening assessment under either protocol 01-M-0254, \"The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers\" or protocol 17-M-0181 (\"Recruitment and Characterization of Research Volunteers for NIMH Intramural Studies\").\n4. Agree to be hospitalized\n\nAdditional Inclusion Criteria: Patients with MDD (Main Study)\n\n1. At the initial study enrollment, subjects must have fulfilled DSM-IV or DSM-5 criteria for Major Depression, single episode or recurrent. Subjects must be experiencing a current major depressive episode of at least 2 weeks duration.\n2. At the initial screening and beginning of Phases II and III, subjects must have a baseline score on the MADRS \\>= 20 and YMRS of \\\u003C 12.\n3. Current or past history of lack of response to one adequate antidepressant trial, operationally defined using the Antidepressant Treatment History Form (ATHF); a failed adequate trial of ECT would count as an adequate antidepressant trial.\n\nKetamine Metabolites Substudy Inclusion Criteria: Healthy Volunteers\n\n1. 18 to 65 years of age.\n2. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.\n3. All subjects must have undergone a screening assessment under either protocol 01-M-0254 \"The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers\") or 17-M-0181 (\"Recruitment and Characterization of Research Volunteers for NIMH Intramural Studies\").\n4. Agree to be hospitalized.\n\nEXCLUSION CRITERIA:\n\nAdditional Exclusion Criteria: Patients with MDD (Main Study)\n\n1. Current diagnosis of Bipolar Disorder including Bipolar I, Bipolar II, or Bipolar NOS diagnoses.\n2. Current psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-5.\n3. Subjects with a history of DSM-IV or DSM-5 drug or alcohol dependency or abuse (except for caffeine or nicotine dependence) within the preceding 3 months. In addition, subjects who currently are using drugs (except for caffeine or nicotine) must not have used illicit substances or known drugs of abuse in the 2 weeks prior to screen and must have a negative alcohol and drug urine test (except for prescribed benzodiazepines or stimulants) urine test at screening.\n4. Treatment with a reversible MAOI within two weeks prior to Phase II.\n5. Subjects who, in the investigator s judgment, pose a current serious suicidal or homicidal risk.\n\nExclusion Criteria: All Subjects (Main Study)\n\n1. Pregnant or nursing women or women who plan to become pregnant. Women who are able to get pregnant must be willing to use at least one form of effective birth control during the entire period of study participation (or until last clinical labs and rating) and have a negative pregnancy test that was obtained no more than 24 hours prior to MRI and infusion of ketamine.\n2. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease, coronary artery disease, atherosclerotic ischemic stroke, and atrial fibrillation), endocrinologic, neurologic, immunologic, or hematologic disease.\n3. Clinically significant abnormal laboratory tests.\n4. Subjects with one or more seizures without a clear and resolved etiology or current use of medication known to lower seizure threshold. History of seizure (regardless of age or etiology), history of epilepsy in self or first-degree relatives, stroke, brain surgery, head injury, or known structural brain lesion will be excluded from the TMS procedures.\n5. Treatment with any other concomitant medication 14 days prior to Phase II. An exception of this would be necessary for those who are taking Fluoxetine or Aripiprazole. Prior to Phase II, treatment with Fluoxetine must be discontinued for at least 5 weeks and treatment with Aripiprazole must be discontinued for at least 3 weeks.\n6. Any use of opioid medication in the past 3 months\n7. Presence of metallic (ferromagnetic) implants (e.g, heart pacemaker, aneurysm clip) (for subjects doing imaging component of the study only).\n8. Presence of any medical illness likely to alter brain morphology and\u002For physiology (e.g., hypertension, diabetes) even if controlled by medications.\n9. Subjects who have hearing loss that has been clinically evaluated and diagnosed\n10. Participants who are uncomfortable in small closed spaces (have claustrophobia), unable to lie comfortably supine for up to 90 minutes, and would feel uncomfortable in the MRI machine (for subjects doing imaging component of the study only).\n11. Positive HIV test\n12. Weight \\> 119 kg\n13. \\[for participants undergoing NPU Threat Test with Auditory Startle\\] Known history of hearing loss\n\nAdditional Exclusion Criteria: Healthy Volunteers (Main Study)\n\n1\\. Current or past history of any DSM-IV or DSM-5 Axis I disorder based on clinical assessment and confirmed by a structured diagnostic interview (SCID).\n\nKetamine Metabolites Substudy Exclusion Criteria: Healthy Volunteers\n\n1. Current or past history of any DSM-IV or DSM-5 Axis I disorder based on clinical assessment and confirmed by a structured diagnostic interview (SCID).\n2. Current (within the past 3 months) or past alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine)\n3. Pregnant or nursing women or women who plan to become pregnant. Women who are able to get pregnant must be willing to use at least one form of effective birth control during the 4-days of the study participation (or until last clinical labs and rating) and have a negative pregnancy test that was obtained no more than 24 hours prior to infusion of ketamine.