[{"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":28},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,208,0,25,[9,41,76,102,138,158,189,215,240,282,309,332,351,373,396,424,444,466,481,506,527,551,576,595,618],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":35,"leadSponsor":37,"locationsCount":40},"100652725","home-based-wearable-rtms-therapy-for-moderate-to-severe-depression-100652725",false,"NCT07775586","Home-Based Wearable rTMS Therapy for Moderate to Severe Depression","Multicenter Randomized Controlled Trial Assessing Wearable Repetitive Transcranial Magnetic Stimulation for Home-Based Treatment of Depression","1\\. Inclusion Criteria\n\n1. Demographics Aged 18-65 years, any gender. Minimum education: primary school completion (≥6 years of formal education).\n2. Diagnostic and Severity Requirements Meet DSM-5 criteria for Major Depressive Disorder (MDD). Current moderate-to-severe depressive episode, defined by Hamilton Depression Rating Scale 17-item (HAMD-17) score ≥18 .\n3. Pharmacological Stability Stable antidepressant regimen for ≥4 weeks prior to enrollment, restricted to SSRIs (Selective Serotonin Reuptake Inhibitors).\n\n   Treatment-naïve patients permitted if no psychotropic medications used within the prior 4 weeks.\n\n   Mandatory maintenance of the same regimen throughout the study and post-treatment follow-up.\n4. Technical Feasibility Medically eligible for both structural MRI and resting-state functional MRI (fMRI) examinations.\n\n2\\. Exclusion Criteria\n\n1. Psychiatric Comorbidities Any concurrent psychiatric diagnosis (e.g., autism spectrum disorder, severe cognitive impairment, epilepsy, mania, psychosis) .\n2. Neurological Structural Abnormalities Structural brain lesions increasing seizure risk or disrupting neural connectivity (e.g., brain tumors, history of stroke).\n3. Systemic Medical Conditions Unstable cardiovascular, respiratory, hepatic, renal diseases, or active malignancies.\n4. Contraindications to Procedures TMS contraindications: Metallic implants, pacemakers, history of epilepsy. MRI contraindications: Ferromagnetic implants, claustrophobia requiring sedation.\n5. Recent Neuromodulation Therapies Prior ECT (Electroconvulsive Therapy) or rTMS (repetitive Transcranial Magnetic Stimulation) within 3 months.\n\nHistory of neurosurgical interventions for depression (e.g., deep brain stimulation).\n\n6）Special Populations Pregnancy, lactation, or planning pregnancy during the study. 7）Medication Instability Planned adjustments to pharmacotherapy during the study period. 3. Withdrawal and Discontinuation Criteria\n\n1. Participant-Initiated Withdrawal Voluntary withdrawal: Participant withdraws consent (e.g., refusal to risk assignment to sham stimulation group).\n2. Investigator-Initiated Withdrawal Non-compliance with inclusion criteria: Post-randomization discovery of ineligibility (e.g., symptom remission, medication non-adherence).\n\n   Serious Adverse Events (SAEs):\n\n   TMS-related SAEs (e.g., seizure, intractable headache, exacerbated suicidality).\n3. Study Discontinuation\n\nPrespecified Efficacy Stoppage:\n\nInterim analysis at n=30\u002Fgroup showing superiority of active intervention (Cohen's d \\>0.8) .\n\nSafety-Driven Discontinuation:\n\nUnacceptable risk profile (e.g., recurrent SAEs such as seizures or suicidality).\n\nLoss to Follow-Up:\n\nTrial termination if attrition rate exceeds pre-specified thresholds compromising statistical power (e.g., \\>20% dropout).","ALL","18 Years","65 Years",{"count":21,"type":22},124,"ESTIMATED","INTERVENTIONAL",[25],"NA","Background and Rationale\n\nWith rapid economic development and increasing societal pressures, the incidence of neuropsychiatric disorders has risen annually, ranking as the leading cause of disability worldwide and imposing a severe societal burden. Among these, depressive disorders represent a primary contributor. However, the efficacy and accessibility of transcranial magnetic stimulation (TMS) for depression face significant challenges. Key limitations include:\n\nLow targeting accuracy with traditional localization methods. Limited clinical penetration of individualized precision paradigms .\n\nIn this context, wearable repetitive TMS (wrTMS) technology offers a transformative solution. The rTMS-Tiny device, developed by the Institute of Automation, Chinese Academy of Sciences, exemplifies this innovation with the following features:\n\nBattery-powered with a pulse capacity exceeding 8,000 pulses per charge. Ultra-lightweight design: Total system weight \\\u003C3 kg, coil helmet \\\u003C2 kg (10% of conventional devices).\n\nPerformance parity: Comparable efficacy to standard rTMS systems while enabling protocols like Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) .\n\nAdvantages of rTMS-Tiny Portable Design and Wearable Application Ergonomically optimized helmet allows near-unrestricted daily activities during treatment .\n\nStreamlined Operational Workflow Simplified protocols significantly reduce clinician workload . Enhanced Treatment Tolerability Improved comfort increases treatment completion rates and long-term adherence, directly enhancing therapeutic outcomes .\n\nThese advantages enable high-dose, intensive regimens (e.g., SAINT-like protocols) in routine clinical practice .\n\nScientific Imperative for a Multicenter RCT\n\nA multicenter randomized controlled trial (RCT) of rTMS-Tiny is clinically and scientifically warranted to:\n\nTest two core hypotheses:\n\nHypothesis 1: Efficacy of rTMS-Tiny in reducing depressive symptoms. Hypothesis 2: Safety of home-based rTMS-Tiny administration . Generate high-level evidence to advance neuromodulation into an era of precision, personalization, and artificial intelligence-driven therapy .",[28],"Major Depressive Disorder","NOT_YET_RECRUITING","2026-08-19",{"date":32,"type":33},"2026-08-20","ACTUAL",{"date":32,"type":22},{"date":36,"type":22},"2028-06-30",{"name":38,"class":39},"Shanghai Mental Health Center","OTHER",1,{"id":42,"slug":43,"hasResults":12,"nctId":44,"briefTitle":45,"officialTitle":46,"acronym":47,"eligibilityCriteria":48,"healthyVolunteers":12,"sex":17,"minAge":49,"maxAge":50,"enrollmentInfo":51,"targetDuration":4,"studyType":23,"phases":53,"briefSummary":54,"conditions":55,"keywords":59,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":69,"startDateStruct":70,"completionDateStruct":72,"leadSponsor":74,"locationsCount":40},"100556310","accelerated-intermittent-theta-burst-in-treatment-naive-adolescents-100556310","NCT06523439","Accelerated Intermittent Theta Burst in Treatment-Naive Adolescents","Investigating a Truncated Version of paiTBS in Treatment-Naive Adolescents With Depression: An Open-Label Acceptability Trial","paiTBS-KID","Inclusion Criteria:\n\n1. Male or Female, between the ages of 13 and 20 at the time of screening.\n2. Able to read, understand, and provide written, dated assent and\u002For consent prior to screening. Proficiency in English sufficient to complete questionnaires and follow instructions during aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.\n3. Diagnosed with Major Depressive Disorder (MDD) with a current Major Depressive Episode (MDE), according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).\n4. No prior major depressive episodes (MDEs) as determined by MINI-KID\n5. CDRS-R score of ≥40 at screening (Visit 1).\n6. Treatment-naive as determined by the ATHF (no adequate antidepressant trials prior to screening defined as fewer than 12 weeks of antidepressant medication in the past 2 years and fewer than 10 psychotherapy sessions for depression in the past year; willingness to taper medications and stop psychotherapy if recently started and within the window defined above.)\n7. TMS naive.\n8. Access to ongoing psychiatric care before and after completion of the study.\n9. In good general health, as evidenced by medical history.\n10. Agreement to adhere to Lifestyle Considerations throughout study duration.\n\nExclusion Criteria:\n\n1. Pregnancy\n2. High-risk for suicide or active suicidal ideation as determined by clinical interview\n3. The presence or diagnosis of prominent anxiety disorder, or dysthymia (\\>4 on SAPAS; \\>16 on GAD-7)\n4. Current severe insomnia (must sleep a minimum of 5 hours each night before stimulation)\n5. Current mania or psychosis\n6. Bipolar Affective Disorder and\u002For primary psychotic disorders.\n7. Autism Spectrum disorder or Intellectual Disability\n8. A diagnosis of obsessive-compulsive disorder (OCD)\n9. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal.\n10. Urine screening test positive for illicit substances.\n11. Any history of ECT (greater than 8 sessions) without meeting responder criteria\n12. Recent (during the current depressive episode) or concurrent use of a rapid acting antidepressant agent (i.e., ketamine or a course of ECT).\n13. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, unexpected seizure\u002Fepilepsy disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma.\n14. Untreated or insufficiently treated endocrine disorder.\n15. Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)\n16. Contraindications to MRI (ferromagnetic metal in their body).\n17. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.\n18. Depth-adjusted aiTBS treatment dose \\> 65% maximum stimulator output (MSO)\n19. Treatment with another investigational drug or other intervention within the study period.\n20. Any other condition deemed by the PI to interfere with the study or increase risk to the participant.","13 Years","20 Years",{"count":52,"type":22},40,[25],"This is a single-site open-label clinical trial of fMRI-guided accelerated intermittent theta burst stimulation. The goal of this clinical trial is to learn if a new form of transcranial magnetic stimulation (TMS)-known generally as accelerated intermittent theta burst stimulation (aiTBS)-is effective as a first-line therapy in treating adolescents aged 13-20 years-old in their first episode of depression who have not undergone a full course of depression treatment prior to starting the trial and who remain antidepressant-free throughout the trial.\n\nThe main questions this trial aims to answer are:\n\n* Does aiTBS relieve symptoms of depression as a first-line therapy in adolescents?\n* Is aiTBS a feasible option as a first-line treatment for adolescent depression?\n\nResearchers will measure the depression symptoms in adolescent participants before and after aiTBS. Parents of the adolescent participant will also participate in the study providing information about their experience and preference for TMS as a first-line treatment.\n\nAdolescent participants will:\n\n* Remain antidepressant-free throughout the study period of 6-7 weeks.