[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"treatment-resistant-depression-trd\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:treatment-resistant-depression-trd":96},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,27,0,25,[9,46,79,116,142,171,206,229,253,279,302,329,350,379,410,446,467,488,508,531,555,576,604,630,655],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":16,"eligibilityCriteria":17,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":21,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":45},"100645335","phase-4-biomarker-guided-antidepressant-selection-100645335",false,"NCT07680140","Biomarker-Guided Antidepressant Selection","Biomarker-Guided Antidepressant Selection for Treatment-Resistant Depression","BioSelect","Inclusion Criteria:\n\n1. Provision of signed and dated informed consent form\n2. Adults of all genders aged 18-70 at the time of screening\n3. Diagnosis of Major Depressive Disorder (by DSM-5 criteria)\n4. Depressive symptoms of at least moderate severity (GRID HDRS-17 score \\>= 14 or as determined by a study clinician)\n5. Failed at least 1 prior trial of standard first-line treatment for MDD per the modified Antidepressant Treatment History form, the Maudsley Staging Method, and APA Practice Guidelines (e.g., SSRI, SNRI, CBT) OR initiated and discontinued a trial of a first-line treatment for MDD (e.g. could not tolerate side effects, etc.)\n6. Not currently taking antidepressants OR on a stable dose of antidepressant for at least 1month prior to screening and plans to remain off antidepressants OR on this stable dose for the duration of participation\n7. Current medication regimen is compatible with safe participation in the trial in the assessment of a study clinician\n8. Access to psychiatric care before, during, and after completion of the study\n9. For females of reproductive potential: agreement to use effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation\n10. Proficiency in English sufficient to complete assessments and follow study procedure instructions\n11. Stated willingness to comply with all study procedures and availability for the duration of the study\n\nExclusion Criteria:\n\n1. Imminent risk of suicide\n2. Presence of primary psychiatric diagnosis other than MDD (e.g., post-traumatic stress disorder, obsessive-compulsive disorder, MDD with psychotic features, primary psychotic illness, bipolar I or II disorder)\n3. History of epilepsy or a history of seizures that would influence the participant's risk for TMS-evoked seizures; history of any condition \u002F concurrent medication that could notably lower seizure threshold in the estimation of a study clinician\n4. Met criteria for any clinically significant substance use disorder (by DSM-V criteria) with active substance misuse in the 6 months prior to screening\n5. Lifetime history of PCP\u002Fketamine abuse\n6. History or presence of significant neurological disorder that may be contributing to current depressive symptoms in the judgment of a study clinician (e.g., traumatic brain injury, stroke, Parkinson's disease or other movement disorder, epilepsy)\n7. Presence of medical contraindications to ketamine, including liver function tests \\> 2.5x normal limit, recent myocardial infarction, congestive heart failure \\> stage 2, angina pectoris, clinically significant bradycardia or tachycardia at the baseline assessment, or uncontrolled hypertension\n8. MRI contraindication, including presence of ferromagnetic foreign metal bodies or implants, implanted or conductive ferromagnetic objects in or near the head (e.g., stents, deep brain stimulators, vagus nerve stimulators, aneurysm coils, ocular implants, cochlear implants), and ferromagnetic permanent make-up that may undergo heating in an MRI scanner\n9. Individuals who are nursing, pregnant, or contemplating pregnancy within the length of study participation\n10. Abnormal bloodwork that may be contributing to depressive symptoms in the estimation of a study clinician (e.g. indicators of clinically significant hypothyroidism, kidney failure, liver failure, etc.)\n11. History or presence of any disorder or medical condition that, in the opinion of the study team, may compromise, interfere, or limit the individual's ability to complete the intervention or study procedures","ALL","18 Years","70 Years",{"count":5,"type":22},"ESTIMATED","INTERVENTIONAL",[25],"PHASE4","Depression is one of the leading causes of disability worldwide. Common treatments like antidepressant medications and talk therapy work well for some people, but many others do not improve, even after trying multiple treatments.\n\nThis study will investigate two alternative treatment options for people whose depression has not responded to standard treatments: repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, and ketamine, a fast-acting medication. It can be difficult to decide between these interventions in clinical practice, and selecting between them often comes down to patient preference and trial and error. This study is working to optimize the selection approach: using biological and behavioral markers to match each person to identify biomarkers that may predict response to rTMS or ketamine. Investigators believe that differences in how individuals respond to rTMS versus ketamine are partly explained by differences in how their brains are organized, and that these differences can be measured and used to guide intervention decisions. This is an early-stage pilot study designed to test whether this biomarker-based approach is practical and acceptable to patients. Investigators will evaluate how well a combination of brain imaging and clinical data can predict, at the individual level, who is likely to respond to rTMS versus ketamine. The ultimate goal is to develop a reliable, scalable tool that helps clinicians make faster and more informed intervention decisions, reducing the time people with treatment-resistant depression spend searching for an antidepressant that works.",[28,29,30,31,32],"Depression - Major Depressive Disorder","Treatment-resistant Depression (TRD)","rTMS","Ketamine","fMRI","NOT_YET_RECRUITING","2026-06-25",{"date":36,"type":37},"2026-07-02","ACTUAL",{"date":39,"type":22},"2026-07",{"date":41,"type":22},"2028-12",{"name":43,"class":44},"Weill Medical College of Cornell University","OTHER",1,{"id":47,"slug":48,"hasResults":12,"nctId":49,"briefTitle":50,"officialTitle":51,"acronym":52,"eligibilityCriteria":53,"healthyVolunteers":54,"sex":18,"minAge":19,"maxAge":55,"enrollmentInfo":56,"targetDuration":4,"studyType":23,"phases":58,"briefSummary":60,"conditions":61,"keywords":63,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":69,"lastUpdatePostDateStruct":70,"startDateStruct":72,"completionDateStruct":74,"leadSponsor":76,"locationsCount":45},"100644817","relationship-of-peripheral-inflammatory-and-neuroprotective-biomarkers-with-response-to-intermittent-theta-burst-stimulation-in-treatment-resistant-depression-100644817","NCT07673913","Relationship of Peripheral Inflammatory and Neuroprotective Biomarkers With Response to Intermittent Theta Burst Stimulation in Treatment-Resistant Depression","Relationship Between Response to Transcranial Magnetic Stimulation and Peripheral Inflammatory and Neuroprotective Biomarkers in Patients With Treatment-Resistant Depression","TRD-BIOTMS","Inclusion Criteria:\n\nTreatment-Resistant Depression Group:\n\nAge between 18 and 55 years. Male or female participants. Diagnosis of Major Depressive Disorder according to DSM-5-TR criteria. Inadequate response to at least two antidepressant treatments administered at adequate doses and durations.\n\nEligible for transcranial magnetic stimulation (TMS) treatment. Able and willing to provide written informed consent. Able to complete neuropsychological assessments. Able to attend study visits and complete the treatment protocol.\n\nHealthy Control Group:\n\nAge between 18 and 55 years. Male or female participants. No current DSM-5-TR psychiatric disorder. Able and willing to provide written informed consent. Able to complete neuropsychological assessments.\n\nExclusion Criteria:\n\nSchizophrenia, bipolar disorder, organic mental disorders, or other major psychiatric disorders.\n\nHistory of epilepsy, brain tumor, severe head trauma, or significant neurological disease.\n\nAny contraindication to TMS. Presence of intracranial metal implants, cardiac pacemakers, cochlear implants, or other incompatible implanted devices.\n\nActive infection. Autoimmune disease or chronic inflammatory disease. Electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation within the previous 5 years.\n\nPrevious intravenous or intranasal ketamine treatment. Pregnancy or breastfeeding. Active alcohol or substance use disorder. Inability to comply with study procedures. Inability to tolerate the iTBS protocol. Withdrawal of informed consent at any stage of the study.",true,"55 Years",{"count":57,"type":22},100,[59],"NA","Treatment-resistant depression (TRD) is a major clinical challenge affecting a substantial proportion of patients with major depressive disorder who do not adequately respond to conventional antidepressant treatments. Intermittent theta burst stimulation (iTBS), a non-invasive neuromodulation technique targeting the left dorsolateral prefrontal cortex, has emerged as an effective treatment option for these patients. However, the biological mechanisms underlying treatment response remain poorly understood.\n\nThis single-center, prospective, investigator-initiated clinical study aims to investigate the effects of iTBS on clinical symptoms, executive functions, and peripheral inflammatory and neuroprotective biomarkers in patients with treatment-resistant depression.\n\nFifty patients with treatment-resistant depression and fifty healthy control participants will be enrolled. Patients will receive active iTBS treatment for four weeks (20 sessions), while healthy controls will undergo baseline clinical, cognitive, and biological assessments without receiving any intervention.\n\nClinical outcomes will be evaluated using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Patient Health Questionnaire-9 (PHQ-9), Clinical Global Impression (CGI), and Insomnia Severity Index (ISI). Executive functions will be assessed using the Wisconsin Card Sorting Test, Trail Making Test A and B, and verbal fluency tests.\n\nPeripheral blood samples will be collected before and after treatment to measure inflammatory, neuroplasticity, and neuroprotective biomarkers, including IL-1β, IL-6, IL-10, TNF-α, high-sensitivity C-reactive protein (hs-CRP), brain-derived neurotrophic factor (BDNF), apolipoprotein D (APOD), serum amyloid A1 (SAA1), and serum amyloid A2 (SAA2). Gene expression analyses will also be performed using quantitative polymerase chain reaction (qPCR).\n\nThe study aims to identify biological mechanisms associated with iTBS treatment response and to explore potential biomarkers that may predict clinical improvement in patients with treatment-resistant depression. The findings may contribute to the development of personalized neuromodulation strategies and biomarker-guided treatment approaches for depression.",[29,62],"Major Depression",[64,65,66,67,68],"Treatment-Resistant Depression","Transcranial Magnetic Stimulation","Biomarkers","Personalized Psychiatry","Neuromodulation","2026-06-23",{"date":71,"type":37},"2026-06-29",{"date":73,"type":22},"2026-09-01",{"date":75,"type":22},"2027-09-01",{"name":77,"class":78},"Gulhane Training and Research Hospital","OTHER_GOV",{"id":80,"slug":81,"hasResults":12,"nctId":82,"briefTitle":83,"officialTitle":84,"acronym":85,"eligibilityCriteria":86,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":87,"enrollmentInfo":88,"targetDuration":4,"studyType":23,"phases":90,"briefSummary":93,"conditions":94,"keywords":97,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":106,"lastUpdatePostDateStruct":107,"startDateStruct":109,"completionDateStruct":110,"leadSponsor":112,"locationsCount":115},"100610401","phase-2-a-randomized-double-blind-controlled-comparison-of-nrx-101-vs-placebo-for-adults-being-treated-with-robotic-transcranial-magnetic-stimulation-for-treatment-resistant-depression-the-sparc-tms-trial-100610401","NCT07227103","A Randomized, Double-Blind Controlled Comparison of NRX-101 vs. Placebo for Adults Being Treated With Robotic Transcranial Magnetic Stimulation for Treatment Resistant Depression: The SPARC-TMS Trial","A Randomized, Double-Blind Controlled Comparison of NRX-101 vs. Placebo for Adults Being Treated With Transcranial Magnetic Stimulation for Treatment Resistant Depression: The SPARC-TMS Trial","SPARC-TMS","18 to 65 years of age, inclusive, at Screening. 2. Participants must be initiating a new course of TMS treatment and must be TMS-naïve. 