[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"depressive-disorder-treatment-resistant\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:depressive-disorder-treatment-resistant":29},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,11,0,[8,50,94,107,130,153,181,210,232,262,298],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":30,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":39,"startDateStruct":42,"completionDateStruct":44,"leadSponsor":46,"locationsCount":49},"100053451","phase-2-acp-211-monotherapy-for-major-depressive-disorder-with-inadequate-antidepressant-response-100053451",false,"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* Documented non-response to ADT, including ketamine or esketamine\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 Additional inclusion\u002Fexclusion criteria apply. Participants will be evaluated at Screening to ensure that all criteria for study participation are met.","ALL","18 Years","65 Years",{"count":21,"type":22},153,"ESTIMATED","INTERVENTIONAL",[25],"PHASE2","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?",[28,29],"Major Depressive Disorder (MDD)","Depressive Disorder, Treatment-Resistant",[28,29,31,32,33,34,35,36],"Antidepressive Agents","Randomized Controlled Trial","Double-Blind Method","Clinical Trial, Phase II","Psychiatric Status Rating Scales","Ketamine","RECRUITING","2026-07-10",{"date":40,"type":41},"2026-07-13","ACTUAL",{"date":43,"type":41},"2025-11-14",{"date":45,"type":22},"2027-09",{"name":47,"class":48},"ACADIA Pharmaceuticals Inc.","INDUSTRY",23,{"id":51,"slug":52,"hasResults":11,"nctId":53,"briefTitle":54,"officialTitle":55,"acronym":4,"eligibilityCriteria":56,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":57,"enrollmentInfo":58,"targetDuration":4,"studyType":23,"phases":60,"briefSummary":61,"conditions":62,"keywords":74,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":83,"lastUpdatePostDateStruct":84,"startDateStruct":86,"completionDateStruct":88,"leadSponsor":90,"locationsCount":93},"100555424","phase-2-investigation-of-the-antidepressant-effects-of-2r6r-hnk-an-enhancer-of-synaptic-glutamate-release-in-treatment-resistant-depression-100555424","NCT06511908","Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression","An Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n1. Ability of participant to understand and willingness to sign a written informed consent document. To verify this, participants must score \\>= 80% on the consent quiz.\n2. Stated willingness to comply with all study procedures and availability for the duration of the study.\n3. 18 to 70 years of age.\n4. All participants must have undergone a screening assessment under protocol 01-M-0254.\n5. Participants must fulfill DSM-IV or DSM-5 criteria for MDD, single episode or recurrent without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). Participants must be experiencing a current major depressive episode lasting at least two weeks.\n6. Participants must have an initial score of \\>= 20 on the MADRS and a YMRS score of \\\u003C12 within one week of study entry and upon entry into Phase II.\n7. Ability to take intravenous medication and be willing to adhere to the (2R,6R)-HNK regimen.\n8. Participants must have a current or past history of lack of response to at least one adequate antidepressant trial (may be from the same chemical class), with at least one in the current major depressive episode, operationally defined using the modified Antidepressant Treatment History Form (ATHF); non-response to an adequate trial of ECT or TMS would count as an adequate antidepressant trial.\n9. For individuals of reproductive potential: use of highly effective contraception starting at the time of enrollment and agreement to use such a method during study participation and for an additional four weeks after the end of Study Phase II.\n10. For males of reproductive potential: use of condoms or other methods from the time of enrollment to ensure effective contraception with partner, and for an additional 90 days after the end of Phase II.\n11. Agreement to adhere to Lifestyle Considerations throughout study duration.\n12. Medically healthy, or with stable, treated, chronic medical conditions (provided any medications are not excluded)\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n1. Current use of disallowed concomitant medications or transcranial magnetic stimulation (TMS) two weeks prior to the start of Phase II.\n2. Treatment with a reversible monoamine oxidase inhibitor (MAOI) four weeks prior to the start of Phase II.\n3. Treatment with fluoxetine, aripiprazole, or brexpiprazole five weeks prior to the start of Phase II.\n4. Treatment with clozapine or electroconvulsive therapy (ECT) four weeks prior to the start of Phase II.\n5. Ongoing treatment with moderate or strong CYP3A4\u002F5 inhibitors or inducers\n6. Lifetime history of deep brain stimulation.\n7. Previous antidepressant non-response to ketamine or esketamine (full course).\n8. No structured psychotherapy will be permitted during the total duration of the study. Participants unable or unwilling to stop psychotherapy will be unable to participate in the study.\n9. Pregnancy or lactation.\n10. Current psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-5.