[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"major-depressive-disorder-mdd\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:major-depressive-disorder-mdd":26},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,108,0,25,[9,46,78,114,148,177,205,239,269,290,317,338,371,394,419,439,459,476,508,537,564,592,619,643,670],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":17,"sex":18,"minAge":19,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":4,"briefSummary":24,"conditions":25,"keywords":27,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":4},"100652266","role-of-kynurenine-pathway-and-its-metabolites-in-depressive-disorders-major-depressive-disorder-is-suspected-to-have-the-greatest-burden-by-2030kynurenine-pathway-is-major-route-through-which-the-essential-amino-acid-tryptophan-is-metabolised-and-activated-in-time-of-stress-and-immune-activation-100652266",false,"NCT07771517","Role of Kynurenine Pathway and Its Metabolites in Depressive Disorders, Major Depressive Disorder is Suspected to Have the Greatest Burden by 2030,Kynurenine Pathway is Major Route Through Which the Essential Amino Acid Tryptophan is Metabolised and Activated in Time of Stress and Immune Activation.","Role of Kynurenine Pathway and Its Metabolites in Depressive Disorders","Inclusion Criteria:\n\n* age group 18: 60 years old\n* cases are drug free of at least 4 months\n\nExclusion Criteria:\n\n* patients with comorbid other psychiatric disorders( SUD,anxiety)\n* patients with IQ below 90\n* patients with psychotic features\n* patients with postpartum depression\n* patients with chronic medical illness that might affect immune function\n* patients under treatment with immune modulating therapy",true,"ALL","18 Years",{"count":21,"type":22},90,"ESTIMATED","OBSERVATIONAL","This is a case control study including simple random cases of 90 persons, 45 of them have depressive disorders and the other 45 are healthy individuals,age group between 18-60 years old, cases will be recruited from outpatient psychiatric clinic in sohag university hospital, all cases will be exposed to psychological assessment and also laboratory assessment of kynurenine metabolites by using biokits",[26],"Major Depressive Disorder (MDD)",[28,29,30,31,32,33],"Kynurenine pathway","MDD","Kynurenine pathway in depressive disorders","Depressive disorder","Bipolar disorder","Role of kynurenine pathway and its Metabolites in depressive disorders","NOT_YET_RECRUITING","2026-08-18",{"date":37,"type":38},"2026-08-20","ACTUAL",{"date":40,"type":22},"2027-03-14",{"date":42,"type":22},"2029-05-20",{"name":44,"class":45},"Sohag University","OTHER",{"id":47,"slug":48,"hasResults":12,"nctId":49,"briefTitle":50,"officialTitle":50,"acronym":51,"eligibilityCriteria":52,"healthyVolunteers":12,"sex":18,"minAge":53,"maxAge":54,"enrollmentInfo":55,"targetDuration":4,"studyType":57,"phases":58,"briefSummary":60,"conditions":61,"keywords":62,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":70,"startDateStruct":72,"completionDateStruct":74,"leadSponsor":76,"locationsCount":4},"100596306","imaging--vs-scalp-targeted-accelerated-tms-for-depression-the-number-needed-to-scan-trial-100596306","NCT07043738","Imaging- vs. Scalp-Targeted Accelerated TMS for Depression: The Number Needed to Scan Trial","NNS","Inclusion Criteria:\n\n* Age 22-80\n* English proficiency sufficient for informed consent, questionnaires\u002Ftasks, and treatment\n* Primary diagnosis of major depressive disorder per DSM-V criteria (Quick Structured Clinical Interview for DSM-5)\n\n  * \\>20 on Beck Depression Inventory (BDI)\n  * \\>20 on the Montgomery-Åsberg Depression Rating Scale (MADRS)\n  * Moderate to severe level of treatment resistance (Maudsley Staging Method)\n* Stable antidepressant medication regimen, or remain medication free, for 4 weeks prior to treatment and to remain on this regimen throughout the study until the 1-month post-treatment visit.\n* Primary clinician (e.g. psychiatrist, therapist, psychologist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial\n* Agreement to lifestyle considerations\n\n  * Abstain from becoming pregnant from screening to one-month after treatment (the MRI visit)\n  * Continue usual intake patterns of caffeine- or xanthine-containing products (e.g. coffee, tea, soft drinks, chocolate) throughout treatment\n  * Abstain from alcohol, tobacco, and recreational drugs for at least 24 hours before the start of each MRI and TMS session","22 Years","80 Years",{"count":56,"type":22},160,"INTERVENTIONAL",[59],"NA","Transcranial magnetic stimulation(TMS) is a non-invasive form of brain stimulation that is cleared by the United States Food and Drug Administration (FDA) for depression. Conventional TMS involves daily weekday treatments for 6-8 weeks. These treatments are targeted using each person's scalp measurements. With conventional TMS, approximately 50-55% of people show a 50% or more improvement in depressive symptoms (in other words, they \"respond\" to treatment).\n\nStudies are trying to make TMS work better and faster. A new form of TMS called accelerated TMS (aTMS) involves mutliple treatments a day. One specific aTMS protocol involves 10 treatments per day for 5 days. These treatments are targeted using each person's brain scan (magentic resonance imaging, MRI). With this specific aTMS protocol, approximately 70-90% of people show a 50% or more imporvement in depressive symptoms. While these results are exciting, scientists are not sure why this specific aTMS protocol works better than conventional TMS. It could be the dose and schedule of treatment, or it could be the MRI-based targeting. Answering this question is important because MRI-based targeting is expensive and difficult to do in many settings.\n\nThis study aims to determine if MRI-based targeting is better than scalp-based targeting for aTMS for depression. In this study, everyone who enrolls and meets criteria will be randomly assigned to MRI- versus scalp-based aTMS targeting.",[26],[63,64,65,66,67,68,69],"Accelerated Transcranial Magnetic Stimulation","Depression","Major Depressive Disorder","Treatment resistant depression","TMS","Transcranial Magnetic Stimulation","Neuromodulation",{"date":71,"type":38},"2026-08-19",{"date":73,"type":22},"2026-10-01",{"date":75,"type":22},"2032-10-01",{"name":77,"class":45},"Brigham and Women's Hospital",{"id":79,"slug":80,"hasResults":12,"nctId":81,"briefTitle":82,"officialTitle":83,"acronym":4,"eligibilityCriteria":84,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":85,"enrollmentInfo":86,"targetDuration":4,"studyType":57,"phases":88,"briefSummary":90,"conditions":91,"keywords":93,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":103,"lastUpdatePostDateStruct":104,"startDateStruct":106,"completionDateStruct":108,"leadSponsor":110,"locationsCount":113},"100597957","phase-2-a-study-to-evaluate-the-efficacy-and-safety-of-spt-300-glyphallo-in-participants-with-major-depressive-disorder-with-or-without-anxious-distress-buoy-1-study-100597957","NCT07065240","A Study to Evaluate the Efficacy and Safety of SPT-300 (GlyphAllo) in Participants With Major Depressive Disorder, With or Without Anxious Distress (BUOY-1 Study)","A Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Monotherapy Study of the Efficacy, Safety, and Tolerability of SPT-300 in Adults With Major Depressive Disorder (MDD), With or Without Anxious Distress","Inclusion Criteria:\n\n* Participant is a male or female between 18 and 65 years of age, inclusive willing and able and have capacity to provide written informed consent.\n* Participants must have a primary diagnosis of MDD. Participants with a diagnosis of comorbid generalized anxiety disorder, social anxiety disorder, or panic disorder (with or without agoraphobia) may be included if not the focus of treatment over the past 6 months prior to Screening and the Investigator considers MDD to be the primary diagnosis at Screening and Baseline.\n* Eligible participants must have a current depressive episode of at least 4 weeks, but no greater than 18 months in duration prior to Screening.\n* Women of childbearing potential (WOCP) must not plan to become pregnant during the course of the study or be currently breastfeeding. WOCP agree to use an acceptable form of highly effective contraception during participation in the study and for 30 days after receiving the last dose of study treatment.\n* Body mass index (BMI) between 18 to 40 kg\u002Fm2, inclusive.\n* Participant is willing and able to refrain from the use of drugs of abuse.\n\nExclusion Criteria:\n\n* History of, or current presentation consistent with:\n\n  1. any depressive episode with psychotic or catatonic features.\n  2. any bipolar manic, hypomanic or mixed episode, and substance-induced (e.g., antidepressant-induced) manic, hypomanic\u002Fmixed episode.\n  3. bipolar disorder, including history of bipolar depression, or current presentation consistent with bipolar depression.\n  4. schizophrenia, schizoaffective, or other psychotic disorder.\n  5. obsessive-compulsive disorder.\n  6. any persistent neurocognitive disorder.\n* History of treatment-resistant depression defined as 2 or more failed treatments of adequate dose and duration in the current depressive episode.\n* Psychiatric hospitalization within current depressive episode.\n* Evidence or history of clinically significant diseases which can affect the patients' participation.\n* Previous history of intolerance or significant adverse effects, including drug allergy to allopregnanolone or any components of the SPT-300\u002Fplacebo formulation.\n* Participant has a history of drug or alcohol use disorder.\n* Participants with a positive test for cannabinoids.\n* Clinically significant risk of suicide or harm to self or others.","65 Years",{"count":87,"type":22},360,[89],"PHASE2","This is a randomized, parallel-group, double-blind, placebo-controlled, monotherapy study to evaluate the efficacy, safety, and tolerability of SPT-300 (GlyphAllo) in adults with major depressive disorder (MDD), with or without anxious distress.",[26,92],"Major Depressive Disorder With Anxious Distress",[65,94,64,95,96,97,98,99,100,101],"Depressive Disorder","Anxiety","Mood Disorders","BUOY-1 Study","SPT-300","LYT-300","GlyphAllo","Glyph Allopregnanolone","RECRUITING","2026-08-14",{"date":105,"type":38},"2026-08-17",{"date":107,"type":38},"2025-06-19",{"date":109,"type":22},"2027-03",{"name":111,"class":112},"Seaport Therapeutics","INDUSTRY",62,{"id":115,"slug":116,"hasResults":12,"nctId":117,"briefTitle":118,"officialTitle":119,"acronym":120,"eligibilityCriteria":121,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":122,"enrollmentInfo":123,"targetDuration":4,"studyType":57,"phases":125,"briefSummary":127,"conditions":128,"keywords":133,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":103,"lastUpdatePostDateStruct":140,"startDateStruct":141,"completionDateStruct":143,"leadSponsor":145,"locationsCount":147},"100577061","phase-3-a-study-of-a-deuterated-psilocin-analog-cyb003-in-humans-with-major-depressive-disorder-100577061","NCT06793397","A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder","An Efficacy and Safety, Phase III, Multi-center, Double-Blind, Randomized Controlled Study Comparing 2 Active Doses of CYB003 and Placebo in Eligible Participants With Major Depressive Disorder","EMBRACE","Inclusion Criteria:\n\nParticipants must meet all the following criteria to be included in the trial:\n\n* Age18 to 85 years.\n* Participant has a diagnosis of MDD (single or recurrent episode as defined by DSM-5 TR \\[if single episode, duration of ≥4 weeks and ≤24 months\\] and established as per evaluation by the Investigator. The first MDD episode must have occurred prior to age 60.\n* Moderate to severe depression at Screening and Baseline, independently confirmed.\n* Participants have been on a stable dose of antidepressant medication (label specified) at an adequate dose in the last 4 weeks prior to Screening and has had an inadequate response (less than 50% improvement), as judged by the Investigator.\n* Participant has a body mass index (BMI) of 40 kg\u002Fm2 or less (BMI ≤40 kg\u002Fm2), inclusive, at Screening.\n* Participant is able to refrain from nicotine use during the dosing session (up to 8 hours).\n* Participants capable of producing sperm must use a condom plus spermicide during the trial and for 12 weeks after their final dose of trial medication, if their partner is a person of childbearing potential.\n* Participants of childbearing potential who have a partner capable of producing sperm must agree to use a highly effective method of contraception in combination with the use of a condom plus spermicide during the trial and for 12 weeks after their final dose of trial medication. Such participants must have a negative pregnancy test at Screening and Day 1 prior to dosing.\n* Participants of non-childbearing potential who are or were capable of producing eggs (ova) must have been postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.\n* Participants have provided written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.\n\nExclusion Criteria\n\nParticipants with any of the following characteristics\u002Fconditions will be excluded from trial participation:\n\n* Current or previously diagnosed schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder, brief psychotic disorder, current or previous history of bipolar disorder, or current borderline personality disorder.\n* Participants with a medical diagnosis of attention deficit hyperactivity disorder (ADHD) will be excluded if currently taking medication for ADHD.\n* Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type 1 (first-degree relatives).