3. Able to understand and provide written and dated informed consent prior to Screening. 4. Deemed likely to comply with the study protocol, including communication of adverse events (AEs) and other clinically important information, including adherence to the text messaging component of the trial. 5. Previously diagnosed with major depressive disorder (MDD) according to the criteria defined in the DSM-5. 6. Has treatment-resistant MDD defined as failure to achieve an adequate response after at least two adequate antidepressant trials of different agents, each given at a therapeutic dose and for sufficient duration. 7. A total score ≥ 25 on the 10 items of the MADRS. 8. Has an identified reliable informant\u002Fcare partner that is willing to provide information and\u002For supportive care as necessary. 9. If heterosexual female, a status of non-childbearing potential or use of an acceptable form of birth control per the following criteria, and agrees to continue use of the same method of birth control for the duration of study participation:\n\n1. Non-childbearing potential: physiologically incapable of becoming pregnant (i.e., permanently sterilized \\[status posthysterectomy, bilateral tubal ligation\\], or post-menopausal with last menses at least one year prior to Screening); or\n2. Childbearing potential, and meets the following criteria:\n\ni. Must agree to use at least one highly effective method of birth control (methods which result in a failure rate of less than 1% per year when used consistently and correctly) during study participation. Examples of acceptable highly effective methods include established use of oral, injected, implanted, or intrauterine hormonal contraception; placement of an intrauterine device or intrauterine system; or a vasectomized partner with documented azoospermia; or true sexual abstinence that is the participant's usual and preferred lifestyle. ii. Negative urinary pregnancy test at Screening, confirmed by a second negative urinary pregnancy test at Day 1, prior to receiving study treatment. 10. Body mass index (BMI) between 18-40 kg\u002Fm2; BMI up to 45 kg\u002Fm2 is allowed with Medical Monitor review and approval. 11. If receiving concurrent psychotherapy, the type and frequency of the therapy (e.g., weekly or monthly) has been stable for at least 3 months prior to Screening and will remain stable for the duration of study participation. 12. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, benzodiazepines, maximum 2 mg daily, or trazodone) will be allowed if the therapy has been stable for at least 4-weeks prior to screening and will remain stable during the course of the patient's participation in the study. 13. Concurrent treatment with benzodiazepines is allowed up to a maximum dose 2 mg\u002Fdaily used for anxiety if therapy has been stable relative to dose and schedule for at least 4 weeks prior to screening and if it is expected to remain stable during the course of the patient's participation in the study. Exclusion criteria: A patient is ineligible for inclusion in this study Heterosexual female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. 2. Female who is pregnant (positive pregnancy test at Screening) or breastfeeding. 3. Active suicidality (without the intention to act) as evidenced by a score of \\>3 on the Columbia Suicide Severity Rating Scale. 4. Current DSM-5 diagnosis of moderate or severe substance use disorder (except marijuana or tobacco use disorder) within the 12 months prior to Screening. (Note: Substance use disorder cannot be the precipitant for study entry). 5. Current DSM-5 diagnosis of alcohol use disorder 6. A lifetime history of phencyclidine (PCP)\u002Fketamine drug abuse 7. History of schizophrenia or schizoaffective disorder 8. History of anorexia nervosa, bulimia nervosa, eating disorder not otherwise specified (NOS), or other specified feeding and eating disorders (OSFED) within 3 years of Screening. 9. Has dementia, delirium, amnestic, or any other cognitive disorder. 10. Renal impairment defined as estimated glomerular filtration rate (eGFR) \\\u003C 60 mL\u002Fmin, calculated using the 2021 CKD-EPI creatinine equation (racefree). 11. Clinically significant hepatic impairment. Clinically significant hepatic impairment is defined as a history of chronic liver disease (e.g., cirrhosis, chronic hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis) or evidence at Screening of acute liver disease or impaired liver function (e.g., ALT or AST \\>3 × ULN, total bilirubin \\>2 × ULN) or in the opinion of the Investigator. 12. A clinically significant abnormality on the Screening physical examination that may affect safety or study participation, or that may confound interpretation of study results according to the study clinician. 13. Risk factors for neurocardiogenic syncope including history of syncope\u002F presyncope related to noxious stimuli, anxiety, micturation, or posture. 14. Co-morbidities as ascertained by medical history, physical examination (including measurement of vital signs), clinical laboratory evaluations, and electrocardiogram (ECG) which might interfere with compliance or the ability to assess efficacy or safety. 15. Diagnosis of moderate to severe heart disease or current episode of:\n\n1. Myocardial infarction within 1 year of Screening.\n2. Diagnosis of angina pectoris.\n3. Prolonged QTc interval, as measured by Fridericia's correction formula (QTcF) ≥450 msec at Screening for males or ≥ 470 msec for females on 2 of 3 measurements at least 15 minutes apart prior to randomization on Day 1. 16. Diagnosis of chronic lung disease, excluding asthma. 17. Lifetime history of any of the following: neurologic conditions with structural cerebral damage, traumatic brain injury, multiple sclerosis, surgical procedures involving the brain or meninges, meningoencephalitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's Disease, Parkinson's Disease), mental retardation, stroke (ischemic or hemorrhagic), intracranial abscess, or any other disease\u002Fprocedure\u002Faccident\u002Fintervention that, according to the clinician, is deemed associated with significant injury to, or malfunction of, the CNS. 18. History of epilepsy, personal history of seizure, family history of epilepsy or seizure in a first degree relative. 19. Diagnosis of parenchymal or leptomeningeal cancer.\n\nDiabetes mellitus fulfilling any of the following criteria:\n\n1. Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) \\>8.0 percent at Screening.\n2. Admitted to the hospital for treatment of diabetes mellitus or diabetes mellitus-related illness in the past 12 weeks.\n3. Not under physician care for diabetes mellitus.\n4. Not on the same dose of oral hypoglycemic drug(s) and\u002For diet for the 4 weeks prior to Screening. 180645 180645 Protocol NRX101-011\\_ MIND1 V3.0 FINAL Pg. 8 NRX101-011 Protocol v3.0 9 Confidential\n5. Not on the same dose of oral thiazolidinediones (glitazones) for the 8 weeks prior to Screening. 21. Any current or past history of any physical condition which, in the opinion of the investigator, may put the patient at risk or interfere with study results interpretation. 22. On exclusionary concomitant psychotropic and non-psychotropic medications (see Section 9.5) 23. Prescribed more than one agent in each of the following categories at randomization:\n\na. Approved SSRIs. b. Approved serotonin and norepinephrine reuptake inhibitors (SNRIs). c. Approved tetracyclic antidepressants (TeCAs). 24. Currently prescribed oxcarbazepine or carbamazepine. 25. Exclusionary laboratory values or any other clinically significant abnormal laboratory result at Screening. Within normal limits (WNL) will be determined based on lab values of the local lab used. 26. Known allergies to lurasidone or Latuda®, cycloserine or Seromycin®, or the following excipients: mannitol, croscarmellose sodium, magnesium stearate, silicon dioxide, and\u002For hydroxypropylmethylcellulose (HPMC). 27. Participation in any clinical trial with an investigational drug or device within the past 3 months or planned concurrent study participation. 28. Study site personnel and\u002For persons employed by NRx Pharma, Inc., the Contract Research Organization (CRO), the investigator, or study site (i.e., permanent, temporary contract worker, or designee responsible for the conduct of the study), or an immediate family member (i.e., spouse, parent, child, or sibling \\[biological or legally adopted\\]) of such persons. Positive urine toxicity screening for use of any cocaine, opiates, nonprescribed amphetamines, or non-prescribed barbiturates. (Note: cannabinoids or marijuana use is not exclusionary, unless patient meets the DSM-5 criteria for cannabis withdrawal). 30. Patients with pacemakers and\u002For any implants including metal in the head except the mouth (cochlear implant, implanted brain stimulators, aneurysm clips) 31. Individuals with an intracranial lesion or increased intracranial pressure","80 Years",{"count":89,"type":22},400,[91,92],"PHASE2","PHASE3","Major depressive disorder (MDD) is a significant public health problem and leading cause of worldwide disability. Treatment resistance is common in MDD, however, for these individuals, targeted noninvasive brain stimulation is an alternative. Repetitive transcranial magnetic stimulation (rTMS) and more recently, theta-burst stimulation (TBS), are the noninvasive brain stimulation modalities with the largest evidence base in MDD. Although efficacious, an unacceptable proportion of patients do not significantly improve, and several aspects of the TMS parameter space are under investigation to enhance clinical outcomes.\n\nDCS has been shown in a randomized trial of more than double the percent response and remission from traditional TMS. When a one day (ONE-D) TMS protocol was combined with DCS, the measured response rate was 87% at one week.\n\nThis trial will compare response and remission at six weeks following neuronavigated robotic-enabled Transcranial Magnetic Stimulation + NRX-101 (D-cycloserine\u002Flurasidone) vs. TMS+placebo.",[95,96],"Treatment Resistant Depression","Treatment Resistant Depression (TRD)",[98,99,65,100,101,102,103,104,105],"Depression","TRD","TMS","neuronavigation","cycloserine","D-cycloserine","NRX-101","NMDA","2026-06-21",{"date":108,"type":37},"2026-06-24",{"date":73,"type":22},{"date":111,"type":22},"2028-03-31",{"name":113,"class":114},"NeuroRx, Inc.","INDUSTRY",3,{"id":117,"slug":118,"hasResults":12,"nctId":119,"briefTitle":120,"officialTitle":121,"acronym":122,"eligibilityCriteria":123,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":124,"targetDuration":4,"studyType":23,"phases":126,"briefSummary":127,"conditions":128,"keywords":129,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":133,"lastUpdatePostDateStruct":134,"startDateStruct":135,"completionDateStruct":137,"leadSponsor":139,"locationsCount":141},"100512455","treatment-resistant-depression-and-vagus-nerve-stimulation-100512455","NCT05952674","Treatment Resistant Depression and Vagus Nerve Stimulation","Resistant Depression and Vagus Nerve Stimulation : a Medico-economic, Multicenter, Randomized and Open Trial","DepVNS","Inclusion Criteria:\n\n* Patients aged 18 years and older ;\n* Childbearing women must have an efficient contraception for the whole study period\n* Diagnosis of recurrent depressive trouble or persistent depressive disorder or bipolar disorder (according to DSM-5)\n* Start of disorder (defined by the occurrence of the first thymus episode: characterized depressive disorder or maniac episode with or without mixed characteristics) for 5 years or more\n* At least one of the following criteria:\n\n  * Criterion A: current characterized depressive disorder and characterized depressive disorder for at least 12 months during the last 24 months despite at least four treatments lines at appropriate dosage and duration\n  * Criterion B: current treatment by ECT\u002F(Es)Ketamine\u002FTMS and criteria A before the start treatment or ECT\u002F(Es)Ketamine\u002FTMS dependency\n* Patients who, after the nature of the study has been explained to them, have given written consent\n\nExclusion Criteria:\n\n* Know pregnancy or breastfeeding\n* Schizophrenia, schizoaffective disorder or persistent delusional disorder (DSM-5)\n* Characterized depressive disorder with psychotic characteristics within 3 months before the inclusion (DSM-5)\n* Concomitant participation to another interventional research not authorized by the coordinating investigator or the scientific lead. Participation to non-interventional researches is allowed.\n* Patients receiving enforced cares (ASPDT, ASPPI, ASPDRE, etc.)