\n4. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease, coronary artery disease, atherosclerotic ischemic stroke, and atrial fibrillation), endocrinologic, neurologic, immunologic, or hematologic disease.\n5. Clinically significant abnormal laboratory tests.\n6. Subjects with one or more seizures without a clear and resolved etiology or current use of medication known to lower seizure threshold.\n7. Treatment with any other concomitant medication.\n8. Any use of opioid medication in the past 3 months\n9. Positive HIV test\n10. Weight \\> 119 kg\n11. Presence of metallic (ferromagnetic) implants (e.g, heart pacemaker, aneurysm clip) (for subjects doing neuroimaging component of the study only).\n12. Participants who are uncomfortable in small closed spaces (have claustrophobia), unable to lie comfortably supine for up to 90 minutes, and would feel uncomfortable in the MRI machine (for subjects requiring clinical MRI scans for safety and\u002For structural MRI scans for MEG coregistration).",{"count":410,"type":21},150,[389],"Background:\n\nMost 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.\n\nObjective:\n\nMain Study: To study the effects of ketamine in treating depression.\n\nKetamine Metabolites Substudy: To study how ketamine effects brain chemistry.\n\nTo study how ketamine effects the brain. This is done by looking at metabolites, which are created when a drug is broken down.\n\nEligibility:\n\nMain Study: People ages 18-65 with major depressive disorder and healthy volunteers\n\nKetamine Metabolites Substudy: Healthy volunteers ages 18-65\n\nDesign:\n\nMain Study:\n\nParticipants will be screened in another study, with:\n\n* Medical and psychiatric history\n* Psychiatric and physical exam\n* Blood, urine, and heart tests\n\nParticipants will be inpatients at NIH for 4 phases totaling 14-20 weeks.\n\nPhase I (2-7 weeks):\n\n* Gradually stop current medications\n* MRI: Participants lie and perform tasks in a machine that takes pictures of the body.\n* Mood and thinking tests\n* Blood and urine tests\n* Sleep test: Monitors on the skin record brain waves, breathing, heart rate, and movement during sleep.\n* Transcranial magnetic stimulation: A coil on the scalp gives an electrical current that affects brain activity.\n* Stress tests: Electrodes on the skin measure reactions to loud noises or electric shocks.\n\nPhase I tests are repeated in Phases II and III and in the final visit.\n\nPhase II (4-5 weeks):\n\n* 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.\n\nPhase III (optional):\n\n* 8 infusions of ketamine over 4 weeks\n\nPhase IV (optional):\n\n* Symptoms monitoring for 4 weeks\n* Participants will have a final visit. They will be offered standard treatment at NIH for up to 2 months.\n\nKetamine Metabolites Substudy:\n\nParticipants will be screened in another study, with:\n\n* Medical and psychiatric history\n* Psychiatric and physical exam\n* Blood, urine, and heart tests\n\nParticipants will be inpatients at NIH for 4 days.\n\nStudy Procedures:\n\nMood and thinking tests\n\nBlood and urine tests\n\n1 infusion of ketamine\n\nSpinal 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",[414,27,31],"Healthy Volunteer",[67,396,27,169,397],{"date":373,"type":40},{"date":418,"type":40},"2017-05-25",{"date":420,"type":21},"2028-01-01",{"name":75,"class":76},{"id":423,"slug":4,"hasResults":11,"nctId":424,"briefTitle":425,"officialTitle":426,"acronym":427,"eligibilityCriteria":428,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":55,"enrollmentInfo":429,"targetDuration":4,"studyType":22,"phases":431,"briefSummary":432,"conditions":433,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":434,"lastUpdatePostDateStruct":435,"startDateStruct":436,"completionDateStruct":437,"leadSponsor":439,"locationsCount":185},"100642282","NCT07633080","Magnesium Bisglycinate in Major Depressive Disorder","Efficacy and Safety of Add-on Magnesium Bisglycinate in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial","DReAM-BiG","Inclusion Criteria:\n\n1. Patients with a diagnosis of Major Depressive Disorder (MDD) as per DSM-5 criteria.\n2. Patients of either sex within the age group of 18-65 years.\n3. Mild to severe depression, defined as a baseline MADRS score ≥7.\n4. Currently receiving a stable dose of antidepressant monotherapy (SSRI or SNRI) in equivalent doses.\n5. Willing and able to provide written informed consent.\n\nExclusion Criteria:\n\n1. Known hypersensitivity or allergy to magnesium supplements or glycine.\n2. History of renal impairment (previous history of AKI, CKD, currently on dialysis).\n3. Diagnosis of bipolar affective disorder, schizoaffective disorder, schizophrenia, or any other psychotic disorder.\n4. Active suicidal ideation with intent or a recent suicide attempt (within the past 6 months), as assessed by the treating psychiatrist.\n5. Current substance use disorder (except nicotine, alcohol and caffeine), as per DSM-5 criteria.\n6. Pregnancy, lactation, or women of childbearing potential not using adequate contraception.\n7. Concurrent use of magnesium-containing supplements, antacids, or laxatives.\n8. History of significant severe medical comorbidity, including uncontrolled hypothyroidism, Cushing's syndrome, active malignancy, myasthenia gravis, or severe hepatic impairment.\n9. Use of medications with significant pharmacokinetic interactions with magnesium (e.g., tetracyclines, fluoroquinolones, bisphosphonates, diuretics) that cannot be temporally separated by ≥2 hours.