\n* Significant suicide risk within the past 6 months, during the Screening Period, or at Baseline; or (b) suicidal behaviors within 12 months of Screening; or (c) clinical assessment of significant suicidal risk during clinical interview; or (d) non-suicidal self-injury within 12 months of Screening.\n* Current or previous diagnosis of treatment-resistant MDD, defined as failure to respond to 2 or more antidepressant treatments of 2 different classes given at an adequate dose (label specified) for an adequate duration as judged by the Investigator and clinical interview.\n* Has had electroconvulsive treatment, transcranial magnetic stimulation, deep brain stimulation, or vagal nerve stimulation for any episode of MDD in the last 6 months.\n* Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressants, mirtazapine, trazodone, moclobemide, buspirone, or an antipsychotic or mood stabilizer. Note: if receiving these medications are for another indication, they must be discontinued ≥ 14 days or 5 half-lives, whichever is longer, prior to Day 1.\n* Participant report of (or if available in medical record) exposure to psilocin, or 5-HT2a receptor agonists, or any other psychedelics, such as ayahuasca, mescaline, lysergic acid diethylamide, peyote, or 3,4-methylenedioxymethamphetamine, more than 10 times over the participant's lifetime or any psychedelic use within 12 months prior to Screening.\n* Participant report of (or if available in medical record) treatment with ketamine or S-ketamine use within 6 months prior to Screening.\n* Clinically relevant history of abnormal physical health interfering with the trial (including but not limited to, neurological, cardiovascular, respiratory, gastrointestinal \\[including dyspepsia or gastroesophageal reflux disease\\], hepatic, or renal disorder).\n* Has hypothyroidism or hyperthyroidism, unless controlled on appropriate medication.\n* Current diagnosis of uncontrolled hypertension or an arrhythmia, or clinically relevant abnormal results for heart rate.\n* Participants have a presence or relevant history of organic brain disorders.\n* Participant is taking or has taken OTC doses of 5-HTP or St John's Wort within prior to trial medication administration.\n* Donation of blood or plasma within 4 weeks prior to first dosing and until 4 weeks after final dosing.\n* Participants capable of producing sperm who will not abstain from sperm donation between first dosing and 12 weeks after final dosing.\n* Participants of childbearing potential who are pregnant, breastfeeding, planning to conceive or unwilling to abstain from egg (ova) donation between first dosing and 12 weeks after final dosing.\n* History of serotonin syndrome.\n* Unwilling to consent to audio and video recording of psychological support and dosing sessions.","85 Years",{"count":124,"type":22},330,[126],"PHASE3","The purpose of this study is to determine the efficacy, safety and tolerability of CYB003 compared to matching placebo as adjunctive treatment in patients with MDD.\n\nFor more information about the EMBRACE study, including participating study locations, and to register your interest in learning more about participation, please visit the study website: https:\u002F\u002Fembrace-mdd-trial.com\u002F",[26,129,130,131,132,64],"Depression in Adults","Depression - Major Depressive Disorder","Depression Disorders","Depression Disorder",[29,134,64,65,135,136,137,138,139],"Psychedelic","CYB003","CYB003-001","CYB003-002","Psilocybin","psilocin-7438",{"date":105,"type":38},{"date":142,"type":38},"2025-12-10",{"date":144,"type":22},"2027-05-08",{"name":146,"class":112},"Cybin IRL Limited",68,{"id":149,"slug":150,"hasResults":12,"nctId":151,"briefTitle":152,"officialTitle":153,"acronym":154,"eligibilityCriteria":155,"healthyVolunteers":12,"sex":18,"minAge":53,"maxAge":156,"enrollmentInfo":157,"targetDuration":4,"studyType":57,"phases":159,"briefSummary":160,"conditions":161,"keywords":162,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":168,"lastUpdatePostDateStruct":169,"startDateStruct":170,"completionDateStruct":172,"leadSponsor":174,"locationsCount":176},"100591151","home-based-tdcs-treatment-of-major-depressive-disorder-100591151","NCT06976697","Home-Based tDCS Treatment Of Major Depressive Disorder","Safety And Efficacy of Remotely Supervised Home-Based tDCS Treatment Of Major Depressive Disorder","REACH-tDCS","In short,\n\nInclusion Criteria:\n\n* 22 - 70 years of age\n* Diagnosis of Unipolar MDD (DSM-V)\n* PHQ-9 score of ≥12 AND MADRS score of ≥ 20 at baseline\n* Antidepressant medication ongoing\n* If in psychotherapy, have maintained stable psychotherapy\n* Have access to a smartphone or other device running Android 7.0+ or iPhone Operating System (iOS) 13+\n* Be under the care of a psychiatrist or a primary care physician\n* Allow communication between the investigators\u002Fstudy staff and any healthcare provider who currently provides and\u002For has provided service to the patient\u002Fsubject within at least two years\n* Provide the name and contact of at least two adult persons who reside within a 60-minute drive of the patient's residence.\n* Be able to give voluntary, written informed consent to participate and have signed an Informed Consent Form specific to this study\n* Be willing and able to comply with all study procedures\n* Agree to meet all of the inclusion criteria throughout their participation in the study. Otherwise, the subject will be discontinued from the study\n* Be able to understand, speak, and read English sufficient for the completion of trial assessments\n\nExclusion Criteria:\n\n* Current state of mania or psychosis, or have a history of mania or psychosis.\n* Treatment resistant depression.\n* Are diagnosed with vitamin or hormonal deficiencies that may mimic mood disorders, as determined by the investigator.\n* Be currently receiving any other interventional therapy for MDD other than a stable regimen of antidepressants or psychotherapy as defined in the inclusion criteria or have a history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or other brain stimulation.\n* Have moderate or greater suicidality risk, or an attempt of suicide during lifetime or any previous hospitalization for suicidal behavior.\n* Diagnosis of sleep apnea with prescribed treatment (unless they are on CPAP treatment and are compliant with treatment) or a diagnosis of insomnia that is unrelated to depression, as determined by the investigator.\n* Have any structural lesion or any neurocranial defect or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results, as determined by the investigator.\n* Have any implant in the brain (e.g., DBS) or neurocranium, or any other active implantable medical device anywhere in the body (e.g. pacemaker, insulin pump).\n* Have a history of epilepsy or seizures.\n* Have shrapnel or any ferromagnetic material in the head.\n* Have any disorder that would impair the ability to complete the study questionnaires.\n* Have been diagnosed with autism spectrum disorder.\n* Have an alcohol use disorder or substance use disorder (past 12 months).\n* Have a cognitive impairment (including dementia).\n* medications that affect cortical excitability, as determined by the investigator.\n* Have ever taken esketamine \u002F ketamine for treatment of depression.\n* Are currently admitted or have ever been admitted to a dedicated psychiatric ward for depression for a period of more than 24 hours.\n* Have ever been diagnosed with obsessive-compulsive disorder (OCD) or bipolar type 1 or 2 disorder.\n* Be diagnosed with PTSD, agoraphobia, anorexia or bulimia, panic or personality disorder, with active symptoms, based on the investigator's judgment.\n* Have any history of myocardial infarction, coronary artery bypass graft (CABG), coronary heart failure (CHF), or history of other cardiac issues.\n* Be currently experiencing or have a history of intractable migraines.\n* Be a chronic nicotine user.\n* Be currently pregnant or breastfeeding or planning to become pregnant or breastfeed any time during the study, or lack a medically acceptable method of contraception in females with child-bearing potential.\n* Be currently incarcerated.\n* Be participating concurrently in another clinical investigation or have participated in a clinical investigation within the last 90 days or intend to participate in another clinical investigation during the study.\n* Have a hairstyle or hair type, such as very thick hair or voluminous hairstyle, that would prevent wearing of the treatment cap tightly enough on the head that the electrodes are held close to the scalp.","70 Years",{"count":158,"type":22},200,[59],"The REACH-tDCS study will evaluate the safety and efficacy of a noninvasive, at-home self-administered Sooma tDCS brain stimulation treatment for Major Depressive Disorder. The study uses randomized, blinded, placebo controlled design. The participants are assessed with video interviews and self-reports during the study, which lasts for 10 weeks followed by an optional continuation period.",[26],[64,163,164,165,166,167],"Brain stimulation","Brain","Sooma","tDCS","tES","2026-08-13",{"date":103,"type":38},{"date":171,"type":38},"2025-06-27",{"date":173,"type":22},"2026-12-23",{"name":175,"class":112},"Sooma Medical Inc",1,{"id":178,"slug":179,"hasResults":12,"nctId":180,"briefTitle":181,"officialTitle":182,"acronym":183,"eligibilityCriteria":184,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":185,"enrollmentInfo":186,"targetDuration":4,"studyType":57,"phases":188,"briefSummary":189,"conditions":190,"keywords":191,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":195,"lastUpdatePostDateStruct":196,"startDateStruct":198,"completionDateStruct":200,"leadSponsor":202,"locationsCount":204},"100639900","phase-2-a-study-to-evaluate-the-effectiveness-of-dt-101-as-an-adjunctive-treatment-in-patients-with-depression-100639900","NCT07610473","A Study to Evaluate the Effectiveness of DT-101 as an Adjunctive Treatment in Patients With Depression","A Phase 2 Double-blind, Randomised, Placebo-controlled Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of DT-101 in Adults With Major Depressive Disorder Receiving Pharmacological Therapy for Depression","AERON-1","Inclusion Criteria:\n\n* The participant is able to read, understand and communicate in the local language used at the study site, and is willing to provide written informed consent\n* Male or female (assigned at birth, inclusive of all gender identities) participant must be 18 to 75 years of age, inclusive at the time of signing the informed consent.\n* Has recurrent depression (defined as at least one prior episode excluding the current one), as diagnosed by DSM 5-TR (Diagnostic and Statistical Manual of Mental Disorders, 2022).\n\nExclusion Criteria:\n\n* Pregnant or breastfeeding or plans to become pregnant during the study.\n* Unstable medical condition or unstable chronic disease.\n* Significant neurological abnormality.\n* History of moderate or severe alcohol or drug use disorder as per DSM-5-TR in the 6 months prior to Screening.\n* History of seizure.\n* In the investigator's opinion, the participant is not capable of adhering to the protocol requirements.","75 Years",{"count":187,"type":22},118,[89],"In this study, researchers will learn more about a study drug called DT-101 in participants with Major Depressive Disorder (MDD), a form of depression. The goal of this clinical trial is to learn if DT-101 can treat depression in adults. The effect of DT-101 will be compared to placebo. A placebo looks the drug but contains no medicine. Subjects will attend the clinic for complete general health checks and to complete questionnaires.",[26],[29,64,192,193,194,65],"DT-101","Randomized","Placebo Controlled","2026-08-11",{"date":197,"type":38},"2026-08-12",{"date":199,"type":38},"2026-05-14",{"date":201,"type":22},"2027-05",{"name":203,"class":112},"Draig Therapeutics Ltd",22,{"id":206,"slug":207,"hasResults":12,"nctId":208,"briefTitle":209,"officialTitle":210,"acronym":211,"eligibilityCriteria":212,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":85,"enrollmentInfo":213,"targetDuration":4,"studyType":57,"phases":215,"briefSummary":216,"conditions":217,"keywords":219,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":230,"lastUpdatePostDateStruct":231,"startDateStruct":233,"completionDateStruct":235,"leadSponsor":237,"locationsCount":176},"100621853","ketogenic-diet-and-neuromodulation-in-treatment-resistant-depression-100621853","NCT07376018","Ketogenic Diet and Neuromodulation in Treatment Resistant Depression","Adjunctive Low-carb Ketogenic Diet to Enhance Imaging-guided Neuromodulation in Treatment Resistant Depression","ALIGN","Inclusion Criteria:\n\n* Age 18-65 of any sex, gender identity, ethnicity and socioeconomic status\n* Currently experiencing a major depressive episode as defined by DSM-5-TR criteria and confirmed by a study physician\n* Presenting with at least moderate symptom severity (PHQ ≥ 10)\n* Meeting criteria for treatment-resistant depression (TRD), defined as either: (1) failure to achieve a clinical response to ≥2 adequate antidepressant treatment trials for unipolar depression, OR (2) inability to tolerate ≥2 separate antidepressant treatment trials for unipolar depression, as assessed using the Antidepressant Treatment History Form (ATHF), with a score of ≥3 in the current episode\n* No rTMS treatment received in the current depressive episode (prior rTMS in a previous episode is permitted); no failure to respond to a course of electroconvulsive therapy (ECT) in the current depressive episode\n* Able to provide informed consent\n* Available for the 12-week intervention and willing to follow either a ketogenic or Canadian Food Guide-aligned diet\n* No increase or initiation of any antidepressant or antipsychotic medication in the 4 weeks prior to screening\n\nExclusion Criteria:\n\n* Concomitant major unstable medical illness as determined by a study physician\n* Lifetime diagnosis of bipolar I or bipolar II disorder, or a primary psychotic disorder, as confirmed by a structured psychiatric interview\n* Current psychotic symptoms\n* Diagnosis of obsessive-compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalised anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD\n* Diagnosis of any personality disorder assessed by a study investigator to be primary and\u002For causing greater impairment than MDD\n* History of epilepsy, stroke, or major neurological conditions, or a history of a primary seizure disorder or a seizure associated with an intracranial lesion\n* Physical or cognitive disability interfering with participation\n* Pregnancy, nursing, or intent to become pregnant during study\n* BMI \\\u003C 20 kg\u002Fm²\n* Suicide attempts in the past 12 months\n* Active suicidal intent as confirmed by study psychiatrist\n* Active eating disorder in the past 12 months\n* Currently following a Ketogenic diet\n* Habitual low-carb diet in the past 6 months\n* GI disorders or food allergies incompatible with dietary protocols\n* Alcohol use \\>3 drinks\u002Fday or \\>14\u002Fweek\n* Use of anticonvulsants (benzodiazepines with a dose of \\\u003C2 lorazepam equivalents will be permitted), GABA agonists, or medications reducing TMS efficacy\n* Contraindications to MRI\n* Unwillingness to perform daily finger-stick testing\n* Inability to access or prepare KD-compliant foods if assigned\n* Unable to provide informed consent on their own",{"count":214,"type":22},60,[59],"The goal of this clinical trial is to learn if combining a ketogenic diet with a personalized, accelerated brain stimulation treatment (iTBS) works better than iTBS with a standard healthy diet to reduce depression symptoms in adults with treatment-resistant depression. The main questions it aims to answer are:\n\n* Does iTBS combined with a ketogenic diet improve depression symptoms more than iTBS combined with a standard healthy diet?