[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"treatment-resistant-depression\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:treatment-resistant-depression":63},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,61,0,25,[9,48,77,125,150,179,201,222,245,270,289,312,338,366,395,417,437,461,482,506,539,570,593,612,632],{"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":24,"phases":25,"briefSummary":27,"conditions":28,"keywords":30,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":36,"lastUpdatePostDateStruct":37,"startDateStruct":40,"completionDateStruct":42,"leadSponsor":44,"locationsCount":47},"100609198","phase-2-evaluating-the-role-of-psilocybin-monitors-in-psilocybin-therapy-for-treatment-resistant-depression-100609198",false,"NCT07211438","Evaluating the Role of Psilocybin Monitors in Psilocybin Therapy for Treatment Resistant Depression","Evaluating the Role of Psilocybin Monitors in Psilocybin Therapy for Treatment Resistant Depression: A Pilot Randomized Clinical Trial","PSI-TNT","Inclusion Criteria:\n\n1. Adults 18 to 70 years old;\n2. Are outpatients;\n3. Must be deemed to have capacity to provide informed consent;\n4. Must read, sign and date the informed consent form independently. Proxy consent, including consent from a Legally Authorized Representative (LAR), is not permitted in this study;\n5. Stated willingness to comply with all study procedures;\n6. Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent\n7. Primary DSM-5 diagnosis of non-psychotic MDD, single or recurrent, and current Major Depressive Episode (MDE) based on the Mini-International Neuropsychiatric Interview (MINI) for DSM-5 administered at the first screening visit;\n8. Participants diagnosed with treatment-resistant depression defined as individuals with a baseline HamD-17 score \\> 14 and that have not responded to two or more separate trials of antidepressants at an adequate dosage and duration (an antidepressant resistance rating score of three or more is considered an adequate trial) based on the Antidepressant Treatment History Form (ATHF) (Sackeim \\& Sackeim, 2001); there is no upper limit on the number of treatment failures;\n9. Ability to take oral medication;\n10. Individuals with an eGFR above 40mL\u002Fmin\u002F1.73m2 and all blood work on clinical laboratory tests assessed as not clinically significant by study delegate physician at Screening (V1)\n11. Individuals who are capable of making their partner pregnant or who are capable of becoming pregnant: use of condoms or highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation;\n12. Individuals who are willing to and tapered off current antidepressants, antipsychotics, mood stabilizers, ketamine, esketamine, monoaminergic medicines, and stimulants used for augmentation of antidepressant therapy for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose prescribing physician confirms that it is safe for them to do so;\n13. Individuals who are willing to and have tapered off current inhibitors of 5'-diphospho-glucuronosyltransferase (UGT)1A9 and 1A10, aldehyde dehydrogenase inhibitors (ALDHs) and alcohol dehydrogenase inhibitors (ADHs) for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so;\n14. Individuals must have a designated caregiver who is able to bring them home after treatment sessions and stay with them for at least 24 hours after psilocybin has been administered;\n15. Individuals who are willing to not receive additional psychotherapy outside of the study throughout the active duration of the study; AND\n16. Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration.\n\nExclusion Criteria:\n\nAn individual who meets any of the following criteria will be excluded from participation in this clinical trial:\n\n1. Pregnant as assessed by a urine pregnancy test at Screening (V1) and Baseline (V2) or individual's that intend to become pregnant during the study or are breastfeeding;\n2. Treatment with another investigational drug or other intervention within 30 days of Screening (V1);\n3. Brain stimulation treatment within 6 months of Screening (V1);\n4. Use of psychedelics within 6 months of Screening (V1);\n5. Have initiated psychotherapy in the preceding 4 weeks prior to Screening (V1);\n6. Have a DSM-5 diagnosis of moderate to severe substance use disorder (recreational use of tobacco, alcohol, cannabis and prescribed opioids are permitted) within the preceding 6 months;\n7. Have active suicidal ideation with intent and plan, certified by the Mental Health Act (MHA), determined by a study physician;\n8. Any DSM-5 lifetime diagnosis of mania or hypomania, a schizophrenia-spectrum disorder, obsessive-compulsive disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the MINI diagnostic interview;\n9. Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition), as determined by the family medical history form and discussions with the participant;\n10. Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history (within preceding six months) , uncontrolled hypertension (consistent blood pressure readings above 160\u002F100 mmHg: measured twice with one hour between measurements), low blood pressure (blood pressure reading lower than 90\u002F60mmHg), labile blood pressure (defined as episodes of both high and low blood pressure within a 24-hour period), recent myocardial infarction (within preceding six months), all types of cardiac arrhythmia, severe coronary artery disease (symptomatic with chest pain, angina heart palpitations or shortness of breath), or moderate to severe renal impairment (eGFR of below 40 mL\u002Fmin ) or hepatic impairment (as a Child-Pugh score of B or C, determined through liver function tests);\n11. Presence of baseline prolonged QTc (defined as greater than 450 milliseconds (ms) in men and greater than 460 ms in women) or Torsade de Pointes as measured by the ECG or a history of long QTc syndrome or related risk factors ;\n12. Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.","ALL","18 Years","70 Years",{"count":22,"type":23},40,"ESTIMATED","INTERVENTIONAL",[26],"PHASE2","Psilocybin, the chemical component of \"magic mushrooms\", has been administered with psychological support in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects.\n\nThe purpose of this study is to determine the role of psilocybin monitors on the effects of psilocybin therapy in adults with treatment resistant depression.",[29],"Treatment-Resistant Depression",[31,32,33,34],"Psilocybin","Psychedelics","Treatment resistant depression","Clinical Trial","RECRUITING","2026-08-19",{"date":38,"type":39},"2026-08-21","ACTUAL",{"date":41,"type":39},"2026-07-03",{"date":43,"type":23},"2029-01",{"name":45,"class":46},"Centre for Addiction and Mental Health","OTHER",2,{"id":49,"slug":50,"hasResults":12,"nctId":51,"briefTitle":52,"officialTitle":53,"acronym":54,"eligibilityCriteria":55,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":56,"enrollmentInfo":57,"targetDuration":4,"studyType":24,"phases":59,"briefSummary":61,"conditions":62,"keywords":64,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":67,"lastUpdatePostDateStruct":68,"startDateStruct":70,"completionDateStruct":72,"leadSponsor":74,"locationsCount":76},"100508426","dutch-depression-outcome-trial-comparing-5-day-multi-daily-neuronavigated-theta-burst-sessions-with-6-weeks-rtms-100508426","NCT05900271","Dutch-Depression Outcome Trial Comparing 5 Day Multi Daily Neuronavigated Theta Burst Sessions With 6 Weeks rTMS","Higher, Faster, Better: Is an Accelerated Intermittent Theta Burst Stimulation Protocol Compared to Standard 10 Hz Repetitive Transcranial Magnetic Stimulation, More (Cost-) Effective in Patients With Treatment-resistant Depression?","DDOTT","Inclusion Criteria:\n\n* 18 years of age or older;\n* Sufficient level of spoken and written Dutch;\n* Ability to freely provide written informed consent;\n* Current DSM-5 diagnosis of a depressive episode, ascertained by the Mini International Neuropsychiatry Interview (MINI-S).\n* A Hamilton depression rating score (HDRS) of \\>16 points: this score will be obtained from the SIGH-ADS, a depression rating scale able to determine the HDRS score and a score for atypical depression.\n* have a treatment resistant depression, defined according to the criteria of Conway, that is, lack of remission for eight consecutive weeks after two different evidence-based treatments anti-depressant medication has to be adequately dosed(7,24).\n* Stable anti-depressant medication 6 weeks prior to study. Benzodiazepines may be used up to a dosage equivalent of 3.0 mg lorazepam, and can be lowered over time during the study based on clinical judgement.\n\nExclusion Criteria:\n\n* \\- Bipolar disorder.\n* Current psychotic disorder¸ including psychotic depression, assessed by treating psychiatrist.\n* Suspected dementia, assessed with a dementia screening tool, i.e., the Montreal Cognitive Assessment (MOCA)(25), with a score of less than 20 points, or a clinical suspicion of dementia, or neuroimaging indication for neurodegeneration with a Fazekas \\> 1 and MTA \\>1. These cut-offs ensure exclusion of patients with (preclinical) dementia.\n* Active suicidal thoughts and intent to act on it, assessed at the baseline interview and before the start of the trial. This assessment is based on the Columbia suicide severity rating scale, i.e., question 5 is answered positive \"Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out this plan?\" (26).