\n11. Participants with a history of DSM-IV substance or alcohol abuse or dependence, or DSM-5 substance use disorder (except for caffeine, nicotine, or cannabis), or moderate to severe alcohol use disorder, within the preceding three months. In addition, participants who are currently using drugs (except for caffeine, nicotine, or cannabis) must not have used illicit substances or known drugs of abuse in the two weeks prior to screen and must have a negative drug urine test (except for prescribed benzodiazepines or stimulants) prior to starting Phase II. Cannabis use is exclusionary if the use is daily, or if participants are unable to abstain during the study, or if function of daily life is impaired by use as determined by a clinician. Due to the interactions between cannabis and SSRIs, frequent cannabis use during previous antidepressant treatment will result in that treatment being considered a failed trial for eligibility purposes.\n12. Participants with a DSM-IV or DSM-5 Axis II diagnosis of borderline or antisocial personality disorder.\n13. Participants with a history of head injury that resulted in loss of consciousness exceeding five minutes (for the imaging component of the study).\n14. No serious, unstable medical illnesses including but not limited to the following body systems and organs or those that in the judgment of the Principal Investigator pose a risk to the participant's ability to safely participate in the study: Hepatic diseases (e.g. active viral hepatitis infection or cirrhosis of the liver, any liver disease with Child-Pugh score \\>=5), cardiovascular disease (including ischemic heart disease, coronary artery disease, congestive heart failure, poorly controlled hypertension due to risk of further blood pressure elevation and increase in demand on cardiac function from study drug), renal\u002Furologic (e.g chronic kidney disease or acute kidney injury, history of bladder dysfunction due to theoretical risk of ketamine-induced cystitis, moderate to severe renal impairment of any etiology), endocrinologic (including uncontrolled diabetes due to association with progressive abnormality of the microvasculature and nervous system), or neurologic disease (e.g. elevated intraocular pressure or history of or presence of diseases that are associated with elevated intracranial pressure).\n15. Participants with unstable clinical hyperthyroidism or hypothyroidism.\n16. Participants with one or more seizures without a clear and resolved etiology.\n17. Clinically significant abnormal laboratory tests specifically defined by:\n\n    * Alkaline phosphatase (Alk Phos) \\> 150 U\u002FL\n    * Alanine aminotransferase (ALT) \\> 55 U\u002FL\n    * Aspartate aminotransferase (AST) \\> 34 U\u002FL\n    * Total bilirubin (TB) \\> 1.2 mg\u002FdL\n    * Direct bilirubin (DB) \\> 0.5 mg\u002FdL\n    * 25-hydroxyvitamin D \\\u003C 20 ng\u002FmL\n    * Folate \\\u003C 2ng\u002FmL\n    * Vitamin B12 \\\u003C 200 pg\u002FmL\n18. Moderate to severe renal impairment with body surface area corrected eGFR \\\u003C60mL\u002Fmin.\n19. Participants who, in the Principal Investigator's judgment, pose a current serious suicidal or homicidal risk.\n20. Positive HIV test.\n21. Contraindications to MRS (metal in body, claustrophobia, etc. for imaging)\n22. Participants with COVID-19 or suspected COVID-19\n23. Inability to read and understand English. Non- English speakers will not be eligible as most of the required monitoring and rating instruments are not validated in languages other than English.","70 Years",{"count":59,"type":22},50,[25],"Background:\n\nMajor depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD.\n\nObjective:\n\nTo test a study drug (HNK) in people with MDD.\n\nEligibility:\n\nPeople aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254.\n\nDesign:\n\nParticipants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity.\n\nHNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule:\n\nThey will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study.\n\nThey will receive no drugs for 2 to 3 weeks.\n\nThey will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study.\n\nOne set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo.\n\n...",[63,29,36,64,65,66,67,68,69,70,71,72,73],"Suicide","Molecular Mechanisms of Pharmacological Action","Neurotransmitter Agents","Excitatory Amino Acid Agents","Physiological Effects of Drugs","Depressive Disorder, Major","Depressive Disorder","Depression","Mental Disorders","Mood Disorders","Behavioral Symptoms",[75,36,76,77,78,79,80,81,82],"Major Depressive Disorder","Biomarkers","Neuropharmacology","Magnetic Resonance Imaging","Magnetoencephalography","Neurobiology","Glutamate","Hydroxynorketamine","2026-06-13",{"date":85,"type":41},"2026-06-16",{"date":87,"type":41},"2024-11-06",{"date":89,"type":22},"2027-07-01",{"name":91,"class":92},"National Institute of Mental Health (NIMH)","NIH",1,{"id":95,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":96,"targetDuration":4,"studyType":23,"phases":97,"briefSummary":26,"conditions":98,"keywords":99,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":100,"lastUpdatePostDateStruct":101,"startDateStruct":103,"completionDateStruct":104,"leadSponsor":105,"locationsCount":106},"100614828",{"count":21,"type":22},[25],[28,29],[28,29,31,32,33,34,35,36],"2026-06-05",{"date":102,"type":41},"2026-06-08",{"date":43,"type":41},{"date":45,"type":22},{"name":47,"class":48},21,{"id":108,"slug":109,"hasResults":11,"nctId":110,"briefTitle":111,"officialTitle":112,"acronym":4,"eligibilityCriteria":113,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":114,"enrollmentInfo":115,"targetDuration":4,"studyType":23,"phases":117,"briefSummary":119,"conditions":120,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":121,"lastUpdatePostDateStruct":122,"startDateStruct":123,"completionDateStruct":125,"leadSponsor":127,"locationsCount":129},"100597042","phase-4-a-study-of-esketamine-nasal-spray-in-korean-participants-with-treatment-resistant-depression-100597042","NCT07053345","A