\n* Does the ketogenic diet change ketone levels over time?\n* Is it safe, tolerable, and feasible to follow a ketogenic diet during accelerated iTBS treatment?\n\nWe will compare a ketogenic diet to a Canadian Food Guide-aligned diet, both combined with iTBS, measuring depression severity using standard clinician-rated and self-report scales.\n\nParticipants will:\n\n* Follow either a ketogenic diet or a standard healthy diet for 12 weeks, starting with a 3-week lead-in period before iTBS begins\n* Undergo a course of personalized, imaging-guided accelerated iTBS while continuing their assigned diet\n* Complete clinical and cognitive assessments, blood tests, and brain MRI scans before and after treatment\n* Have their ketone levels checked regularly throughout the 12-week period",[26,218],"Treatment Resistant Depression (TRD)",[65,29,220,67,221,222,223,68,224,225,226,227,228,229],"TRD","Glucose Control","Ketogenic Diet","Metabolic Health","iTBS","Dietary Intervention","Metabolic Psychiatry","MRS","fMRI","Intermittent Theta-Burst Stimulation","2026-08-04",{"date":232,"type":38},"2026-08-07",{"date":234,"type":22},"2026-08",{"date":236,"type":22},"2028-01",{"name":238,"class":45},"Sunnybrook Health Sciences Centre",{"id":240,"slug":241,"hasResults":12,"nctId":242,"briefTitle":243,"officialTitle":244,"acronym":245,"eligibilityCriteria":246,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":85,"enrollmentInfo":247,"targetDuration":4,"studyType":57,"phases":249,"briefSummary":250,"conditions":251,"keywords":253,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":230,"lastUpdatePostDateStruct":260,"startDateStruct":262,"completionDateStruct":264,"leadSponsor":266,"locationsCount":268},"100614828","phase-2-acp-211-monotherapy-for-major-depressive-disorder-with-inadequate-antidepressant-response-100614828","NCT07284667","ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response","A Double-Blind, Placebo-Controlled, Parallel Group, Efficacy and Safety Study of ACP-211 Monotherapy in Adults With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment","NORLIGHT","Inclusion Criteria:\n\n* Adults ≥18 and ≤65 years of age\n* Provides written informed consent\n* Clinical diagnosis of MDD\n* History of inadequate response to at least two antidepressants, with at least one inadequate response documented during the current episode\n* Currently treated with an approved antidepressant at a stable dose prior to Screening\n* MADRS total score ≥28, CGI-S score ≥4 , and QIDS-SR16 score ≥16 at Screening and Baseline\n* Females of childbearing potential must have a negative pregnancy test and agree to use acceptable contraception; males must agree to use barrier protection and refrain from sperm donation\n\nExclusion Criteria:\n\n* Current diagnosis of certain personality disorders or persistent depressive disorder\n* Recent substance use disorders, excluding caffeine or nicotine\n* Active suicidal risk or recent suicidal attempt\n* History of schizophrenia, psychotic disorders, bipolar disorder, or MDD with psychotic features\n* Current treatment requirement for PTSD, acute stress disorder, panic disorder, or OCD\n* History of neuroleptic malignant syndrome, serotonin syndrome, or epilepsy (except single febrile seizure in infancy)\n* Allergy or sensitivity to ketamine or esketamine\n* Significant cardiovascular disease\n* Positive history of hepatitis B, hepatitis C, or HIV infection\n* Unstable diabetes or uncontrolled medical conditions\n* Positive urine drug test for an illicit drug or cannabis\n* Received neuromodulation therapies (ECT, TMS, VNS, DBS) in the current depressive episode\n* Recent initiation or change in psychotherapy\n\nAdditional inclusion\u002Fexclusion criteria apply. Participants will be evaluated at Screening to ensure that all criteria for study participation are met.",{"count":248,"type":22},153,[89],"The goal of this clinical trial is to learn if ACP-211 can help treat adults with major depressive disorder (MDD) who have not improved with antidepressant therapy (ADT), including those with treatment resistant depression (TRD).\n\nThe main questions the study aims to answer are:\n\n* Does ACP-211 work better than a placebo (a look-alike capsule with no medicine) to reduce symptoms of depression?\n* What adverse events do participants have when taking ACP-211?",[26,252],"Depressive Disorder, Treatment-Resistant",[26,252,254,255,256,257,258,259],"Antidepressive Agents","Randomized Controlled Trial","Double-Blind Method","Clinical Trial, Phase II","Psychiatric Status Rating Scales","Ketamine",{"date":261,"type":38},"2026-08-06",{"date":263,"type":38},"2025-11-14",{"date":265,"type":22},"2027-09",{"name":267,"class":112},"ACADIA Pharmaceuticals Inc.",26,{"id":270,"slug":271,"hasResults":12,"nctId":272,"briefTitle":273,"officialTitle":274,"acronym":4,"eligibilityCriteria":275,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":276,"enrollmentInfo":277,"targetDuration":4,"studyType":57,"phases":278,"briefSummary":279,"conditions":280,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":281,"lastUpdatePostDateStruct":282,"startDateStruct":284,"completionDateStruct":286,"leadSponsor":288,"locationsCount":176},"100650017","context-guided-personalized-itbs-for-depression-100650017","NCT07743398","Context-Guided Personalized iTBS for Depression","Research on Intelligent Optimization of Neuromodulation for Depression Based on Contextual Neuroimaging","Inclusion Criteria:\n\n* Male or female outpatients or inpatients aged 18 to 55 years, inclusive.\n* Right-handed.\n* Diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed using the Mini International Neuropsychiatric Interview (MINI). Both first and recurrent depressive episodes are eligible.\n* A 17-item Hamilton Depression Rating Scale (HAMD-17) total score of at least 14 at both screening and baseline.\n* At enrollment, participants may be antidepressant-free or may have received an antidepressant at no less than the minimum effective dose for at least 4 weeks. The antidepressant may be combined with no more than two other medications, and the type and dosage of medications must remain unchanged from enrollment until study completion.\n* At least primary school education and able to understand the study procedures and requirements.\n* Able to undergo magnetic resonance imaging and intermittent theta burst stimulation safely.\n* Voluntarily agrees to participate and provides written informed consent.\n\nExclusion Criteria:\n\n* Serious or unstable medical or neurological illness.\n* Pregnancy or breastfeeding.\n* History of seizure, epilepsy, hydrocephalus, or central nervous system tumor.\n* Contraindication to magnetic resonance imaging, including claustrophobia, an electronic or metallic implant, or a non-removable metallic dental prosthesis.\n* Receipt of systematic modified electroconvulsive therapy, transcranial magnetic stimulation, deep brain stimulation, vagus nerve stimulation, or another physical neuromodulation treatment within 3 months before screening.\n* Excessive head motion during MRI scanning (rotation exceeding 3.0° and\u002For translation exceeding 3 mm)\n* Resting motor threshold remaining at or above 70% of the device maximum stimulator output after repeated testing, when the investigator considers continued treatment to present a safety concern.","55 Years",{"count":214,"type":22},[59],"The goal of this randomized clinical trial is to learn whether context-guided personalized intermittent theta burst stimulation (iTBS) works better than standard iTBS for adults with major depressive disorder. iTBS is a noninvasive treatment that uses magnetic pulses to stimulate specific areas of the brain.\n\nParticipants will be assigned by chance to one of two treatment groups. The standard treatment group will receive iTBS at a commonly used target in the left dorsolateral prefrontal cortex after watching a neutral video. The personalized treatment group will receive iTBS at an individual brain target selected using magnetic resonance imaging data. Before each treatment session, participants in this group will watch a positive emotional video intended to activate brain functions related to the selected target.\n\nBoth groups will receive five iTBS sessions per day for five consecutive treatment days. Participants will continue their stable antidepressant treatment during the study.\n\nThe main question is whether context-guided personalized iTBS results in a higher treatment response rate than standard iTBS two weeks after treatment. Treatment response is defined as a reduction of at least 50% from baseline in the 17-item Hamilton Depression Rating Scale score.\n\nResearchers will also compare early changes in depression, anxiety and other clinical symptoms, changes in brain imaging measures, and any side effects. Clinical and brain imaging assessments will be conducted before and after the treatment course, and clinical symptoms will be assessed again two weeks after treatment.",[26],"2026-08-03",{"date":283,"type":38},"2026-08-05",{"date":285,"type":22},"2026-09",{"date":287,"type":22},"2027-10-30",{"name":289,"class":45},"Capital Medical University",{"id":291,"slug":292,"hasResults":12,"nctId":293,"briefTitle":294,"officialTitle":295,"acronym":296,"eligibilityCriteria":297,"healthyVolunteers":17,"sex":18,"minAge":19,"maxAge":185,"enrollmentInfo":298,"targetDuration":4,"studyType":23,"phases":4,"briefSummary":300,"conditions":301,"keywords":303,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":281,"lastUpdatePostDateStruct":309,"startDateStruct":310,"completionDateStruct":312,"leadSponsor":314,"locationsCount":316},"100615616","prediction-of-response-to-depression-interventions-accelerated-rtms-using-clinical-and-td-fnirs-measurements-100615616","NCT07294924","Prediction of REsponse to Depression Interventions (Accelerated rTMS) Using Clinical and TD-fNIRS Measurements","PREDICT-ACC: Prediction of REsponse to Depression Interventions (Accelerated rTMS) Using Clinical and TD-fNIRS Measurements","PREDICT-ACC","Inclusion Criteria for:\n\nAccelerated TMS cohort\n\n* Adults aged 18-75 at the time of enrollment\n* Primary diagnosis of MDD as defined by the DSM-5\n* Determined by the clinic to be eligible for accelerated rTMS treatment and agrees to receive accelerated rTMS treatment\n* Agrees to start accelerated rTMS treatment in conjunction with study participation to capture baseline measurements\n* Has not received rTMS treatment in the past 1 month\n* Has not received SPRAVATO treatment in the past 1 month\n* Can speak and understand English\n* Ability to provide informed consent\n\nHealthy controls cohort\n\n* Adults aged 18-75 at time of enrollment\n* Can speak and understand English\n* Ability to provide informed consent\n\nExclusion Criteria for:\n\nAll cohorts\n\n* Pregnant or may become pregnant during the treatment course\n* Unable or unwilling to wear the fNIRS headset\n* Has had electroconvulsive therapy (ECT) in the past 3 months\n* Major medical illnesses including neurological and psychiatric conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, schizophrenia, or stroke.\n* Any other clinically significant medical condition that in the opinion of the clinician or study team, could affect patient safety, wellbeing, or the participant's ability to comply with study procedures.\n* Not an appropriate candidate for the study based on the discretion of the study investigator(s).\n\nHealthy controls cohort only\n\n* Clinical diagnosis of depression in the past year\n* Undergoing any treatments for depression in the past year",{"count":299,"type":22},100,"This observational, longitudinal, multi-cohort study aims to evaluate functional brain activity in adults undergoing treatment for Major Depressive Disorder (MDD) at participating clinical sites. A separate cohort of healthy adults will be enrolled as a control group. All data collected in this study are for research purposes only and will not influence clinical decision-making or treatment plans.