\n10. Electroconvulsive therapy (ECT) received within the past 3 months.",{"count":430,"type":21},84,[24],"Depression is a common illness that can affect a person's mood, sleep, energy, ability to work, and overall quality of life. While medicines are available to treat depression, many people do not get complete relief from their symptoms. This study will evaluate whether adding a magnesium supplement in the form of magnesium bisglycinate to regular antidepressant treatment can help improve symptoms of depression. Adults with depression who are already receiving treatment will be randomly assigned to receive either magnesium bisglycinate or a placebo (an inactive substance) along with their usual medication. The study will compare the two groups to see whether the supplement leads to greater improvement in symptoms, sleep, and day-to-day functioning. Information on any side effects will also be collected. The findings may help determine whether magnesium bisglycinate can be used as a safe and affordable additional treatment for people with depression.",[27],"2026-06-12",{"date":371,"type":40},{"date":434,"type":40},{"date":438,"type":21},"2028-06-12",{"name":440,"class":47},"All India Institute of Medical Sciences, Bhubaneswar",{"id":442,"slug":4,"hasResults":11,"nctId":443,"briefTitle":444,"officialTitle":445,"acronym":4,"eligibilityCriteria":446,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":219,"enrollmentInfo":447,"targetDuration":4,"studyType":22,"phases":449,"briefSummary":450,"conditions":451,"keywords":454,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":434,"lastUpdatePostDateStruct":456,"startDateStruct":457,"completionDateStruct":459,"leadSponsor":461,"locationsCount":463},"100570302","NCT06705478","Pramipexole Versus Escitalopram to Treat Major Depressive Disorder (MDD) and Comorbid MDD With Mild Neurocognitive Disorder (MND) in Persons With HIV","An Open-Label, Randomized Controlled Trial of Pramipexole Versus Escitalopram to Treat Major Depressive Disorder (MDD) and Comorbid MDD With Mild Neurocognitive Disorder (MND) in Persons With HIV","Inclusion Criteria:\n\n* Documented HIV-1 infection.\n* Diagnosis of MDD.\n* On current ART regimen for at least 90 days prior to study entry with no interruption in treatment greater than 7 consecutive days.\n* No plans to change ART while on study.\n* Plasma HIV-1 RNA levels of less than 200 copies\u002FmL obtained within 90 days prior to enrollment.\n* Study candidates previously treated for depression are eligible provided the study candidate's last dose of antidepressant taken is at least 4 weeks prior to study entry, with the exception of fluoxetine, which the last dose taken must have been at least 8 weeks prior to study entry.\n* Laboratory values obtained within 30 days prior to study entry that meet protocol criteria as determined by the site investigator of record.\n* Study candidates of child-bearing potential must have a negative serum or urine pregnancy test performed at screening and within 2 days prior to study entry.\n* Study candidates of child-bearing potential who are participating in sexual activity that could lead to pregnancy must agree to use at least one highly effective method for contraception.\n\nExclusion Criteria:\n\n* Active suicidality, and\u002For severe MDD, psychotic disorders, manic or hypomanic symptoms occurring in the context of bipolar disorder type I or II, or cyclothymic disorder, or another current Axis I diagnosis judged by the investigator to interfere with the trial.\n* Study candidate self-report of depressive symptoms that have persisted for over 50 percent of waking hours and for over 50 percent of days over the 24 months prior to study entry.\n* Severe, active alcohol or substance use disorder by DSM-5-TR criteria in the 6 months prior to study entry.\n* Active alcohol or substance use judged by the investigator to interfere with the trial.\n* Any acute infection within 14 days prior to study entry.\n* Acute or serious illness requiring systemic treatment and\u002For hospitalization within 90 days prior to study entry.\n* Active coronary artery disease (CAD) or myocardial infarction (MI) within 180 days prior to study entry.\n* Presence of rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus (SLE), dermatomyositis, ulcerative colitis, Crohn's disease, or other chronic inflammatory conditions.\n* Immune reconstitution inflammatory syndrome (IRIS) or a history of IRIS within 180 days prior to study entry.\n* Unstable or advanced liver disease.\n* Receipt of medications judged by the site investigator to significantly influence depression or neurocognitive function within 30 days prior to study entry.\n* Non-HIV-associated neurological disorder comorbidity.\n* Diagnosis of epilepsy with antiepileptic drug treatment.\n* Untreated HCV infection and HCV viremia.\n* Current CNS malignant tumor or CNS opportunistic infection (OI).\n* Current systemic malignant tumor or of a current systemic AIDS-defining OI.\n* History of completed treatment of CNS or systemic malignant tumor within the 5 years prior to study entry.\n* History of completed treatment of CNS OI within the 5 years prior to study entry.\n* Documented history of completed treatment of systemic AIDS-defining OI, as well as Mycobacterium Tuberculosis Infection, within the 180 days prior to study entry.