\n* Receive an fMRI of their head for precision targeting\n* Receive 5 days of aiTBS",[28,56,57,58],"Depression in Adolescence","Depression","Major Depressive Episode",[60,61,62,63,64,65,66],"Stanford Accelerated Intelligent Neuromodulation Therapy","SAINT","Transcranial Magnetic Stimulation","Accelerated Theta Burst Stimulation","Accelerated Intermittent Theta Burst Stimulation","TMS","TMS in Adolescents","RECRUITING","2026-08-18",{"date":30,"type":33},{"date":71,"type":33},"2025-04-01",{"date":73,"type":22},"2027-12",{"name":75,"class":39},"University of Texas at Austin",{"id":77,"slug":78,"hasResults":12,"nctId":79,"briefTitle":80,"officialTitle":81,"acronym":82,"eligibilityCriteria":83,"healthyVolunteers":84,"sex":17,"minAge":49,"maxAge":18,"enrollmentInfo":85,"targetDuration":4,"studyType":23,"phases":87,"briefSummary":88,"conditions":89,"keywords":90,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":95,"startDateStruct":96,"completionDateStruct":98,"leadSponsor":100,"locationsCount":40},"100450222","effectiveness-of-an-integrated-care-pathway-for-depression-cluster-randomized-controlled-trial-100450222","NCT05142683","Effectiveness of an Integrated Care Pathway for Depression: Cluster Randomized Controlled Trial","Effectiveness of an Integrated Care Pathway for Adolescent Depression: A Quasi-experimental, Multi-site, Cluster Controlled Trial","CARIBOU-2","Inclusion Criteria:\n\n* Youth is aged 13 to 18 years, inclusive.\n* Youth and\u002For their caregiver is expressing that 'depression\" (or some synonym) is a concern.\n* Clinician agrees that depressive symptoms are a treatment target.\n* Mood and Feelings Questionnaire score is ≥22 at two sequential visits (screening and baseline assessment).\n* Youth must be new to the site (in past 3 months) or have a period of no treatment for 3 months\n\nExclusion Criteria:\n\n* Known or highly suspected presentations of psychotic symptoms that are persistent, affect functioning, and have observable effects on behaviour.\n* Severe substance use disorder, bipolar disorder, autism spectrum disorder or intellectual disability, severe eating disorder, imminent risk of suicide requiring hospitalization as per judgment of the assessing clinician.\n* Inability to provide informed consent to the study for any reason\n* Youth currently in Day Treatment",true,{"count":86,"type":22},300,[25],"This is a quasi-experimental, multi-site cluster controlled clinical trial design with two intervention arms--Treatment As Usual (TAU) and an Integrated Care Pathway (ICP). Eligible participants are between the ages of 13 and 18, who present to community mental health agencies with depressive symptoms as the primary concern. The primary clinical outcome of interest is the difference between treatment groups in the rate of change of depressive symptoms from baseline to 24-week endpoint as measured by the Mood and Feelings Questionnaire. The secondary outcomes include rate of change of functional improvement, as measured by the Childhood Anxiety and Depression Life Interference Scale, and caregiver-rated internalizing symptoms as rated by the Childhood Behaviour Checklist. This study will also be examining implementation outcomes such as feasibility, fidelity cost and acceptability.",[28],[91,92,57,93,94],"Adolescents","Integrated Care Pathway","Measurement Based Care","Implementation",{"date":32,"type":33},{"date":97,"type":33},"2022-02-01",{"date":99,"type":22},"2027-09-30",{"name":101,"class":39},"Centre for Addiction and Mental Health",{"id":103,"slug":104,"hasResults":12,"nctId":105,"briefTitle":106,"officialTitle":107,"acronym":108,"eligibilityCriteria":109,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":110,"targetDuration":4,"studyType":23,"phases":112,"briefSummary":113,"conditions":114,"keywords":119,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":128,"lastUpdatePostDateStruct":129,"startDateStruct":130,"completionDateStruct":132,"leadSponsor":134,"locationsCount":137},"100585170","enhancing-veteran-clinical-collaboration-in-va-prrcs-100585170","NCT06898879","Enhancing Veteran-Clinical Collaboration in VA PRRCs","Enhancing Veteran-Clinical Collaboration in VA Psychosocial Rehabilitation and Recovery Centers","EVCC VPRRC","Inclusion Criteria:\n\n1. Be a Veteran currently receiving Psychosocial Rehabilitation and Recovery Center (PRRC), Mental Health Intensive Case Management (MHICM) and\u002For Behavioral Health Interdisciplinary Program (BHIP) services at VA San Diego, Los Angeles, or Albuquerque (e.g., seen in the clinic in the past month or based on clinic criteria)\n2. Meet Substance Abuse and Mental Health Services Administration (SAMHSA) criteria of serious mental illness; i.e., \"having (within the past year) a diagnosable mental, behavior, or emotional disorder that causes serious functional impairment that substantially interferes with or limits one or more major life activities,\" based on chart review and clinician consultation if needed\n3. Be fluent and literate in English\n4. Agree to have a subset of VA mental health treatment appointments audiotaped\n\nExclusion Criteria:\n\n1. Primary substance use or organic neurological disorder diagnosis determined by chart review\n2. Are determined by clinician and\u002For study staff to be at significant risk of exacerbation of symptoms, suicidal ideation, or other risk due to study participation\n3. Have a history and\u002For current risk of violence that clinicians and\u002For study staff determine to be too high risk to manage effectively in the study setting (e.g., poses a risk to Veterans or study staff)",{"count":111,"type":22},119,[25],"Over 60% of Veterans with serious mental illness have a service-connected disability that impairs their ability to work, go to school, and\u002For have successful personal lives. Although traditional treatments tend to focus on symptom remission, Veterans prioritize a range of treatment goals, including personal empowerment and gaining personally meaningful skills. Increasing Veteran-clinician collaboration can help effectively align care with each Veteran's goals and support an empowering therapeutic experience. This project will evaluate the effectiveness of a group-based intervention intended to increase Veterans' comfort, confidence, knowledge, and skills to collaborate with their treatment teams. Findings from this study will contribute important knowledge about this intervention's effectiveness and how to enhance its effectiveness, especially for Veterans from minoritized groups. If the decision-making intervention is effective, it would help Veterans with serious mental illness, and might also help Veterans with other chronic health conditions, like PTSD and chronic pain.",[115,116,117,118,28],"Schizophrenia","Schizoaffective Disorder","Delusional Disorder","Bipolar Disorder",[120,121,122,123,124,125,126,127],"serious mental illness","psychosis","collaborative decision-making","shared decision-making","veterans","recovery","personal recovery","empowerment","2026-08-17",{"date":30,"type":33},{"date":131,"type":33},"2026-08-12",{"date":133,"type":22},"2029-09-30",{"name":135,"class":136},"VA Office of Research and Development","FED",3,{"id":139,"slug":140,"hasResults":12,"nctId":141,"briefTitle":142,"officialTitle":143,"acronym":4,"eligibilityCriteria":144,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":145,"targetDuration":4,"studyType":23,"phases":147,"briefSummary":148,"conditions":149,"keywords":4,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":128,"lastUpdatePostDateStruct":151,"startDateStruct":152,"completionDateStruct":154,"leadSponsor":156,"locationsCount":137},"100523301","positive-processes-and-transition-to-health-path-100523301","NCT06093906","Positive Processes and Transition to Health (PATH)","Treatment of Stress-Related Psychopathology: Targeting Maladaptive and Adaptive Event Processing","Inclusion Criteria:\n\n* Destabilizing life event involving profound loss or threat, with a minimum duration of 12 weeks since the event, but occurred within the last 5 years.\n* Between the ages of 18 and 65.\n* Elevated target: Scores of at least moderate (1 or higher) on at least 2 of the 3 target mechanisms: re- experiencing or ruminative processing of the destabilizing event (PSS-I items: 1, 2, 3, 4 or QIDS-C item 11), avoidance (PSS-I items 6, 7, 8), or reward deficits (PSS-I items 12, 13, or QIDS-C item 13).\n\nExclusion Criteria:\n\n* Current diagnosis of schizophrenia, delusional disorder, or organic mental disorder as defined by DSM-5.\n* Current diagnosis of bipolar disorder, depression with psychotic features, or depression severe enough to require immediate psychiatric treatment (i.e., serious suicide risk with intent and plan).\n* Severe self-injurious behavior or suicide attempt within the previous three months.\n* Unwilling or unable to discontinue current cognitive behavioral psychotherapy.\n* No clear memory of the destabilizing event or event occurred before age 3.\n* Unstable dose of psychotropic medications in prior 3 months.\n* Ongoing intimate relationship with the perpetrator (in assault related event).\n* Current diagnosis of a substance use disorder (DSM-5).",{"count":146,"type":22},135,[25],"The R33 will be a randomized controlled trial to replicate changes in the targets (unproductive processing, avoidance, reward deficits) from the R61 phase in a larger sample of 135 participants who have experienced a destabilizing life event involving profound loss or threat, report persistent stressor-related symptoms of PTSD and\u002For depression, and are elevated on symptoms related to 2 of the 3 therapeutic targets. Additionally, this study will examine Positive Processes and Transition to Health (PATH)'s impact on stressor-related psychopathology in comparison to Progressive Muscle Relaxation (PMR). In the R33 phase, the investigators will examine changes in target mechanisms predicting improvements in PTSD and depressive symptoms, as well as feasibility and acceptability. Patients will receive 6 sessions of PATH or PMR (with 2 boosters, if partial responders). Primary targets will be assessed at pre-treatment, week 3, post-treatment, and at 1- and 3-month follow-up; secondary targets at pre-treatment, weekly during treatment, post-treatment, and at 1- and 3-month follow-ups.",[150,28],"Posttraumatic Stress Disorder",{"date":30,"type":33},{"date":153,"type":33},"2023-09-12",{"date":155,"type":22},"2027-07-31",{"name":157,"class":39},"Case Western Reserve University",{"id":159,"slug":160,"hasResults":12,"nctId":161,"briefTitle":162,"officialTitle":163,"acronym":4,"eligibilityCriteria":164,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":165,"targetDuration":4,"studyType":23,"phases":167,"briefSummary":169,"conditions":170,"keywords":171,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":179,"lastUpdatePostDateStruct":180,"startDateStruct":181,"completionDateStruct":183,"leadSponsor":185,"locationsCount":188},"100652308","phase-2-a-study-to-evaluate-bms-986511-in-adults-with-major-depressive-disorder-100652308","NCT07772531","A Study to Evaluate BMS-986511 in Adults With Major Depressive Disorder","A Phase 2, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Monotherapy, Multicenter Study to Evaluate the Efficacy and Safety of BMS-986511 in Two Sequential Parts in Participants With Major Depressive Disorder","Inclusion Criteria:\n\n* Participants must meet the MDD diagnosis per DSM-5 criteria confirmed by structured interview.\n* Participant must have current moderate to severe MDE confirmed by clinical assessment and validated scale.\n* Participant must have current MDE duration \\>12 weeks at screening.\n* Outpatient participants able to comply with study procedures.\n* Participant require medication washout completed before baseline.