Study of Esketamine Nasal Spray in Korean Participants With Treatment-resistant Depression","An Interventional, Open-label, Single Arm, Multicenter Study to Evaluate the Efficacy and Safety of Esketamine Nasal Spray in Korean Participants With Treatment-Resistant Depression(TRD)","Inclusion Criteria:\n\n* Must have a confirmed diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition at the time of enrollment, without psychotic features, based on clinical assessment, and confirmed by mini international neuropsychiatric interview (MINI)\n* Must have a Hamilton depression rating scale (HAM-D; 17-item) total score greater than or equal to (\\>=) 22 at screening and Day 1\n* Participants must have had non-response (less than or equal to \\[\\\u003C=\\] 25 percent \\[%\\] improvement of symptoms) to \\>= 2 oral antidepressant treatments in the current moderate to severe episode of depression after having been given at an adequate dosage for an adequate duration of at least 6 weeks\n* At baseline (Day 1), the investigator will evaluate any changes in the participant's signs\u002Fsymptoms of depression since the screening assessment and confirm that the inclusion criteria for the current antidepressant (AD) treatment are still met (that is, nonresponse and minimal clinical improvement)\n* A female participant of childbearing potential must have a negative serum pregnancy test at screening and urine prior to the first dose of study intervention on Day 1\n\nExclusion Criteria:\n\n* Participants with hyperthyroidism that has not been sufficiently treated\n* History of malignancy within 5 years of enrollment before screening\n* Known allergies, hypersensitivity, or intolerance to esketamine\u002Fketamine or its excipients\n* Received an investigational intervention or used an invasive investigational medical device within 60 days before the planned first dose of study intervention or first data collection time point\n* Currently enrolled in an investigational study that involves treatments for MDD or may otherwise be expected to impact mood","64 Years",{"count":116,"type":22},47,[118],"PHASE4","The purpose of this study is to evaluate how well esketamine nasal spray works in improving depressive symptoms in participants with treatment resistant depression (TRD). This will be assessed by the change from baseline in the Hamilton depression rating scale (HAM-D; 17-item) total score from Day 1 (baseline) to the end of the 4-week treatment phase (Day 28).",[29],"2026-06-04",{"date":100,"type":41},{"date":124,"type":41},"2025-06-09",{"date":126,"type":22},"2027-06-25",{"name":128,"class":48},"Janssen Korea, Ltd., Korea",6,{"id":131,"slug":132,"hasResults":11,"nctId":133,"briefTitle":134,"officialTitle":134,"acronym":4,"eligibilityCriteria":135,"healthyVolunteers":136,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":137,"targetDuration":4,"studyType":23,"phases":139,"briefSummary":141,"conditions":142,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":143,"lastUpdatePostDateStruct":144,"startDateStruct":146,"completionDateStruct":148,"leadSponsor":150,"locationsCount":93},"100285345","phase-1-nmda-receptor-antagonist-nitrous-oxide-targets-affective-brain-circuits-100285345","NCT02994433","NMDA Receptor Antagonist Nitrous Oxide Targets Affective Brain Circuits","Inclusion Criteria:\n\n* Adults 18-65 years of age\n* Right-handed\n* Controls: Not meet The Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depressive disorder (MDD) by scoring ≤7 on the Hamilton Depression Rating Scale (HDRS), 17-item; Treatment-Resistant Major Depression (TRMD) patients: Must meet a ≥17 score on the HDRS.\n* Controls: Must not have any history of depression as determined by reported history and medical record review; TRMD: Documented (chart review) failure to respond to ≥3-4 adequate dose\u002Fduration antidepressant treatments; ≥1 in the current depressive episode.\n* Good command of the English language\n\nExclusion Criteria:\n\n* Meets criteria for any DSM-IV Axis I diagnosis as documented in medical records and as determined by structured clinical interview (except MDD for the TRMD group)\n* Known primary neurological disorders or medical disorders including dementia, stroke, encephalopathy Parkinson's Disease, brain tumors, multiple sclerosis, seizure disorder, severe cardiac or pulmonary disease\n* Any central nervous system active medication as determined by study investigator\n* Any known disease affecting drug metabolism and excretion (e.g. renal or liver disease) as determined by study investigator\n* Left-handedness\n* Not eligible for MRI scans (e.g. history of claustrophobia\u002Fimplanted metal as per MRI Screening Tool)\n* Current use of psychotropic medications, antidepressants, or prescription or non-prescription drugs\u002Fherbals intended to treat depression or anxiety (control group only)\n* Any recent (within past 12 months) history of substance dependence or abuse, determined by reported history or urine drug screen\n* Ability to become pregnant and not using effective contraception\n* Contraindication against the use of nitrous oxide:\n\n  1. Pneumothorax\n  2. Bowel obstruction\n  3. Middle ear occlusion\n  4. Elevated intracranial pressure\n  5. Chronic cobalamin and\u002For folate deficiency treated with folic acid or vitamin B12\n  6. Pregnant patients\n  7. Breastfeeding women\n* Inability to provide informed consent\n* Any other factor that in the investigators' judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic).",true,{"count":138,"type":22},60,[140],"PHASE1","Most clinical major depression responds to standard treatments (medication and psychotherapy); however, a significant subset of depressed patients (15-20%) do not respond to these treatments and are referred to as treatment-resistant major depression (TRMD). New treatments for TRMD are needed, and one promising line of research are drugs known as N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. In a recent pilot study, our group demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD. This application proposes to take the next important step in understanding how nitrous oxide exerts its effects in the human brain by using state-of-the-art brain neuroimaging (functional connectivity magnetic resonance imaging) in a group of non-depressed, healthy volunteers and comparing the results to a group of TRMD patients.