\n* New diagnosis of syphilis or treatment for syphilis within the 180 days prior to study entry.\n* History of neurosyphilis.\n* Severe chronic obstructive pulmonary disease.\n* Congestive heart failure (CHF).\n* Use of systemic steroids daily (except testosterone).\n* Diseases that cause a known bleeding diathesis.\n* Immunostimulant therapies and trials of non-FDA-approved ARV medications within 30 days prior to study entry.\n* Immunosuppressive medications if judged by the investigator to affect study outcomes.\n* Currently pregnant, planning to become pregnant during the study period, or currently breastfeeding.\n* Known allergy\u002Fsensitivity or any hypersensitivity to the study drugs or their formulations.\n* Study candidates on prohibited medications at the time of screening will be excluded from study participation.\n\nInclusion Criteria for Participants at US Sites Who Consent to the Lumbar Puncture (LP) Procedure:\n\n* Non-focal neurological examination. Study candidates with focal findings should have expert assessment for mass effect prior to the LP.\n* Laboratory values that meet LP protocol criteria as determined by the site investigator.\n\nExclusion Criteria for Participants at US Sites who Consent to the LP Procedure:\n\n* Current use of anti-coagulants.\n* Known presence of intracerebral mass or lesion that is judged to affect the safety of an LP.\n* Known presence of an active CNS infection that could alter CNS\u002FCSF inflammatory measures.\n* Known allergy to lidocaine.\n* Individuals who are unable to safely tolerate an LP due to physical limitation or condition.\n* Body mass index (BMI) greater than 40 kg\u002Fm\\^2.",{"count":448,"type":21},186,[59],"A phase II, randomized, open-label, two-arm clinical trial evaluating the safety and efficacy of pramipexole extended release (ER) versus escitalopram for the treatment of major depressive disorder (MDD) and comorbid MDD with mild neurocognitive disorder (MND) in persons with HIV (PWH). Participants will be assessed comprehensively and briefly at intercurrent visits to monitor for toxicity, response to therapy, and to assess for dose changes.\n\nAn optional sub-study to evaluate treatment impact on the cerebrospinal fluid (CSF) profile will be conducted in a subset of 36 participants.",[27,452,453],"Mild Neurocognitive Disorder","HIV",[455],"Comorbid MND",{"date":371,"type":40},{"date":458,"type":40},"2026-05-17",{"date":460,"type":21},"2026-12-02",{"name":462,"class":76},"National Institute of Allergy and Infectious Diseases (NIAID)",41,{"id":465,"slug":4,"hasResults":11,"nctId":466,"briefTitle":467,"officialTitle":468,"acronym":4,"eligibilityCriteria":469,"healthyVolunteers":15,"sex":16,"minAge":84,"maxAge":55,"enrollmentInfo":470,"targetDuration":4,"studyType":22,"phases":472,"briefSummary":473,"conditions":474,"keywords":476,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":434,"lastUpdatePostDateStruct":484,"startDateStruct":485,"completionDateStruct":487,"leadSponsor":489,"locationsCount":185},"100514357","NCT05977439","RECOVERS - Realigning Emotion and COgnition Via prEcision Regulation networkS","A Multiphase Program of Multimodal Computational Modeling and Hybrid Interventions Including EEG-Synchronized Transcranial Magnetic Stimulation and Cognitive Behavioral Therapy","Study 1 (Healthy Participants)\n\nInclusion Criteria:\n\n* Age 18-65 years\n* Medically and psychiatrically healthy with no history of psychiatric or neurological disorders\n* English-speaking\n* Capacity to provide informed consent\n* Willingness and ability to complete study procedures\n* Negative pregnancy test for participants of childbearing potential\n\nExclusion Criteria:\n\n* Any current or past psychiatric diagnosis\n* Neurological disorders or history of central nervous system disease\n* History of seizure or epilepsy or use of medications that lower seizure threshold\n* Significant head injury or loss of consciousness\n* Implanted metal or contraindications to MRI or TMS\n* Substance use disorder (excluding nicotine or caffeine)\n* Pregnancy or plans to become pregnant during study participation\n* Inability to complete study procedures\n\nStudies 2, 3, and 4 (Participants with Depression)\n\nInclusion Criteria:\n\n* Age 18-65 years\n* Current diagnosis of Major Depressive Disorder (MDD)\n* Depression severity consistent with study criteria (e.g., HAM-D ≥ 17)\n* No history of psychotic or bipolar disorders\n* English-speaking\n* Capacity to provide informed consent\n* Willingness and ability to complete study procedures\n* Negative pregnancy test for participants of childbearing potential\n\nExclusion Criteria:\n\n* Neurological disorders or history of central nervous system disease\n* History of seizure or epilepsy or use of medications that lower seizure threshold\n* Significant head injury or loss of consciousness\n* Implanted metal or contraindications to MRI or TMS\n* Substance use disorder (excluding nicotine or caffeine)\n* Current participation in another interventional clinical trial\n* Pregnancy or plans to become pregnant during study participation\n* Any condition that would interfere with safe participation or completion of study procedures",{"count":471,"type":21},120,[24],"In this research study, investigators examine how brain activity changes during tests of emotional processing, attention, and memory using multimodal neuroimaging methods including electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and functional near-infrared spectroscopy (fNIRS). Transcranial magnetic stimulation (TMS) is used to probe and modulate brain networks related to cognitive flexibility and emotion regulation.