\n* Participant must have BMI within protocol range.\n* Participants must meet reproductive safety requirements.\n\nExclusion Criteria:\n\n* Participants must not have other primary psychiatric disorders or a history of treatment-resistant depression during the current episode.\n* Participants must not have recent history of active suicidal ideation or attempt within the past year.\n* Participants must not have prior lifetime treatment with electroconvulsive therapy, ketamine\u002Fesketamine, deep brain stimulation, or transcranial magnetic stimulation.\n* Participants must not have recent history of alcohol\u002Fsubstance abuse or use of cannabis.\n* Participants must not have significant ECG abnormalities, or poorly controlled diabetes.\n* Other protocol defined inclusion\u002Fexclusion criteria apply.",{"count":166,"type":22},200,[168],"PHASE2","A Study to Evaluate BMS-986511 in Adults with Major Depressive Disorder",[28],[28,57,172,173,174,175,176,177,178],"BMS-986511","Evifacotrep","TRPC4\u002F5 Inhibitor","Antidepressant","Mood Disorders","Central Nervous System","MDD","2026-08-14",{"date":30,"type":33},{"date":182,"type":22},"2026-10-30",{"date":184,"type":22},"2028-11-06",{"name":186,"class":187},"Bristol-Myers Squibb","INDUSTRY",26,{"id":190,"slug":191,"hasResults":12,"nctId":192,"briefTitle":193,"officialTitle":193,"acronym":4,"eligibilityCriteria":194,"healthyVolunteers":84,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":195,"targetDuration":4,"studyType":23,"phases":197,"briefSummary":199,"conditions":200,"keywords":202,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":179,"lastUpdatePostDateStruct":207,"startDateStruct":208,"completionDateStruct":210,"leadSponsor":212,"locationsCount":40},"100290790","phase-1-neuropharmacologic-imaging-and-biomarker-assessments-of-response-to-acute-and-repeated-dosed-ketamine-infusions-in-major-depressive-disorder-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":196,"type":22},150,[198],"PHASE1","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",[201,28,57],"Healthy Volunteer",[203,204,28,205,206],"Magnetic Resonance Imaging","Magnetoencephalography","Ketamine","Neuropharmacology",{"date":128,"type":33},{"date":209,"type":33},"2017-05-25",{"date":211,"type":22},"2028-01-01",{"name":213,"class":214},"National Institute of Mental Health (NIMH)","NIH",{"id":216,"slug":217,"hasResults":12,"nctId":218,"briefTitle":219,"officialTitle":219,"acronym":4,"eligibilityCriteria":220,"healthyVolunteers":84,"sex":17,"minAge":221,"maxAge":19,"enrollmentInfo":222,"targetDuration":4,"studyType":23,"phases":224,"briefSummary":225,"conditions":226,"keywords":228,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":179,"lastUpdatePostDateStruct":233,"startDateStruct":234,"completionDateStruct":236,"leadSponsor":238,"locationsCount":239},"100059514","phase-2-study-of-neuro-cognitive-correlates-of-pediatric-anxiety-disorders-100059514","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",{"count":223,"type":22},3500,[168],"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.",[227,28],"Anxiety Disorders",[229,230,231,203,232],"fMRI","Emotion","Normal Volunteers","CBT",{"date":128,"type":33},{"date":235,"type":33},"2001-10-02",{"date":237,"type":22},"2029-01-01",{"name":213,"class":214},2,{"id":241,"slug":242,"hasResults":12,"nctId":243,"briefTitle":244,"officialTitle":244,"acronym":4,"eligibilityCriteria":245,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":246,"enrollmentInfo":247,"targetDuration":4,"studyType":249,"phases":4,"briefSummary":250,"conditions":251,"keywords":271,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":275,"lastUpdatePostDateStruct":276,"startDateStruct":277,"completionDateStruct":279,"leadSponsor":281,"locationsCount":40},"100551600","natural-history-of-depression-bipolar-disorder-and-suicide-risk-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":248,"type":22},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.",[252,253,254,255,256,257,258,259,260,261,262,263,264,265,266,205,267,268,269,28,270],"Behavioral Symptoms","Suicide","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","Depression, Unipolar","Depressive Symptoms","Treatment Resistant Depression","Depression, Bipolar",[272,253,28,118,273,274,269],"Neurobiology","Biomarkers","Suicide Risk","2026-08-13",{"date":179,"type":33},{"date":278,"type":33},"2024-09-09",{"date":280,"type":22},"2030-06-01",{"name":213,"class":214},{"id":283,"slug":284,"hasResults":12,"nctId":285,"briefTitle":286,"officialTitle":287,"acronym":288,"eligibilityCriteria":289,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":290,"targetDuration":4,"studyType":23,"phases":292,"briefSummary":293,"conditions":294,"keywords":296,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":275,"lastUpdatePostDateStruct":302,"startDateStruct":303,"completionDateStruct":305,"leadSponsor":307,"locationsCount":40},"100486430","integrated-suicide--trauma-therapy-for-suicide-risk-100486430","NCT05613972","Integrated Suicide & Trauma Therapy for Suicide Risk","Using Integrated Suicide and Trauma Therapy to Reduce Suicide Risk Among Adults With a History of Childhood Trauma","ISTT","Inclusion Criteria:\n\n* Beck Scale for Suicidal Ideation \\> 10\n* Presence of childhood trauma defined by a minimum moderate score on any of the Childhood Trauma Questionnaire subscales (emotional abuse, physical, abuse, sexual abuse, emotional neglect, and physical neglect\n* any psychiatric diagnosis as long as there are no impairments that limit consent or understanding of ISTT (e.g. active psychosis)\n* Ability to provide informed consent\n* Not receiving other psychotherapy concurrently\n* Ability to undergo psychotherapy in English\n\nExclusion Criteria:\n\n* The presence of cognitive impairment and\u002For active psychosis that would limit consent or understanding of ISTT\n* Unwilling or unable to provide informed consent",{"count":291,"type":22},20,[25],"The investigators have developed a novel suicide intervention, Integrated Suicide and Trauma Therapy (ISTT). ISTT combines Brief-Skills for Safer Living (Brief-SfSL)-a promising method to enhance coping skills and reduce suicidality-with a trauma therapy component to alleviate the specific impacts of childhood trauma on suicide risk. The aim of this pilot is to test 12-weeks of ISTT to alleviate suicide risk among individuals with a history of childhood trauma and current suicidality.",[253,295,28],"Trauma",[297,298,299,300,301],"Childhood trauma","Early life adversity","Adverse childhood experiences","Suicide intervention","Psychotherapy",{"date":128,"type":33},{"date":304,"type":33},"2025-12-08",{"date":306,"type":22},"2027-07",{"name":308,"class":39},"Unity Health Toronto",{"id":310,"slug":311,"hasResults":12,"nctId":312,"briefTitle":313,"officialTitle":314,"acronym":4,"eligibilityCriteria":315,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":316,"targetDuration":4,"studyType":23,"phases":318,"briefSummary":319,"conditions":320,"keywords":321,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":131,"lastUpdatePostDateStruct":325,"startDateStruct":326,"completionDateStruct":328,"leadSponsor":330,"locationsCount":40},"100652099","accelerated-versus-standard-intermittent-theta-burst-stimulation-for-major-depressive-disorder-100652099","NCT07768397","Accelerated Versus Standard Intermittent Theta Burst Stimulation for Major Depressive Disorder","A Randomized Rater-Blinded Trial Comparing Accelerated and Standard Intermittent Theta Burst Stimulation Combined With Pharmacotherapy for Major Depressive Disorder","Inclusion Criteria:\n\n* Age 18 to 65 years.\n* Diagnosis of major depressive disorder (MDD), confirmed by a specialist according to DSM-5 criteria.\n* Hamilton Depression Rating Scale, 17-item version (HAM-D17) score ≥18 at screening\u002Fbaseline.\n* Stable background pharmacotherapy for at least 4 weeks before randomization, with no planned changes in medication regimen or drug class during the intervention period unless clinically required.\n* Right-handed.\n* Able and willing to provide written informed consent and comply with study procedures.\n\nExclusion Criteria:\n\n* History of epilepsy or seizures, except childhood febrile seizures.\n* Bipolar disorder or psychotic disorder.\n* Acute suicide risk, including HAM-D17 item 3 score ≥3 or clear suicidal intent or behavior.\n* Alcohol or illicit drug abuse or dependence within the previous 6 months.\n* Significant structural brain lesions.\n* Intracranial or head\u002Fneck metallic objects or implants considered unsafe for TMS, including metallic clips, fragments, or cochlear implants.\n* Implanted electronic devices such as pacemakers, implantable cardioverter-defibrillators, or deep brain stimulation devices.\n* Other conditions associated with a high risk of seizure or history of cranial surgery considered unsafe for TMS.\n* Uncontrolled thyroid dysfunction.\n* Severe untreated vitamin D deficiency (\\\u003C20 ng\u002FmL).\n* Acute infection, elevated C-reactive protein, or other clinically significant medical abnormalities that may interfere with study participation.\n* Pregnancy or breastfeeding.\n* Benzodiazepine use exceeding the equivalent of lorazepam 2 mg\u002Fday that cannot be reduced.\n* Use of medications associated with a substantially lowered seizure threshold, including clozapine, high-dose tricyclic antidepressants, or bupropion \\>300 mg\u002Fday.\n* Unstable doses of antiepileptic medications used as mood stabilizers.\n* Previous rTMS treatment.\n* Failure to respond to an adequate course of electroconvulsive therapy (≥8 lifetime sessions).\n* Unable or unwilling to comply with study procedures.",{"count":317,"type":22},80,[25],"This randomized clinical trial aims to compare the effectiveness and safety of accelerated intermittent theta burst stimulation (iTBS) with standard iTBS in adults with major depressive disorder.\n\nParticipants will be randomly assigned to receive either accelerated or standard iTBS targeting the left dorsolateral prefrontal cortex, in addition to pharmacotherapy. The accelerated iTBS group will receive 45 treatment sessions over approximately 15 treatment days, while the standard iTBS group will receive 20 treatment sessions over 4 weeks.\n\nThe primary objective is to compare changes in depressive symptom severity between the two treatment groups from baseline to the end of treatment. Depressive symptoms will be assessed using the 17-item Hamilton Depression Rating Scale (HAM-D17). The study will also evaluate other clinical outcomes, cognitive function, quality of life, sleep quality, neurophysiological measures, and treatment safety.",[28],[322,323,62,324,28],"Intermittent Theta Burst Stimulation","iTBS","Accelerated iTBS",{"date":128,"type":33},{"date":327,"type":22},"2026-08",{"date":329,"type":22},"2028-06",{"name":331,"class":39},"Military Hospital 175",{"id":333,"slug":334,"hasResults":12,"nctId":335,"briefTitle":336,"officialTitle":336,"acronym":4,"eligibilityCriteria":337,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":338,"enrollmentInfo":339,"targetDuration":4,"studyType":23,"phases":340,"briefSummary":342,"conditions":343,"keywords":4,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":344,"lastUpdatePostDateStruct":345,"startDateStruct":346,"completionDateStruct":348,"leadSponsor":349,"locationsCount":40},"100535131","phase-3-the-effects-of-psilocybin-on-self-focus-and-self-related-processing-in-major-depressive-disorder-100535131","NCT06247839","The Effects of Psilocybin on Self-Focus and Self-Related Processing in Major Depressive Disorder","Inclusion Criteria:\n\n1. Must be able to sign the informed consent form (ICF). Participants will demonstrate capacity to provide informed consent by demonstrated understanding of the protocol and what their involvement in the study requires from them.