\n\nThis study involves exposing approximately 25 non-depressed healthy participants and 25 TRMD participants to nitrous oxide and a placebo gas, to compare their brain images before and after each of the inhalation sessions. Sessions will be separated by at least one month to prevent treatment effects from carrying over into the following session. All willing and eligible subjects will undergo up to six functional connectivity MRI scans, and two inhalation sessions. Functional imaging in the brain will allow us to trace the interconnections between various parts of the brain, including those involved with emotion and depression.\n\nOther procedures will involve screening materials to ensure safety of the participants before beginning the study (i.e. no MRI scan contraindications) and that subjects meet eligibility criteria to being in the targeted age range, depression\u002Fnon-depressed state, neurological disorder history, and no medication exclusions.",[68,29],"2026-04-24",{"date":145,"type":41},"2026-04-29",{"date":147,"type":41},"2017-01-27",{"date":149,"type":22},"2027-04-30",{"name":151,"class":152},"Washington University School of Medicine","OTHER",{"id":154,"slug":155,"hasResults":11,"nctId":156,"briefTitle":157,"officialTitle":158,"acronym":4,"eligibilityCriteria":159,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":160,"targetDuration":4,"studyType":23,"phases":162,"briefSummary":164,"conditions":165,"keywords":166,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":171,"lastUpdatePostDateStruct":172,"startDateStruct":174,"completionDateStruct":176,"leadSponsor":178,"locationsCount":180},"100483077","rtms-with-and-without-text4support-for-the-treatment-of-resistant-depression-100483077","NCT05570344","rTMS With and Without Text4Support for the Treatment of Resistant Depression.","Repetitive Transcranial Magnetic Stimulation With and Without Text4Support for the Treatment of Resistant Depression: Patient-centered Multicentral Randomized Controlled Pilot Trial. Protocol.","Inclusion Criteria:\n\n* aged 18 and above and diagnosed with MDD based upon the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and who have at least failed two or more standard antidepressant treatments during the current episode. Participants may be on psychotropic medications including antidepressants, antipsychotics, benzodiazepines, and anticonvulsants. They must have a good understanding of the English language. Must have access to a smartphone and be able to receive and read text messages. Must be willing to provide written informed consent upon acceptance into the study.\n\nExclusion Criteria:\n\n* Patients below the age of 18.\n* Having diagnosis such as the following conditions (current unless otherwise stated): A neurological disorder, including a history of seizures, having primary or secondary tumors in the central nervous system, cerebrovascular disease, stroke, cerebral aneurysm, movement disorder,\n* Having a current psychotic disorder such as substance-induced psychosis, psychotic disorder due to a medical condition, or MDD with psychotic features at the time of screening\n* Having a current personality disorder that may hinder the patient's participation in this research or may have the potential of affecting cognition and ability to fully participate in the study.\n* Having a learning disability as per identified through medical history or by the investigator during the assessment process.\n* Participants involved in any drug or device clinical trial within the last six weeks before the screening visit and\u002For involvement in another clinical trial for the duration of this study.\n* Pregnant and breastfeeding women.\n* Identification and\u002For the sudden appearance of any condition or instance from the mentioned above and based on the expertise of the investigators that have the potential to hinder the progress and completion and\u002For become a confounding factor on the outcome assessments.",{"count":161,"type":22},200,[163],"NA","This study is a multicenter prospective, parallel design, two-arm, rater-blinded randomized controlled pilot trial. Participants will be randomly assigned to one of two treatment conditions. In the first condition, treatment consists of rTMS sessions combined with Text4Support. The second condition is made up of the treatment as usual (rTMS sessions alone). The recruitment process is scheduled to last 12 months. It will involve active treatment for six weeks and follow-up period observation periods of 1,3, and 6 months for participants in both arms of the study. Participants will be recruited from four different centers for this project. Two centers (the Addiction and Mental Health clinic and the Alberta day hospital) will be from the large, sociodemographic diverse city of Edmonton in Alberta Western Canada. The remaining two centers will be in Halifax and Annapolis Valley