\n\nThe study includes multiple related sub-studies involving healthy participants and participants with depression. Some study components focus on mechanistic modeling using non-therapeutic neurostimulation in healthy participants, while other components include interventional approaches such as individualized EEG-synchronized repetitive TMS (rTMS), cognitive tasks, and brief cognitive behavioral therapy (CBT) in participants with depression. Certain study components also evaluate CBT alone without TMS to assess behavioral intervention effects.",[31,27,475],"Suicidal Ideation",[477,478,479,480,481,482,483],"transcranial magnetic stimulation","EEG-synchronized rTMS","closed-loop neurostimulation","depression","suicide prevention","cognitive behavioral therapy (CBT)","neuroplasticity",{"date":373,"type":40},{"date":486,"type":40},"2024-02-01",{"date":488,"type":21},"2028-10-01",{"name":490,"class":47},"Medical University of South Carolina",{"id":492,"slug":4,"hasResults":11,"nctId":493,"briefTitle":494,"officialTitle":495,"acronym":496,"eligibilityCriteria":497,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":219,"enrollmentInfo":498,"targetDuration":4,"studyType":22,"phases":499,"briefSummary":500,"conditions":501,"keywords":502,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":505,"lastUpdatePostDateStruct":506,"startDateStruct":507,"completionDateStruct":509,"leadSponsor":510,"locationsCount":185},"100627100","NCT07444242","Accelerated Treatment of Depressive Patients With tDCS","Accelerated Treatment of Depressive Patients With tDCS (Twice Per Day) - a Placebo Controlled Home-based Treatment","AcctDCS","Inclusion Criteria:\n\n* Sex: female, male, non-binary\n* Age: 18-70 years\n* Diagnosis of depression: no current or past psychiatric medication (current episode and history)\n* Provision of informed consent to participate\n* Sufficient proficiency in the German language\n\nExclusion Criteria:\n\n* Presence of contraindications for tDCS (e.g., electrical implants or metallic objects in the body such as a cardiac pacemaker or insulin pump, dermatological conditions affecting the scalp)\n* Neurological disorders (e.g., cerebrovascular events, neurodegenerative diseases, epilepsy, brain malformations, or a history of severe head injury)\n* Participation in another clinical trial on depression within the 3 months prior to treatment initiation\n* Pregnancy or breastfeeding",{"count":221,"type":21},[24],"A randomized, controlled three-arm study is planned to investigate the effectiveness and feasibility of an accelerated home-based tDCS application (3 weeks of transcranial direct current stimulation at home, twice daily). A total of 30 patients with depression (10 per group), who are currently not taking and have no history of taking antidepressant medication, will be randomly assigned to either an active tDCS condition, a sham (placebo) tDCS condition, or a waitlist control group. The latter two groups will receive active tDCS treatment after completion of the control phase.\n\nThis study represents a continuation of the pilot study GSUND DAHOAM (Ethics approval: 20-2091-101; Dragon et al., 2024).",[27],[31,503,504],"tDCS","Accelerated","2026-06-11",{"date":371,"type":40},{"date":508,"type":40},"2026-04-01",{"date":311,"type":21},{"name":511,"class":47},"University of Regensburg",{"id":513,"slug":4,"hasResults":11,"nctId":514,"briefTitle":515,"officialTitle":516,"acronym":4,"eligibilityCriteria":517,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":55,"enrollmentInfo":518,"targetDuration":4,"studyType":22,"phases":520,"briefSummary":521,"conditions":522,"keywords":523,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":505,"lastUpdatePostDateStruct":525,"startDateStruct":526,"completionDateStruct":528,"leadSponsor":530,"locationsCount":532},"100614238","NCT07276997","A Study to Assess Change in Disease Activity and Adverse Events of Oral Icalcaprant in Adult Participants With Major Depressive Disorder","A Phase 2, Multicenter, 6-Week, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Icalcaprant in Subjects With Major Depressive Disorder","Inclusion Criteria:\n\n* Participants with a diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM-5-TR) without psychotic features, confirmed by the Mini International Neuropsychiatric Interview (MINI) 7.0.\n* Body Mass Index (BMI) is ≥ 18.0 to ≤ 35.0 kg\u002Fm\\^2\n* Currently experiencing an major depressive episode (MDE) beginning at least 4 weeks prior to consent and not exceeding 6 months prior to Screening\n* Normal physical examination findings, clinical laboratory test results, vital signs, and 12-lead ECG results at Visit 1 or abnormal results that are judged not clinically significant by the investigator and documented as such in the eCRF.\n\nExclusion Criteria:\n\n* Has failed (no more than 25% response on Antidepressant Treatment History Questionnaire (ATRQ)) 3 or more antidepressant treatments during the current depressive episode despite an adequate dose (per ATRQ) and duration (at least 6 weeks).