\n2. Be 18-55 years of age at screening.\n3. At least moderate Major Depressive Disorder (MDD; single or recurrent episode as informed by Diagnostic and Statistical Manual Version 5 (DSM-V); if single episode, duration of ≥ 3 months and ≤ 3 years) based on clinical assessment and a structured clinical interview, the Mini International Neuropsychiatric Interview Version 7.02 (MINI).43\n4. Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS)44 score ≥ 18 at Screening and at Baseline.\n5. Failure to respond to an adequate dose and duration of 1, 2, 3, or 4 pharmacological treatments for the current episode as determined through the Massachusetts General Hospital Antidepressant Treatment History Response Questionnaire (MGH-ATRQ)45 and using the supplementary advice on additional antidepressants not included in MGH-ATRQ. Augmentation with an add-on treatment counts as a second treatment, provided it is approved for the adjunctive treatment of MDD.\n6. McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) \\\u003C 7 at Screening.\n7. Participants will also have to successfully undergo a taper off of all psychotropic medications under the supervision of a study psychiatrist and in coordination with their treatment team, which will be completed at least 2 weeks prior to Baseline Scan. Please see below regarding details about discontinuation of antidepressants.\n8. A score \\> 40 on the Wechsler Test of Adult Reading.46\n9. Be right-handed as determined by the Edinburgh Handedness Inventory.48\n10. Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.\n11. Have ongoing established mental health care.\n\nExclusion Criteria:\n\nPatients meeting any of the following criteria are to be excluded from the study:\n\n1. Current, past history, or family history, of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, or any serious psychiatric comorbidity as assessed by medical history and a structured clinical interview (version 7.0.2 MINI).\n2. Positive Magnetic Resonance screen (e.g., metal implant, claustrophobia, etc).\n3. Prior electroconvulsive therapy and\u002For ketamine for current episode.\n4. Current cognitive behavioral therapy (CBT) that will not remain stable for the duration of the study. CBT cannot be initiated within 21 days of Baseline.\n5. Current (within the last year) alcohol or substance abuse as informed by DSM-5 at Screening.\n6. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS)49 within the past year, at Screening or at Baseline, or; (2) suicidal behaviors within the past year, or; (3) clinical assessment of significant suicidal risk during clinical interview.\n7. Significant homicide risk as defined by clinical interview.\n8. Depression secondary to other severe medical conditions.\n9. Currently taking benzodiazepines daily.\n10. Other personal circumstances and behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin, as well as exposure to psilocybin or other psychedelics within one year of screening.\n11. Women who are pregnant, nursing, or planning a pregnancy. Participants who are sexually active must agree to use a highly effective contraceptive method throughout their participation in the study. Women of childbearing potential must have a negative urine pregnancy test at Screening and Day Before Psilocybin.\n12. Cardiovascular conditions: recent stroke (\\\u003C 1 year from signing of consent), recent myocardial infarction (\\\u003C 1 year from signing of ICF), hypertension (blood pressure \\> 140\u002F90 mmHg) or corrected QT interval \\> 450 msec) or clinically significant arrhythmia within 1 year of signing the ICF, current anticoagulant therapy, aneurysmal disease.\n13. Uncontrolled insulin dependent diabetes.\n14. Seizure disorder.\n15. Positive urine drug screen for illicit drugs or drugs of abuse (to include but not limited to opiates, phenylcyclohexyl piperidine(PCP), cocaine, amphetamines, methamphetamines, benzodiazepines, barbiturates, and cannabis) at Screening and Day Before Psilocybin. Any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator's discretion.\n16. Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease\u002Fprocedure\u002Faccident\u002Fintervention which, according to the screening clinician, is deemed associated with significant injury to or malfunction of the CNS, or history of significant head trauma within the past 2 years.\n17. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.\n18. Current enrollment in any investigational drug or device study or participation in such within 6 months of Screening.\n19. Current enrollment in an interventional study for depression or participation in such within 6 months of Screening Visit.\n20. Non-native speakers of English.","55 Years",{"count":291,"type":22},[341],"PHASE3","This open-label functional Magnetic Resonance Imaging (fMRI) study will assess the effects of a single dose of psilocybin on rumination and the neural correlates of rumination in individuals with major depressive disorder.",[28],"2026-08-11",{"date":275,"type":33},{"date":347,"type":33},"2024-09-10",{"date":36,"type":22},{"name":350,"class":39},"Sharmin Ghaznavi",{"id":352,"slug":353,"hasResults":12,"nctId":354,"briefTitle":355,"officialTitle":355,"acronym":356,"eligibilityCriteria":357,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":358,"targetDuration":4,"studyType":23,"phases":360,"briefSummary":362,"conditions":363,"keywords":364,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":365,"lastUpdatePostDateStruct":366,"startDateStruct":367,"completionDateStruct":369,"leadSponsor":371,"locationsCount":40},"100524057","phase-4-positioning-of-esketamine-treatment-in-the-real-world-management-of-depression-100524057","NCT06103760","Positioning of Esketamine Treatment in the Real-world Management of Depression","PoET","Inclusion Criteria:\n\n1. Adults aged 18-65 years old\n2. Diagnosis of Major Depressive Disorder (MDD)\n3. Currently depressed\n4. Had an inadequate response to 2 or more courses of antidepressants (of adequate dose and duration)\n5. Be maintained on their current antidepressant medication or psychological therapy at the time of enmrolment\n6. Able to understand and provide informed consent\n\nExclusion Criteria:\n\n1. Concurrent diagnoses:\n\n   * Participants with other 'Diagnostic and Statistical Manual of Mental Disorders' (DSM-5) e.g., current substance misuse disorder, bipolar disorder, schizophrenia\n   * Participants who are unable to understand the study and therefore unable to provide informed consent\n2. Pregnancy:\n\n   * Participants who are pregnant and\u002For breastfeeding\n   * Participants who are not willing to avoid pregnancy for themselves or their partners during the study by using effective birth control methods\n3. Current medications:\n\n   * Participants taking a total daily dose of benzodiazepines greater than the equivalent of 6mg\u002Fday of lorazepam\n   * Participants on complementary and alternative medicine therapies i.e., St John's wort, Chinese medicines, and various herbal and homeopathic treatments\n4. Stimulants\n\n   * Participants taking stimulants such as methylphenidate, amphetamine, and dextroamphetamine for a diagnosis such as ADHD can still have Esketamine provided they do not continue taking stimulants concurrently for the duration of the study.\n   * Concurrent use is excluded due to the synergistic effect with Esketamine that can cause increased blood pressure.\n5. Medical history:\n\n   * Participants with current or past history of seizures (uncomplicated childhood febrile seizures with no sequelae are not exclusionary)\n   * Participants with a history of uncontrolled hypertension\n   * Participants with uncontrolled diabetes mellitus\n   * Participants with aneurysmal vascular disease including thoracic and abdominal aorta, intracranial and peripheral arterial vessels, or arteriovenous malformation, intracerebral haemorrhage\n   * Participants with untreated glaucoma, current penetrating or perforating eye injury, brain injury, hypertensive encephalopathy, intrathecal therapy with ventricular shunts, or any other condition associated with increased intracranial pressure or increased intraocular pressure or planned eye surgery\n   * Participants who are currently receiving electroconvulsive therapy (ECT) or have received ECT in the past month.\n6. Substance Misuse History:\n\n   * Participants who have ever had a substance misuse disorder involving any of the following over their lifetime: ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3,4-methylenedioxy-methamphetamine (MDMA), or other hallucinogen use history\n   * Participants with hypersensitivity to Esketamine, Ketamine, or any of the excipients",{"count":359,"type":22},162,[361],"PHASE4","The goal of this naturalistic, open label, single arm intervention study is to investigate the effects of Esketamine in treating depression.The main aims to answer are:\n\n* to investigate whether Esketamine is effective when added to ongoing antidepressant treatment\n* to identify patient characteristics that will determine a therapeutic response to Esketamine in real-world practice\n\nParticipants will:\n\n* attend the clinic for supervised self-administration of intranasal Esketamine treatment\n* be observed for 2 hours following Esketamine administration including blood pressure monitoring\n* be asked to complete a battery of questionnaires\n* be reimbursed for travel expenses",[28],[57],"2026-08-10",{"date":131,"type":33},{"date":368,"type":33},"2023-10-31",{"date":370,"type":22},"2028-08-15",{"name":372,"class":39},"Royal North Shore Hospital",{"id":374,"slug":375,"hasResults":12,"nctId":376,"briefTitle":377,"officialTitle":378,"acronym":4,"eligibilityCriteria":379,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":380,"targetDuration":4,"studyType":23,"phases":382,"briefSummary":383,"conditions":384,"keywords":385,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":389,"lastUpdatePostDateStruct":390,"startDateStruct":391,"completionDateStruct":393,"leadSponsor":394,"locationsCount":239},"100606361","remote-evaluation-and-alerting-for-collaborative-health-reach-in-depression-100606361","NCT07174557","Remote Evaluation and Alerting for Collaborative Health (REACH) in Depression","Beyond the Clinic: Enhancing Depression Surveillance With a Digital Biomarker","Inclusion Criteria:\n\n* Adult patients (18 years or older)\n* Treated for depression within Dartmouth Health collaborative care model (CoCM) sites who are discharged from CoCM without depression (PHQ-9 \\\u003C 10)\n* Have access to and ability to use a smartphone (Android version ≥ 6 or iOS version ≥ 11).