in Nova Scotia, Canada.",[29],[167,168,169,170],"Repetitive Transcranial Magnetic Stimulation","Treatment of Resistant Depression","Patient - Centered Randomized Controlled Pilot Trial","Supportive Text messages (Text4Support)","2026-04-07",{"date":173,"type":41},"2026-04-13",{"date":175,"type":41},"2023-02-01",{"date":177,"type":22},"2026-12-31",{"name":179,"class":152},"University of Alberta",2,{"id":182,"slug":183,"hasResults":11,"nctId":184,"briefTitle":185,"officialTitle":185,"acronym":186,"eligibilityCriteria":187,"healthyVolunteers":11,"sex":17,"minAge":188,"maxAge":4,"enrollmentInfo":189,"targetDuration":4,"studyType":23,"phases":191,"briefSummary":192,"conditions":193,"keywords":196,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":201,"lastUpdatePostDateStruct":202,"startDateStruct":204,"completionDateStruct":206,"leadSponsor":208,"locationsCount":180},"100581750","accelerated-vs-conventional-theta-burst-stimulation-for-late-life-depression-100581750","NCT06854367","Accelerated vs. Conventional Theta Burst Stimulation for Late-life Depression","ACT-LLD","Inclusion Criteria:\n\n1. are voluntary and competent to consent to treatment\n2. are an outpatient\n3. are ≥ 60 years old\n4. have a Mini International Neuropsychiatric Interview (MINI 7.0) confirmed diagnosis of MDD, with a current MDE\n5. have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of ≥ 3 in the current episode or have failed to tolerate two separate trials of an antidepressant\n6. have a score ≥ 10 on the Patient Health Questionnaire (PHQ-9)\n7. have had no increase or initiation of any antidepressant or antipsychotic medication in the 4 weeks prior to screening\n8. are able to adhere to the treatment schedule\n9. pass the TMS adult safety screening (TASS) questionnaire\n\nExclusion Criteria:\n\n1. have a Mini International Neuropsychiatric Interview (MINI 7.0) confirmed diagnosis of substance dependence or abuse within the last 3 months\n2. have a concomitant major unstable medical illness as determined by one of the study physicians\n3. have active suicidal intent\n4. have presumed or probable dementia or clinical evidence of dementia as assessed by Short Blessed Test score ≥ 10\n5. have a lifetime MINI diagnosis of bipolar I or II disorder, or primary psychotic disorder\n6. have current psychotic symptoms\n7. have a diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD\n8. have a diagnosis of any personality disorder as assessed by a study investigator to be primary and causing greater impairment than MDD\n9. did not respond to a course of ECT in the current depressive episode\n10. have received rTMS in the current episode; patients who have had rTMS in a previous episode would be eligible\n11. have a history of a primary seizure disorder or a seizure associated with an intracranial lesion\n12. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed\n13. have an implanted electronic device that is currently in function such as a defibrillator\n14. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)\n15. have clinically significant laboratory abnormality, in the opinion of a study investigator\n16. currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant\n17. if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study","60 Years",{"count":190,"type":22},280,[163],"The purpose of this trial is to compare the treatment efficacy (improvement in depressive symptoms) of accelerated TBS protocol (where participants receive multiple TBS treatments daily) to conventional TBS protocol (where participants receive a single TBS treatment daily) in late life depression. In addition, the study also aims to determine if specific patterns of stimulation are more or less effective. To do this, all participants will receive active treatments, but some of the participants in this study will receive accelerated TBS and some will receive once daily TBS.",[194,195,29,72],"Late Life Depression (LLD)","Depression - Major Depressive Disorder",[197,198,199,200],"Brain stimulation","rTMS","Theta burst stimulation","Accelerated theta burst stimulation","2026-01-27",{"date":203,"type":41},"2026-01-28",{"date":205,"type":41},"2025-03-27",{"date":207,"type":22},"2029-12",{"name":209,"class":152},"Centre for Addiction and Mental Health",{"id":211,"slug":212,"hasResults":11,"nctId":213,"briefTitle":214,"officialTitle":215,"acronym":216,"eligibilityCriteria":217,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":218,"targetDuration":4,"studyType":23,"phases":220,"briefSummary":221,"conditions":222,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":223,"lastUpdatePostDateStruct":224,"startDateStruct":226,"completionDateStruct":228,"leadSponsor":230,"locationsCount":93},"100435883","effects-of-a-classic-high-frequency-rtms-treatment-versus-a-deep-rtms-treatment-100435883","NCT04956016","Effects of a Classic High-frequency rTMS Treatment Versus a Deep rTMS Treatment","Open-label Randomized Comparative Study of the Effects of a Classic High-frequency rTMS Treatment Versus a Deep rTMS Treatment in the Management of Resistant Depression","HAUVERDEEP","Inclusion Criteria:\n\n* Volunteer subjects over 18 years old\n* Having signed a free and informed consent\n* Having a diagnostic of caracterised depressive episod recurrent or isolated according to DSM IV criteria (A.P.A 1994).\n* Having an antidepressant treatment not modified since 3 weeks\n* Score to MADRS scale ≥ 21\n* Subject affiliated to a social security regimen\n\nExclusion Criteria:\n\n* Depression with psychotic caracteristics\n* Co-morbid diagnosis according to axis I (DSM IV) of schizophrenia, dependence (or abuse) on alcohol and \u002F or another substance (lifetime)\n* Patient who has already undergone seismotherapy for current episode and non-responder to this treatment\n* Patient hospitalized under duress or under legal protection (guardianship, curatorship)\n* Patient with a high risk of suicide (item 10 of MADRS \\> 4) in the absence of hospitalization.