\n* Non-affiliation to a social security regimen or any other social protection regimen\n* Disability, according to the investigator, to understand the study or refusal to sign the study consent form (non-francophone patient, cognitive disorders)\n* Anticipated disability to attend all the visits, treatments and measures planned by the protocol: severe personality disorder, severe substance addiction, severe intellectual development disorder. In any of those cases, the notion of severity is at the indiscretion of the investigator\n\nSecondary Exclusion Criteria:\n\n* Surgical contraindication to the VNS\n* Positive β-HCG (results obtained after the informed consent is signed but before the randomization)",{"count":125,"type":22},166,[59],"Depression is a common illness, affecting 17% of the population over the course of a lifetime. A third of depressions relapses and progresses to recurrence and resistance to treatments. Despite the optimization of antidepressant medical strategies, 20 to 40% of depressions do not respond to treatment. This is particularly worrying as 6% of non-responder patients will die by committing suicide.\n\nDepression has a major impact on quality of life, socio-professional functioning and healthcare consumption.\n\nSometimes, TRD is part of a bipolar illness. In this case, the challenge is even bigger because antidepressants are no well tolerated, further reducing the therapeutic options in case of resistance, the severity and duration of the depressive episodes are the main factors explaining the deterioration of the quality of life and the increasing cost of cares for these patients.\n\nThe standard treatment for TRD is electroconvulsive therapy (ECT), which results in a response in 60 to 70% of cases after a few weeks of treatment. However, the improvement is often transient and 40% of patients relapse within 6 months of the initial ECT session. Moreover, ECT is often not well tolerated. This therapeutic impasse therefore makes TRD a priority public health target to which it is urgent to provide a realistic medico-economical response.\n\nThe literature suggests that Vagus Nerve Stimulation (VNS) has unique kinetics of efficacy in depression, particularly in preventing long-term recurrences, and therefore responding to the lack of effective maintenance treatment in TRD. In fact, the benefits of VNS gradually accumulate over 12-24 months, which makes it complementary to more incisive treatments like ECT. Finally, its efficacy-tolerance profile appears to be similar in uni and bipolar TRD, giving VNS a potentially unique place in the therapeutic arsenal in psychiatry.\n\nThe DepVNS hypothesis is that VNS is a medico-economically efficient therapeutic option to overcome the therapeutic impasse in which patients suffering from uni and bipolar DR currently find themselves due to the frequency of relapses under treatment.\n\nThe primary objective is to estimate, from a collective point of view, the incremental cost-utility ratio of VNS to treat patients suffering from RD.",[96],[96,130,131],"Vagus Nerve Stimulation (VNS)","Best Medical Treatment (BMT)","RECRUITING","2026-06-18",{"date":69,"type":37},{"date":136,"type":37},"2024-02-19",{"date":138,"type":22},"2033-02-19",{"name":140,"class":44},"Assistance Publique - Hôpitaux de Paris",24,{"id":143,"slug":144,"hasResults":12,"nctId":145,"briefTitle":146,"officialTitle":146,"acronym":147,"eligibilityCriteria":148,"healthyVolunteers":12,"sex":18,"minAge":149,"maxAge":4,"enrollmentInfo":150,"targetDuration":4,"studyType":23,"phases":151,"briefSummary":152,"conditions":153,"keywords":156,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":161,"lastUpdatePostDateStruct":162,"startDateStruct":164,"completionDateStruct":166,"leadSponsor":168,"locationsCount":170},"100638441","phase-3-lumateperone-for-late-life-depression-100638441","NCT07623135","Lumateperone for Late-Life Depression","IRL Grey-C","Inclusion Criteria:\n\n* Age \\>=60\n* Current unipolar non-psychotic major depression determined by SCID-5\n* MADRS score \\>=20 at screening and \\>=18 at baseline\n* Treatment-resistance defined as documented history of non-response to at least two oral medications of adequate dose and duration in this episode or previous episode, OR clinician determination that treatment augmentation is appropriate\n* Currently taking oral antidepressant prescribed at least minimum therapeutic dose and for at least six weeks duration\n* MMSE score of \\>\u002F=24\n\nExclusion Criteria:\n\n* Dementia\n* High risk for suicide, defined as a 4 or 5 on C-SSRS (indicating active suicidal ideation with current or recent intent or plan), and unable to be managed safely in the clinical trial. Urgent psychiatric referral will be made in these cases.\n* High risk alcohol use: defined as a score of 6 or more on the AUDIT-C\n* Medically inappropriate for participation as determined by PIs.","60 Years",{"count":57,"type":22},[92],"The purpose of this research study is to examine how well a medication called lumateperone (Caplyta) works to relieve depression in older adults with treatment-resistant depression. Lumateperone (Caplyta) is approved by the U.S. Food and Drug Administration to treat Major Depressive Disorder in adults who are also taking another antidepressant medication. This study will compare lumateperone (Caplyta) to placebo (a sugar pill without medication).",[96,154,155],"Late Life Depression (LLD)","Depression \u002F Major Depressive Disorder",[157,158,159,160],"Late life depression treatment","Treatment resistant depression in older adults","major depression","lumateperone","2026-05-28",{"date":163,"type":37},"2026-06-03",{"date":165,"type":22},"2026-06",{"date":167,"type":22},"2028-06",{"name":169,"class":44},"Eric Lenze",2,{"id":172,"slug":173,"hasResults":12,"nctId":174,"briefTitle":175,"officialTitle":176,"acronym":177,"eligibilityCriteria":178,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":179,"enrollmentInfo":180,"targetDuration":4,"studyType":23,"phases":182,"briefSummary":183,"conditions":184,"keywords":186,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":197,"lastUpdatePostDateStruct":198,"startDateStruct":200,"completionDateStruct":202,"leadSponsor":204,"locationsCount":45},"100637249","accelerated-itbs-for-major-depression-100637249","NCT07603804","Accelerated iTBS for Major Depression","Investigation of the Relationship Between Changes in Neurobiological Biomarkers After Accelerated Transcranial Magnetic Stimulation Treatment and Treatment Response in Patients With Major Depressive Disorder","AIM-D","Inclusion Criteria:\n\n* Age between 18 and 65 years\n* Diagnosis of Major Depressive Disorder according to DSM-5 criteria\n* Inadequate response to at least one adequate antidepressant treatment trial\n* Hamilton Depression Rating Scale (HAM-D) score ≥14 at baseline\n* Stable dose of antidepressant medication for at least 4 weeks prior to study entry\n* Ability to provide written informed consent\n\nExclusion Criteria:\n\n* History of bipolar disorder, schizophrenia, schizoaffective disorder, or psychotic depression\n* Current substance use disorder\n* Neurological disorders that may affect brain function (e.g., epilepsy, multiple sclerosis, dementia, Parkinson's disease)\n* History of epileptic seizures\n* Severe head trauma\n* Presence of metal implants in the head or neck region\n* Cochlear implants\n* Cardiac pacemaker or implanted electronic devices\n* History of deep brain stimulation or vagus nerve stimulation\n* Previous neurosurgical procedures\n* Pregnancy or breastfeeding\n* Use of medications that may significantly affect neuroendocrine or inflammatory markers (e.g., corticosteroids, immunomodulators)\n* Endocrine disorders affecting the hypothalamic-pituitary-adrenal axis (e.g., Cushing's syndrome, Addison's disease, thyroid disorders)\n* Autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, Hashimoto thyroiditis)\n* Recent surgery or acute infection\n* Active suicidal crisis, severe agitation, or inability to comply with study procedures","65 Years",{"count":181,"type":22},35,[59],"Major depressive disorder (MDD) is a common and disabling psychiatric condition, and many patients do not achieve adequate response to standard antidepressant treatments. Accelerated intermittent theta burst stimulation (iTBS) is a promising neuromodulation approach that may provide rapid antidepressant effects. This prospective interventional study aims to evaluate the clinical effectiveness of accelerated bilateral dorsomedial prefrontal cortex iTBS in patients with MDD and to investigate treatment-related changes in neurobiological biomarkers, including cortisol, ACTH, BDNF, IL-1β, IL-6, TNF-α, and CRP. Associations between biomarker changes and treatment response will also be examined.",[185,96],"Major Depressive Disorder (MDD)",[187,95,98,65,100,188,189,190,191,192,66,193,194,195,196],"Major Depressive Disorder","Intermittent Theta Burst Stimulation","iTBS","Accelerated TMS","Accelerated iTBS","Dorsomedial Prefrontal Cortex","Neuroinflammation","BDNF","Cortisol","ACTH","2026-05-21",{"date":199,"type":37},"2026-05-22",{"date":201,"type":37},"2026-03-08",{"date":203,"type":22},"2026-12-31",{"name":205,"class":44},"Istanbul University - Cerrahpasa",{"id":207,"slug":208,"hasResults":12,"nctId":209,"briefTitle":210,"officialTitle":210,"acronym":4,"eligibilityCriteria":211,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":212,"targetDuration":4,"studyType":23,"phases":214,"briefSummary":215,"conditions":216,"keywords":217,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":220,"lastUpdatePostDateStruct":221,"startDateStruct":223,"completionDateStruct":225,"leadSponsor":227,"locationsCount":170},"100636298","coaching-as-an-adjunct-to-ketamine-therapy-for-treatment-resistant-depression-100636298","NCT07563868","Coaching as an Adjunct to Ketamine Therapy for Treatment-Resistant Depression","Inclusion Criteria:\n\n1. Age 18 years or older at the time of informed consent\u002Fstudy enrollment.\n2. Ability to understand and provide informed consent.\n3. Fluent in English (spoken and written).\n4. Willingness to have coaching sessions recorded via HIPAA-compliant MGB approved video-based platform.\n5. Has a QIDS-SR score ≥ 11, indicating at least moderate depressive symptom severity at screening visit.\n6. Lifetime diagnosis of a depressive disorder according to the MINI.\n7. In the maintenance phase of ketamine or esketamine treatment, defined as the period following the initial acute treatment series (typically 2 treatments per week for 3 weeks).\n8. Patients must have completed at least 3 maintenance treatments prior to screening visit with a QIDS-SR score ≥ 11 noted from EPIC medical records from the 3 most recent maintenance treatments.\n9. Currently receiving maintenance IV ketamine or intranasal esketamine at the MGH Ketamine Clinic, with at least one treatment administered within the past 8 weeks, and planning to continue to be an active patient at the MGH Ketamine Clinic for the duration of the study.\n10. Has established care with a mental health provider (e.g., psychiatrist, therapist, or other licensed mental health clinician), and, if outside the MGB-healthcare system, agrees to sign a Release of Information form (ROI) with the study team.\n\nExclusion Criteria:\n\n1. Presence of an unstable medical condition, as determined by the study clinician.\n2. Significant neurocognitive impairment that impairs with individual's ability to maintain ADLs and would interfere with study participation, per study clinician judgment.\n3. Newly initiated psychotherapy within the past 3 months.\n4. Any condition or circumstance that, in the judgment of the Principal Investigator, makes participation unsafe or unsuitable.\n5. Any psychiatric condition that is currently primary, clinically predominant to their depression, or insufficiently stable such that it would interfere with study participation, per clinician judgment.\n6. Plan to switch from IV ketamine treatment to intranasal esketamine or plan to switch from intranasal esketamine to IV ketamine treatment at any point during study.\n7. Suicidality determined by the judgment of the study clinicians at screen, with a plan to act in next 6 months.