\n* Metallic devices implanted above the neck, assessed at the baseline interview.\n* Patients diagnosed with epilepsy, by a neurologist, assessed at the baseline interview.\n* Substance abuse 4 weeks prior to the study, including high dosage of benzodiazepine, a dosage equivalent higher than 3.0 mg lorazepam, assessed at the baseline interview.\n* Inability to understand or comply with study requirements as judged by the investigators, assessed at the baseline interview.\n* Pregnancy","99 Years",{"count":58,"type":23},108,[60],"NA","INTRODUCTION Recent findings from three small studies (total n=59) suggest that three changes in repetitive Transcranial Magnetic Stimulation (rTMS) protocols, called the Stanford Neuromodulation Therapy (SNT) protocol, contribute to extreme high overall remission of 79% in patients with treatment resistant depression (TRD), whereas remission using a standard 10 Hz rTMS protocol is 25%. The improvement using the SNT protocol is achieved by combining 1) accelerated treatment with multiple sessions per day, 2) applying a higher overall pulse dose of stimulation, using intermittent Theta Burst Stimulation (iTBS), and 3) precise targeting of the region in the left dorsolateral prefrontal cortex (DLPFC), using functional MRI guided neuronavigation.\n\nOBJECTIVE To determine if the SNT protocol is more (cost-) effective compared to standard 10 Hz rTMS in patients with TRD, even though the number of pulses given in both protocols is equal, i.e., 90,000.\n\nSTUDY DESIGN Multicenter randomized controlled trial comparing SNT with standard 10Hz rTMS with a follow-up of 25 weeks.\n\nSTUDY POPULATION 108 Patients with TRD (no response to 2 or more evidence-based treatments).\n\nINTERVENTION 50 sessions using the SNT protocol in 5 days. The region of the left DLPFC most anticorrelated with the subgenual anterior cingulate cortex in each participant will be targeted based on subject-specific functional resting state MRI.\n\nCOMPARISON 30 standard daily 10 Hz rTMS sessions in six weeks, targeting the left DLPFC based on standard measurement procedures of the skull.\n\nOUTCOME MEASURES\n\n* Remission, based on the Hamilton depression rating scale\n* Cost effectiveness, based on healthcare resource use\n* Quality of life and positive mental health\n* Tolerability and safety\n* Relapse\n* Description of opportunities and difficulties with regard to implementation\n\nSAMPLE SIZE The investigators will enrol 108 patients (α=0.05, power is 0.80) including adjustment for attrition.\n\nCOST EFFECTIVENESS ANALYSIS SNT is faster and possibly more effective than 10Hz rTMS leading to a total cost reduction of 22 million each year considering less expensive healthcare, reduced illness duration and absence from work.\n\nTIME SCHEDULE Within 36 months, the investigators will recruit and treat 108 patients with TRD: each center will recruit 9 patients per year. After the last follow-up assessments, the investigators will finalise the study within 12 months and report the results.",[63],"Treatment Resistant Depression",[65,66],"TMS","treatment resistant depression","2026-08-17",{"date":69,"type":39},"2026-08-20",{"date":71,"type":39},"2023-11-15",{"date":73,"type":23},"2027-12",{"name":75,"class":46},"Amsterdam UMC, location VUmc",4,{"id":78,"slug":79,"hasResults":12,"nctId":80,"briefTitle":81,"officialTitle":81,"acronym":4,"eligibilityCriteria":82,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":83,"enrollmentInfo":84,"targetDuration":4,"studyType":86,"phases":4,"briefSummary":87,"conditions":88,"keywords":109,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":114,"lastUpdatePostDateStruct":115,"startDateStruct":117,"completionDateStruct":119,"leadSponsor":121,"locationsCount":124},"100551600","natural-history-of-depression-bipolar-disorder-and-suicide-risk-100551600","NCT06462196","Natural History of Depression, Bipolar Disorder and Suicide Risk","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n* Signed consent for Protocol 01-M-0254: The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers\n* Age 18 years or older\n* Able to provide informed consent\n* Able to read and write English\n\nEXCLUSION CRITERIA:\n\n* Unstable medical conditions in the opinion of the investigator that would preclude participation in outpatient or inpatient treatment.\n* Pregnancy\n* Participation in the Protocol 01-M-0254: The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers, as a healthy volunteer.