\n\nThis study will use TD-fNIRS to measure hemodynamic brain responses at rest and\u002For during tasks in patients receiving accelerated transcranial magnetic stimulation (TMS). Imaging will occur at multiple timepoints (pre-treatment, post-treatment, and follow-ups). Healthy control participants will complete similar measurements at one visit, with the option for a follow-up visit. The primary objectives are to assess feasibility, characterize brain activity patterns, and explore potential biomarkers associated with treatment response.",[26,302],"fNIRS",[304,305,306,307,308],"Accelerated TMS","Healthy Controls","Observational","Longitudinal","Neuroimaging",{"date":283,"type":38},{"date":311,"type":38},"2026-01-01",{"date":313,"type":22},"2026-12-15",{"name":315,"class":112},"Kernel",2,{"id":318,"slug":319,"hasResults":12,"nctId":320,"briefTitle":321,"officialTitle":322,"acronym":4,"eligibilityCriteria":323,"healthyVolunteers":12,"sex":18,"minAge":324,"maxAge":85,"enrollmentInfo":325,"targetDuration":4,"studyType":57,"phases":327,"briefSummary":329,"conditions":330,"keywords":4,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":281,"lastUpdatePostDateStruct":331,"startDateStruct":332,"completionDateStruct":334,"leadSponsor":336,"locationsCount":176},"100576665","early-phase-1-pilot-study-establishing-glutamatergic-changes-in-rapid-antidepressant-effects-of-ketamine-100576665","NCT06788249","Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Ketamine","Establishing Glutamatergic Changes as the Mechanism of Action in the Rapid Antidepressant Effects of Ketamine","Inclusion Criteria:\n\n1. Age between 25 and 65 years;\n2. Current depression as assessed on the SCID;\n3. Treatment-resistant depression, as defined by failure of at least two previous antidepressant or mood stabilizing treatments within the current depressive episode. Failed antidepressant or mood stabilizing treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks\n4. Able to comprehend English, as all questionnaires are in this language\n5. Ability to provide informed consent Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria.\n\nExclusion Criteria:\n\n1. A sleep disorder other than insomnia, as determined by history;\n2. History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia and other psychotic disorders as assessed on the SCID;\n3. Alcohol or drug abuse in the past year based upon the SCID or urine toxicology screen;\n4. A current smoker;\n\n4\\) Any significant medical or neurological illness that impacts brain function or impedes participation; 5) History of head trauma with significant loss of consciousness; 6) Metallic implants, pacemakers or tattoos, or other contraindications to MRI; Claustrophobic, or intolerant of the scanner environment; 7) For women, pregnancy will exclude participation. 8) Untreated hypertension\n\nBased on ketamine's known difficulties with induction of perceptual\u002Fpsychomimetic symptoms, exclusion criteria for this study are as follows:\n\n1. Patients with a BMI over 40.\n2. Ongoing prescription of 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment;\n3. Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression;\n4. Use of any MAOI is prohibited two weeks prior to administration of study drug; if patients are on an MAOI when enrolled, study drug will not be administered until two weeks off MAOI;\n5. CYP3A4 inducers carbamazepine and modafinil are prohibited two weeks prior to administration of study drug and at least 24 hours after last dose of study drug.\n6. Current use of Naltrexone;\n7. Developmental delay, mental retardation, or intellectual disorder;\n8. Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months;\n9. Prior participation in another study of ketamine for depression\n10. Prior treatment and\u002For recreational use of ketamine","25 Years",{"count":326,"type":22},10,[328],"EARLY_PHASE1","In the treatment of Major Depressive Disorder (MDD), ketamine can produce rapid but short-lasting improvements in mood. In order to develop a new generation of treatments with rapid and sustained efficacy, a better understanding of the mechanism of action is urgently needed. One candidate mechanism is the modulation of synaptic strength mediated by glutamatergic activity as ketamine has been suggested to increase synaptic strength. Although determining how ketamine impacts the glutamatergic system is essential to isolating its mechanism of action, the invasive nature of most assessment methods has limited our ability to do so in humans. The proposed research aims to determine if changes in glutamatergic activity, reflecting the modulation of synaptic strength, underlie the antidepressant effects of ketamine. In this project, the investigators will utilize a novel measure of glutamate imaging, GluCEST, to assess changes in glutamatergic activity to assess synaptic strength following ketamine administration. Ten individuals (aged 25-65) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging prior to and following ketamine infusion. Both clinician-administered and subjective mood measures will be collected. It is predicted that ketamine will improve mood and increase glutamatergic activity and synaptic strength. Results from this project have the potential to identify the modifiable mechanisms by which rapid antidepressants work which could ultimately stimulate the development of novel interventions that work through the modulation of glutamatergic activity.",[26],{"date":230,"type":38},{"date":333,"type":38},"2026-04-01",{"date":335,"type":22},"2026-09-15",{"name":337,"class":45},"University of Pennsylvania",{"id":339,"slug":340,"hasResults":12,"nctId":341,"briefTitle":342,"officialTitle":343,"acronym":4,"eligibilityCriteria":344,"healthyVolunteers":17,"sex":18,"minAge":19,"maxAge":345,"enrollmentInfo":346,"targetDuration":347,"studyType":23,"phases":4,"briefSummary":348,"conditions":349,"keywords":358,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":365,"lastUpdatePostDateStruct":366,"startDateStruct":367,"completionDateStruct":368,"leadSponsor":369,"locationsCount":176},"100650371","eeg-microstate-parameters-and-neuroinflammatory-biomarkers-in-patients-with-treatment-resistant-major-depressive-disorder-receiving-ect-100650371","NCT07748091","EEG Microstate Parameters and Neuroinflammatory Biomarkers in Patients With Treatment-Resistant Major Depressive Disorder Receiving ECT","The Relationship of EEG Microstate Parameters and Neuroinflammatory Biomarkers With Treatment Response in Patients With Treatment-Resistant Major Depressive Disorder Receiving Electroconvulsive Therapy","Inclusion Criteria:\n\nPatient Group\n\n* Age 18-60 years\n* Diagnosis of Major Depressive Disorder, current major depressive episode, according to DSM-5 criteria.\n* Clinical indication for electroconvulsive therapy (ECT).\n* Ability to provide written informed consent.\n* Willingness to participate in the study.\n\nHealthy Control Group:\n\n* Age ≥55 years.\n* No current psychiatric disorder.\n* No known neurological disorder.\n* Good general physical health.\n* No current use of medications known to affect EEG activity or inflammatory biomarkers significantly.\n* Ability to provide written informed consent.\n* Willingness to participate in the study.\n\nExclusion Criteria:\n\n* Primary neurological disorders (e.g., dementia or traumatic brain injury).\n* Schizophrenia or other psychotic disorders.\n* Bipolar disorder diagnosis,\n* Intracranial space-occupying lesions.\n* Increased intracranial pressure.\n* Myocardial infarction within the previous 3 months.\n* Cerebrovascular disease within the previous month.\n* Unstable cerebral aneurysm.\n* Pheochromocytoma.\n* Electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the previous month.\n* Cognitive impairment severe enough to prevent adequate cooperation during EEG recording.\n* Current alcohol or substance use disorder.\n* Active infectious disease.\n* Autoimmune or chronic inflammatory disorders.\n* Current use of systemic corticosteroids, immunosuppressive agents, or other medications known to affect inflammatory biomarkers significantly.","60 Years",{"count":113,"type":22},"2 Months","This study aims to investigate the neurophysiological and inflammatory changes associated with electroconvulsive therapy (ECT) in patients diagnosed with Major Depressive Disorder who are resistant to at least two antidepressant treatments, using microstate analysis derived from resting-state electroencephalography (EEG) recordings. Within this scope, EEG recordings obtained before and after ECT will be compared to determine the relationships between changes in microstate parameters and inflammatory marker levels, clinical variables, and psychometric scale scores reflecting clinical improvement.\n\nPeripheral blood samples collected from the same patient group will be analyzed for complete blood count parameters as well as levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), soluble glycoprotein 130 (sgp-130), soluble interleukin-6 receptor (sIL-6R), interferon gamma-induced protein 10 kDa (IP-10), and C-reactive protein (CRP). In addition, inflammatory indices, including the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR), will be calculated. The association between baseline levels of these biomarkers and treatment response will be evaluated. Moreover, changes in biomarker levels following ECT will be statistically examined in relation to clinical scale scores and EEG microstate parameters.\n\nAlthough microstate analysis and inflammatory biomarkers have each been extensively investigated in psychiatric disorders, studies evaluating these two biomarkers together, particularly with the inclusion of healthy control participants, remain limited. In this regard, the present study aims to evaluate the effects of ECT on patients with treatment-resistant depression using objective neurophysiological indicators, to contribute to the understanding of the pathophysiology of depression at the level of brain networks, and to provide a scientific basis for the development of personalized treatment approaches in the future.",[350,351,352,353,354,355,356,357],"Major Depression Moderate","Major Depression Severe","Major Depression With Comorbid Anxiety Symptoms","Major Depression With Panic Attacks","Major Depression With Psychotic Features","Major Depressive Episode","Major Depressive Disorder (MDD","Major Depression",[359,360,361,362,363,364,357,355],"ECT","EEG","Treatment Resistant Depression","Difficult to Treat Depression","Microstate","Inflammatory biomarker","2026-07-31",{"date":283,"type":38},{"date":311,"type":38},{"date":109,"type":22},{"name":370,"class":45},"Istanbul University - Cerrahpasa",{"id":372,"slug":373,"hasResults":12,"nctId":374,"briefTitle":375,"officialTitle":376,"acronym":377,"eligibilityCriteria":378,"healthyVolunteers":17,"sex":18,"minAge":379,"maxAge":380,"enrollmentInfo":381,"targetDuration":383,"studyType":23,"phases":4,"briefSummary":384,"conditions":385,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":386,"lastUpdatePostDateStruct":387,"startDateStruct":388,"completionDateStruct":390,"leadSponsor":392,"locationsCount":176},"100649449","imore-study-a-multi-omics-cohort-study-of-major-depressive-disorder-100649449","NCT07735143","iMORE+ Study: A Multi-Omics Cohort Study of Major Depressive Disorder","iMORE+ Study: An Enhanced Prospective Observational Cohort Study of Major Depressive Disorder Integrating Longitudinal Clinical Characterization and Multi-Omics Profiling","iMORE+","Inclusion Criteria:\n\nGeneral criteria:\n\n* Participants aged 14-45 years.\n* Participants are able to understand the study procedures and provide written informed consent. For participants younger than 18 years, both the participant and their legal guardian must provide consent.\n\nMajor Depressive Disorder (MDD) cohort:\n\n* Meet DSM-5 criteria for major depressive disorder (single or recurrent episode).\n* Have a baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥24 and 17-item Hamilton Depression Rating Scale (HAMD-17) score ≥18.\n\nHealthy Control (HC) cohort:\n\n\\- Healthy participants without a current or lifetime diagnosis of major psychiatric disorders.\n\nExclusion Criteria:\n\nFor all participants:\n\n\\- Severe or unstable medical conditions, pregnancy or breastfeeding, or other conditions considered unsuitable for study participation.\n\nFor the MDD cohort:\n\n* Current or lifetime diagnosis of other major psychiatric disorders, including schizophrenia spectrum disorders, schizoaffective disorder, or bipolar disorder.\n* Substance use disorder within 12 months prior to screening.\n* Depression secondary to medical or neurological conditions.\n* Regular antidepressant treatment within 2 weeks prior to enrollment.\n* Electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation (VNS), or immunosuppressive therapy during the current depressive episode.\n* Current active suicidal plan or recent suicidal behavior considered unsuitable for participation.\n\nFor the HC cohort:\n\n* Current or lifetime diagnosis of any psychiatric disorder.\n* Significant depressive, anxiety, manic, or psychotic symptoms.\n* Previous treatment with antidepressants, antipsychotics, or mood stabilizers.\n* Significant family history of major psychiatric disorders.","14 Years","45 Years",{"count":382,"type":22},150,"1 Year","Major depressive disorder (MDD) is a common mental health condition characterized by substantial clinical heterogeneity and variability in treatment response. Current diagnosis and treatment selection for MDD mainly rely on clinical assessments, and reliable biological markers that can support diagnosis, predict antidepressant treatment response, guide personalized treatment, and improve understanding of disease mechanisms remain limited.