\n\nExclusion Criteria:\n\n* Identified as high risk due to active suicidality, psychosis, or bipolar disorder - Discharged from CoCM with ongoing depressive symptoms (PhQ-9 \\> 10",{"count":381,"type":22},320,[25],"Researchers hope to see if the data smartphones collect continuously can be used to predict if patient's depression symptoms will return. They will do this by collecting data from patient's smartphones and comparing it to their depression symptoms. If this method is successful, researchers could develop a smartphone application to help healthcare providers better monitor patient's depression and intervene earlier if symptoms return.",[57,28],[57,386,387,388],"Smartphone monitoring","Risk detection","Collaborative care","2026-08-09",{"date":344,"type":33},{"date":392,"type":33},"2026-05-20",{"date":36,"type":22},{"name":395,"class":39},"Dartmouth-Hitchcock Medical Center",{"id":397,"slug":398,"hasResults":12,"nctId":399,"briefTitle":400,"officialTitle":401,"acronym":402,"eligibilityCriteria":403,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":404,"enrollmentInfo":405,"targetDuration":4,"studyType":23,"phases":407,"briefSummary":408,"conditions":409,"keywords":412,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":389,"lastUpdatePostDateStruct":417,"startDateStruct":418,"completionDateStruct":420,"leadSponsor":422,"locationsCount":40},"100556739","phase-2-low-amplitude-pulse-seizure-therapy-versus-standard-ultra-brief-right-unilateral-electroconvulsive-therapy-100556739","NCT06529029","Low Amplitude Pulse Seizure Therapy Versus Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy","Efficacy of Low Amplitude Pulse Seizure Therapy Versus Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy in Remission of Suicidal Ideation","LAP-ST vs ECT","Inclusion Criteria:\n\n1. Patients in whom ECT is clinically indicated: The referrals to ECT by the primary psychiatrist (before a consult by the ECT consultant) will serve to both increase the feasibility of the study and address any ethical concerns that the patient would not undergo ECT without having a valid full indication for the procedure as well as increase the external validity and generalizability of the study.\n2. Male or female patients 18 to 90 years of age\n3. Current DSM-5 criteria for MDE with any SI of major depressive, bipolar, or schizoaffective disorders\n4. Montgomery-Asberg depression rating scale (MADRS) with 2 or more on SI item\n5. Use of effective method of birth control for women of child-bearing capacity\n6. Patient is medically stable\n7. No anticipated need to alter psychotropic medications for the duration of the study (except for urgent\u002Femergent situations)\n8. Ability of patient to fully participate in the informed consent process\n\nExclusion Criteria:\n\n1. Unstable or serious medical condition that substantially increases risks of ECT or cognitive impairment\n2. Female patients who are pregnant or plan to be pregnant during the study or are breast-feeding\n3. History of neurological disorder if deemed by the treating ECT physician or PI to pose a significant risk with ECT, or if there is any metal in the head or history of known structural brain lesion or skull defect that is deemed to affect cognition or safe ECT treatment\n4. Implanted devices that make ECT unsafe\n5. Clinical presentation of delirium or dementia\n6. Active substance use disorders within 1 week of randomization\n7. ECT in the past 1 month or prior failure to respond to an adequate course of ECT as deemed by the ECT physician treating the patient or the PI","90 Years",{"count":406,"type":22},30,[168,341],"This protocol proposes an initial randomized clinical trial that includes all patients with suicidal ideation (SI) at baseline, and with SI as the primary outcome measure to examine whether Right Unilateral Low-Amplitude Pulse - Seizure Therapy (RUL LAP-ST) treatment has more magnitude and rate of remission of SI as conventional pulse amplitude Right Unilateral Electroconvulsive Therapy (RUL ECT) (based on our prior secondary analysis). Our central hypothesis is that RUL LAP-ST has significantly less cognitive\u002Fmemory side effects (no memory side effects were noted in our prior studies for 500mA and 600mA) and thus is more favorable in terms of side effects compared to RUL conventional pulse amplitude ECT, while maintaining better anti-suicidal effect.",[410,28,411,118],"Suicidal Ideation","Schizo Affective Disorder",[410,253,57,28,411,118,413,414,415,416],"Low Amplitude Seizure Therapy","Electroconvulsive Therapy","Neuromodulation","Brain Stimulation",{"date":131,"type":33},{"date":419,"type":33},"2024-07-03",{"date":421,"type":22},"2026-12-01",{"name":423,"class":39},"Michigan State University",{"id":425,"slug":426,"hasResults":12,"nctId":427,"briefTitle":428,"officialTitle":429,"acronym":4,"eligibilityCriteria":430,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":431,"enrollmentInfo":432,"targetDuration":4,"studyType":23,"phases":434,"briefSummary":435,"conditions":436,"keywords":4,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":437,"lastUpdatePostDateStruct":438,"startDateStruct":439,"completionDateStruct":441,"leadSponsor":442,"locationsCount":406},"100641561","a-phase-3-trial-of-dt120-for-major-depressive-disorder-ascend-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":433,"type":22},165,[341],"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",[28],"2026-08-07",{"date":365,"type":33},{"date":440,"type":33},"2026-05-10",{"date":329,"type":22},{"name":443,"class":187},"Definium Therapeutics US, Inc.",{"id":445,"slug":446,"hasResults":12,"nctId":447,"briefTitle":448,"officialTitle":449,"acronym":4,"eligibilityCriteria":450,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":451,"targetDuration":4,"studyType":23,"phases":452,"briefSummary":453,"conditions":454,"keywords":455,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":437,"lastUpdatePostDateStruct":459,"startDateStruct":460,"completionDateStruct":462,"leadSponsor":463,"locationsCount":465},"100590100","nbi-1065845-mdd3026-study-to-assess-the-efficacy-and-safety-of-nbi-1065845-as-an-adjunctive-treatment-in-participants-with-major-depressive-disorder-mdd-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":166,"type":22},[341],"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.",[28],[178,57,28,456,457,458],"NBI-1065845","TAK-653","MADRS",{"date":365,"type":33},{"date":461,"type":33},"2025-05-30",{"date":306,"type":22},{"name":464,"class":187},"Neurocrine Biosciences",35,{"id":467,"slug":468,"hasResults":12,"nctId":469,"briefTitle":470,"officialTitle":449,"acronym":4,"eligibilityCriteria":450,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":471,"targetDuration":4,"studyType":23,"phases":472,"briefSummary":453,"conditions":473,"keywords":474,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":437,"lastUpdatePostDateStruct":475,"startDateStruct":476,"completionDateStruct":478,"leadSponsor":479,"locationsCount":480},"100586110","phase-3-nbi-1065845-mdd3025-study-to-assess-the-efficacy-and-safety-of-nbi-1065845-as-an-adjunctive-treatment-in-participants-with-major-depressive-disorder-mdd-100586110","NCT06911112","NBI-1065845-MDD3025: Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)",{"count":166,"type":22},[341],[28],[178,57,28,456,457,458],{"date":344,"type":33},{"date":477,"type":33},"2025-03-31",{"date":306,"type":22},{"name":464,"class":187},39,{"id":482,"slug":483,"hasResults":12,"nctId":484,"briefTitle":485,"officialTitle":485,"acronym":4,"eligibilityCriteria":486,"healthyVolunteers":84,"sex":17,"minAge":18,"maxAge":487,"enrollmentInfo":488,"targetDuration":4,"studyType":23,"phases":490,"briefSummary":491,"conditions":492,"keywords":495,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":437,"lastUpdatePostDateStruct":499,"startDateStruct":500,"completionDateStruct":502,"leadSponsor":504,"locationsCount":40},"100480663","defining-neurobiological-links-between-substance-use-and-mental-illness-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":489,"type":22},620,[25],"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.",[28,493,494],"Substance Use Disorder","Normal Physiology",[229,496,497,498],"Reward Function","Affective Processing","Interoceptive Awareness",{"date":365,"type":33},{"date":501,"type":33},"2023-02-02",{"date":503,"type":22},"2027-12-31",{"name":505,"class":214},"National Institute on Drug Abuse (NIDA)",{"id":507,"slug":508,"hasResults":12,"nctId":509,"briefTitle":510,"officialTitle":511,"acronym":4,"eligibilityCriteria":512,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":513,"enrollmentInfo":514,"targetDuration":4,"studyType":23,"phases":516,"briefSummary":517,"conditions":518,"keywords":520,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":437,"lastUpdatePostDateStruct":521,"startDateStruct":522,"completionDateStruct":524,"leadSponsor":525,"locationsCount":40},"100405247","pain-and-major-depressive-disorder-100405247","NCT04556890","Pain and Major Depressive Disorder","Multi-target Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment for Major Depressive Disorder (MDD) and Comorbid Pain","Inclusion Criteria:\n\n* All Subjects must be between 18-75 years of age\n* Language: Participants must speak English fluently, as demonstrated by verbal skills sufficient to answer questions at a level that assures adequate understanding of the study\n* Must have confirmed diagnosis of moderate Major Depressive Disorder (single or recurrent episode), minimum score of 17 on the 17-item Hamilton Rating Scale for Depression (HAM-D17). No minimal MDD duration necessary for study participation\n* Failure to respond to a minimum of 2 trials of antidepressant medication\n* Failure to respond from at least two different agent classes\n* Accompanied by at least two evidence-based augmentation therapies (Benzodiazepines do not count)\n* Must have a trial of psychotherapy known to be effective in the treatment of MDD of an adequate frequency and duration\\*\n* Must have a confirmed FM or ME\u002FCFS diagnoses and moderate pain complaints, minimum score of 15 on the McGill Pain Questionnaire.\n* Pain chronicity for at least 3 months prior to study enrollment.\n* Subjects are willing and able to adhere to the treatment schedule and required study visits.\n\nExclusion Criteria:\n\n* Are mentally or legally incapacitated, unable to give informed consent.\n* Are pregnant.\n* Have an active suicidal intent or plan.\n* Have had prior Transcranial Magnetic Stimulation treatment.\n* Have an infection or poor skin condition over the scalp where the device will be positioned.\n* Have increased risk of seizure because of family history, stroke, or currently use medications that lead to increased risk for seizure.\n* Psychotic depression or other acute or chronic psychotic symptoms or disorders (such as schizophrenia, schizophreniform or schizoaffective disorder) in the current depressive episode.\n* Neurological conditions that include epilepsy, cerebrovascular disease, dementia, increased intracranial pressure, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the central nervous system.