\n* History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and\u002For other products in the same class.",{"count":519,"type":21},195,[59],"Major depressive disorder (MDD; depression) is a mood disorder that causes a continued feeling of sadness and loss of interest. It is a common and serious illness that can cause both emotional and physical symptoms such as feelings of sadness, irritability, not being able to focus on activities, tiredness, changes in eating habits, and aches and pains. This study will assess the changes in disease activity and adverse events of oral Icalcaprant in adult participants with major depressive disorder who are currently experiencing a major depressive episode (MDE).\n\nIcalcaprant is an investigational drug being developed for the treatment of depressive episodes in adult participants with major depressive disorder. Participants are placed in 1 of 3 groups, called treatment arms. There is a 1 in 3 chance that a participant will be assigned to placebo treatment. Around 195 adult participant with major depressive disorder will be enrolled in approximately 35 sites in North America.\n\nParticipants will receive oral capsules of Icalcaprant or matching placebo once daily for 6 weeks, with a 30-day safety follow-up.\n\nThere may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.",[27],[27,524],"Icalcaprant",{"date":371,"type":40},{"date":527,"type":40},"2025-12-18",{"date":529,"type":21},"2027-09",{"name":531,"class":107},"AbbVie",33,{"id":534,"slug":4,"hasResults":11,"nctId":535,"briefTitle":536,"officialTitle":536,"acronym":537,"eligibilityCriteria":538,"healthyVolunteers":15,"sex":16,"minAge":84,"maxAge":55,"enrollmentInfo":539,"targetDuration":4,"studyType":22,"phases":541,"briefSummary":542,"conditions":543,"keywords":544,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":553,"lastUpdatePostDateStruct":554,"startDateStruct":555,"completionDateStruct":557,"leadSponsor":559,"locationsCount":561},"100440593","NCT05017311","Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)","CAN-BIND-17","Patients\n\nInclusion Criteria:\n\n* Outpatients 18 to 65 years of age.\n* Meet DSM-5 criteria for MDE in MDD as determined by SCID-5.\n* Free of psychotropic medications for at least 5 half-lives (e.g. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1 (exceptions: stable use of hypnotics; stable use of stimulants for attention-deficit\u002Fhyperactive disorder).\n* MADRS score ≥ 24.\n* Fluency in English, sufficient to complete the interviews and self-report questionnaires.\n\nExclusion Criteria:\n\n* Any diagnosis, other than MDD, that is considered the primary diagnosis.\n* Bipolar I or Bipolar-II diagnosis.\n* Presence of a significant Axis II diagnosis (borderline, antisocial).\n* High suicidal risk, defined by clinician judgment.\n* Substance dependence\u002Fabuse in the past 6 months.\n* Presence of significant neurological disorders, head trauma, or other unstable medical conditions.\n* Pregnant or breastfeeding.\n* Failure of 4 or more adequate pharmacologic interventions (as determined by the Antidepressant Treatment History Form).\n* Started psychological treatment within the past 3 months with the intent of continuing treatment.\n* Patients who have previously failed escitalopram or showed intolerance to escitalopram or brexpiprazole, and patients at risk for hypomanic switch (i.e. with a history of antidepressant induced hypomania).\n\nHealthy Comparison (HC) Participants\n\nInclusion Criteria:\n\n* 18 to 65 years of age.\n* No history of psychiatric disorders (as determined by SCID-5) or significant physical conditions (e.g. arthritis, fibromyalgia).\n* Fluency in English, sufficient to complete the interviews and self-report questionnaires.",{"count":540,"type":21},400,[363],"This is a study that will test a predictive biomarker algorithm based on results from a previous study. The goal of this study is to integrate clinical, imaging, EEG, and molecular data across 8 sites to predict treatment outcome for patients experiencing a major depressive episode (MDE).",[27],[545,546,30,547,548,549,550,551,552],"major depression","major depressive disorder","escitalopram","brexpiprazole","neuroimaging","genomics","proteomics","metabolomics","2026-06-09",{"date":505,"type":40},{"date":556,"type":40},"2023-01-20",{"date":558,"type":21},"2029-04-30",{"name":560,"class":47},"Nova Scotia Health Authority",10,{"id":563,"slug":4,"hasResults":11,"nctId":564,"briefTitle":565,"officialTitle":566,"acronym":4,"eligibilityCriteria":567,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":55,"enrollmentInfo":568,"targetDuration":4,"studyType":22,"phases":570,"briefSummary":571,"conditions":572,"keywords":573,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":574,"lastUpdatePostDateStruct":575,"startDateStruct":577,"completionDateStruct":579,"leadSponsor":580,"locationsCount":185},"100636964","NCT07572526","tDCS: Sleep to Mood in Depression (S2M-D)","Sleep Consolidation as a Mechanistic Pathway Linking Home-Based tDCS to Antidepressant Response (S2M-D)","Inclusion Criteria:\n\n1. Ability to read and understand study materials in English, as demonstrated by a standard score \\>85 on the WRAT-5 Reading Recognition Subtest\n2. MADRS-S ≥18 during screening\n3. Confirmed diagnosis of MDD, based on clinician interview\n4. If taking antidepressant medication, the dose must be stable for at least 30 days prior to pre-screening.\n5. Confirmed access to a local provider that has primary responsibility for the subjects' clinical care, and who is available for contact in case of increased subject risk due to depressive symptoms OR confirmed acknowledgement and identification of local resources.