\n\nThe goal of this prospective observational cohort study is to develop and optimize multi-omics-based models for MDD diagnosis and antidepressant treatment response prediction using longitudinal clinical characteristics and biological data collected from an independent prospective cohort. The study also aims to evaluate the generalizability and predictive performance of existing multi-omics-based models in this independent cohort of participants aged 14-45 years.\n\nThe main questions it aims to answer are:\n\nCan integrated clinical and multi-omics features identify biomarkers and develop predictive models for MDD diagnosis and antidepressant treatment response? Can existing multi-omics-based models for MDD diagnosis and treatment response prediction be replicated and validated in an independent prospective cohort?\n\nParticipants with MDD and healthy controls will undergo standardized clinical assessments, longitudinal follow-up, and biological sample collection for multi-omics profiling. Clinical and multi-omics data will be integrated to identify biomarkers, develop and validate predictive models for MDD diagnosis, antidepressant treatment response, and long-term outcomes, and explore biological pathways and potential therapeutic targets associated with MDD.\n\nThe study is expected to improve understanding of the biological heterogeneity of MDD and contribute to the development of objective approaches for diagnosis, treatment response prediction, personalized care, and future therapeutic discovery.",[26],"2026-07-30",{"date":281,"type":38},{"date":389,"type":22},"2027-09-01",{"date":391,"type":22},"2028-02-01",{"name":393,"class":45},"Shanghai Mental Health Center",{"id":395,"slug":396,"hasResults":12,"nctId":397,"briefTitle":398,"officialTitle":399,"acronym":4,"eligibilityCriteria":400,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":401,"enrollmentInfo":402,"targetDuration":4,"studyType":57,"phases":404,"briefSummary":406,"conditions":407,"keywords":408,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":386,"lastUpdatePostDateStruct":413,"startDateStruct":414,"completionDateStruct":415,"leadSponsor":417,"locationsCount":176},"100603637","phase-4-understanding-the-role-of-the-kappa-opioid-receptor-in-ketamines-attenuation-of-suicidal-thoughts-100603637","NCT07139106","Understanding the Role of the Kappa Opioid Receptor in Ketamine's Attenuation of Suicidal Thoughts","Dynorphin\u002FKappa Opioid Receptor Signaling Role in Ketamine's Anti-suicidal Ideation Effect","Inclusion Criteria:\n\n* DSM5 unipolar major depressive episode\n* Persons of child-bearing potential must agree to use an acceptable method of birth control throughout the study.\n\nExclusion Criteria:\n\n* Current or past ketamine abuse or dependence ever (lifetime)\n* Any medical contraindication to ketamine, including prior ineffective trial of or medically significant adverse reaction to ketamine.\n* Clinically significant EKG abnormality in terms of ketamine administration (e.g., Ventricular tachycardia, evidence of myocardial ischemia, symptomatic bradycardia, unstable tachycardia, second degree (or greater) AV block).\n* Lifetime schizophrenia, schizoaffective illness, bipolar disorder, current psychotic depression; mild drug or alcohol use disorder in past 2 months; moderate or severe drug or alcohol use disorder in past 6 months; suicidal ideation with plan and\u002For intent within 6 months; suicide attempt in the past month.\n* A first-degree family history of schizophrenia if the subject is less than 33 years old (mean age of onset for schizophrenia plus two standard deviations).\n* Current or recent use of antidepressants within 14 days or benzodiazepines within 1 day. Use of fluoxetine or other long-acting antidepressant within 6 weeks.\n* Current or recent use of medications known to affect brain biology of interest such as competing for binding sites of PET tracer within 1 month.\n* Uncontrolled moderate or severe hypertension (≥160 mmHg systolic or ≥100 mmHg diastolic\\[41\\]), history of Raynaud's phenomenon, seizures, an open cut, sore, or bone fracture on or near the hands to be used for the cold pressor test.\n* Use of more than incidental NSAIDs (including aspirin), anti-inflammatories, immune suppressants or other pain medications.\n* Significant active physical illness, particularly if it may affect the brain biology being studied; including chronic pain syndrome and medically compromising eating disorders or epilepsy.\n* Lacks capacity to consent\n* Aggressive behavior that is a significant threat to others such as physically assaultive behavior (in the last month).\n* Pregnancy, abortion or miscarriage in the previous two months or plans to conceive during the course of study participation.\n* Currently lactating\n* Previous head injury with evidence of cognitive impairment. Subjects who endorse a history of prior head trauma and score 1.5 standard deviations below the mean on Trail-making A or B will be excluded from study participation.\n* Any condition or material in the body that is a contraindication for MRI procedures.\n* Current, past or anticipated exposure to radiation except if the exposure was at our PET center where the precise exposure is known\n* ECT within past 6 months\n* For A-Line Subjects: Unstable relevant medical condition (i.e., condition not adequately stabilized for 3 months). Including bleeding disorders, the need to take medications that affect blood clotting, and certain platelet and hemoglobin cutoffs\n* Blind or with visual impairment that cannot be corrected with corrective lenses (glasses or contact lenses)\n* No emergency contact","59 Years",{"count":403,"type":22},12,[405],"PHASE4","This study explores how stress, suicidal thoughts, and ketamine's effects are connected in people with major depressive disorder. Stress increases the risk for suicidal thoughts, but the biological basis is unclear. Ketamine may help reduce suicidal thoughts by affecting stress-linked brain systems. This study will use smartphone tracking to monitor real-time responses to stress and positron emission tomography (PET) brain scans to study how ketamine affects brain pathways related to stress and suicidal thoughts in depressed individuals.",[26],[409,410,411,412],"ketamine","positron emission tomography (PET)","kappa opioid receptor","major depressive disorder (MDD)",{"date":281,"type":38},{"date":73,"type":22},{"date":416,"type":22},"2028-10-01",{"name":418,"class":45},"New York State Psychiatric Institute",{"id":420,"slug":421,"hasResults":12,"nctId":422,"briefTitle":423,"officialTitle":424,"acronym":4,"eligibilityCriteria":425,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":85,"enrollmentInfo":426,"targetDuration":4,"studyType":57,"phases":428,"briefSummary":429,"conditions":430,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":432,"lastUpdatePostDateStruct":433,"startDateStruct":434,"completionDateStruct":435,"leadSponsor":437,"locationsCount":176},"100649009","probiotic-ibni617-for-moderate-to-severe-depression-100649009","NCT07728253","Probiotic IBNI617 for Moderate to Severe Depression","A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Efficacy and Safety of Probiotic IBNI617 Enteric-Coated Capsules in Patients With Moderate to Severe Depression","Inclusion Criteria:\n\n* Meets DSM-5 criteria for a single episode or recurrent episode;\n* HAM-D-17 ≥ 22, total score of HAM-D-17 items 4, 5, and 6 ≥ 3;\n* MADRS ≥ 20, CGI-S ≥ 4;\n* Absence of antidepressant medication use or discontinuation of antidepressant medication prior to screening.\n\nExclusion Criteria:\n\n* Treatment-resistant depression;\n* Suicide attempt or suicide behavior within the past 6 months;\n* Used antibiotics within the past 2 weeks;\n* Currently use insomnia medication, excluding non-benzodiazepine drugs taken consistently for 4 weeks;\n* With medical history or surgical history that may affect probiotic colonization.",{"count":427,"type":22},148,[59],"IBNI617 is a live biotherapeutic product(LBP). This is a randomized, double-blind, placebo-controlled, parallel-group Phase II clinical trial to evaluate the efficacy and safety of IBNI617 in adult patients with major depressive disorder (MDD).\n\nEligible participants will be randomized in a 1:1 ratio to receive either IBNI617 or matched placebo twice daily for 8 weeks.\n\nThe primary objective is to assess the efficacy of IBNI617 compared with placebo, as measured by the change from baseline in HAM-D-17 total score at Week 8.",[26,431],"IBNI617","2026-07-29",{"date":386,"type":38},{"date":234,"type":22},{"date":436,"type":22},"2028-04",{"name":438,"class":112},"IBIOME BIOTECHNOLOGY CO., LTD",{"id":440,"slug":441,"hasResults":12,"nctId":442,"briefTitle":443,"officialTitle":444,"acronym":4,"eligibilityCriteria":445,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":85,"enrollmentInfo":446,"targetDuration":4,"studyType":57,"phases":448,"briefSummary":449,"conditions":450,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":451,"lastUpdatePostDateStruct":452,"startDateStruct":453,"completionDateStruct":455,"leadSponsor":457,"locationsCount":4},"100649980","phase-3-a-study-of-kh607-as-monotherpy-in-adults-participants-with-major-depressive-disorder-100649980","NCT07741240","A Study of KH607 as Monotherpy in Adults Participants With Major Depressive Disorder","A Multicenter, Randomized, Double-Blind, Placebo-Controlled Parallel-Group Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of KH607 Tablets in the Treatment of Major Depressive Disorder","Inclusion Criteria:\n\n1. Age: 18 to 65 years old (inclusive), Male or female.\n2. Based on investigator's clinical assessment, study participants meet the diagnostic criteria for Major Depressive Disorder (MDD) as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with a diagnosis of single episode or recurrent episodes (ICD-10 codes: 296.2\u002F296.3), without psychotic features. For patients with first-episode depression, the current episode must have a duration of ≥3 months; for patients with recurrent depression, the current depressive episode must have a duration of ≥1 month\n3. Depressive episode confirmed by the Mini International Neuropsychiatric Interview Version 7.0.0 (M.I.N.I. 7.0.0).\n4. Patients must have a 17-item Hamilton Depression Rating Scale (HAM-D17) total score ≥24, a Clinical Global Impression-Severity (CGI-S) score ≥4, and a score ≥2 on Item 1 (Depressed Mood) of the HAM-D17 at screening and baseline\n5. Body weight ≥45.0 kg for females or ≥50.0 kg for males, with a body mass index (BMI) ≥19 kg\u002Fm²\n6. Participants who is taking antidepressants must have stopped for 7 days or 5 half-lives of the antidepressant prior to Day 1.\n7. Participant is willing to stop other antidepressants, antipsychotics, mood stabilizers, sedatives and hypnotics during the trial.\n8. Fully understand the procedures and sigh the informed consent.\n\n   Only for long-term studys:\n9. Participants who complete the short-term study (Visit 8 completion), have a ≥50% reduction from short-term study baseline in HAM-D17 total score at Visit 8, and volunteer to enter the long-term study.\n\nKey Exclusion Criteria:\n\n1. Other psychiatric disorders meeting DSM-5 criteria, including but not limited to schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, panic disorder, agoraphobia, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, anorexia nervosa and bulimia nervosa, neurodevelopmental disorders, schizoaffective disorder, or any other psychiatric disorder that, in the Investigator's judgment, may compromise subject compliance.\n2. A reduction of ≥25% in HAM-D17 total score at baseline compared with the screening visit (this criterion does not apply if baseline and screening assessments are performed at the same visit).\n3. Participants with clinically significant risk of suicide or self-harm, defined as any of the following:\n\n   1. A score ≥4 on Item 10 (Suicidal Thoughts) of the MADRS;\n   2. An answer of \"Yes\" to Question 4 (active suicidal ideation with intent without specific plan) or Question 5 (active suicidal ideation with specific plan and intent) of the C-SSRS within the past 6 months at screening, or a suicide-related behavior within the past 6 months (any \"Yes\" response for Actual Attempt, Interrupted Attempt, or Aborted Attempt).\n4. Participants meeting any of the following depressive disorder diagnoses:\n\n   1. Poor response to adequate dose and adequate duration (at least 6 weeks) of two or more antidepressants with distinct pharmacological mechanisms during a prior depressive episode (based on Investigator interview, to be adjudicated and documented by the Investigator);\n   2. Depressive disorder secondary to other psychiatric disorders or somatic diseases (e.g., depression induced by hypothyroidism);\n   3. Substance\u002Fmedication-induced depressive disorder.\n5. Participants receiving structured psychotherapy (interpersonal therapy, psychodynamic therapy, cognitive behavioral therapy, etc.), music therapy, exercise therapy, acupuncture, or other therapies from screening through baseline, who require continuation of such therapies during the study.\n6. Receipt of depression-related neuromodulation therapies within 1 month prior to enrollment, including but not limited to modified electroconvulsive therapy (MECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), deep brain stimulation (DBS).\n7. Prior use of atypical antipsychotics or mood stabilizers during the current depressive episode (e.g., olanzapine, risperidone, quetiapine, aripiprazole, brexpiprazole, ziprasidone, cariprazine, valproate, lithium carbonate).