\n* Contra-indication for IRM exam or rTMS : personnal history of comitial crisis, of neurological or neurochirurgical pathologies, metallic prosthetic material or foreign body (pacemaker, intraoculare ferromagnetic material, implanted cardiac defibrillator, cochlear implant, metal clip\n* Pregnancy\n* Simultaneous participation to another interventionnal study",{"count":219,"type":22},152,[163],"The main objective is to demonstrate that dTMS is more efficient than high frequency rTMS with a conventional coil.\n\nThe patient will receive treatment arm A or B :\n\nArm A : classic rTMS treatment (use of the 8-shaped coil) and standard therapy Arm B: treatment with deep rTMS (use of the H-shaped coil (helmet)) and standard therapies.\n\n20 rTMS sessions are planned (5 sessions per week) and 3 follow-up visits : at Day 30, Day 60 and Day 90.",[29],"2026-01-12",{"date":225,"type":41},"2026-01-13",{"date":227,"type":41},"2021-08-23",{"date":229,"type":22},"2028-08",{"name":231,"class":152},"Centre Hospitalier Henri Laborit",{"id":233,"slug":234,"hasResults":11,"nctId":235,"briefTitle":236,"officialTitle":237,"acronym":238,"eligibilityCriteria":239,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":240,"targetDuration":4,"studyType":23,"phases":242,"briefSummary":243,"conditions":244,"keywords":246,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":253,"lastUpdatePostDateStruct":254,"startDateStruct":256,"completionDateStruct":258,"leadSponsor":260,"locationsCount":93},"100567467","phase-2-intravenous-ketamine-for-treatment-resistant-depression-100567467","NCT06668571","Intravenous Ketamine for Treatment-Resistant Depression","Central and Peripheral GABA and Glutamate Modulation With Intravenous Ketamine for Treatment-Resistant Depression (G2K): A Randomized, Double-Blind, Placebo-Controlled Study","G2K","Inclusion Criteria:\n\n* Ability to provide informed consent\n* Meets diagnostic criteria for major depressive disorder without psychotic features per the SCID DSM-IV-TR\n* PHQ-9 total score ≥ 15 at screening\n* Treatment-resistant depression, as defined by failure of at least two previous antidepressant treatments within the current depressive episode. Failed antidepressant treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, trial of transcranial magnetic stimulation (TMS) or an acute series of at least 6 administrations of electroconvulsive therapy (ECT)\n* Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria\n\nExclusion Criteria:\n\n* Inability to speak English\n* Inability to provide consent or have a legal guardian\n* Patients with a BMI \\> 40 kg\u002Fm2.\n* Personality disorder being the primary diagnosis\n* Diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or active psychotic symptoms\n* Active post-traumatic stress disorder symptoms based on clinical assessment\n* Ongoing prescription of \\> 2 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment\n* Medications known to affect glutamate (i.e., Riluzole, Carbamazepine) or GABA (zaleplon, zolpidem, zopiclone, Valproate, Gabapentin, Pregabalin, tiagabine, and vigabatrin) are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug\n* Monoamine Oxidase Inhibitors (MAOIs) are prohibited two weeks prior to administration of study drug\n* Opioid antagonists (naltrexone, naloxone, nalmefene, methylnaltrexone, buprenorphine and naloxone combination) are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug\n* CYP3A4 inducers carbamazepine and modafinil are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug.\n* Currently undergoing TMS, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression\n* ECT in the past 6 months\n* Any active or unstable medical condition judged by the study psychiatrist as conferring too great a level of medical risk to allow inclusion in the study\n* A history of bleeding in the brain\n* Arteriovenous malformation or a history of aneurysm\n* Use of methamphetamine, cocaine, or cannabis. Abuse of stimulant (s) within the prior 12 months\n* Any current substance use disorder (excluding nicotine and caffeine). Note: Persons will be allowed to enroll in this study if their substance use is in complete (not partial) and sustained (\\> 1 year) remission\n* History of traumatic brain injury that resulted in loss of consciousness with brain bleeding\n* History of tonic-clonic (grand mal) seizures\n* Developmental delay, intellectual disability, or intellectual disorder\n* Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months\n* Minor or Major Neurocognitive disorder\n* Received ketamine treatment for depression within the prior 2 months\n* History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered\n* History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 3 months\n* Hepatic insufficiency (2.5 X ULN for AST or ALT) within 3 months of consent, past liver transplant recipient, and\u002For clinical diagnosis of cirrhosis of the liver\n* Gastroesophageal reflux disease that is poorly managed\n* A diagnosis of Complex Regional Pain Syndrome (CRPS)\n* Pregnancy, or nursing\n* History of claustrophobia with active symptoms that would interfere with the MRI\n* Any contraindication to MRI safety questionnaire\n* Poorly controlled hypertension.",{"count":241,"type":22},30,[25],"The purpose of this study is to to evaluate the relationships between peak (% change