\n8. A ≥25% reduction in QIDS total score from screen to baseline visit.",{"count":213,"type":22},20,[59],"This study is being conducted at Massachusetts General Hospital (MGH) to explore whether adding psychedelic coaching can enhance the effects of ketamine or esketamine maintenance treatment in individuals with treatment-resistant depression (TRD). The investigators are currently enrolling participants who are receiving ongoing maintenance intravenous (IV) ketamine or intranasal esketamine (Spravato) treatment at the MGH Ketamine Clinic. Participation in the study will involve adding coaching sessions to your existing ketamine maintenance treatment.",[96],[218,219,98],"Psychedelic Coaching","Ketamine Coaching","2026-04-30",{"date":222,"type":37},"2026-05-04",{"date":224,"type":22},"2026-04",{"date":226,"type":22},"2028-04-01",{"name":228,"class":44},"Massachusetts General Hospital",{"id":230,"slug":231,"hasResults":12,"nctId":232,"briefTitle":233,"officialTitle":234,"acronym":4,"eligibilityCriteria":235,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":179,"enrollmentInfo":236,"targetDuration":4,"studyType":23,"phases":238,"briefSummary":239,"conditions":240,"keywords":242,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":245,"lastUpdatePostDateStruct":246,"startDateStruct":247,"completionDateStruct":249,"leadSponsor":251,"locationsCount":45},"100634718","transcranial-photobiomodulation-tpbm-for-somatic-symptoms-in-treatment-resistant-depression-100634718","NCT07543328","Transcranial Photobiomodulation (tPBM) for Somatic Symptoms in Treatment-Resistant Depression","The Clinical Efficacy of Prefrontal Transcranial Photobiomodulation (tPBM) in Patients With Treatment-Resistant Major Depressive Disorder: A Subgroup Analysis Focusing on Somatic Symptoms","Inclusion Criteria:\n\nMust have a current diagnosis of Major Depressive Disorder (MDD).\n\nThe clinical severity must be evaluated by a psychiatrist as moderate or above, defined as a Clinical Global Impression-Severity (CGI-S) score \\> 4 and a 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 18.\n\nMust be currently receiving stable antidepressant treatment for at least four weeks but showing inadequate response (treatment-resistant). This study will be conducted as an add-on therapy.\n\nMust have full behavioral capacity, normal intellectual functioning, and the ability to comprehend and sign the informed consent form.\n\nExclusion Criteria:\n\nIndividuals diagnosed with Bipolar Disorder or Schizophrenia.\n\nIndividuals with current or recent Substance Use Disorder.\n\nHistory of organic brain lesions (e.g., neurodegenerative diseases, epilepsy, stroke) or any medical conditions affecting central nervous system function.\n\nIndividuals with abnormal intellectual functioning based on clinical judgment (e.g., suspected intellectual disability, severe learning difficulties).\n\nIndividuals who are currently pregnant (due to limited evidence regarding the safety of tPBM during pregnancy).\n\nAny other condition that, in the investigator's judgment, would render the participant unable to cooperate, unsuitable for the study, or unwilling to sign the informed consent.",{"count":237,"type":22},40,[59],"The primary objective of this study is to evaluate the clinical efficacy of moderate-dose transcranial photobiomodulation (t-PBM) at different frequencies (10 Hz and 40 Hz) in patients with treatment-resistant depression (TRD). It further aims to explore the differential efficacy across various symptom subtypes, with a particular focus on the somatic symptom-dominant subtype. Additionally, this study will collect paired-pulse neurophysiological parameters (e.g., the ratio of cortical inhibition to excitation) to preliminarily explore the neural mechanisms underlying the modulation of cortical excitability by t-PBM intervention, and to analyze their correlation with the magnitude of clinical symptom improvement.\n\nThe specific aims of this study are as follows:\n\nTo evaluate the differential efficacy of t-PBM at varying frequencies (10 Hz vs. 40 Hz) in improving clinical depressive symptoms (as measured by scales such as HAM-D and MADRS).\n\nTo investigate the therapeutic response to t-PBM in patients with the somatic symptom-dominant depression subtype, analyzing its potential suitability for targeting specific symptoms.\n\nTo explore the changes in paired-pulse TMS parameters (e.g., SICI, ICF, and LICI) before and after t-PBM treatment, gaining preliminary insights into the potential association between its cortical modulatory effects and clinical outcomes.",[29,241],"Major Depression Disorder",[243,241,244],"Photobiomodulation","tPBM","2026-04-24",{"date":220,"type":37},{"date":248,"type":37},"2026-01-06",{"date":250,"type":22},"2027-03-31",{"name":252,"class":78},"Taipei Veterans General Hospital, Taiwan",{"id":254,"slug":255,"hasResults":12,"nctId":256,"briefTitle":257,"officialTitle":257,"acronym":4,"eligibilityCriteria":258,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":179,"enrollmentInfo":259,"targetDuration":4,"studyType":23,"phases":261,"briefSummary":262,"conditions":263,"keywords":264,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":245,"lastUpdatePostDateStruct":271,"startDateStruct":273,"completionDateStruct":275,"leadSponsor":277,"locationsCount":45},"100599148","phase-4-algorithm-guided-treatment-versus-treatment-as-usual-tau-for-patients-with-treatment-resistant-depression-100599148","NCT07080723","Algorithm Guided Treatment Versus Treatment as Usual (TAU) for Patients With Treatment Resistant Depression","Inclusion Criteria:\n\n1. A diagnosis of unipolar depressive disorder according to ICD-10 based on documented completion of the Mini International Neuropsychiatric Interview, version 7.0.2 (MINI 7.0.2) at Screening and confirmed by medical records or a healthcare professional.\n2. Have not achieved stable remission of depression in 12 months at investigator's clinical assessment.\n3. Severity of depression: A score of at least 21 on the self-reported Major Depression Inventory (MDI).\n4. Age criteria: Subjects must be at least 18 years old and below 65 at the time of randomization.\n5. Signed document of informed consent.\n6. The participant is an outpatient.\n7. No significant change in medical treatment in the last 4 weeks before screening visit.\n8. The patient is pharmacologically treated for depression.\n\nExclusion Criteria:\n\n1. A diagnosis of dementia.\n2. Substance misuse influencing study participation as judged by the investigator.\n3. High risk of non-adherence at the investigator's discretion.\n4. Not understanding the Danish language as judged by the investigator.\n5. Suicidality according to C-SSRS with a positive response to question 4 or 5 within the last three months or upon investigator's discretion.\n6. Medical conditions such as cancer, kidney failure, epilepsy, deep brain stimulation device, or other medical conditions interfering with study the outcome and safety as judged by investigator's discretion.",{"count":260,"type":22},80,[25],"The trial utilizes a pragmatic, randomized, open label design with two parallel arms. Participants aged 18-65 with a diagnosis of unipolar depressive disorder and without stable remission in the past 12 months are randomized 1:1 to receive either algorithm guided treatment (AGT) or treatment as usual (TAU). The AGT approach incorporates pre-defined treatment steps, critical decision points, and \"if-then\" rules based on symptom response. It leverages prior treatment history, current symptomatology, and tolerability profiles to personalize the therapeutic sequence and reduce treatment inertia. In contrast, TAU reflects standard clinical practice, where treatment decisions are left to clinician discretion without algorithmic structure. The primary objective of the study is to determine whether AGT leads to a greater reduction in depressive symptoms over a 12-week treatment period, as measured by the 6-item Hamilton Depression Rating Scale (HAMD-6). Secondary objectives include evaluating cognitive and psychosocial functioning, suicide risk, treatment adherence, tolerability, number of medication changes, and long-term outcomes at a 24-week follow-up, providing insights into the longer-term trajectory of TRD management.",[96],[265,266,267,268,269,270,99,98],"Algorithm guided treatment","AGT","ALGO","Treatment as usual","TAU","Treatment resistant depression",{"date":272,"type":37},"2026-04-27",{"date":274,"type":37},"2025-08-13",{"date":276,"type":22},"2027-06",{"name":278,"class":44},"Aalborg University Hospital",{"id":280,"slug":281,"hasResults":12,"nctId":282,"briefTitle":283,"officialTitle":284,"acronym":4,"eligibilityCriteria":285,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":286,"enrollmentInfo":287,"targetDuration":4,"studyType":23,"phases":289,"briefSummary":290,"conditions":291,"keywords":4,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":292,"lastUpdatePostDateStruct":293,"startDateStruct":295,"completionDateStruct":297,"leadSponsor":299,"locationsCount":301},"100635511","phase-2-alto-207-in-adults-with-treatment-resistant-depression-trd-100635511","NCT07553637","ALTO-207 in Adults With Treatment-resistant Depression (TRD)","A Randomized, Double-blind, Placebo-controlled Trial of ALTO-207 in Adults With Treatment-resistant Depression","Inclusion Criteria:\n\n* Male and female participants, ages 18 to 75 years, inclusive, at the time of signing the ICF.\n* Prior diagnosis of MDD without psychotic symptoms (in the current episode) and have confirmatory diagnosis of current MDD (moderate to severe).\n* Failure to respond (\\\u003C50% improvement) to at least 2-5 antidepressant treatments (including the current treatment)\n* Currently taking a stable dose of at least 1 but no more than 2 oral antidepressants at baseline\n\nExclusion Criteria:\n\n* Evidence of unstable medical condition\n* Concurrent use of any prohibited medications or substance use disorder\n* Diagnosed bipolar disorder or a psychotic disorder or symptoms\n* Significant current PTSD symptoms or history of PTSD\n* Clinically significant current impulse control difficulties\n* Has a history of hypersensitivity or allergic reaction to ALTO-207 or any of its components\u002Fexcipients\n* Concurrent or recent participation in another clinical trial for mental illness involving an investigational product or device","75 Years",{"count":288,"type":22},178,[91],"The purpose of this trial is to measure depressive symptoms following treatment with ALTO-207 compared with placebo in participants with TRD.",[29],"2026-04-23",{"date":294,"type":37},"2026-04-28",{"date":296,"type":22},"2026-05",{"date":298,"type":22},"2027-12",{"name":300,"class":114},"Alto Neuroscience",48,{"id":303,"slug":304,"hasResults":12,"nctId":305,"briefTitle":306,"officialTitle":307,"acronym":4,"eligibilityCriteria":308,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":309,"targetDuration":4,"studyType":23,"phases":311,"briefSummary":313,"conditions":314,"keywords":315,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":321,"lastUpdatePostDateStruct":322,"startDateStruct":323,"completionDateStruct":325,"leadSponsor":327,"locationsCount":45},"100576368","early-phase-1-personalized-dbs-targeting-for-treating-depression-100576368","NCT06784388","Personalized DBS Targeting for Treating Depression","Clinical Application of Personalized DBS Target Optimization for Treating Depression","Inclusion Criteria:\n\n1. A psychiatrist-confirmed diagnosis of major depressive disorder in accordance with the Diagnostic And Statistical Manual Of Mental Disorders.5th Ed (DSM-V);\n2. A psychiatric examination by two trained psychiatrists and a diagnosis consistent with the DSM-V;\n3. A history of depression of at least 12 months duration in depressed patients (including MECT) who have failed to respond to a full dose and course of treatment with 2 or more antidepressants of different mechanisms;\n4. A 17-item score on the HAMD scale ⩾ 20 at initial screening;\n5. A score of ≤ 50 on the Gross Assessment of Functioning (GAF) scale;\n6. The patient himself\u002Fherself or legal guardian was able to fully understand the therapy and agreed to enroll after signing an informed consent form.\n\nExclusion Criteria:\n\n1. Persons with severe or unstable cardiac, hepatic, renal, endocrine, hematologic, and other medical disorders and co-morbidities with psychotic symptoms, including personality disorders diagnosed by history, questioning, and clinical examination;\n2. Persons with psychiatric disorders other than depression (except generalized anxiety);\n3. Persons with a history of substance abuse within 12 months; persons with a previous history of epilepsy, and persons with febrile convulsions in childhood;\n4. Patients with a history of suicide attempts within the past 6 months or more than 2 suicide attempts within the past 2 years;\n5. Women who are breastfeeding, pregnant, and patients who are pregnant or intend to become pregnant during the clinical study;\n6. Contraindications to DBS surgery and MRI;\n7. Years of education less than or equal to 9 years;\n8. Patients who are involuntarily hospitalized.",{"count":310,"type":22},5,[312],"EARLY_PHASE1","The goal of this clinical trial is to optimize the target brain areas for deep brain stimulation (DBS) for depression based on personalized brain imaging and stereo-electroencephalography（SEEG), to administer long-term DBS treatment in the target brain areas, to assess the effectiveness and safety of DBS for refractory depression and to validate the method of personalized optimization of DBS targets. The main questions it aims to answer are:\n\n1. Where is the optimal DBS target brain region for each patient?