\n8. Use of any strong CYP3A4 inhibitor or inducer within 14 days (or 5 half-lives, whichever is longer) prior to enrollment.\n9. Abnormal hepatic or renal function prior to enrollment: liver function abnormalities (ALT or AST \\>2×ULN), renal function abnormalities (Cr \\>1.5×ULN), or other conditions deemed inappropriate for enrollment by the Investigator.\n10. Positive test results at screening for active hepatitis B (HBV-DNA ≥1000 copies\u002FmL or 200 IU\u002FmL), hepatitis C antibody, syphilis antibody, or human immunodeficiency virus (HIV) antibody.\n11. 12-lead electrocardiogram (ECG) showing second-degree or third-degree atrioventricular block, long QT syndrome, or QTcF \\>450 ms (male) \u002F 460 ms (female) prior to enrollment; or other conditions unsuitable for participation as judged by the Investigator (e.g., clinically significant tachyarrhythmia requiring intervention).\n12. Severe hypothyroidism (TSH ≥10.0 mIU\u002FL).\n13. Participants with current obstructive sleep apnea and\u002For narcolepsy.\n14. Known or suspected history of hypersensitivity to the investigational product or its excipients, or participants with multiple allergies (defined as allergies to at least 2 different substances).\n15. Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test at screening.\n16. Participants or their partners planning pregnancy, sperm donation, or oocyte donation during the study and within 6 months after the last study drug administration, and unwilling to use adequate and effective contraception throughout this period.\n17. Participants who cannot avoid driving, operating hazardous machinery, or working at heights from the first dose of study drug until 2 weeks after the last dose.\n18. Any other conditions that, in the Investigator's opinion, render the subject unsuitable for participation in this study.",{"count":447,"type":22},232,[126],"This trial includes a short-term study and a long-term study. The short-term study is a multicenter, randomized, double-blind, placebo-controlled parallel-group study with a 6-week duration. The long-term study is a multicenter, open-label, single-arm study with a maximum duration of 27 weeks.",[26],"2026-07-28",{"date":281,"type":38},{"date":454,"type":22},"2026-07",{"date":456,"type":22},"2027-12",{"name":458,"class":112},"Chengdu Kanghong Pharmaceutical Group Co., Ltd.",{"id":460,"slug":461,"hasResults":12,"nctId":462,"briefTitle":463,"officialTitle":464,"acronym":4,"eligibilityCriteria":465,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":85,"enrollmentInfo":466,"targetDuration":4,"studyType":57,"phases":468,"briefSummary":469,"conditions":470,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":451,"lastUpdatePostDateStruct":471,"startDateStruct":472,"completionDateStruct":473,"leadSponsor":475,"locationsCount":4},"100649948","phase-3-compare-the-efficacy-and-safety-of-kh607-tablets-versus-vortioxetine-hydrobromide-tablets-in-adult-patients-with-major-depressive-disorder-100649948","NCT07741331","Compare the Efficacy and Safety of KH607 Tablets Versus Vortioxetine Hydrobromide Tablets in Adult Patients With Major Depressive Disorder","Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel-Controlled Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of KH607 Tablets in the Treatment of Major Depressive Disorder With Vortioxetine Hydrobromide Tablets as the Active Control","Inclusion Criteria:\n\n1. Age: 18 to 65 years old (inclusive), Male or female.\n2. Based on investigator's clinical assessment, study participants meet the diagnostic criteria for Major Depressive Disorder (MDD) as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with a diagnosis of single episode or recurrent episodes (ICD-10 codes: 296.2\u002F296.3), without psychotic features. For patients with first-episode depression, the current episode must have a duration of ≥3 months; for patients with recurrent depression, the current depressive episode must have a duration of ≥1 month\n3. Depressive episode confirmed by the Mini International Neuropsychiatric Interview Version 7.0.0 (M.I.N.I. 7.0.0).\n4. Patients must have a Montgomery and Åsberg Depression Rating Scale (MADRS) total score ≥26, a Clinical Global Impression-Severity (CGI-S) score ≥4, and a score ≥2 on Item 1 (Depressed Mood) of the HAM-D17 at screening and baseline\n5. Body weight ≥45.0 kg for females or ≥50.0 kg for males, with a body mass index (BMI) ≥19 kg\u002Fm²\n6. Participants who is taking antidepressants must have stopped for 7 days or 5 half-lives of the antidepressant prior to Day 1.\n7. Participant is willing to stop other antidepressants, antipsychotics, mood stabilizers, sedatives and hypnotics during the trial.\n8. Fully understand the procedures and sigh the informed consent.\n\n   Only for long-term trials:\n9. Subjects who complete the short-term trial (Visit 8 completion), have a ≥50% reduction from short-term trial baseline in MADRS total score at Visit 8, and volunteer to enter the long-term trial.\n\nExclusion Criteria:\n\n1. Other psychiatric disorders meeting DSM-5 criteria, including but not limited to schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, panic disorder, agoraphobia, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, anorexia nervosa and bulimia nervosa, neurodevelopmental disorders, schizoaffective disorder, or any other psychiatric disorder that, in the Investigator's judgment, may compromise subject compliance.\n2. A reduction of ≥25% in MADRS total score at baseline compared with the screening visit (this criterion does not apply if baseline and screening assessments are performed at the same visit).\n3. Participants with clinically significant risk of suicide or self-harm, defined as any of the following:\n\n   1. A score ≥4 on Item 10 (Suicidal Thoughts) of the MADRS;\n   2. An answer of \"Yes\" to Question 4 (active suicidal ideation with intent without specific plan) or Question 5 (active suicidal ideation with specific plan and intent) of the C-SSRS within the past 6 months at screening, or a suicide-related behavior within the past 6 months (any \"Yes\" response for Actual Attempt, Interrupted Attempt, or Aborted Attempt).\n4. Participants meeting any of the following depressive disorder diagnoses:\n\n   1. Poor response to adequate dose and adequate duration (at least 6 weeks) of two or more antidepressants with distinct pharmacological mechanisms during a prior depressive episode (based on Investigator interview, to be adjudicated and documented by the Investigator);\n   2. Depressive disorder secondary to other psychiatric disorders or somatic diseases (e.g., depression induced by hypothyroidism);\n   3. Substance\u002Fmedication-induced depressive disorder.\n5. Participants receiving structured psychotherapy (interpersonal therapy, psychodynamic therapy, cognitive behavioral therapy, etc.), music therapy, exercise therapy, acupuncture, or other therapies from screening through baseline, who require continuation of such therapies during the study.\n6. Receipt of depression-related neuromodulation therapies within 1 month prior to enrollment, including but not limited to modified electroconvulsive therapy (MECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), deep brain stimulation (DBS).\n7. Prior use of atypical antipsychotics or mood stabilizers during the current depressive episode (e.g., olanzapine, risperidone, quetiapine, aripiprazole, brexpiprazole, ziprasidone, cariprazine, valproate, lithium carbonate).\n8. Use of any strong CYP3A4 inhibitor or inducer within 14 days (or 5 half-lives, whichever is longer) prior to enrollment.\n9. Abnormal hepatic or renal function prior to enrollment: liver function abnormalities (ALT or AST \\>2×ULN), renal function abnormalities (Cr \\>1.5×ULN), or other conditions deemed inappropriate for enrollment by the Investigator.\n10. Positive test results at screening for active hepatitis B (HBV-DNA ≥1000 copies\u002FmL or 200 IU\u002FmL), hepatitis C antibody, syphilis antibody, or human immunodeficiency virus (HIV) antibody.\n11. 12-lead electrocardiogram (ECG) showing second-degree or third-degree atrioventricular block, long QT syndrome, or QTcF \\>450 ms (male) \u002F 460 ms (female) prior to enrollment; or other conditions unsuitable for participation as judged by the Investigator (e.g., clinically significant tachyarrhythmia requiring intervention).\n12. Severe hypothyroidism (TSH ≥10.0 mIU\u002FL).\n13. Participants with current obstructive sleep apnea and\u002For narcolepsy.\n14. Participants who have known or suspected hypersensitivity to vortioxetine hydrobromide, the investigational product or their excipients, or those with allergic diathesis (defined as allergy to at least two different substances).\n15. Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test at screening.\n16. Participants or their partners planning pregnancy, sperm donation, or oocyte donation during the study and within 6 months after the last study drug administration, and unwilling to use adequate and effective contraception throughout this period.\n17. Participants who cannot avoid driving, operating hazardous machinery, or working at heights from the first dose of study drug until 2 weeks after the last dose.\n18. History of seizures, or any other medical conditions associated with an increased seizure risk (e.g., stroke, severe head trauma, significant metabolic disturbances).\n19. History of narrow-angle glaucoma or other conditions resulting in elevated intraocular pressure.\n20. Any other conditions that, in the Investigator's opinion, render the subject unsuitable for participation in this study.",{"count":467,"type":22},326,[126],"This trial includes a short-term study and a long-term study. The short-term study is a multicenter, randomized, double-Blind, double-Dummy, Parallel-Controlled study with a 6-week duration. The long-term study is a withdrawal follow-up study; participants meeting relapse criteria may receive one cycle of KH607 Tablets treatment.",[26],{"date":281,"type":38},{"date":454,"type":22},{"date":474,"type":22},"2028-12",{"name":458,"class":112},{"id":477,"slug":478,"hasResults":12,"nctId":479,"briefTitle":480,"officialTitle":481,"acronym":482,"eligibilityCriteria":483,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":156,"enrollmentInfo":484,"targetDuration":4,"studyType":57,"phases":486,"briefSummary":487,"conditions":488,"keywords":495,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":500,"lastUpdatePostDateStruct":501,"startDateStruct":502,"completionDateStruct":504,"leadSponsor":506,"locationsCount":176},"100636708","phase-2-ketamine-with-dialectical-behavioural-therapy-dbt-for-suicidality-in-individuals-with-treatment-resistant-depression-and-borderline-personality-disorder-ket-dbt-100636708","NCT07569198","Ketamine With Dialectical Behavioural Therapy (DBT) for Suicidality in Individuals With Treatment-Resistant Depression and Borderline Personality Disorder (KET-DBT)","Combining Ketamine With Dialectical Behavioural Therapy (DBT) for Suicidality in Individuals With Treatment-Resistant Depression and Borderline Personality Disorder: A Phase II Randomized, Midazolam-Controlled Clinical Trial (KET-DBT)","KET-DBT","Inclusion Criteria:\n\n1. Adults between the age of 18 to 70, inclusive;\n2. Meets criteria for BPD, as determined by clinical assessment by a psychiatrist or psychologist and confirmed by the International Personality Disorder Examination (IPDE);\n3. Meets DSM-5 criteria for MDD or BD (I or II), currently experiencing a MDE without psychotic features, as diagnosed by a study psychiatrist or psychologist. Diagnosis will be confirmed using the Mini- International Neuropsychiatric Interview (MINI);\n4. Current MDE must be moderate to severe, as determined by the MADRS score \\>20 with an inadequate response to two or more guideline-concordant treatment trials as defined by the Antidepressant Treatment History Form-Short Form (ATHF- SF);\n5. No changes in pharmacotherapy for MDD\u002FBD in the last month or changes in psychotherapy in the past month;\n6. Baseline SI as shown by two consecutive MSSI scores \\> 10 two weeks apart.\n\nExclusion Criteria:\n\n1. Past or current history of a psychotic disorder as determined by clinical assessment and MINI;\n2. Current or recent (within the past 3 months) manic or hypomanic episode as determined by clinical assessment via YMRS (score \\> 12) and the MINI;\n3. Meeting criteria for Moderate to Severe Alcohol or substance use disorders currently or within the past 3 months;\n4. Lifetime history of ketamine use disorder or illicit ketamine use.\n5. Acute suicide risk requiring involuntary inpatient treatment under the Mental Health Act (MHA).\n6. Presence of a relative or absolute contraindication to ketamine or midazolam, including a drug allergy, lifetime history of stroke, uncontrolled hypertension (Systolic BP \\> 160 or Diastolic BP \\> 100), low or labile blood pressure (Systolic BP \\\u003C 100 or Diastolic BP \\\u003C 60), recent (within the past 6 months) myocardial infarction, severe coronary artery disease (ascertained through participant's medical history), or moderate to severe renal (GFR scores ≤ 44) or hepatic impairment (A Child-Pugh score of ≥ 7);\n7. Currently pregnant or breastfeeding or planning on getting pregnant within the first two months of the trial or planning on getting someone else pregnant within the first two months of trial. Participants who are sexually active must agree to use a highly effective contraceptive method (please see exhaustive list in Section 3.6.1);\n8. Current use of prohibited concomitant medications, including other forms of ketamine or esketamine, high dose daily benzodiazepines (greater than 4 mg lorazepam equivalent daily) or monoamine oxidase inhibitors;\n9. Currently engaged (or completed within the past year) in DBT treatment. NOTE: Individuals who have received only DBT skills training in the past year will be considered eligible to participate;\n10. Those engaged in other forms of psychotherapy must be willing to discontinue for the duration of the 6-month DBT intervention (standard for DBT). There should be no changes in psychotherapy 30 days prior to baseline (i.e., Screening Visit 2).",{"count":485,"type":22},120,[89],"The goal of this clinical trial is to learn if intravenous (IV) ketamine with Dialectical Behavioural Therapy (DBT) reduces suicidal ideation in individuals with suicidality who have been diagnosed with Borderline Personality Disorder and either Major Depressive Disorder or Bipolar Disorder. The main question it aims to answer is:\n\nDoes IV ketamine and DBT produce more rapid and robust improvements in suicidal ideation (SI) severity between baseline and Day 35 compared to IV midazolam and DBT, as measured by changes in the Modified Scale for Suicidal Ideation (MSSI) scores ?