\n6. Able to provide informed consent and comply with study procedures.\n7. Access to a quiet space suitable for home-based tDCS stimulation sessions.\n\nExclusion Criteria:\n\n1. Current major medical condition that, in the opinion of the study clinician, would interfere with study participation, safety, or interpretation of study outcomes.\n2. Current or past bipolar disorder, psychotic disorder, or current (past 6 months) alcohol or substance use disorder, as determined by clinician assessment at screening.\n3. Clinically significant suicidal ideation or behavior, based on clinician assessment and the Columbia-Suicide Severity Rating Scale (C-SSRS).\n4. Use of prescription or over-the-counter sleep-promoting medications or initiation of behavioral interventions specifically targeting sleep in the past 30 days from pre-screening.\n5. History of seizure disorder or epilepsy.\n6. Presence of an active implanted medical device above the neck (e.g., deep brain stimulator, cochlear implant) or non-MRI-compatible metallic implants in the head or neck region.\n7. Current use of prescription or over-the-counter sleep medications, or active participation in any behavioral or pharmacologic treatment specifically targeting sleep.\n8. Pregnancy and Breastfeeding: Currently pregnant, planning pregnancy during the study period, or breastfeeding o If able to become pregnant, participants will be required to use medically accepted birth control methods, including hormonal methods (e.g., pills, patches, implants), barrier methods (e.g., condoms or diaphragm with spermicide), intrauterine device (IUD), or abstinence. Participants will be advised not to become pregnant during the study.",{"count":569,"type":21},35,[24],"The purpose of this study is to determine whether changes in sleep consolidation occur during home-based transcranial direct current stimulation (tDCS) in adults with moderate depression and whether these changes are temporally associated with improvements in depressive symptoms.",[27,30,31,197],[30,199,31,503,202,201,203],"2026-06-05",{"date":576,"type":40},"2026-06-08",{"date":578,"type":40},"2026-06-04",{"date":311,"type":21},{"name":211,"class":47},{"id":582,"slug":4,"hasResults":11,"nctId":583,"briefTitle":584,"officialTitle":585,"acronym":4,"eligibilityCriteria":586,"healthyVolunteers":11,"sex":16,"minAge":84,"maxAge":587,"enrollmentInfo":588,"targetDuration":4,"studyType":22,"phases":590,"briefSummary":591,"conditions":592,"keywords":593,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":578,"lastUpdatePostDateStruct":596,"startDateStruct":597,"completionDateStruct":599,"leadSponsor":601,"locationsCount":185},"100519939","NCT06050070","Targeting Large-scale Networks in Depression With Real-time Functional Magnetic Resonance Imaging (fMRI) Neurofeedback","Targeting Large-scale Networks in Depression With Real-time fMRI Neurofeedback","Inclusion Criteria:\n\n* Meets The Diagnostic and Statistical Manual of Mental Disorders five (DSM5) criteria for Major Depressive Disorder, single or recurrent, active or in partial remission\n* Patient Health Questionnaire (PHQ9) greater or equal (≥)6, and approximately (\\~) 50% with PHQ9≥10\n* If participants are taking antidepressant medications, on stable dosage for 4 weeks\n* No history of active substance use disorder in the past 6 months\n* Absence of suicidal thoughts with plans or intentions, as assessed by Columbia Suicide Severity Rating Scale (C-SSRS)\n* If a woman of child-bearing age, not pregnant or trying to become pregnant\n* Ability to tolerate small, enclosed spaces without anxiety\n* No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (for example metal workers with exposures, protocol has more details), etc.\n* Size compatible with scanner gantry (per protocol)\n* Ability and willingness to give informed consent to participate.\n\nExclusion Criteria:\n\n* Size not compatible with scanner\n* Not meeting diagnostic criteria for bipolar disorder, schizophrenia, other psychosis, obsessive-compulsive disorder, active eating disorder or Post-traumatic stress disorder (PTSD)\n* No history of serious neurological illness (including, but not limited to, seizures\u002Fepilepsy) or current medical condition that could compromise brain function, such as liver failure\n* No history of closed head injury, e. g. loss of consciousness \\> \\~5 min, hospitalization, neurological sequela","55 Years",{"count":589,"type":21},58,[24],"The purpose of this study is to develop a technique called real time fMRI neurofeedback.\n\nThis technique uses a regular MRI scanner, except that special software allows the researchers to measure activity in participants brain, using fMRI, and then give information, in the form of a feedback signal, which indicates brain activity in real time, while in the MRI scanner. The larger goal of this study is to develop ways to help people, including those with depression, better regulate brain activity. The researchers think that this may be helpful in managing psychiatric symptoms.