\n* Presence of an implanted metallic and magnetic-sensitive medical device present in the body scan, including but not limited to a cochlear implant, infusion pump, implanted cardioverter defibrillator, pacemaker, vagus nerve stimulator, aneurysm clip, metal prosthesis, or metal aneurysm clips or coils, staples, or stents. (Note: Dental amalgam fillings are not affected by the magnetic field and are acceptable for use with transcranial magnetic stimulation and MRI)","75 Years",{"count":515,"type":22},54,[25],"This study will examine the effects of brain stimulation on pain symptoms associated with Major depressive disorder. This study will enroll 54 Subjects. Study subjects will be asked to complete surveys about their mood and well-being, 2 blood draws, 2 MRIs, 3 electroencephalograms, and receive 30 treatments of blinded transcranial magnetic stimulation. There is no control group as all subjects will receive some form of active treatment. Subjects are required to participate in 30-33 study visits and volunteer 40 hours of their time. Compensation for this study is $150 for completing all study activities.",[28,519],"Chronic Pain",[65,178,519],{"date":344,"type":33},{"date":523,"type":33},"2023-03-01",{"date":503,"type":22},{"name":526,"class":39},"University of California, Los Angeles",{"id":528,"slug":529,"hasResults":12,"nctId":530,"briefTitle":531,"officialTitle":532,"acronym":4,"eligibilityCriteria":533,"healthyVolunteers":12,"sex":17,"minAge":534,"maxAge":535,"enrollmentInfo":536,"targetDuration":4,"studyType":23,"phases":538,"briefSummary":539,"conditions":540,"keywords":541,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":543,"lastUpdatePostDateStruct":544,"startDateStruct":546,"completionDateStruct":548,"leadSponsor":549,"locationsCount":406},"100608650","phase-3-a-study-of-vortioxetine-in-japanese-pediatric-patients-with-major-depressive-disorder-100608650","NCT07204314","A Study of Vortioxetine in Japanese Pediatric Patients With Major Depressive Disorder","A Randomized, Double-blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Once-Daily Oral Administration of Vortioxetine in Japanese Pediatric Patients 12 to 17 Years of Age With Major Depressive Disorder (MDD)","Inclusion Criteria:\n\n1. The Japanese participant is a male or female, aged 12 to 17 years at the time of informed consent (patients who turn 18 years during the trial will be allowed to continue in the trial).\n2. The participant is capable of communicating with the site personnel.\n3. The participant is able to understand the informed assent form or the ICF and parent(s)\u002Flegal guardian(s) are able to read and understand the ICF. The participant is able and willing to accept video recording at the assessment by the trial site and evaluation by third party evaluators (Central Evaluating Committee).\n4. The participant has provided the written informed assent as much as possible to participation and parent(s)\u002Flegal guardian(s) signed the ICF.\n5. The participant and parent(s)\u002Flegal guardian(s) are willing and able to attend trial appointments within the specified time windows.\n6. The participant is an outpatient consulting a clinician.\n7. The participant has a primary diagnosis of MDD or persistent depressive disorder and fully meet the criteria for major depressive episodes according to DSM-5-TR without psychotic features although co-morbid anxiety disorders will be permitted. The diagnoses will be confirmed using the MINI-KID.\n8. The participant has a CDRS-R total score greater than or equal to 45 at the Screening Visit and at the Baseline A Visit (Week 0).\n9. The participant has a CGI-S score greater than or equal to4 at the Screening Visit and at the Baseline A Visit (Week 0).\n10. The participant has a PHQ-A score of greater than or equal to10 at the Baseline A Visit (Week 0).\n11. The participant, if a female and is capable of producing viable ova, agrees to the following, for the period from the signing of ICF until 30 days after the last dose of trial intervention.\n\n    * To use a highly effective or acceptable contraceptive method\n    * To avoid donating ova\n12. The participant, if a female, must have a confirmed negative urine pregnancy test at the Screening Visit\n\nExclusion Criteria:\n\n1. The participant has previously been entered and moved to Phase A in this trial.\n2. The participant has participated in a clinical trial less than 30 days before the Screening Visit.\n3. The participant is a member of the trial personnel or of their immediate families or is a subordinate (or immediate family member of a subordinate) to any of the trial personnel.\n4. The participant has been previously treated with vortioxetine.\n5. The participant has the current or previous major depressive episode which was considered by the investigators to have been resistant to 2 or more adequate antidepressants treatments of at least 6-weeks duration each at sufficient doses.\n6. The participant is under forced treatment.\n7. The participant has experienced any environmental change (eg, hospitalization, change of residence) considered by the investigator to have the potential impact on the participant's disease situation or plans such environmental changes during the trial.\n8. The participant is pregnant or breast-feeding.\n9. The participant receives on-going psychotherapy (except for a supportive psychotherapy) that is started less than 3 months before the Baseline A Visit (Week 0) and\u002For that is planned to be intensified during the trial.\n10. The participant has a history of severe drug allergy or hypersensitivity or known hypersensitivity to any of the IMPs or their excipients.\n11. The participant has hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltose insufficiency.\n12. The participant has any current psychiatric disorder (DSM-5-TR criteria), including posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), autism spectrum disorder (ASD), and attention-deficit\u002Fhyperactivity disorder (ADHD) established as the primary diagnosis, as assessed using the MINI-KID.\n13. The participant has a medical history of substance use disorder (excluding nicotine, and caffeine) or alcohol use disorder (DSM-5-TR criteria) less than 6 months before the Screening Visit.\n14. The participant has reported current use of or has tested positive for drugs of abuse (opiates, methadone, cocaine, amphetamines \\[including ecstasy\\], barbiturates, benzodiazepines, and cannabinoids, etc).\n15. The participant suffers from medical, organic or drug cause mental disorders (DSM-5-TR criteria).\n16. The participant has a known intellectual disability; or clinical evidence or known social or school history indicative of intellectual disability.\n17. The participant has any other disorder for which the treatment takes priority over treatment of MDD or is likely to interfere with trial treatment or impair treatment compliance.\n18. The participant has a history of moderate or severe head trauma; or other neurological disorders or systemic medical diseases that are, in the investigator's opinion, likely to affect central nervous system functioning.\n19. The participant has a known first degree relative with a history of bipolar disorder.\n20. The participant is unable to swallow tablets.\n21. The participant has a history of cancer that has not been in remission for more than 5 years before the first dose of trial intervention.\n22. The participant has or has had 1 or more of the following conditions that is\u002Fare considered clinically relevant in the context of the trial: neurological disorder, other psychiatric disorder, cardiovascular disease, seizure disorder or encephalopathy, congestive heart failure, cardiac hypertrophy, arrhythmia, bradycardia (pulse less than 50 bpm), respiratory disease, hepatic impairment or renal insufficiency, metabolic disorder, endocrinological disorder, gastrointestinal disorder, hematological disorder, infectious disorder, any clinically significant immunological condition, dermatological disorder, venereal disease, congenital or juvenile glaucoma or is at risk of acute narrow-angle glaucoma\n23. The participant takes or has taken disallowed recent or concomitant medication, or it is anticipated that the participant will require treatment with at least one of the disallowed concomitant medications\u002Fprocedures or treatment during the trial.\n24. The participant has clinically significant abnormal vital signs at the Screening Visit.\n25. The participant has 1 or more clinical laboratory test values outside the reference range, based on the blood and urine samples taken at the Screening Visit, which are of potential risk to the participant's safety; or the participant has, at the Screening Visit:\n\n    * a serum creatinine value more than 1.5 times the upper limit of the reference range\n    * a serum total bilirubin value more than 1.5 times the upper limit of the reference range\n    * a serum ALT or AST value more than 2 times the upper limit of the reference range\n26. The participant has an abnormal TSH level. Participant with thyroid disease may be enrolled in the trial provided they are stable and euthyroid at the discretion of the investigator.\n27. The participant has, at the Screening Visit:\n\n    * an abnormal ECG that is, in the investigator's opinion, clinically significant\n    * a QTcF interval more than 450 ms (based on the Fridericia correction where QTcF = QT\u002FRR0.33)\n28. The participant has a disease or takes medication that could, in the investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with the conduct or interpretation of the trial.\n29. The participant is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.\n30. The participant has attempted suicide within the last 12 months or is at significant risk of suicide (either in the opinion of the investigator or defined as a 'yes' to suicidal ideation questions 4 or 5 or answering 'yes' to suicidal behavior questions on the C-SSRS within the last 12 months).","12 Years","17 Years",{"count":537,"type":22},180,[341],"The main aim of the study is to check how well vortioxetine 10 mg\u002Fday or 20 mg\u002Fday works and to check for side effects compared to a placebo on depression symptoms in Japanese teenagers aged 12 to 17 years with a diagnosis of Major Depressive Disorder (MDD).\n\nThe overall time each participant will be in the study is about 20 weeks. This includes up to 15 days (about 2 weeks) to check who can take part, a 14-week period where everyone receives vortioxetine or a placebo, and after that, a 4-week period to check for any side effects after treatment.\n\nDuring the study, participants will visit their clinic 13 times.",[28],[542],"Drug Therapy","2026-08-04",{"date":545,"type":33},"2026-08-05",{"date":547,"type":33},"2025-10-01",{"date":133,"type":22},{"name":550,"class":187},"Takeda",{"id":552,"slug":553,"hasResults":12,"nctId":554,"briefTitle":555,"officialTitle":556,"acronym":557,"eligibilityCriteria":558,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":431,"enrollmentInfo":559,"targetDuration":4,"studyType":23,"phases":561,"briefSummary":562,"conditions":563,"keywords":564,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":567,"lastUpdatePostDateStruct":568,"startDateStruct":570,"completionDateStruct":572,"leadSponsor":573,"locationsCount":575},"100598816","phase-3-a-randomized-study-of-azetukalner-versus-placebo-in-major-depressive-disorder-x-nova3-100598816","NCT07076407","A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder (X-NOVA3)","A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate Azetukalner in Moderate-to-Severe Major Depressive Disorder","X-NOVA3","Key Inclusion Criteria:\n\n* Adults ≥18 and ≤74 years of age and experienced their first major depressive episode (MDE) prior to 50 years of age\n* Body Mass Index (BMI) ≤40 kg\u002Fm2\n* Meets the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) criteria for current major depressive disorder and is currently in an MDE, confirmed using the Mini International Neuropsychiatric Interview (MINI)\n* Participant's current MDE has a duration of ≥6 weeks and ≤24 months.