\n\nResearchers will compare six IV ketamine infusions and DBT to an active placebo (a look-alike substance that mimics some of ketamine's effects and not others) and DBT to see if IV ketamine with DBT is more effective at reducing SI severity.\n\nParticipants will:\n\n* Complete six infusions of either IV ketamine or IV midazolam\n* Take part in 6 months of DBT (includes both weekly one-on-one sessions, and group sessions, starting week 5 of the trial)\n* Visit the hospital for scheduled in-person visits\n* Join a call or videocall for scheduled remote visits\n* Complete a variety of different mood, cognitive and behavioral assessments",[489,490,491,26,492,493,494],"Borderline Personality Disorder (BPD)","Treatment-Resistant Major Depressive Disorder","Treatment-resistant Bipolar Depression","Bipolar Disorder (BD)","Bipolar Disorder I or II","Suicidal Ideation",[496,409,497,498,492,26,499],"Dialectical Behavioural Therapy (DBT)","Borderline Personality Disorder","Treatment-Resistant Depression","Suicidality","2026-07-27",{"date":432,"type":38},{"date":503,"type":22},"2026-07-16",{"date":505,"type":22},"2029-08",{"name":507,"class":45},"Joshua Rosenblat",{"id":509,"slug":510,"hasResults":12,"nctId":511,"briefTitle":512,"officialTitle":512,"acronym":4,"eligibilityCriteria":513,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":122,"enrollmentInfo":514,"targetDuration":4,"studyType":57,"phases":516,"briefSummary":517,"conditions":518,"keywords":519,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":500,"lastUpdatePostDateStruct":531,"startDateStruct":532,"completionDateStruct":533,"leadSponsor":535,"locationsCount":176},"100601046","evaluating-conversational-artificial-intelligence-for-depression-management-100601046","NCT07105397","Evaluating Conversational Artificial Intelligence for Depression Management","1. Participant is between 18 to 85 years old.\n2. Participant has been, or are likely to be, diagnosed with moderate to severe Major Depressive Disorder without signs of bipolar depression.\n3. Participant is not in active suicidal crisis and do not face imminent risk of suicide within the next 3 hours.\n4. Participant is not pregnant or seeking to be pregnant.\n5. Participant able to communicate in English on the Internet.\n6. Participant must reside in the United States.\n7. Participant has access to a mental health clinician, or the participant is willing to see study clinicians to help review the advice and medication adjustments recommended by the AI Intake System to the participant.\n8. If the participant is seeing study clinicians, the participant must reside in a state where study clinicians are licensed.\n9. Participant must be using a device (phone or computer) that is located in the United States.",{"count":515,"type":22},130,[59],"The goal of this clinical trial is to evaluate how a conversational method of collecting medical history affects patients' perceptions and experiences compared to clinical care as usual. This conversational AI intake system collects medical history information, can be completed by participants at home, and do not disrupt routine clinical care.\n\nThe primary questions this study aims to answer are:\n\n1\\) Does conversational intake affect patients' perceptions of empathy during their clinical interactions?\n\nThis will be a prospective study that follows a cohort of participants for four (4) months after engaging with the AI intake system. Because each participant serves as his\u002Fher own control, both comparators will be administered within-subject, and the order of exposure (AI intake vs. usual care) will be randomized to minimize sequence effects.\n\nAfter completing the AI intake method, participants will rate their experience, particularly in terms of empathy and compare it to their usual interactions with their own clinicians.",[26],[520,521,522,523,524,525,526,527,528,529,530],"major depression","antidepressant","large language model","conversational agent","artificial intelligence","AI","NLP","major depressive disorder","medical record augmented generation","patient simulation","testbed",{"date":451,"type":38},{"date":335,"type":22},{"date":534,"type":22},"2028-06-30",{"name":536,"class":45},"George Mason University",{"id":538,"slug":539,"hasResults":12,"nctId":540,"briefTitle":541,"officialTitle":542,"acronym":543,"eligibilityCriteria":544,"healthyVolunteers":12,"sex":18,"minAge":545,"maxAge":276,"enrollmentInfo":546,"targetDuration":4,"studyType":57,"phases":547,"briefSummary":548,"conditions":549,"keywords":551,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":556,"lastUpdatePostDateStruct":557,"startDateStruct":558,"completionDateStruct":560,"leadSponsor":562,"locationsCount":316},"100649351","phase-2-pregnenolone-treatment-for-alcohol-use-disorder-and-major-depressive-disorder-100649351","NCT07734701","Pregnenolone Treatment for Alcohol Use Disorder and Major Depressive Disorder","Targeting Neurosteroid Pathways in Alcohol Use Disorder: Clinical and Neural Impact of Pregnenolone Therapy","PREG-AUD-RO1","Inclusion Criteria:\n\n* Age 21 to 55 years.\n* Meets DSM-5 criteria for Alcohol Use Disorder (AUD).\n* Meets DSM-5 criteria for Major Depressive Disorder (MDD).\n* Able to provide informed consent.\n* Willing and able to comply with study procedures and assessments\n\nExclusion Criteria:\n\n* Current diagnosis of bipolar disorder, schizophrenia spectrum disorder, or other psychotic disorder.\n* Current substance use disorder requiring immediate treatment other than alcohol or nicotine.\n* Significant unstable medical or neurologic illness that would interfere with participation or study assessments.\n* Contraindications to magnetic resonance imaging (MRI).\n* Current pregnancy or breastfeeding.\n* Current use of medications or treatments that would interfere with study participation or interpretation of results.\n* Significant suicide risk requiring a higher level of care.\n* Any condition that, in the investigator's judgment, would make participation unsafe or compromise study integrity.","21 Years",{"count":299,"type":22},[89],"This study will evaluate whether pregnenolone is an effective treatment for adults with Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD). Participants will be randomly assigned to receive either pregnenolone or placebo for 12 weeks in a double-blind study. Researchers will assess alcohol consumption, alcohol craving, depressive symptoms, and anxiety symptoms throughout treatment. The study will also use magnetic resonance imaging (MRI) to examine how pregnenolone affects brain circuits involved in addiction and mood regulation. The goal is to determine whether pregnenolone can improve both alcohol-related and mood-related outcomes and to identify the neural mechanisms associated with treatment response.",[550,26],"Alcohol Use Disorder (AUD)",[552,553,65,554,228,95,555],"Pregnenolone","Alcohol Use Disorder","Neurosteroids","Substance Use Disorders","2026-07-23",{"date":432,"type":38},{"date":559,"type":22},"2026-10",{"date":561,"type":22},"2031-03",{"name":563,"class":45},"Sherwood Brown, MD, PhD",{"id":565,"slug":566,"hasResults":12,"nctId":567,"briefTitle":568,"officialTitle":569,"acronym":570,"eligibilityCriteria":571,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":572,"targetDuration":4,"studyType":57,"phases":573,"briefSummary":574,"conditions":575,"keywords":578,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":584,"lastUpdatePostDateStruct":585,"startDateStruct":586,"completionDateStruct":588,"leadSponsor":590,"locationsCount":176},"100648893","effectiveness-of-clustered-versus-tapered-repetitive-transcranial-magnetic-stimulation-rtms-as-maintenance-therapy-following-successful-acute-rtms-treatment-in-patients-with-depressive-syndrome-100648893","NCT07727005","Effectiveness of Clustered Versus Tapered Repetitive Transcranial Magnetic Stimulation (rTMS) as Maintenance Therapy Following Successful Acute rTMS Treatment in Patients With Depressive Syndrome","Effectiveness of rTMS as Maintenance Therapy; Clustered rTMS vs. Tapered rTMS","ERTE","Inclusion Criteria:\n\n* Age ≥18 years\n* Diagnosis of a depressive syndrome\n* Completion of an acute treatment course consisting of 20 sessions of theta burst stimulation (TBS) over 4 weeks\n* Response or remission following acute treatment. Response is defined as a ≥50% reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score\n* Remission is defined as a MADRS total score ≤10.\n* Clinical eligibility for maintenance TBS\n* Provision of written informed consent\n\nExclusion Criteria:\n\n* Non-response to acute TBS treatment\n* Contraindications to transcranial magnetic stimulation (TMS) or theta burst stimulation (TBS)\n* Active substance use disorder (substance use within the past 3 months)\n* Acute psychiatric or medical conditions that preclude study participation\n\nAdditional exclusion criteria for the MRI component:\n\n\\- Contraindications to MRI (e.g., non-MRI-compatible metallic implants or severe claustrophobia)",{"count":299,"type":22},[59],"The goal of this clinical trial is to compare two maintenance transcranial magnetic stimulation (rTMS) strategies following successful acute theta burst stimulation (TBS) treatment in adults with depressive syndrome. It will also evaluate whether the two maintenance strategies differ in their ability to maintain the antidepressant treatment response over 24 weeks. The main questions it aims to answer are:\n\nDoes clustered maintenance rTMS reduce the risk of depressive relapse or clinically relevant symptom worsening compared with tapered maintenance rTMS? Do the two maintenance strategies differ in depressive symptoms, global clinical status, psychosocial functioning, and MRI-based biomarkers over time?\n\nResearchers will compare a clustered maintenance rTMS protocol with a tapered maintenance rTMS protocol.\n\nParticipants will:\n\n* Complete successful acute TBS treatment before study enrollment\n* Be randomly assigned to either clustered or tapered maintenance rTMS\n* Receive 20 maintenance stimulation sessions over 20 weeks\n* Attend clinical follow-up assessments every 4 weeks for a total follow-up -period of 24 weeks\n* Undergo optional multimodal MRI examinations at the Munich study site",[26,576,577],"Depressive Episodes","Depressive Syndrome",[579,580,581,582,29,583],"MaintenanceTMS","NIBS","TaperingTMS","ClusterTMS","DepressiveSyndrome","2026-07-21",{"date":500,"type":38},{"date":587,"type":22},"2026-08-01",{"date":589,"type":22},"2028-09-30",{"name":591,"class":45},"Technical University of Munich",{"id":593,"slug":594,"hasResults":12,"nctId":595,"briefTitle":596,"officialTitle":597,"acronym":4,"eligibilityCriteria":598,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":276,"enrollmentInfo":599,"targetDuration":4,"studyType":57,"phases":601,"briefSummary":602,"conditions":603,"keywords":605,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":503,"lastUpdatePostDateStruct":611,"startDateStruct":613,"completionDateStruct":615,"leadSponsor":617,"locationsCount":4},"100647560","temporal-interference-transcranial-alternating-current-stimulation-for-major-depressive-disorder-and-generalized-anxiety-disorder-100647560","NCT07712159","Temporal Interference Transcranial Alternating Current Stimulation for Major Depressive Disorder and Generalized Anxiety Disorder","A Double-Blind, Randomized, Sham-Controlled Clinical Trial of Temporal Interference Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder and Generalized Anxiety Disorder","Inclusion Criteria:\n\n1. Age between 18 and 55 years (inclusive), any gender;\n2. Diagnosis of a single or recurrent episode of Major Depressive Disorder (MDD) or Generalized Anxiety Disorder (GAD) according to DSM-5 criteria, assessed by trained researchers using the Structured Clinical Interview for DSM-5 (SCID), without psychotic features;\n3. For MDD participants: HAMD-17 score ≥14; inadequate response to stable, regular antidepressant medication for at least 1 month at an adequate dose;\n4. For GAD participants: HAMA score ≥14; stable, regular medication for at least 2 months;\n5. Education level: junior high school or above; adequate cognitive and language ability to understand and complete study assessments;\n6. Voluntary participation with signed informed consent; ability to comply with study visits, treatment schedules, laboratory tests, and other study procedures.