\n2. What are the optimal DBS parameters for each patient ?\n3. What are the neural biomarkers of depression symptoms for each patient?\n4. Are the optimized DBS strategies effective in treating refractory depression?",[29],[316,317,318,319,320],"Treatment-resistant depression (TRD)","DBS","stimulation target","stimulation parameters","neural biomarker","2026-04-22",{"date":272,"type":37},{"date":324,"type":37},"2025-01-05",{"date":326,"type":22},"2028-12-30",{"name":328,"class":44},"Second Affiliated Hospital, School of Medicine, Zhejiang University",{"id":330,"slug":331,"hasResults":12,"nctId":332,"briefTitle":333,"officialTitle":333,"acronym":4,"eligibilityCriteria":334,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":335,"targetDuration":4,"studyType":23,"phases":336,"briefSummary":337,"conditions":338,"keywords":340,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":343,"lastUpdatePostDateStruct":344,"startDateStruct":345,"completionDateStruct":346,"leadSponsor":348,"locationsCount":45},"100611932","phase-2-ketamine-assisted-psychotherapy-for-treatment-resistant-depression-100611932","NCT07247006","Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression","Inclusion Criteria\n\nThe following inclusion criteria must be met for all subjects to be considered eligible to participate:\n\n1. 18 years old or older\n2. Able to speak, read, and understand English\n3. In generally stable health\n4. Must have treatment resistant depression, as defined as scoring in the moderate or above range on the HDRS and having failed two adequate trials of antidepressants in the last two years.\n\nExclusion Criteria\n\nGeneral exclusion criteria for all subjects include:\n\n1. Uncontrolled hypertension\n2. Impaired cardiac status\n\n   a. Abnormal ECG report in the last month prior to screening\n3. Chronic Obstructive Pulmonary Disease\n4. Congenital Long QT Syndrome\n5. ≥265lbs or 120kg\n6. Severe obesity (BMI ≥40)\n7. Increased intracranial or cerebrospinal pressure\n8. Pregnancy or breastfeeding\n9. Hyperthyroidism\n10. Prior adverse response to ketamine, including allergic reaction\n11. Symptoms of psychosis or prodromal phase\n12. Severe personality disorder\n13. Autistic Spectrum Disorders\n14. Bipolar disorder\n15. History of substance abuse, defined as a score of three or more on Drug Abuse scale (prior use of psychedelics allowed)\n16. Past-year suicide attempt or ongoing ideation with intent to act\n17. All exclusion criteria for magnetic resonance imaging safety: any metallic implants, brain or skull abnormalities, tattoos on large body parts, and claustrophobia.\n18. Taking medications that could interact with ketamine. Examples include but are not limited to: any types of stimulants, aripiprazole, diphenhydramine, hydromorphone, escitalopram, fluoxetine, alprazolam, and sertraline. Each subject's current medications will be evaluated for interactions with ketamine before admission into the trial.",{"count":7,"type":22},[91],"The goal of this clinical trial is to understand the effect of ketamine on the brain in people with treatment-resistant depression (TRD). TRD occurs in around a third of people with depression and leads to higher suicide rates compared to those with major depressive disorder. A desperate need for a rapid acting antidepressant drug (RAAD) is needed to help improve quality of life for people with TRD. Ketamine has been shown to be a RAAD, and esketamine (a form of ketamine) was approved by the FDA to treat TRD. Ketamine has been known to cause dissociative experiences, that can lead to an increase in the \"Openness to Experience\" personality trait and psychological flexibility that occurs at \"peak experience\". This has been shown to improve mental health conditions and lower suicide risk. This study aims to further understand if there is a connection between this new change of mind and changes in brain activity. Ketamine has been shown to improve brain plasticity as well, specifically in the frontolimbic region of the brain, an area associated with depression. The investigators are analyzing the brain using functional magnetic resonance imaging (fMRI), a method used to measure brain activity. The frontolimbic region is also associated with cognitive flexibility and emotional processing, an important hurdle in treating TRD. Due to this, the investigators are pairing the ketamine treatment with psychotherapy sessions, to guide the processing experience, which can lead to higher emotional flexibility.\n\nThe main questions this study aims to answer are:\n\n* Are frontolimibic plasticity circuitry changes associated with openness to experience and peak experience?\n* Is it feasible to recruit and retain people through a two-month KAP study?\n* Is the structure of the study effective for treating TRD?\n\nParticipants will:\n\n* Visit the facilities 6-8 times\n* Complete 2 MRI brain scans\n* Complete 3-4 psychotherapy sessions\n* Receive 1-2 doses of ketamine\n* Complete online surveys between 3-4 visits",[96,339],"Chronic Pain",[341,342],"depression","fmri","2026-04-21",{"date":292,"type":37},{"date":165,"type":22},{"date":347,"type":22},"2028-03",{"name":349,"class":44},"University of Rochester",{"id":351,"slug":352,"hasResults":12,"nctId":353,"briefTitle":354,"officialTitle":355,"acronym":356,"eligibilityCriteria":357,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":358,"enrollmentInfo":359,"targetDuration":4,"studyType":360,"phases":4,"briefSummary":361,"conditions":362,"keywords":4,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":370,"lastUpdatePostDateStruct":371,"startDateStruct":373,"completionDateStruct":375,"leadSponsor":377,"locationsCount":310},"100604206","esketamine-nasal-spray-in-real-world-settings-in-treatment-resistant-depression-100604206","NCT07146503","Esketamine Nasal Spray in Real-World Settings in Treatment-Resistant Depression","ESKPSY: Esketamine in Real-World Settings: Clinical Outcomes, Predictors of Response, Life Functioning and Biological Pathways","ESKPSY","Inclusion criteria were: (a) age 18-74, (b) DSM-5 diagnosis of a major depressive episode (MDE), (c) failure to respond to at least 2 prior antidepressant treatments (ADTs), and (d) current treatment with an SSRI or SNRI for which esketamine nasal spray was deemed appropriate.","74 Years",{"count":57,"type":22},"OBSERVATIONAL","This observational study investigates the use of Esketamine Intranasal Spray in patients with Treatment-Resistant Depression in Real-World Settings. The study aims to evaluate the clinical outcomes, including efficacy and safety, of esketamine treatment. It also explores predictors of treatment response, focusing on biological pathways such as genetics, neuroimaging, and psychophysical measures. Additionally, the study examines how esketamine impacts patients' life functioning, including social and occupational aspects. The goal is to better understand who benefits most from esketamine and how it affects daily life, to improve personalized care for patients with difficult-to-treat depression.",[363,96,364,365,366,367,368,369],"Depression and Quality of Life","Anhedonia","Apathy","Anxiety","Cognition","Temperament","Psychiatric Comorbidities","2026-03-25",{"date":372,"type":37},"2026-03-31",{"date":374,"type":37},"2022-11-01",{"date":376,"type":22},"2030-08",{"name":378,"class":44},"Riccardo Guglielmo",{"id":380,"slug":381,"hasResults":12,"nctId":382,"briefTitle":383,"officialTitle":384,"acronym":385,"eligibilityCriteria":386,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":179,"enrollmentInfo":387,"targetDuration":4,"studyType":23,"phases":389,"briefSummary":390,"conditions":391,"keywords":392,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":401,"lastUpdatePostDateStruct":402,"startDateStruct":404,"completionDateStruct":406,"leadSponsor":408,"locationsCount":45},"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 (MADRS ≥ 20)\n* Meeting criteria for treatment-resistant depression (TRD), defined as non-response to at least two adequate antidepressant trials\n* Neuromodulation-naïve (no past rTMS or electroconvulsive therapy)\n* Able to provide informed consent\n* Available for the 15-week intervention and willing to follow either a ketogenic or Canadian Food Guide-aligned diet\n\nExclusion Criteria:\n\n* Medical\u002Fpsychiatric co-morbidities that prevent participation in the study or where depression is not the primary psychiatric symptom of concern\n* History of epilepsy, stroke, or major neurological conditions, psychosis, or substance dependence within the last 6 months\n* Physical or cognitive disability interfering with participation\n* Females who are pregnant (self-report or via blood work), nursing, or planning a pregnancy during the timespan of the study 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 KD\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* Serious medical illness\n* Contraindications to MRI\n* Unwillingness to perform daily finger-stick testing",{"count":388,"type":22},60,[59],"The goal of this clinical trial is to test whether combining a ketogenic diet (KD) with personalized, accelerated intermittent theta burst stimulation (iTBS) produces greater reductions in depressive symptoms than iTBS combined with a standard healthy diet in adults with treatment-resistant depression. The trial also aims to determine whether participants can feasibly follow a ketogenic diet during an accelerated iTBS treatment course and whether the diet produces measurable changes in ketone levels.\n\nSpecifically, the study aims to determine whether the combined intervention:\n\n1. Reduces depressive symptoms\n2. Increases circulating ketone levels\n3. Is feasible and tolerable during accelerated iTBS treatment\n\nParticipants will begin either a KD or a Canadian Food Guide-aligned diet (CFGD) with a 3-week dietary lead-in period, after which they will undergo a course of personalized, accelerated iTBS while continuing their assigned diet. Before and after the iTBS treatment course, participants will complete clinical assessments, provide blood samples for metabolic testing, and undergo MRI scans to assess brain connectivity. Ketone levels will be measured daily throughout the 12-week dietary intervention. Within-group and between-group differences will be compared to characterize changes in clinical outcomes, metabolism, and brain functioning.",[185,96],[187,393,99,100,394,395,396,65,189,397,398,399,32,400],"MDD","Glucose Control","Ketogenic Diet","Metabolic Health","Dietary Intervention","Metabolic Psychiatry","MRS","Intermittent Theta-Burst Stimulation","2026-02-03",{"date":403,"type":37},"2026-02-05",{"date":405,"type":22},"2026-04-01",{"date":407,"type":22},"2027-10-01",{"name":409,"class":44},"Sunnybrook Health Sciences Centre",{"id":411,"slug":412,"hasResults":12,"nctId":413,"briefTitle":414,"officialTitle":415,"acronym":416,"eligibilityCriteria":417,"healthyVolunteers":12,"sex":18,"minAge":418,"maxAge":179,"enrollmentInfo":419,"targetDuration":4,"studyType":23,"phases":420,"briefSummary":421,"conditions":422,"keywords":423,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":437,"lastUpdatePostDateStruct":438,"startDateStruct":440,"completionDateStruct":442,"leadSponsor":444,"locationsCount":170},"100621321","phase-4-esketamine-with-or-without-integration-therapy-for-treatment-resistant-depression-100621321","NCT07369102","Esketamine With or Without Integration Therapy for Treatment-Resistant Depression","Esketamine With or Without Psychedelic Preparation and Integration for Treatment-Resistant Depression: A Randomized Controlled Trial","KIND-PR","Inclusion Criteria:\n\n* Age: Adults aged 21 to 65 years.\n* Diagnosis: Current Major Depressive Disorder (MDD) as confirmed by Structured Clinical Interview for DSM5 (SCID-5).\n* Treatment Resistance: Failure to achieve remission with at least two antidepressants of adequate dose and duration (TRD criteria) as confirmed by SCID-5.\n* Symptom Severity: Baseline Montgomery-Åsberg Depression Rating Scale (MADRS) ≥30.\n* Suicidal Ideation: Participants with baseline passive or active suicidal ideation may be included, provided they do not meet criteria for inpatient admission and are deemed clinically stable for outpatient care. This will be measured with the Columbia Suicide Severity Rating Scale (C-SSRS).\n* Consent: Ability to understand and voluntarily provide written informed consent.