\n\nThis study design has three phases, however, only two phases (phase 2 and 3) are considered to be a clinical trial. Phase 2 (part 2) was registered and is NCT05934604. This is the phase 3 (part 3) for this project and is funded by the National Institutes of Health.",[27],[594,595],"Functional MRI","Neurofeedback",{"date":576,"type":40},{"date":598,"type":40},"2024-03-18",{"date":600,"type":21},"2026-09-01",{"name":602,"class":47},"University of Michigan",{"id":604,"slug":4,"hasResults":11,"nctId":605,"briefTitle":606,"officialTitle":607,"acronym":4,"eligibilityCriteria":608,"healthyVolunteers":11,"sex":16,"minAge":609,"maxAge":587,"enrollmentInfo":610,"targetDuration":4,"studyType":22,"phases":612,"briefSummary":613,"conditions":614,"keywords":615,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":618,"lastUpdatePostDateStruct":619,"startDateStruct":620,"completionDateStruct":622,"leadSponsor":624,"locationsCount":185},"100485204","NCT05598034","Evaluating tDCS Brain-stimulation in Depression Using MRI","Optimization of tDCS Brain Network Engagement in Depression","Inclusion Criteria:\n\n1. Age between 20 to 55 years, inclusive\n2. Gender: all\n3. Race\u002Fethnicity: all races and ethnic groups\n4. Capacity to provide informed consent\n5. Hamilton Rating Scale for Depression score of ≥17 and \\\u003C24, with or without symptoms of anxiety.\n6. Treatment naïve or on a stable standard antidepressant regimen (including selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MOAIs) or tricyclic's (TCAs)) with no change in treatment 6-weeks prior to and during the tDCS intervention.\n7. Work at UCLA or live within 1-hr driving distance of UCLA\n\nExclusion Criteria:\n\n1. Pregnancy\n2. Non-English speaking (due to scales administered)\n3. Substance Use Disorder within last 12 months\n4. Neurological condition associated with brain abnormalities (e.g., traumatic brain injury; recent stroke, tumor)\n5. Any contraindication to tDCS (e.g., skin disease or treatment causing irritation)\n6. Any condition that would contraindicate scanning (metal implants, claustrophobia or a breathing or movement disorder)\n7. Currently receiving any form of psychotherapy\n8. Change in antidepressant medication within 6-weeks of starting the trial\n9. Severe or treatment resistant depression - HAMD scores \\> 24 and a history of a major depressive episode lasting \\>2- years or failure to 2 or more antidepressant trials in the current index episode\n10. Any neuromodulation therapy (e.g., ECT, rTMS, DBS, VNS or tDCS) within the last 3-months\n11. Current or past (within the last 1-month) use of anticonvulsants, lithium, psychostimulant, dexamphetamine\n12. Current use of decongestants or other medication previously shown to interfere with cortical excitability\n13. Diagnosis: Schizophrenia Axis I disorder, or dementia of any type\n14. Bipolar I disorder (due to possible risk of mania and because lithium and anticonvulsants are excluded).\n15. On regular benzodiazepine medication that it is not clinically appropriate to discontinue for the 2-week duration of the trial\n16. Depression related to serious medical illness (i.e., mood disorder due to general medical condition) 17. Actively suicidal as defined by a score of 4 on item 3 of HAMD","20 Years",{"count":611,"type":21},144,[24],"Patients, physicians, and those who fund depression research are keenly interested in depression treatments that do not involve taking medications. One promising candidate treatment is transcranial direct current stimulation (tDCS), a low-cost technique that involves placing electrodes on specific scalp locations and using a 9-volt battery to cause a small amount of electricity to pass through parts of the brain. Depending on the direction of electrical flow, tDCS can make brain cells (neurons) more likely or less likely to generate their own electrical signals. When evaluated as a treatment, tDCS is typically done in daily sessions over a period of two weeks.\n\nOne of the challenges of tDCS is to work out the best possible positioning of electrodes and direction of electricity flow to gradually cause lasting changes in brain activity in ways that might be expected to improve depression. To address this challenge, the investigators are using MRI to take pictures of the brain during tDCS. This data will help us better understand the short-term effects of tDCS in depression and help us learn how to customize future treatments to cause a lasting beneficial response.\n\nPatients with depression between the ages of 20-55 years are eligible to take part in this research. Potential participants will undergo:\n\n1. An assessment to confirm eligibility. This will take place over a secure videoconference call lasting no more than 3 hours.\n2. Two in-person study visits lasting 30 min and 2-1\u002F2 hours respectively. In the first visit, the investigators will use the MRI to take a picture of the brain and head structure to determine appropriate locations for placing the tDCS electrodes at the start of the second visit. Following electrode placement, an MRI scan will be performed to take pictures of the brain during tDCS. Depending on the study arm,\n\n   1. Participants may receive 'active' or 'sham' tDCS. The 'sham' condition is identical to the 'active' tDCS in every way except that it involves minimal tDCS and is designed to help rule out effects unrelated to the administered tDCS electricity.\n   2. Participants may also be asked to perform a mental task during MRI.",[27],[616,617,392],"Transcranial Direct Current Stimulation (tDCS)","MRI","2026-06-03",{"date":576,"type":40},{"date":621,"type":40},"2022-10-20",{"date":623,"type":21},"2028-05-01",{"name":625,"class":47},"University of California, Los Angeles",""]