\n* Participants with a history of DSM-IV substance or alcohol abuse or dependence, or DSM-5 substance use disorder (except for caffeine, nicotine, or cannabis), or moderate to severe alcohol use disorder, within the preceding three months. In addition, participants who are currently using drugs (except for caffeine, nicotine, or cannabis) must not have used illicit substances or known drugs of abuse in the two weeks prior to consent and must have a negative drug urine test (except for prescribed benzodiazepines or stimulants) prior to enrolling in the study. Cannabis use is exclusionary if the use is daily, or if participants are unable to abstain during the study, or if function of daily life is impaired by use as determined by a clinician.","120 Years",{"count":85,"type":23},500,"OBSERVATIONAL","Mood disorders, such as depression and bipolar disorder, are difficult to treat. One reason is that there are no objective ways to measure how these disorders affect the body and respond to different treatments. In this study, researchers want to perform tests on people undergoing clinical care for mood disorders. The purpose is to understand the experience of receiving treatment for depression, bipolar disorder, and suicide risk. We also hope that this study will help us to predict which medications will improve thoughts of suicide.\n\nPeople 18 years or older who are receiving treatment for depression, bipolar disorder, or suicide risk may take part in this study. Participants must have also been enrolled in protocol 01-M-0254.\n\nThis study will be conducted at the NIH Clinical Center in Bethesda, MD. The study typically lasts up to 12 weeks, but may last longer if a participant s treatment continues past that time.\n\nParticipants will have weekly interviews and questionnaires while they are being treated for their mood disorder. Other tests are optional and include psychological testing, blood draws, sleep tests, and imaging scans. These will be done at the start and the end of research participation.",[89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,63,107,108],"Behavioral Symptoms","Suicide","Self-Injurious Behavior","Sensory System Agents","Analgesics","Peripheral Nervous System Agents","Physiological Effects of Drugs","Anesthetics, Dissociative","Anesthetics, General","Anesthetics","Central Nervous System Depressants","Excitatory Amino Acid Antagonists","Excitatory Amino Acid Agents","Neurotransmitter Agents","Molecular Mechanisms of Pharmacological Action","Ketamine","Depression, Unipolar","Depressive Symptoms","Major Depressive Disorder","Depression, Bipolar",[110,90,107,111,112,113,63],"Neurobiology","Bipolar Disorder","Biomarkers","Suicide Risk","2026-08-13",{"date":116,"type":39},"2026-08-14",{"date":118,"type":39},"2024-09-09",{"date":120,"type":23},"2030-06-01",{"name":122,"class":123},"National Institute of Mental Health (NIMH)","NIH",1,{"id":126,"slug":127,"hasResults":12,"nctId":128,"briefTitle":129,"officialTitle":130,"acronym":131,"eligibilityCriteria":132,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":133,"targetDuration":4,"studyType":24,"phases":135,"briefSummary":137,"conditions":138,"keywords":139,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":142,"lastUpdatePostDateStruct":143,"startDateStruct":144,"completionDateStruct":146,"leadSponsor":148,"locationsCount":124},"100576161","phase-3-intravenous-ketamine-and-immersive-virtual-reality-to-treat-depression-100576161","NCT06781697","InTRavenous kEtAmine and immerSive virtUal Reality to Treat dEpression","InTRavenous kEtAmine and immerSive virtUal Reality to Treat dEpression (TREASURE Trial): a Pilot, Randomized Controlled Trial","TREASURE","Inclusion Criteria:\n\n* Age ≥ 18, able to provide informed consent\n* Patient diagnosed with treatment-resistant depression\n* Outpatient recommended and approved by psychiatrist for ketamine treatment\n* Patients who are on IV ketamine and requiring at least 4 treatments of IV ketamine per course (prescribed by their physiatrist)\n* Cognitively alert, oriented, and able to watch immersive content and respond to questions\n* Negative human chorionic gonadotropin test before treatment, for female participants of childbearing potential who are not practicing medically appropriate methods of birth control (e.g., hormonal contraceptives, implants, injectables, intrauterine devices, intrauterine systems, etc.)