\n* Contraception: For participants of reproductive potential, willingness to use at least one highly effective method of contraception (e.g., intrauterine device, hormonal contraception, sterilization) or two effective methods (e.g., barrier method plus spermicide) during the study and for at least one month after the final esketamine dose. Contraceptive method(s) will be documented at baseline via self-report on a standardized form and reaffirmed at each esketamine session by research staff. Participants who become pregnant or are unable to confirm adequate contraception will be withdrawn from the study for safety reasons.\n* Availability: Willingness and ability to attend all scheduled sessions and complete study procedures.\n* Motivation for Engagement: Demonstrates willingness and psychological readiness to engage in guided reflective work before and after esketamine dosing (as assessed during clinical intake).\n\nExclusion Criteria:\n\n* Acute Suicide Risk: Immediate need for inpatient psychiatric hospitalization due to suicidal ideation with plan or intent as identified through the C-SSRS.\n* Psychotic or Bipolar Disorders: Current diagnosis of bipolar I disorder (manic phase), schizophrenia, schizoaffective disorder, or other primary psychotic disorders if stated by participants as a past diagnosis or identified during the SCID-5.\n* Substance Use Disorder: Active moderate to severe substance use disorder (except nicotine) in the past 6 months as self-identified by participant or during the SCID-5.\n* Cognitive\u002FDevelopmental Impairments: Intellectual disability, dementia, or other cognitive\u002Fdevelopmental disorders that impair ability to engage meaningfully in structured psychotherapeutic sessions such as preparation or integration, per clinician judgment.\n* Medical Contraindications: Any medical condition judged to pose undue risk during esketamine administration (e.g., aneurysmal vascular disease, arteriovenous malformation, history of intracerebral hemorrhage, or hypersensitivity to esketamine\u002Fketamine).\n* Pregnancy\u002FBreastfeeding: Current pregnancy or breastfeeding.\n* Ongoing Structured Psychotherapy Likely to Confound Outcomes: Participation in any formal psychotherapy within the past 3 months that involves structured, weekly sessions focused on behavioral change or emotional processing (e.g., CBT, ACT, psychodynamic therapy), unless the therapy was completed or stabilized at a low-intensity level for at least 8 weeks prior to enrollment.\n* Prior Non-Response to Esketamine: Six or more prior esketamine (≥56 mg) or IV ketamine sessions (0.4-0.7 mg\u002Fkg) without clinical response.\n* Recent Ketamine Use: Use of ketamine\u002Fesketamine in the past 12 weeks.\n* Inability to Consent: Any condition rendering the participant unable to provide informed consent.\n* Prior Enrollment: Previous participation in this study.","21 Years",{"count":213,"type":22},[25],"This study will explore the effects of esketamine (Spravato®), an FDA-approved nasal spray, on adults diagnosed with treatment-resistant depression (TRD). All participants will receive esketamine as prescribed by a healthcare professional in a clinical setting.\n\nThe purpose of this research is to understand whether adding therapeutic support in the form of preparation and integration sessions - before and after the esketamine doses - can enhance the treatment experience and lead to longer-lasting improvements in mood and functioning.\n\nParticipants will be randomly assigned to one of two groups:\n\nEsketamine with therapeutic support sessions (integration group) Esketamine without additional support (standard care group) Both groups will receive standard monitoring and psychiatric evaluation during the study. The support sessions offered in the integration group are designed to help participants prepare for their treatment sessions and make sense of their experiences afterward, using a structured, evidence-based approach.\n\nThe study will last approximately 8 weeks per participant, with follow-up assessments. The goal is to learn whether integration therapy can improve treatment outcomes, safety, and satisfaction for individuals with depression that hasn't responded to other treatments.",[29],[424,64,425,426,427,98,428,429,430,431,432,433,434,435,436],"esketamine","Spravato","Ketamine-Assisted Psychotherapy","Psychedelic Integration","Integration Therapy","Preparation and Integration","Mental Health","Dissociation","Intranasal Esketamine","Randomized Controlled Trial","Psychiatric Treatment","Therapeutic Support","Psychedelic Medicine","2026-01-23",{"date":439,"type":37},"2026-01-27",{"date":441,"type":22},"2026-02-01",{"date":443,"type":22},"2026-12-01",{"name":445,"class":44},"University of Puerto Rico",{"id":447,"slug":448,"hasResults":12,"nctId":449,"briefTitle":450,"officialTitle":451,"acronym":4,"eligibilityCriteria":452,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":179,"enrollmentInfo":453,"targetDuration":4,"studyType":23,"phases":455,"briefSummary":456,"conditions":457,"keywords":458,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":459,"lastUpdatePostDateStruct":460,"startDateStruct":462,"completionDateStruct":463,"leadSponsor":465,"locationsCount":115},"100618248","neuronavigated-aitbs-for-trd-100618248","NCT07329153","Neuronavigated aiTBS for TRD","Neuronavigated and Non-Neuronavigated Accelerated Intermittent Theta-Burst Stimulation for Treatment-Resistant Depression A Sham-Controlled Randomized Controlled Trial","Inclusion Criteria:\n\n1. Age: 18 to 65 years at the time of consent\n2. Diagnosis: Current major depressive episode (MDE) in the context of unipolar major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed by clinical psychiatric interview\n3. Treatment Resistance: Documented failure to respond to at least two adequate antidepressant trials on the Antidepressant Treatment History Form-Short Form (ATHF-SF). An adequate trial is defined as:\n\n   1. Antidepressant medication at the maximum tolerated dose for at least 6 weeks, OR\n   2. Evidence-based psychotherapy consisting of at least 12 sessions\n4. Depression Severity: Montgomery-Åsberg Depression Rating Scale (MADRS) score \\>19 at screening, indicating moderate to severe depression\n5. Medication Stability: No changes in antidepressant medication type or dose for at least 6 weeks prior to randomization. Stable doses of permitted medications must be maintained throughout the trial\n6. Informed Consent: Demonstrated capacity to provide written informed consent and comply with study procedures\n7. Availability: Ability to attend treatment sessions for 15 consecutive workdays (approximately 90 minutes per day) and complete assessments including 4-hour evaluations at baseline and endpoint\n\nExclusion Criteria:\n\nPsychiatric Exclusions:\n\n1. Any psychiatric disorder other than MDD and comorbid anxiety disorders, including but not limited to:\n\n   (i) Bipolar disorder (Type I or II) (ii) Schizophrenia spectrum or other psychotic disorders (iii) Post-traumatic stress disorder (PTSD) (iv) Attention-deficit\u002Fhyperactivity disorder (ADHD) (v) Autism spectrum disorder (ASD) (vi) Obsessive-compulsive disorder (OCD) (vii) Current DSM-5 substance-use disorder (abuse or dependence) within the past 6 months, except nicotine dependence\n2. Personality disorder confirmed on clinical interview by an experienced study psychiatrist\n3. Severe suicidal ideation with structured plan (HDRS-17 item 3 score \\>2) or as determined by the evaluating psychiatrist\n4. Depressive symptoms better explained by another psychiatric condition, a medical condition, substance use, or use of medications\n\nMedical and Neurological Exclusions:\n\n1. Any neurological disorder including but not limited to:\n\n   (i) History of seizure disorder or epilepsy (ii) Family history of epilepsy (first-degree relatives) (iii) Significant head trauma with loss of consciousness \\>5 minutes (iv) Stroke or transient ischemic attack (v) Neurodegenerative disorders (e.g., Parkinson's disease, multiple sclerosis, dementia) (vi) Brain tumor or intracranial mass lesion\n2. Unstable medical condition, defined as any condition requiring acute medical intervention or hospitalization within the past 3 months, or any condition that in the investigator's judgment could affect participant safety or study outcomes\n\nContraindications to TMS\u002FMRI:\n\n1. Presence of ferromagnetic material in or near the head, including:\n\n   (i) Intracranial implants (e.g., aneurysm clips, shunts, stimulators) (ii) Cochlear implants or hearing aids (iii) Metallic facial tattoos or permanent makeup (iv) Other implanted medical devices deemed unsafe for MRI\u002FTMS\n2. Inability to tolerate MRI scanning due to claustrophobia or other reasons\n\nMedication Exclusions:\n\nCurrent use of medications known to significantly alter cortical excitability:\n\n1. Anticonvulsants (including those used for mood stabilization)\n2. Psychostimulants\n3. Lithium\n4. Benzodiazepines exceeding 10mg diazepam-equivalent daily dose\n\nPrior Treatment Exclusions:\n\n1. Electroconvulsive therapy (ECT) (≥ 6 sessions) in the current depressive episode\n2. Ketamine or esketamine treatment (≥ 6 sessions) in the current depressive episode\n3. Use of rTMS\u002FiTBS (≥ 15 sessions) during the current depressive episode\n4. Vagus nerve stimulation (VNS) or deep brain stimulation (DBS) implantation\n\nPsychotherapy:\n\n• Concurrent evidence-based psychotherapy is permitted if initiated \\>4 weeks prior to enrollment and maintained at stable frequency throughout the tria\n\nOther reasons:\n\n1. Unable to adhere to the study visit schedule\n2. Planning to relocate outside the study catchment area during the trial period\n3. No reliable transportation to attend study visits\n4. Current participation in another research study\n5. Current pregnancy (confirmed by in interview and clinical evaluation and, if deemed necessary, urine pregnancy test at screening)\n6. Currently breastfeeding",{"count":454,"type":22},247,[59],"The purpose of this study is to confirm the efficacy of two recently introduced repetitive transcranial magnetic stimulation (rTMS) interventions - accelerated intermittent theta-burst stimulation (aiTBS) and individualized neuronavigation - in treatment-resistant depression (TRD). Using a three-arm design (neuronavigated aiTBS, non-neuronavigated aiTBS, and sham), this randomized controlled trial (RCT) is the first to specifically investigate the incremental benefit of neuronavigation within an accelerated stimulation protocol, as well as the first confirmatory RCT comparing the efficacy of each of these active treatments vs. sham, overcoming previous generalizability issues and being conducted in an independent, multicenter US TRD sample.",[96],[341,100],"2026-01-07",{"date":461,"type":37},"2026-01-09",{"date":39,"type":22},{"date":464,"type":22},"2031-09",{"name":466,"class":44},"University of Texas Southwestern Medical Center",{"id":468,"slug":469,"hasResults":12,"nctId":470,"briefTitle":471,"officialTitle":471,"acronym":4,"eligibilityCriteria":472,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":473,"enrollmentInfo":474,"targetDuration":4,"studyType":23,"phases":476,"briefSummary":477,"conditions":478,"keywords":479,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":459,"lastUpdatePostDateStruct":481,"startDateStruct":482,"completionDateStruct":484,"leadSponsor":486,"locationsCount":45},"100609641","spaced-transcranial-direct-current-stimulation-for-treatment-resistant-depression-a-home-based-feasibility-and-safety-study-100609641","NCT07217223","Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression: A Home-Based Feasibility and Safety Study","Inclusion Criteria:\n\n1. People between the ages of 18 and 85 at the time of screening.\n2. Currently diagnosed with Major Depressive Disorder (MDD) as measured by the MINI and a MADRS score of ≥ 20.\n3. Safe for TMS as measures by the TMS Adult Safety Screening (TASS).\n4. Medical records confirming a history of failing to achieve clinical response to an adequate antidepressant trial as defined an Antidepressant Treatment History Form (ATHF) score ≥ 3 or ) or shown intolerance to at least two inadequate trials (score 1 or 2), without psychiatric illness due to a general medical condition.\n5. Stable internet connection and a device compatible with Microsoft Teams.\n\nExclusion Criteria:\n\n1. History of psychotic or bipolar disorder or depression with psychotic features;\n2. Significant borderline personality disorder;\n3. Significant comorbid obsessive-compulsive or post-traumatic stress:\n4. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal;\n5. Clinically significant suicidality disorder;\n6. Chronic depression (defined as of over 5 years duration);\n7. Pregnancy or lactation, lack of adequate birth control in women of childbearing age;\n8. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent symptoms;\n9. Unstable medical illness;\n10. Contraindication to receiving tDCS (e.g., ferromagnetic implant, history of seizure, known brain lesion);\n11. History of TMS (greater than 15 sessions) without a clinically meaningful response.; History of ketamine (greater than 4 sessions) without a clinically meaningful response;\n12. Require a benzodiazepine with a dose \\> lorazepam 2 mg\u002Fday;\n13. dermatological conditions contraindicating tDCS;\n14. Non-correctable sensory impairments;\n15. Inability to consent or participate as an outpatient","85 Years",{"count":475,"type":22},10,[59],"The investigators propose a single-arm, open-label study to evaluate the effectiveness, safety, tolerability and feasibility of at-home transcranial direct current stimulation (tDCS) as a treatment for depression, particularly in cases where patients have not responded well to traditional therapies. Treatment will be delivered over a 2-week period with daily weekday treatments i.e., five tDCS sessions, each lasting 20 minutes, spaced by approximately 20-minute inter-session intervals, for a total of three hours a day. Participants will self-administer treatment at home under direct remote supervision. Pre- and post- treatment neurophysiological biomarkers sessions will also be carried out. The study aims to examine changes in mood, brain activity, and related clinical outcomes before, during, and after treatment, with the goal to provide more information that can be used for future studies.\n\nPLEASE NOTE: THERE WILL BE 4 APPOINTMENTS THAT MUST OCCUR IN PERSON IN SAN DIEGO, CA.",[96,185],[480,95,187,393],"Treatment",{"date":461,"type":37},{"date":483,"type":37},"2025-09-27",{"date":485,"type":22},"2027-03",{"name":487,"class":44},"University of California, San Diego",{"id":489,"slug":490,"hasResults":12,"nctId":491,"briefTitle":492,"officialTitle":493,"acronym":494,"eligibilityCriteria":495,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":496,"targetDuration":4,"studyType":23,"phases":498,"briefSummary":499,"conditions":500,"keywords":4,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":248,"lastUpdatePostDateStruct":501,"startDateStruct":502,"completionDateStruct":504,"leadSponsor":506,"locationsCount":45},"100617857","electroconvulsive-therapy-augmented-with-transcranial-magnetic-stimulation-for-treatment-resistant-depression-100617857","NCT07324070","Electroconvulsive Therapy Augmented With Transcranial Magnetic Stimulation for Treatment Resistant Depression","New Methods Electroconvulsive Therapy Augmentation","RMTSECT2","Inclusion Criteria:\n\n* Age equal to 18 or higher\n* MADRS (Montgomery-Asberg Depression Scale) qual or higher than 20\n* Major depressive disorder according to ICD 10\n\nExclusion Criteria:\n\n* Other axis 1 disorder (for example schizofrenia, addiction, etc.)\n* No dementia\n* ECT in the last 3 months\n* TMS in the last 3 months\n* Psychotic disease or symptoms\n* Ppregnancy or lactation\n* Any neurological disease (for example epilepsy, etc.)\n* Participation in another clinical trial within the last 30 days\n* somatic condition which contraindicates ECT",{"count":497,"type":22},50,[59],"The RTMSECT2 study was design to compare the application of electroconvulsive therapy augmented by transcranial magnetic stimulation. Subject will be compared both within groups and in group using psychometric scales and different deliver energy",[185,96],{"date":459,"type":37},{"date":503,"type":37},"2026-01-05",{"date":505,"type":22},"2029-01-05",{"name":507,"class":44},"Charles University, Czech Republic",{"id":509,"slug":510,"hasResults":12,"nctId":511,"briefTitle":512,"officialTitle":513,"acronym":4,"eligibilityCriteria":514,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":149,"enrollmentInfo":515,"targetDuration":4,"studyType":23,"phases":516,"briefSummary":517,"conditions":518,"keywords":519,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":522,"lastUpdatePostDateStruct":523,"startDateStruct":525,"completionDateStruct":527,"leadSponsor":529,"locationsCount":4},"100615071","phase-2-parcel-guided-rtms-for-major-depressive-disorder-100615071","NCT07287839","Parcel-guided rTMS for Major Depressive Disorder","Phase-2 Trial of Parcel-guided rTMS for Major Depressive Disorder","Inclusion Criteria:\n\n* DSM-5 diagnosis of major depressive disorder confirmed using the Mini International Neuropsychiatric Interview (MINI30) Axis 1 and mood modules\n* Treatment-resistant MDD during the current major depressive episode documented in the MGH Antidepressant Treatment History Questionnaire (ATRQ31), which will be defined as being non-responders (less than 50% of symptom improvement) to two or more depression treatment trials of adequate dose and duration as defined by the MGH ATRQ.\n* At least moderate depression severity, operationalized as Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20\n\nExclusion Criteria:\n\n* Ever met criteria for a psychotic disorder (Sz, SzAff, Bipolar disorder)\n* Anorexia nervosa or bulimia nervosa within the last year\n* Unstable medical condition by history, physical exam or laboratory results\n* Currently pregnant or breastfeeding women; fecund women not using adequate contraceptive methods or with plan to become pregnant\n* Contraindications to MRI (based on metal screening form)\n* Meets criteria for claustrophobia\n* Recent drug or alcohol use disorder with DSM-5 specifier of moderate or severe within 6 months, or mild within 2 months; or lifetime history of IV drug use A- ctively suicidal, as defined by expressive ideation with a plan or with suicidal ideation that requires immediate medical or treatment intervention.\n* Neurological or neuromuscular disorder\n* Requires medications for a general medical condition that contraindicate the TMS treatment\n* Prior non-response to ECT, vagal nerve stimulation (VNS) or deep brain stimulation (DBS)\n* History of ketamine treatment within 6 months\n* History of monoamine oxidase inhibitor (MAOI) within the past month\n* Lacks capacity to consent\n* Taking medications that increase the risk of seizures.\n* For patients on permitted concomitant psychotropic agents (antidepressants, anticonvulsants, benzodiazepines, hypnotics, opiates, triiodothyronine (T3), modafinil, psychostimulants, buspirone, melatonin, omega-3 fatty acids, folate, l-methylfolate, s-adenosyl methionine, lithium) dosing must be stable for at least four weeks prior to study entry and patients must agree to continue at the same dose during the study",{"count":388,"type":22},[91],"Study comparing standard repetitive transcranial magnetic stimulation (rTMS) for Depression to a novel targeting approach using brain surface parcellation to locate a specific brain target.",[96],[30,100,520,521],"parcel-guided","beam-F3","2025-12-17",{"date":524,"type":37},"2025-12-18",{"date":526,"type":22},"2025-12-15",{"date":528,"type":22},"2028-06-15",{"name":530,"class":114},"Soterix Medical",{"id":532,"slug":533,"hasResults":12,"nctId":534,"briefTitle":535,"officialTitle":536,"acronym":4,"eligibilityCriteria":537,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":538,"enrollmentInfo":539,"targetDuration":4,"studyType":23,"phases":540,"briefSummary":542,"conditions":543,"keywords":544,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":526,"lastUpdatePostDateStruct":548,"startDateStruct":550,"completionDateStruct":552,"leadSponsor":554,"locationsCount":45},"100616604","phase-1-ketamine-biomarker-validation-100616604","NCT07307768","Ketamine Biomarker Validation","EEG Biomarker Development for Ketamine Administration","Inclusion Criteria:\n\n* Physically healthy patients who meet DMS-5 criteria for a major depressive episode (MDE) in the context of MDD and who score at least 22 on the Montgomery-Åsberg Depression Rating Scale (MADRS)\n* If taking antidepressants, dose is stable for at least 6 weeks.\n\nExclusion Criteria:\n\n* Lifetime history of bipolar disorder, schizoaffective disorder, schizophrenia, or any other psychotic disorder, including MDD with psychotic features\n* A first-degree relative with bipolar disorder, schizoaffective disorder, or schizophrenia, with the potential participant younger than 33 years (i.e., still at age of risk for a psychotic disorder)\n* Receipt of electroconvulsive therapy within 3 months of enrolling in the study\n* History of IV drug use\n* Nonresponse or intolerance to ketamine administered either clinically or as part of a prior research study\n* Pregnancy, planning to conceive, or sexually active but not using adequate birth control.\n* Actively suicidal (CSSRS≥3)\n* No antipsychotics or medications (e.g. benzodiazepines, anti-epileptics) that are likely to interact with GABA or glutamate,","59 Years",{"count":213,"type":22},[541],"PHASE1","We will be developing an EEG-based biomarker for the effects of ketamine infusion in patients with Depression. We will be analyzing the effects of ketamine infusion on Depression symptoms and EEG signals.",[96],[31,545,98,393,546,547],"EEG","unipolar Depression","Biomarker",{"date":549,"type":37},"2025-12-29",{"date":551,"type":22},"2025-12-20",{"date":553,"type":22},"2028-03-01",{"name":530,"class":114},{"id":556,"slug":557,"hasResults":12,"nctId":558,"briefTitle":559,"officialTitle":560,"acronym":4,"eligibilityCriteria":561,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":286,"enrollmentInfo":562,"targetDuration":4,"studyType":23,"phases":563,"briefSummary":564,"conditions":565,"keywords":566,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":569,"lastUpdatePostDateStruct":570,"startDateStruct":571,"completionDateStruct":572,"leadSponsor":574,"locationsCount":45},"100575566","feasibility-trial-of-exercise-as-a-priming-strategy-for-rtms-treatment-in-difficult-to-treat-depression-100575566","NCT06773949","Feasibility Trial of Exercise as a Priming Strategy for rTMS Treatment in Difficult-to-Treat Depression","Randomized Trial Assessing the Feasibility of Exercise as a Priming Strategy for rTMS Treatment in Difficult-to-Treat Depression","Inclusion Criteria:\n\n1. Are between 18-75 years old.\n2. Able to provide voluntary informed consent.\n3. Diagnosis of MDD or Persistent Depressive Disorder, without psychotic features, confirmed by MINI for DSM-5.\n4. Depressive symptoms have not improved after ≥ 1 adequate antidepressant trial in the current episode (i.e., difficult-to-treat MDD), based on the Antidepressant Treatment History Form (ATHF).\n5. Baseline score of ≥15 on the HRSD-17.\n6. No change in psychotropic medications or psychotherapy regimen at least 4 weeks prior to entering the trial\n7. Physically inactive as per the International Physical Activity Questionnaire - Short Form (IPAQ-SF).\n8. Able to engage in structured exercise as per the Get Active Questionnaire (GAQ).\n9. Able to adhere to the proposed treatment schedule.\n\nExclusion Criteria:\n\n1. Diagnosis of bipolar I or II disorder, based on DSM-5 criteria.\n2. Current or past (\\\u003C3 months) substance (excluding caffeine or nicotine) or alcohol abuse\u002Fdependence, as defined in DSM-5 criteria.\n3. Current use of illegal substances.\n4. Current use of cannabis.\n5. Concomitant major unstable medical or neurologic illness (e.g., uncontrolled diabetes or renal dysfunction).\n6. Organic cause of the depressive symptoms (e.g. thyroid dysfunctions), determined by the referring physician.\n7. Acute suicidality or threat to life from self-neglect.\n8. Pregnant or breastfeeding, or thinking of becoming pregnant during course of treatment.\n9. Contraindication for TMS and MRI (e.g., personal history of epilepsy or seizure, metallic head implant, pacemaker), confirmed by TMS Adult Safety Scale (TASS) and MRI pre-screener.\n10. Unwilling to maintain current psychotropic medication and\u002For psychotherapy regimen for the four weeks prior to and for the duration of the study.\n11. Taking more than 1 mg\u002Fday of lorazepam or equivalent.\n12. Any other condition that, in the opinion of the investigators which would adversely affect the participant's ability to complete the study.