from baseline) central GABA and Glu levels during a 40-min IV ketamine or normal saline infusion utilizing fMRS, and change in peripheral GABA and Glu levels from baseline to 24-hr postinfusion utilizing LCMS, with baseline to 24-hr post-infusion change in depression (MADRS) in 30 TRD adults.",[29,245],"Treatment Resistant Depression (TRD)",[247,29,248,249,250,251,36,252],"Major Depression","MDD","TRD","Treatment-Resistant Depression","Treatment-Resistant Major Depression","Intravenous Ketamine","2025-10-09",{"date":255,"type":41},"2025-10-14",{"date":257,"type":41},"2025-02-10",{"date":259,"type":22},"2027-12-31",{"name":261,"class":152},"Mayo Clinic",{"id":263,"slug":264,"hasResults":11,"nctId":265,"briefTitle":266,"officialTitle":267,"acronym":268,"eligibilityCriteria":269,"healthyVolunteers":11,"sex":17,"minAge":270,"maxAge":19,"enrollmentInfo":271,"targetDuration":4,"studyType":23,"phases":273,"briefSummary":274,"conditions":275,"keywords":279,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":288,"lastUpdatePostDateStruct":289,"startDateStruct":291,"completionDateStruct":293,"leadSponsor":295,"locationsCount":297},"100488554","phase-2-osu6162-as-add-on-in-ssrisnri-resistant-depression-100488554","NCT05641623","OSU6162 as add-on in SSRI\u002FSNRI-resistant Depression","OSU6162 as add-on in SSRI\u002FSNRI-resistant Depression (ODEN): a Double-blind, Placebo-controlled Evaluation of Efficacy and Safety","ODEN","Inclusion Criteria\n\nIn order to be included in the study, subjects must meet the following criteria:\n\n1. Signed informed consent.\n2. Age: 25-65 on the day of screening.\n3. Meeting DSM-5 criteria for major depressive disorder as confirmed by the Mini International Neuropsychiatric Interview (MINI).\n4. A symptom-free period preceding the current episode within the past two years confirmed at interview.\n5. Not significantly improved, as judged by both doctor and patient, after having been treated with one of the following SSRIs\u002FSNRIs: citalopram, escitalopram, paroxetine, sertraline, fluoxetine, duloxetine, or venlafaxine for at least 6 weeks.\n6. Displaying a sum score of MADRS ≥22.\n7. In women of childbearing potential (WOCBP): negative result of a pregnancy test and a method of contraception with a failure rate of less than 1 %. Contraception must be used during the treatment and follow-up period. Acceptable forms of contraception are:\n\n   1. Use of combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation\n\n      * oral\n      * intravaginal\n      * transdermal\n   2. progestogen-only hormonal contraception associated with inhibition of ovulation:\n\n      * oral\n      * injectable\n      * implantable\n   3. Placement of intrauterine device (IUD) or intrauterine hormone releasing system (IUS)\n   4. Bilateral tubal occlusion or ligation\n   5. Vasectomised partner (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate and provided that male partner is the sole sexual partner of the WOCBP trial participant).\n   6. Sexual abstinence.\n8. Male patients must agree to use condoms during the study and for 2 weeks after the end of the study\u002Flast dose of IMP, unless their partner is using a highly efficient method of contraception, as described above.\n\nExclusion criteria\n\nSubjects must not be included in the study if any of the following criteria are met:\n\n1. Meeting MINI criteria at interview for suicidality, manic episode, hypomanic episode, bipolar I, bipolar II, bipolar unspecified, bipolar I with psychotic symptoms, panic disorder (current), agoraphobia, posttraumatic stress disorder, alcohol dependency, alcohol abuse, substance dependency (non-alcoholic), substance abuse (non-alcoholic), psychotic disorders, mood disorders with psychotic features, anorexia nervosa, bulimia nervosa, anorexia nervosa binge eating \u002F purging type, or antisocial personality disorder.\n\n   Meeting MINI criteria at interview for generalised anxiety disorder, obsessive compulsive disorder or social anxiety (social phobia), unless the present symptoms can predominantly be attributed to a diagnosis of major depressive disorder.\n2. A history of substance\u002Falcohol abuse within 2 years prior to screening.\n3. A previous diagnosis of a personality disorder, autism spectrum disorder, attention-deficit\u002Fhyperactivity disorder, or intellectual disability.\n4. Any other previously diagnosed or suspected CNS disorder that according to the investigator renders the patient unsuitable for participation in the trial.\n5. Any factor that according to the investigator renders it unlikely that the patient will comply with the instructions regarding treatment, visits etc.\n6. Any somatic illness that according to the investigator renders the patient unsuitable for participation in the trial.\n7. Any signs or symptoms of somatic illness resulting from assessment of vital signs, physical examination, clinical laboratory tests, and 12-lead ECG that according to the investigator renders the patient unsuitable for participation for safety reasons, including a QTc-time on ECG exceeding 450 ms in men and 460 ms in women.\n8. Any change in dosage of said SSRI\u002FSNRI within 4 weeks prior to screening or at any time during the course of the trial.\n9. Treatment with any other psychoactive drug than said SSRI\u002FSNRI with the exception of using mirtazapine up to 15 mg for sleep, occasional use of benzodiazepines and benzodiazepine-like anxiolytics or hypnotics and occasional use of antihistaminergic sedatives (without anti-dopaminergic effects) within 4 weeks prior to screening and at any time during the course of the trial.