\n\nKey Exclusion Criteria:\n\n* Participant has a primary diagnosis of a mood disorder other than MDD.\n* Participant has a history of any of the following: MDD with psychotic or catatonic features; MDD with mixed features; Bipolar I or II disorder; Obsessive-compulsive disorder; Schizophrenia, primary thought disorder, or other psychotic disorder.\n* Participant has a current diagnosis of any of the following: MDD with seasonal pattern; Depression with peripartum or perimenopausal onset; Post traumatic stress disorder; Antisocial or borderline personality disorder (or presence of clinically significant borderline personality traits); Panic disorder and\u002For agoraphobia; ADHD treated with a psychostimulant, diagnosed during the current MDE, or with unstable symptoms, as judged by the investigator.\n* Participant has a substance (excluding tobacco) or alcohol use disorder within the 12 months prior to screening.\n* Participant has had an active suicidal plan\u002Fintent within the 6 months prior to screening, presence of suicidal behavior in the last 2 years, or \\>1 suicide attempt \\> 24 years of age.\n* Participant has a history of non-suicidal self-harm behavior in the 12 months prior to screening.\n* Participant has used antidepressants or other prohibited medications (including benzodiazepines), within the 2 weeks (4 weeks for fluoxetine) or within a period less than 5 times the drug's half-life, whichever is longer, prior to randomization.\n* Participant has a history of non-response to ≥2 antidepressant drugs of adequate dose and duration in the current MDE as determined by the Antidepressant Treatment Response Questionnaire (ATRQ).\n* Participants with medical conditions that may interfere with the purpose or conduct of the study\n* Participant is pregnant, breastfeeding, or planning to become pregnant.",{"count":560,"type":22},450,[341],"X-NOVA3 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD)",[28],[57,175,565,566],"XEN1101","Azetukalner","2026-07-30",{"date":569,"type":33},"2026-08-03",{"date":571,"type":33},"2025-07-08",{"date":306,"type":22},{"name":574,"class":187},"Xenon Pharmaceuticals Inc.",48,{"id":577,"slug":578,"hasResults":12,"nctId":579,"briefTitle":580,"officialTitle":556,"acronym":581,"eligibilityCriteria":582,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":431,"enrollmentInfo":583,"targetDuration":4,"studyType":23,"phases":584,"briefSummary":585,"conditions":586,"keywords":587,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":567,"lastUpdatePostDateStruct":588,"startDateStruct":589,"completionDateStruct":591,"leadSponsor":593,"locationsCount":594},"100575676","phase-3-a-randomized-study-of-azetukalner-versus-placebo-in-major-depressive-disorder-100575676","NCT06775379","A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder","X-NOVA2","Key Inclusion Criteria:\n\n* Adults ≥18 and ≤74 years of age and experienced their first major depressive episode (MDE) prior to 50 years of age\n* Body Mass Index (BMI) ≤40 kg\u002Fm2\n* Meets the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) criteria for current major depressive disorder and is currently in an MDE, confirmed using the Mini International Neuropsychiatric Interview (MINI)\n* Participant's current MDE has a duration of ≥6 weeks and ≤24 months.\n\nKey Exclusion Criteria:\n\n* Participant has a primary diagnosis of a mood disorder other than MDD.\n* Participant has a history of any of the following: MDD with psychotic or catatonic features; MDD with mixed features; Bipolar I or II disorder; Obsessive-compulsive disorder; Schizophrenia, primary thought disorder, or other psychotic disorder.\n* Participant has a current diagnosis of any of the following: MDD with seasonal pattern; Depression with peripartum or perimenopausal onset; Post traumatic stress disorder; Antisocial or borderline personality disorder (or presence of clinically significant borderline personality traits); Panic disorder and\u002For agoraphobia; ADHD treated with a psychostimulant, diagnosed during the current MDE, or with unstable symptoms, as judged by the investigator.\n* Participant has a substance (excluding tobacco) or alcohol use disorder within the 12 months prior to screening.\n* Participant has had an active suicidal plan\u002Fintent within the 6 months prior to screening, presence of suicidal behavior in the last 2 years, or \\>1 suicide attempt \\>24 years of age.\n* Participant has a history of non-suicidal self-harm behavior in the 12 months prior to screening.\n* Participant has used antidepressants or other prohibited medications (including benzodiazepines), within the 2 weeks (4 weeks for fluoxetine) or within a period less than 5 times the drug's half-life, whichever is longer, prior to randomization.\n* Participant has a history of non-response to ≥2 antidepressant drugs of adequate dose and duration in the current MDE as determined by the Antidepressant Treatment Response Questionnaire (ATRQ).\n* Participants with medical conditions that may interfere with the purpose or conduct of the study\n* Participant is pregnant, breastfeeding, or planning to become pregnant.",{"count":560,"type":22},[341],"X-NOVA2 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD)",[28],[57,175,565,566],{"date":569,"type":33},{"date":590,"type":33},"2024-12-20",{"date":592,"type":22},"2026-10",{"name":574,"class":187},51,{"id":596,"slug":597,"hasResults":12,"nctId":598,"briefTitle":599,"officialTitle":600,"acronym":601,"eligibilityCriteria":602,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":603,"enrollmentInfo":604,"targetDuration":4,"studyType":23,"phases":606,"briefSummary":607,"conditions":608,"keywords":609,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":567,"lastUpdatePostDateStruct":611,"startDateStruct":612,"completionDateStruct":614,"leadSponsor":615,"locationsCount":617},"100558159","phase-2-zelquistinel-or-placebo-for-the-reduction-of-symptoms-of-major-depressive-disorder-100558159","NCT06547489","Zelquistinel or Placebo for the Reduction of Symptoms of Major Depressive Disorder","A Phase 2, Multicenter, Randomized, Double-blind Evaluation of the Efficacy and Safety of Oral GATE-251 or Placebo for the Reduction of Symptoms of Major Depressive Disorder in Adults","GATE-251","Inclusion Criteria:\n\nEach subject must meet all of the following inclusion criteria to be eligible to participate in the study:\n\n1. Male or female subjects.\n2. Aged 18 to 64 years, inclusive.\n3. Subject has a diagnosis of major depressive disorder (MDD), single or recurrent episode, defined by the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5); if single episode, the duration must be ≥8 weeks and ≤24 months. The diagnosis of MDD will be made by a site rater and supported by the Structured Clinical Interview for DSM-5 - Clinical Trials version (SCID-5-CT) and confirmed by remote, independent raters from the Massachusetts General Hospital Clinical Trials Network and Institute with a State versus trait, Assessability, Face validity, Ecological validity, and Rule of three Ps (pervasive, persistent, and pathological) (SAFER) interview:\n\n   1. The current depressive episode is ≥8 weeks and ≤24 months in duration prior to the Screening Visit (V1);\n   2. Have an appropriate severity of illness of at least moderately ill corresponding to a CGI-S score of ≥4 at the Screening and Baseline Visits (V1 and V2, respectively); and\n   3. Importantly, have a sufficient history and\u002For independent report verifying that the current depressive episode is causing clinically significant distress or impairment in functioning.\n4. Subject has a Hamilton Depression Rating Scale-17 (HDRS-17) using the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-D) total score of ≥18 at the Screening Visit (V1) and Baseline Visit (V2) with no more than a 25% change from the Screening Visit (V1) to the Baseline Visit (V2).\n5. (Inclusion 5 removed in protocol amendment 4)\n6. (Inclusion 6 removed in protocol amendment 4)\n7. Female subjects must meet 1 of the following:\n\n   1. Surgically sterile or at least 2 years menopausal (ie, postmenopausal is defined as a woman with the absence of menses for at least 12 consecutive months). Menopausal status is to be confirmed by assessing the follicle stimulating hormone level at Screening Visit (V1), or,\n   2. If a woman of child bearing potential, subject must use an acceptable method of birth control from date of Screening to the last evaluation at Day 71. Must have a documented negative point of care urine pregnancy test within 24 hours prior to first dosing.\n8. Male subjects, including those who are surgically sterile, must use a medically acceptable form of contraception from the time of randomization until the last evaluation at Day 71. Male subjects are strongly advised to inform female partners of the need for them to use highly effective birth control during this time period.\n9. Subject must be medically stable by physical examination, medical history, vital signs, laboratory evaluations, and 12-lead electrocardiogram performed at the Screening Visit (V1) and Baseline (V2). If abnormalities are found, the subject may be included if the Investigator, contract research organization (CRO) and sponsor medical monitors judge the abnormalities to be not clinically significant.\n10. Ability to understand the nature and requirements of the study and is willing to comply with the study restrictions and agree to return for the required assessments.\n11. Provides written informed consent to participate in the trial.\n12. Is able to communicate with investigational site personnel, able to complete patient-reported outcome measures and in the opinion of the Investigator, can be reliably rated on assessment scales\n\nExclusion Criteria:\n\nAny subject who meets any of the following criteria will be excluded from study participation:\n\n1. Evidence of treatment-resistant MDD, defined by having an inadequate response (≤25%) to 2 or more different medications approved for the treatment of MDD at an adequate dose (per locally approved label) for an adequate duration during the current episode using the Massachusetts General Hospital Antidepressant Treatment Rating Questionnaire (ATRQ).\n2. Current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, obsessive compulsive disorder, borderline personality disorder, post-traumatic stress disorder, panic disorder, or attention-deficit\u002Fhyperactivity disorder. Subjects not meeting full DSM 5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded.\n3. Subject has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features.