\n\nExclusion Criteria:\n\n1. History of psychiatric disorders other than MDD or GAD;\n2. Pregnancy or lactation;\n3. Neurologic disorders or serious systemic diseases (e.g., thyroid disease, lupus erythematosus, diabetes, hepatic or renal impairment, active infection, major trauma);\n4. History of significant head injury or coma\n5. Receipt of physical therapies such as electroconvulsive therapy or rTMS within the past six months before enrollment\n6. Suspected or confirmed history of alcohol or substance dependence;\n7. Current severe suicidal ideation or recent suicide attempt;\n8. Current participation in another clinical trial or recent use of prohibited psychotropic medications;\n9. Positive urine drug screening or abnormal thyroid function tests;\n10. Contraindications to magnetic resonance imaging (MRI) or electroencephalography (EEG);\n11. Inability to provide fully informed consent.",{"count":600,"type":22},192,[59],"This multi-center, double-blind study, randomized controlled trial aims to evaluate the efficacy and safety of Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) in patients with major depressive disorder (MDD) and generalized anxiety disorder (GAD).\n\nAll participants will be enrolled as two independent cohorts and randomized separately within each diagnostic group. Participants with major depressive disorder will be randomized to receive high-frequency TI-tACS(130 Hz), low-frequency TI-tACS(2Hz), or sham stimulation targeting the right amygdala. Participants with generalized anxiety disorder will be randomized to receive high-frequency TI-tACS(80Hz), low-frequency TI-tACS(5Hz), or sham stimulation targeting the right amygdala.\n\nThe intervention consists of 20 stimulation sessions administered over 2 weeks (twice a day for 5 consecutive days, followed by a 2-day break, and another 5 consecutive days). Clinical assessments will be conducted at baseline, during treatment, and at multiple follow-up time points up to 6 months.\n\nThe primary outcome for the MDD cohort is the change from baseline in the Hamilton Depression Rating Scale (HAMD-17) at week 2. The primary outcome for the GAD cohort is the change from baseline in the Hamilton Anxiety Rating Scale (HAMA) at week 2. Secondary outcomes include changes in clinical symptoms, cognitive function, and safety profiles in both the MDD and GAD cohorts.",[26,604],"Generalized Anxiety Disorder (GAD)",[65,606,607,608,255,609,69,610],"Generalized Anxiety Disorder","Temporal Interference Transcranial Alternating Current Stimulation","Multi-center","Non-invasive brain stimulation","double-blind",{"date":612,"type":38},"2026-07-17",{"date":614,"type":22},"2026-06",{"date":616,"type":22},"2028-06",{"name":618,"class":45},"Central South University",{"id":620,"slug":621,"hasResults":12,"nctId":622,"briefTitle":623,"officialTitle":624,"acronym":4,"eligibilityCriteria":625,"healthyVolunteers":17,"sex":18,"minAge":626,"maxAge":85,"enrollmentInfo":627,"targetDuration":4,"studyType":57,"phases":628,"briefSummary":629,"conditions":630,"keywords":631,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":635,"lastUpdatePostDateStruct":636,"startDateStruct":637,"completionDateStruct":639,"leadSponsor":641,"locationsCount":176},"100633983","investigating-functional-changes-in-the-frontotemporal-cortex-of-patients-with-major-depressive-disorder-following-electroconvulsive-therapy-or-magnetic-seizure-therapy-using-functional-near-infrared-spectroscopy-fnirs-100633983","NCT07533773","Investigating Functional Changes in the Frontotemporal Cortex of Patients With Major Depressive Disorder Following Electroconvulsive Therapy or Magnetic Seizure Therapy Using Functional Near-infrared Spectroscopy (fNIRS)","Investigating Functional Changes in the Frontotemporal Cortex of Patients With Major Depressive Disorder Following Electroconvulsive Therapy or Magnetic Seizure Therapy Using Functional Near-infrared Spectroscopy","Inclusion Criteria:\n\n* A depressive episode diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed by two psychiatrists;\n* Meets the treatment criteria for ECT or MST;\n* At least 5 years of education, with no significant hearing or visual impairments;\n* Voluntary participation in this study, with a signed written informed consent form, and willingness to cooperate with the collection of general demographic information, neuropsychological testing, and fNIRS resting-state and task-based data acquisition.\n\nExclusion Criteria:\n\n* Co-occurring mental disorders (such as substance use disorders or schizoaffective disorder);\n* Severe physical illness;\n* History of neurological disorders (such as traumatic brain injury or dementia);\n* Low educational attainment;\n* Receipt of ECT or MST treatment within the past six months.","12 Years",{"count":214,"type":22},[59],"Against the clinical backdrop of the growing global burden of neuropsychiatric disorders, the rapid rise in depression prevalence, and the frequent association of these conditions with cognitive impairment, this study highlights the limitations of current cognitive assessment tools-such as their time-consuming nature and lack of specificity-and underscores the urgent need to develop simple and efficient assessment methods. In terms of treatment, modified electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) are rapidly acting neuromodulation therapies; however, their effects on cognitive function and underlying brain mechanisms remain controversial, and there is a lack of direct comparative studies. Functional near-infrared spectroscopy (fNIRS) technology can non-invasively monitor changes in cerebral hemodynamics, providing a powerful tool for assessing brain function before and after treatment. Therefore, this study aims to combine resting-state and task-based fNIRS with multidimensional cognitive and emotional assessments to systematically compare the effects of ECT and MST on frontal-temporal cerebral hemodynamics. We seek to clarify the differences in brain function regulation between the two treatment modalities and their association with improvements in cognition and mood, with the goal of providing scientific evidence to elucidate the brain mechanisms underlying neurostimulation therapies and optimize individualized treatment plans.",[26],[65,632,633,634],"Electroconvulsive Therapy","Magnetic Seizure Therapy","Functional Near-Infrared Spectroscopy","2026-07-15",{"date":612,"type":38},{"date":638,"type":38},"2026-04-30",{"date":640,"type":22},"2029-04-30",{"name":642,"class":45},"The Second Hospital of Anhui Medical University",{"id":644,"slug":645,"hasResults":12,"nctId":646,"briefTitle":647,"officialTitle":648,"acronym":4,"eligibilityCriteria":649,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":650,"enrollmentInfo":651,"targetDuration":4,"studyType":57,"phases":653,"briefSummary":655,"conditions":656,"keywords":657,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":661,"lastUpdatePostDateStruct":662,"startDateStruct":664,"completionDateStruct":666,"leadSponsor":668,"locationsCount":176},"100603693","phase-1-pattern-separation-in-major-depressive-disorder-100603693","NCT07139834","Pattern Separation in Major Depressive Disorder","Examining the Effects of Escitalopram and Memantine on Pattern Separation in Major Depressive Disorder","Inclusion Criteria:\n\n* Age 18-50\n* Current diagnosis of MDD without psychotic features assessed within three weeks of study enrollment\n* 17-item Hamilton Depression Rating Scale score ≥17 assessed within 3 weeks of study enrollment\n* Using an effective form of contraception at study enrollment and agrees to continue throughout study participation for individuals of child-bearing potential\n* Capacity to provide informed consent\n* Proficient in English\n* Willing to provide emergency contact\n\nExclusion Criteria:\n\n* Currently taking an antidepressant medication at study enrollment\n* Pregnant or breastfeeding at time of enrollment\n* Evidence of current unstable medical illness, including liver or renal impairment, or unstable cardiovascular or respiratory illness\n* QTc interval greater than 500 ms\n* Current genitourinary conditions that raise urine pH such as a) renal tubular acidosis or b) severe infection of the urinary tract.\n* Clinically significant neurological conditions, including a) history of stroke, b) previous head injury with evidence of cognitive impairment, c) history of malignancy or d) history of seizure disorder. (headache, migraines, pain disorders, and other conditions not exclusionary)\n* Lifetime diagnosis of a) bipolar disorder, b) psychotic disorder, or c) dementia\n* Current active suicidal ideation\n* Current substance use disorder other than tobacco use disorder\n* Current or recent (past 6 months) treatment with antipsychotics; current or recent (past 1 month) treatment with benzodiazepines; current use of prescribed stimulant medication; current use of other NMDA antagonists (amantadine, ketamine, dextromethorphan)\n* Current use of disulfiram with oral concentrate, MAOIs (including linezolid or IV methylene blue), or pimozide\n* History of hypersensitivity or allergic reaction to a) memantine hydrochloride or any of its components\u002Fexcipients, b) citalopram, escitalopram, or any other component of the product, or c) sertraline or any other component of the product\n* Concurrent or recent (past 6 months) participation in another clinical trial for mental illness involving an investigational product or device\n* Lack of response to or intolerable side-effects from trials of two or more selective serotonin reuptake inhibitors of adequate dose and duration at study enrollment\n* Electroconvulsive therapy (ECT) in the past 6 months\n* Any condition or material in the body that is a contraindication for MRI procedures\n* Weight that exceeds 300 lbs or inability to fit into MRI scanner\n* MST LDI score greater than 0.5","50 Years",{"count":652,"type":22},30,[654],"PHASE1","This study seeks to examine the effects of treatment with a selective serotonin reuptake inhibitor (SSRI), escitalopram, a first-line treatment for depression, in combination with placebo or with extended-release memantine, on neuropsychological function, regional brain activity assessed by functional magnetic resonance imaging, and depressive symptoms, in participants with Major Depressive Disorder. Escitalopram is administered in an open-label fashion in this study; extended release memantine is administered in a double-blind, randomized, placebo-controlled manner.",[26],[64,658,29,659,660],"Major depressive disorder","Pattern separation","Memantine","2026-07-13",{"date":663,"type":38},"2026-07-14",{"date":665,"type":38},"2026-06-01",{"date":667,"type":22},"2027-06-30",{"name":669,"class":45},"Jeffrey Miller",{"id":671,"slug":672,"hasResults":12,"nctId":673,"briefTitle":674,"officialTitle":675,"acronym":676,"eligibilityCriteria":677,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":678,"targetDuration":4,"studyType":57,"phases":680,"briefSummary":681,"conditions":682,"keywords":684,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":692,"lastUpdatePostDateStruct":693,"startDateStruct":694,"completionDateStruct":695,"leadSponsor":697,"locationsCount":699},"100636169","phase-2-inhaled-dmt-for-major-depressive-disorder-100636169","NCT07562191","Inhaled DMT for Major Depressive Disorder","Randomized, Double-Blind, Placebo-Controlled Phase IIb Trial of Inhaled N,N-Dimethyltryptamine (DMT) for Major Depressive Disorder","DMT-MDD","Inclusion Criteria:\n\n* 18 years or older, capable of making decisions, and able to provide informed consent.\n* Major Depressive Disorder (MDD) according to DSM-5 criteria\n* Current depressive episode of moderate to severe intensity\n* Episode duration of at least two weeks\n* Baseline MADRS score ≥ 20\n* No treatment changes (including antidepressants) in the 4 weeks prior to the study\n* Abstain from psychedelics ≥14 days before dosing (D0)\n\nExclusion criteria:\n\n* Major cardiac, hepatic, or renal disease; unstable cardiovascular conditions\n* Uncontrolled hypertension, QTc prolongation, arrhythmias, or valvular disease COPD or asthma\n* Severe obesity, uncontrolled diabetes, coagulopathy, thyroid disease, or glaucoma\n* Neurological risk (e.g., aneurysm, ↑ICP, epilepsy\u002Fseizures, severe disorders)\n* MAO deficiency or history of serotonin syndrome\n* Pregnant, breastfeeding, positive test, or no effective contraception\n* Secondary depression\n* Cluster B personality disorders (incl. borderline with ≥2 suicidal behaviors in past 12 months) or poor therapeutic rapport\n* Psychotic disorders, MDD with psychotic features, or first-degree family history of psychosis\u002Fbipolar disorder\n* Mania\u002Fhypomania\n* OCD, dissociative disorders, active PTSD, or decompensated eating disorders\n* Moderate-severe use disorder (past 6 months; except nicotine\u002Fcaffeine)\n* Lifetime ketamine, PCP, psychedelics, or MDMA use disorder\n* Current use of MAO inhibitors, unless discontinued at least 14 days prior to dosing\n* Psychedelic trial participation in past 12 months\n* Cognitive impairment affecting valid assessment",{"count":679,"type":22},140,[89],"This Phase 2b, randomized, double-blind, active-controlled clinical trial will evaluate the efficacy and safety of inhaled N,N-dimethyltryptamine (DMT) in adults with Major Depressive Disorder (MDD).\n\nThe study will test whether inhaled DMT can rapidly reduce depressive symptoms and suicide risk compared with a low-dose active comparator. A total of 140 participants will be randomized 1:1 to receive either 15 mg followed 1 hour later by 60 mg of inhaled DMT, or 1 mg followed 1 hour later by 4 mg of inhaled DMT.\n\nParticipants who do not achieve remission at Day 7 will enter an open-label extension and receive a high-dose DMT session on Day 14 (±3 days). All participants will be followed for up to 12 months to evaluate the durability of response, safety, functioning, and quality of life.",[29,26,357,494,683],"Suicide",[685,527,686,687,688,689,690,691],"DMT","N,N-dimethyltryptamine","psychedelic therapy","inhaled DMT","vaporized DMT","suicidality","non invasive","2026-07-09",{"date":661,"type":38},{"date":587,"type":22},{"date":696,"type":22},"2027-08-01",{"name":698,"class":45},"Universidade Federal do Rio Grande do Norte",5]