\n10. Patients who are receiving concomitant therapy with potent cytochrome P450 enzyme inhibitors (e.g., bupropion, fluvoxamin, ketoconazole, itraconazole, telithromycin, clarithromycin, protease inhibitors, quinidine, and terbinafine).\n11. Ongoing treatment with drugs with a narrow therapeutic window where either lower or higher serum levels are potentially harmful (including but not limited to warfarin along with other anticoagulants, digoxin along with other antiarrythmics, anticonvulsants prescribed for treatment of epilepsy, cyclosporine, immunosuppressants, and lithium).\n12. Current treatment with any prescribed or OTC drug that according to the investigator renders the subject unsuitable for participation in the trial.\n13. Previous intake of OSU6162.\n14. Current participation in another clinical trial.\n15. Nursing women.","25 Years",{"count":272,"type":22},180,[25],"This is a randomised, placebo-controlled, parallel-group trial comparing OSU6162 at flexible dosage with placebo as add-on to treatment with an SSRI\u002FSNRI in patients with depression that have not responded to treatment with an SSRI\u002FSNRI per se for at least 6 weeks. The study will last for 6 weeks, after which those not having responded will leave the trial and those having responded will be offered to continue treatment without unblinding for another 4 weeks. Optional Substudy 1 and 2: Baseline and treatment-associated change in reward-related striatal activity per fMRI-assessment. (Substudy 1).\n\nBrain signal variability per fMRI-assessment. (Substudy 1). Probabilistic Reward Task (PRT). (Substudy 2).\n\nWhile assessment of the efficacy and safety of OSU6162 is the main objective of this study, possible differences between the two treatment groups with respect to a number of biomarkers in serum will also be explored.\n\nMulticenter trial: Multiple sites four Gothenburg, Lund, Stockholm and Uppsala.",[70,29,69,276,277,278],"Depressive Episode","Recurrent Depressive Disorder","Recurrent Depression",[280,281,282,283,284,285,286,287],"Antidepressant","drug therapy, combination","Dopamine Drugs","Dopamine","Selective Serotonin Reuptake Inhibitor","SNRI","SSRI","Serotonin and Norepinephrine Reuptake Inhibitors","2025-03-19",{"date":290,"type":41},"2025-03-24",{"date":292,"type":41},"2022-04-21",{"date":294,"type":22},"2026-08-31",{"name":296,"class":152},"Göteborg University",4,{"id":299,"slug":300,"hasResults":11,"nctId":301,"briefTitle":302,"officialTitle":303,"acronym":4,"eligibilityCriteria":304,"healthyVolunteers":11,"sex":17,"minAge":19,"maxAge":4,"enrollmentInfo":305,"targetDuration":4,"studyType":23,"phases":307,"briefSummary":308,"conditions":309,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":311,"lastUpdatePostDateStruct":312,"startDateStruct":314,"completionDateStruct":316,"leadSponsor":318,"locationsCount":93},"100422613","neuromodulation-in-the-elderly-depressed-a-brain-imaging-pilot-study-100422613","NCT04783103","Neuromodulation in the Elderly Depressed: a Brain Imaging Pilot Study","Neuromodulation in the Elderly Depressed: a Brain Im-aging Pilot Study","Inclusion Criteria:\n\n* • In- and outpatients (age 65 year or older).\n\n  * Meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM 5) criteria for unipolar depression according 17-item Hamilton depression rating scale (HDRS-17) score of 17 or more.\n  * Failed to respond to at least one adequate course with an antidepressant medication trial, including the current one.\n  * Intention to continue the current (\\>6 weeks) antidepressant treatment at a stable dose dur-ing the stimulation.\n  * Benzodiazepines are permitted up to a maximum dose of 40 mg diazepam or equivalent. If the dosage has been recently changed, it should be stable for at least 2 weeks.\n  * Able to read, understand and sign the Informed Consent Form.\n\nExclusion Criteria:\n\n* • Psychosis (except depression with psychotic features).\n\n  * A personal history of seizures or epilepsy, a history of seizures or epilepsy in first degree relatives and the presence of any known factor that can lower the seizure threshold (sleep deprivation, substance abuse, etc.), previous head injury and the presence of metallic implants in the cephalic region (e.g., aneurysm clips, shunts, stimulators, cochlear implants, electrodes) with the exception of dental fillings. The presence of cardiac pacemakers, neurostimulators, surgical clips or other electronic equipment, comorbidity with the following neurological disorders: increased intracranial pressure, space-occupying lesion, history of stroke or transient ischemic attack, brain aneurysm and any structural brain damage with increased risk for epilepsy detected with (study related) MRI.\n  * Patients with cognitive disturbances or dementia (Mini Mental State) \\\u003C 24.\n  * Suicide attempt within 6 months before the start of the study or present high risk of suicide per the investigator's clinical judgment and indicative response\\* on the Columbia-Suicide Severity Rating Scale (C-SSRS) and 21-items Beck Scale for Suicide Ideation (BSI). \\*'yes' on Item 5 (active suicidal ideation with specific plan and intent).\n  * Any change in the habitual psychopharmacological agents will be considered as dropout.",{"count":306,"type":22},44,[163],"To evaluate safety and efficacy of an accelerated deep brain Transcranial Magnetic stimulation (adTMS) and transcutaneous direct current stimulation (tDCS) protocol in an elderly depressed patient population",[310,29],"Old Age","2022-11-02",{"date":313,"type":41},"2022-11-03",{"date":315,"type":41},"2021-05-07",{"date":317,"type":22},"2026-07",{"name":319,"class":152},"Universitair Ziekenhuis Brussel"]