\n4. Current concomitant treatment with Food and Drug Administration (FDA)-approved antidepressants, antipsychotics, mood stabilizers, sedatives, or stimulants. Current or past treatment with esketamine, ketamine, or psychedelics is prohibited. Subject must have current concomitant treatment discontinued at least 14 days prior to the Baseline Visit (V2). Subjects may continue anxiolytic agents, except for drugs that are also used to treat depression, or benzodiazepines, or sleep aids \\[see Section 5.5.1 for a nonexhaustive list\\] (except trazodone) so long as they have been on a stable dose for at least 3 months and do not intend to change dose during double-blind treatment period (Day 1, Week 1 through end of Week 6 \\[Day 43\\]). Subjects who use cannabis or cannabis-derived molecules, including tetrahydrocannabinol (THC), whether natural or chemically-synthesized, hemp seed oil, or cannabidiol (CBD) products (eg, gummies), must be discontinued for at least 14 days prior to the Baseline Visit (V2).\n5. Treatment with any experimental antidepressant agent or treatment with a psychedelic agent in an FDA-approved clinical study within the past 12 months.\n6. History of electroconvulsive therapy, vagus nerve stimulation, deep brain stimulation, or repetitive transcranial magnetic stimulation within the past 5 years or has had a failure of response to electroconvulsive therapy at any time.\n7. Subject has clinically significant renal dysfunction as assessed by the estimated glomerular filtration rate \\\u003C70 mL\u002Fmin using the Chronic Kidney Disease Epidemiology Collaboration - creatinine (CKD-EPI creatinine) methodology.\n8. Subject has liver protein and enzyme (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, total bilirubin, lactate dehydrogenase test result \\>1.5 times the upper limit of normal (subjects with a diagnosis of Gilbert's Syndrome may be eligible if no liver function or enzyme test results other than total bilirubin are \\>1.5 times upper limit of normal).\n9. Subject has resting pulse rate (supine) \\\u003C50 or \\>100 bpm at the Screening Visit (V1) or predose Baseline (V2).\n10. Subject has resting diastolic blood pressure \\\u003C50 mmHg at the Screening Visit (V1) or predose Baseline (V2).\n11. Subject has cardiac PR interval \\>250 msec at the Screening Visit (V1) or predose Baseline (V2), or QTcF or QTcB interval \\>450 msec in males or \\>470 msec in females, or QRS interval \\>120 msec.\n12. Evidence of alcohol abuse (\\>4 units of alcohol on most days; 1 unit=½ pint of beer, 1 glass of wine, or 1 ounce of hard liquor\u002Fspirits) or a positive saliva alcohol screen at Screening (V1) and predose at the Baseline Visit (V2). Alcohol consumption should be avoided for at least 24 hours prior to Baseline Visit (V2). Note: Subject may not be rescreened.\n13. Abuse of illicit substances, including psychedelic mushrooms by DSM-5 definition of substance use disorder within the 12 months prior to the Screening Visit (V1). Positive urine test for any drug of abuse is exclusionary.\n14. Positive urine test for any drug of abuse (except cannabis or cannabis-derived molecules such as THC whether natural or chemically-synthesized \\[see exclusion criterion 4\\]). Prescribed barbiturates may be continued so long as subjects have been on a stable dose for at least 3 months and may not change dose during the double-blind treatment period. Subjects may not be rescreened after failing a drug screen for a drug of abuse.\n15. HIV infection, COVID-19 infection, or active hepatitis B or C, syphilis, or other ongoing infectious disease at the Screening Visit (V1).\n16. Has laboratory evidence of hypothyroidism at Screening (V1) as measured by thyroid stimulating hormone (TSH) and reflex free thyroxine (T4). If TSH is abnormal and reflex T4 is normal, the subject may be included.\n17. Has current unstable diabetes or glycosylated hemoglobin (HbA1c) \\>7% at Screening (V1).\n18. Currently pregnant, planning to become pregnant during the course of the study, or nursing.\n19. Currently working a night shift or may be required to work night shift during the course of this study, from Screening through completion of final polysomnography.\n20. Malignancy in the last 5 years, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.\n21. Subject has received new onset psychotherapy or had a change in the intensity of psychotherapy within 8-weeks prior to the Screening Visit (V1).\n22. Currently taking prohibited prescription or over-the-counter medications including herbal therapies (eg, echinacea, ginseng, ginko, elderberry, turmeric, ginger, valerian, chamomile, or St John's wort) and THC or cannabis-containing products \\[see exclusion criterion 4\\], which may interfere with the required study psychiatric assessments.\n23. History of allergy or sensitivity, or intolerance to zelquistinel, NMDAR ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.\n24. Treatment with any other investigational study drugs not used to treat depression within 90 days of screening in this study.\n25. Previously participated in this study or currently enrolled in any other clinical study.\n26. Body mass index of \\>35 kg\u002Fm2 at the Screening Visit (V1).\n27. Subject is an employee of Worldwide Clinical Trials (hereafter referred to as Worldwide), the Investigator or study site with direct involvement in the study or other studies under the direction of that Investigator or study site, as well as a family member of an employee or of the Investigator, or an employee of Gate Neurosciences, Inc., or a family member of an employee.\n28. In the opinion of the Investigator,\n\n    1. The subject has a significant risk for suicidal behavior during the course of participation in the study, or\n    2. At the Screening Visit (V1) (the subject scores \"Yes\" on Items 4 or 5 in the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS) with reference to a 6-month period prior to Screening Visit (V1), or\n    3. At Screening (V1) the subject has had 1 or more suicidal attempts with reference to a 2-year period prior to Screening Visit (V1), or\n    4. The subject is considered to be an imminent danger to themself or others, or\n    5. At the Baseline Visit (V2) (the subject scores \"Yes\" on Items 4 or 5 in the Suicidal Ideation section of the C-SSRS\n29. The subject is judged by the Investigator or CRO and Sponsor medical monitors to be inappropriate for the study for any reason.","64 Years",{"count":605,"type":22},164,[168],"The goal of this clinical trial is to learn if zelquistinel works to treat depression in adults. It will also learn about the safety of zelquistinel. The main questions it aims to answer are:\n\nDoes zelquistinel reduce depression scores in participants compared to participants who take a placebo (a look-alike tablet that contains no zelquistinel)?\n\nWhat medical problems are observed in participants who take zelquistinel?\n\nParticipants will take one tablet of zelquistinel or placebo every week for 6 weeks. Participants will visit the clinic every week of the 6 week period to have the severity of their depression evaluated.",[28],[610,601],"zelquistinel",{"date":569,"type":33},{"date":613,"type":33},"2025-02-03",{"date":73,"type":22},{"name":616,"class":187},"Syndeio Biosciences, Inc",34,{"id":619,"slug":620,"hasResults":12,"nctId":621,"briefTitle":622,"officialTitle":623,"acronym":4,"eligibilityCriteria":624,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":625,"targetDuration":4,"studyType":23,"phases":627,"briefSummary":628,"conditions":629,"keywords":630,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":567,"lastUpdatePostDateStruct":632,"startDateStruct":634,"completionDateStruct":636,"leadSponsor":638,"locationsCount":640},"100504619","phase-3-study-of-lumateperone-as-adjunctive-therapy-in-the-treatment-of-patients-with-major-depressive-disorder-100504619","NCT05850689","Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder","A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder","Inclusion Criteria:\n\n1. Male or female patients between the ages of 18 and 65 years, inclusive;\n2. Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmed by the Investigator or Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT) and meets all of the following criteria:\n\n   1. The start of the current major depressive episode (MDE) is at least 12 weeks but not more than 18 months prior to Screening;\n   2. Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 at Screening and at Baseline;\n   3. Has at least moderate severity of illness based on CGI-S score ≥ 4 at Screening and at Baseline;\n   4. Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥ 14 at Screening and at Baseline;\n   5. Has sufficient history and medical record confirmation verifying the ADT and the current MDE is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.\n3. Currently having an inadequate response (less than 50% improvement) to 2 or more ADTs in the current MDE as confirmed by the Investigator using the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration:\n\n   1. citalopram\u002Fescitalopram\n   2. fluoxetine\n   3. paroxetine\n   4. sertraline\n   5. duloxetine\n   6. levomilnacipran\u002Fmilnacipran (if locally approved for MDD)\n   7. venlafaxine\u002Fdesvenlafaxine\n   8. bupropion\n   9. vilazodone\n   10. vortioxetine\n\nExclusion Criteria:\n\n1. Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD, including:\n\n   1. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder;\n   2. Bipolar Disorder;\n2. Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDD including:\n\n   1. Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses. Note: Anxiety symptoms may be allowed if secondary to MDD, provided these symptoms do not require concurrent treatment;\n   2. Eating disorder;\n   3. Substance use disorders (excluding nicotine);\n   4. Personality disorder of sufficient severity to have a major impact on the patient's psychiatric status;\n   5. Within 12 months of Screening, has had any other psychiatric condition (other than MDD) that has been the main focus of treatment;\n3. The patient experiences a ≥ 25% decrease in the MADRS total score between Screening and Baseline;\n4. The patient experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening and Baseline;\n5. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during participation in the study or:\n\n   1. At Screening, the patient scores \"yes\" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline, the patient scores \"yes\" on Suicidal Ideation Items 4 or 5 since the Screening Visit;\n   2. At Screening, the patient has had 1 or more suicide attempts within 2 years prior to Screening;\n   3. At Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts), or\n   4. The patient is considered to be in imminent danger to him\u002Fherself or others.\n6. The patient has a first MDE at age 60 years or older.",{"count":626,"type":22},470,[341],"This is a multicenter, randomized, double-blind, placebo-controlled parallel-group, fixed-dose study in patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who have an inadequate response to ongoing ADT.",[28],[631],"Adjunctive MDD Therapy",{"date":633,"type":33},"2026-07-31",{"date":635,"type":33},"2023-05-02",{"date":637,"type":22},"2027-04-05",{"name":639,"class":187},"Intra-Cellular Therapies, Inc.",69]