\n13. Physically active: performing exercise and\u002For physical activity levels meeting the cut-off for \"minimally active\" on the IPAQ-SF.",{"count":213,"type":22},[59],"The goal of this study is to collect feasibility data on combining structured exercise aimed to improve physical fitness, and intermittent TBS (iTBS) in treating individuals diagnosed with difficult-to-treat depression who are physically inactive. By conducting this trial, we will compare the therapeutic benefits of the combined approach against the standard treatment of iTBS alone (without exercise). These findings will be used to inform future large-scale projects in which we will investigate, in a larger sample size, whether structured exercise aimed to improve fitness as recommended by most public exercise guidelines (i.e., ≥3x\u002Fweek, moderate-to-vigorous intensity) serves as an active ingredient that amplifies the effectiveness of iTBS. Ultimately, the insights gained from this study will be valuable for clinicians seeking to alleviate depressive symptoms in MDD through neuromodulation techniques such as iTBS.",[185,96],[189,30,567,568],"Exercise","Physical inactivity","2025-12-09",{"date":522,"type":37},{"date":526,"type":22},{"date":573,"type":22},"2027-01-31",{"name":575,"class":44},"The Royal Ottawa Mental Health Centre",{"id":577,"slug":578,"hasResults":12,"nctId":579,"briefTitle":580,"officialTitle":580,"acronym":4,"eligibilityCriteria":581,"healthyVolunteers":54,"sex":18,"minAge":19,"maxAge":179,"enrollmentInfo":582,"targetDuration":4,"studyType":23,"phases":583,"briefSummary":584,"conditions":585,"keywords":589,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":595,"lastUpdatePostDateStruct":596,"startDateStruct":598,"completionDateStruct":600,"leadSponsor":602,"locationsCount":45},"100613274","comparison-of-the-efficacy-of-accelerated-intermittent-theta-burst-stimulation-and-accelerated-continuous-theta-burst-stimulation-in-patients-with-treatment-resistant-depression-100613274","NCT07264452","Comparison of the Efficacy of Accelerated Intermittent Theta Burst Stimulation and Accelerated Continuous Theta Burst Stimulation in Patients With Treatment-Resistant Depression","Inclusion Criteria:\n\n1. 18 to 65 years old\n2. Patients diagnosed with Major Depressive Disorder according to DSM 5 and the severity of their illness\n3. Scoring 7 points or more on the Maudsley staging method\n4. Having depression unresponsive to 2 different antidepressants\n5. No clinical mental retardation\n6. Agree to participate in the study\n7. Hamilton Depression Rating Scale-17 \\[HDRS\\] score of 20 or higher\n8. Montgomery Asberg Depression Rating Scale \\[MADRS\\] score of 20 or above\n9. Being right hand dominant\n10. Having used the same antidepressant at the same dose for the last 4 weeks\n\nExclusion Criteria:\n\n1. Diagnosed with a neurological or metabolic disease that affects cognitive functions (Systemic diseases such as diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic renal failure, Parkinson's disease, multiple sclerosis, polyneuropathy, inflammatory rheumatologic disease and malignancies)\n2. Having a foreign body such as a pacemaker, intracranial implant that can magnetically interact\n3. Hearing and visual impairments that prevent communication\n4. Unstable or acute medical conditions\n5. Pregnancy or breastfeeding\n6. Having a primary psychiatric disorder other than major depressive disorder\n7. Being diagnosed with severe MDD with psychotic features",{"count":388,"type":22},[59],"In recent years, research on the effectiveness of transcranial magnetic stimulation (TMS) in patients with treatment-resistant depression (RTD) has been steadily increasing. The aim of this study was to examine the effectiveness of accelerated unilateral application of two different forms of theta burst stimulation (TBU), a variation of repetitive TMU (rTMS)-intermittent TBU (iTBU) and continuous TBU (cTBU)-in TDD patients. The study aimed to compare the advantages of iTBU and cTBU protocols on depression, suicidal thoughts, anxiety levels, sleep disturbances, cognitive performance, and overall functioning following a two-week intensive treatment period and a 12-week follow-up period.",[96,65,586,188,587,588],"Accelerated Protocol","Continuous Theta Burst Stimulation","Unilateral rTMS",[96,65,590,591,592,588,593,594],"Accelerated protocol","intermittent theta burst stimulation","Continuous theta burst stimulation","unipolar major depressive disorder","non-invasive brain stimulation","2025-12-02",{"date":597,"type":37},"2025-12-04",{"date":599,"type":37},"2025-11-15",{"date":601,"type":22},"2027-01-15",{"name":603,"class":44},"Ataturk University",{"id":605,"slug":606,"hasResults":12,"nctId":607,"briefTitle":608,"officialTitle":609,"acronym":610,"eligibilityCriteria":611,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":179,"enrollmentInfo":612,"targetDuration":4,"studyType":23,"phases":614,"briefSummary":615,"conditions":616,"keywords":618,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":621,"lastUpdatePostDateStruct":622,"startDateStruct":624,"completionDateStruct":626,"leadSponsor":628,"locationsCount":45},"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":613,"type":22},30,[91],"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.",[617,96],"Depressive Disorder, Treatment-Resistant",[62,617,393,99,64,619,31,620],"Treatment-Resistant Major Depression","Intravenous Ketamine","2025-10-09",{"date":623,"type":37},"2025-10-14",{"date":625,"type":37},"2025-02-10",{"date":627,"type":22},"2027-12-31",{"name":629,"class":44},"Mayo Clinic",{"id":631,"slug":632,"hasResults":12,"nctId":633,"briefTitle":634,"officialTitle":634,"acronym":635,"eligibilityCriteria":636,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":637,"targetDuration":4,"studyType":23,"phases":639,"briefSummary":640,"conditions":641,"keywords":642,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":646,"lastUpdatePostDateStruct":647,"startDateStruct":649,"completionDateStruct":651,"leadSponsor":653,"locationsCount":45},"100609096","phase-2-efficacy-of-psilocybin-and-trazodone-combination-in-treatment-resistant-depression-a-randomized-controlled-proof-of-concept-study-psilotraz-100609096","NCT07210112","Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ)","PSILOTRAZ","Inclusion Criteria:\n\n* Patient with major depressive episode without psychotic features according to DSM-5 criteria;\n* Treatment-resistant depressive episode, i.e. failure to respond to at least two lines of antidepressant medication at an adequate dose and for a sufficient period of time (6 weeks according to the MGH-ATRQ);\n* MADRS ≥ 20;\n* Written signed informed consent;\n* Patient covered by the social security system.\n\nExclusion Criteria:\n\nPsychiatric comorbidities known from medical history or identified during inclusion assessment:\n\n* Bipolar disorder;\n* Schizophrenia and psychosis;\n* Personal or family history of psychotic disorder;\n* History of personality disorder;\n* Post-traumatic stress disorder, obsessive-compulsive disorder, eating disorders;\n* Alcohol or substance use disorder in past 12 months or positive urine toxins at time of assessment;\n* Significant suicide risk, as defined by: (a) suicidal ideation as indicated by items 4 or 5 on the C-SSRS within the past six months, at Screening, during the Screening Period, or at Baseline (b) demonstrating suicidal behaviors in the past six months, or; (c). clinical assessment of significant suicidal risk or risk of self-injury during participant interview;\n* Patient with a psychiatric decompensation following a previous use of psychedelic substance like LSD;\n\nComorbidities or somatic specificities:\n\n* Pregnancy and breastfeeding women;\n* Cardiovascular history (myocardial infarction, stroke, heart rhythm disorder, uncontrolled hypertension, QT interval prolongation, tachycardia and poor cardiovascular health);\n* Uncontrolled diabetes;\n* Uncontrolled thyroid disorder;\n* Epilepsy;\n* Parkinson's disease treated by selegiline or levodopa;\n* HIV treated by ritonavir and indinavir;\n* Active infection treated by erythromycin;\n* Fungal infection treated by ketoconazole and itraconazole;\n* Contraindications to MRI;\n\nConcomitant therapies:\n\n* 5-HT antagonist treatment2A (including quetiapine, olanzapine, aripiprazole);\n* Lithium treatment;\n* Treatment with buprenorphine or opioids, clonidine, methyldopa, digoxin, Monoamine oxidase inhibitors (MAOI), aldehyde dehydrogenase (ALDH) inhibitors and alcohol dehydrogenase (ADH) inhibitors, St. John's Wort, or warfarin should be discontinued completely before study drug administration;\n* Use of electroconvulsive therapy and\u002For transcranial magnetic stimulation, during the current depressive episode; or lifetime vagus nerve stimulation, deep brain stimulation, and\u002For ablative neurosurgery;\n* Use of psychedelics (psilocybin, lysergic acid, ayahuasca, mescaline and derivatives) during current episode;\n\nLegal status:\n\n* Persons deprived of their liberty by judicial or administrative decision, persons under compulsory psychiatric care;\n* Persons under legal protection or unable to give consent;\n\nOther:\n\n\\- Any clinical manifestation which, in the opinion of the investigator, may interfere with the interpretation of study results or constitute a health risk to the participant if he or she participates in the study.",{"count":638,"type":22},112,[91],"Psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improves depressive symptoms while inducing profound acute subjective effects.\n\nThe benefit-risk ratio of psilocybin in treatment-resistant depression seems favorable, but needs to be confirmed. Moreover, the role of 5-HT2A receptors, involved in the psychedelic experience, on the therapeutic efficacy of psilocybin is still poorly understood. For example, pre-administration of trazodone, a 5-HT2A antagonist antidepressant, could annihilate the acute subjective effects of psilocybin without altering its beneficial effects (Rosenblat et al., 2023). We intend to test this hypothesis by comparing, in a randomized, double-blind, placebo-controlled study, the effect of two possible doses of trazodone (total or partial occupancy of 5-HT2A receptors) on the benefit\u002Frisk ratio of psilocybin.\n\nWe hypothesize that the therapeutic effects of psilocybin are partially independent of 5-HT2A receptor activation and thus persist even after total or partial neutralization of its acute subjective effects.",[28,29],[643,644,99,645],"psilocybin","trazodone","RCT","2025-09-29",{"date":648,"type":37},"2025-10-07",{"date":650,"type":22},"2025-10-08",{"date":652,"type":22},"2030-06-30",{"name":654,"class":44},"Centre Hospitalier St Anne",{"id":656,"slug":657,"hasResults":12,"nctId":658,"briefTitle":659,"officialTitle":660,"acronym":4,"eligibilityCriteria":661,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":179,"enrollmentInfo":662,"targetDuration":4,"studyType":23,"phases":663,"briefSummary":664,"conditions":665,"keywords":666,"overallStatus":132,"whyStopped":4,"lastUpdateSubmitDate":670,"lastUpdatePostDateStruct":671,"startDateStruct":673,"completionDateStruct":675,"leadSponsor":677,"locationsCount":45},"100600230","focused-ultrasound-neuromodulation-in-patients-with-treatment-resistant-depression-100600230","NCT07094789","Focused Ultrasound Neuromodulation in Patients With Treatment-Resistant Depression","Assessment of Safety and Feasibility of Focused Ultrasound Next Generation Dome Helmet (NGDH) to Perform Neuromodulation in Patients With Treatment-Resistant Depression","Inclusion Criteria:\n\n1. Deemed to have the capacity to provide informed consent.\n2. Aged between 18 and 65 years.\n3. Diagnosis of major depressive disorder (MDD) according to DSM-5 criteria.\n4. Total score \\>20 on the Hamilton Depression Rating Scale (HAMD-17).\n5. On a stable regimen of psychiatric medications for at least 30 days prior to enrollment.\n6. Documented previous trial of at least two first-line antidepressant agents at adequate dose and duration, as assessed by two psychiatrists.\n7. Documented previous trial of cognitive behavioral therapy (CBT) or psychotherapy for MDD, sustained for at least 6 weeks.\n\nExclusion Criteria:\n\n1. Pregnant or intending to become pregnant during the study period.\n2. Diagnosis of a substance use disorder (excluding cannabis or nicotine) of moderate severity or greater, or when the substance is the primary focus of treatment, based on DSM-5 criteria.\n3. Known active seizure disorder, significant head injury with an imaging-verified lesion\n4. Unstable medical illness.\n5. Not eligible for 3-Tesla MRI (i.e. MRI-incompatible pacemaker)\n6. Inability to reliably attend required screening, treatment, or follow-up appointments.\n7. Severe claustrophobia, as identified by the participant, that would prevent completion of MRI procedures.",{"count":213,"type":22},[59],"The goal of this clinical trial is to evaluate the safety and initial effectiveness of Magnetic Resonance-guided focused ultrasound neuromodulation using the Next Generation Dome Helmet (NGDH) device in patients with treatment-resistant depression. This is a prospective, single-arm, non-randomized study.\n\nParticipants will:\n\n* Undergo two focused ultrasound treatment sessions targeting nodes of the cortical-striatal-thalamic circuit (CSTC) , spaced four weeks apart.\n* Return for follow-up visits at 24 hours, 2 weeks, and 4 weeks after each treatment session, during which clinical scales and imaging assessments will be conducted to monitor safety and clinical effects.",[64,29],[68,667,64,668,99,669],"Focused Ultrasound","FUS","CSTC Circuit","2025-08-05",{"date":672,"type":37},"2025-08-11",{"date":674,"type":37},"2025-07-11",{"date":676,"type":22},"2027-08",{"name":409,"class":44}]