\n\nExclusion Criteria:\n\n* History of psychosis\u002Fcomorbid psychiatric disorders\u002Fpsychotic depression\u002Fdissociative syndromes, significant personality disorder, as clinically assessed by psychiatrist\n* Using non-prescribed substance (e.g., cannabis) or alcohol use within the preceding 48 hours of treatment\n* History of substance misuse and\u002For dependence, including chronic alcohol abuse\n* Previous ketamine use\n* Acute dementia\u002Fdelirium\n* Acute risk of suicide at baseline, as determined by the study psychiatrist\n* Pregnancy\u002Fbreastfeeding\n* Previous sensitivity to ketamine or related compounds\n* Unstable medical condition which may require anesthesia consult\n* History of elevated intracranial pressure or cerebrovascular accident\n* Recent (within 6 weeks) major cardiovascular event (such as myocardial infarction)\n* Significant motion sickness (i.e. occur during exposure to physical\u002Fvisual and virtual motion, cybersickness, etc.) self-identified by patient\n* Inability to communicate with the study team",{"count":134,"type":23},31,[136],"PHASE3","Depression is a common condition, with serious negative effects on the health and quality of life of those affected. While there are currently various medications which attempt to treat depression, they often take a long time to begin to work and do not work at all for many people. There is therefore a need for new treatments which work quickly and effectively.\n\nOne such medication is called ketamine. Studies have shown that ketamine can treat symptoms of depression quickly. This quick action sets ketamine apart from many antidepressants that take weeks to show noticeable effects. One way that it may do this is by creating a transient sense or feeling of being separated from reality, such as seeing or hearing things that are not really there. Another way to create these same feelings is with virtual reality (VR), where a person can feel as though they are entering a 3-dimensional virtual computer-generated world by wearing a special headset or goggles with a computer inside.\n\nIn this study, all participants will receive standard ketamine treatments for depression. Half of the participants will also use a VR headset while receiving the ketamine treatments to see if ketamine and VR acting together provide a better treatment for symptoms of depression than ketamine alone.\n\nThis is a small pilot trial. The main purpose of this trial is to learn if it is possible to run a larger clinical trial comparing \"ketamine and VR\" with \"ketamine alone\", for adults with treatment-resistant depression. The researchers will study this by seeing how many participants take part in the study within 1-2 years, and how many complete the study treatments and tests. The researchers will also compare the two study groups to see if \"ketamine and VR\" provide a better treatment for symptoms of depression than \"ketamine alone\".",[63],[140,104,141,63],"Depression","Virtual Reality","2026-08-11",{"date":114,"type":39},{"date":145,"type":39},"2026-05-03",{"date":147,"type":23},"2028-12",{"name":149,"class":46},"Sunnybrook Health Sciences Centre",{"id":151,"slug":152,"hasResults":12,"nctId":153,"briefTitle":154,"officialTitle":155,"acronym":156,"eligibilityCriteria":157,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":158,"enrollmentInfo":159,"targetDuration":4,"studyType":24,"phases":161,"briefSummary":162,"conditions":163,"keywords":165,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":170,"lastUpdatePostDateStruct":171,"startDateStruct":173,"completionDateStruct":175,"leadSponsor":177,"locationsCount":124},"100629461","iprgc-as-a-potential-biomarker-for-predicting-transcranial-magnetic-stimulation-treatment-response-in-major-depressive-disorder-100629461","NCT07474974","ipRGC as a Potential Biomarker for Predicting Transcranial Magnetic Stimulation Treatment Response in Major Depressive Disorder","Illuminating Depression: ipRGC as a Potential Biomarker for Predicting Transcranial Magnetic Stimulation Treatment Response in Major Depressive Disorder","BRIGHT","Inclusion Criteria:\n\n* Diagnosis of MDD, confirmed via the structured clinical interview;\n* TRD type;\n* Age between 18-65 years;\n* Visual acuity of 20\u002F32 or better.\n\nExclusion Criteria:\n\n* Prior rTMS treatment;\n* Contraindications for TMS;\n* Psychiatric disorders other than MDD;\n* Systemic diseases affecting the eyes (e.g., diabetes mellitus);\n* Ocular conditions;\n* Head injuries causing loss of consciousness;\n* Current or past alcohol\u002Fsubstance dependence within 6 months;\n* Neurodegenerative diseases;\n* Major neurological illnesses;\n* Use of medications affecting iris mechanics or the autonomic nervous system.","65 Years",{"count":160,"type":23},44,[60],"This research explores the potential of retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs), as biomarkers for predicting response to transcranial magnetic stimulation (TMS) in treatment-resistant depression (TRD). We also aim to assess the impact of TMS treatment on RGCs and ipRGCs in TRD patients, investigating associations with clinical improvements and cognitive status. A clinical trial involving 44 patients with treatment-resistant depression (TRD) will be conducted. All participants will receive rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Data will be collected pre- and post-intervention, as well as at a 2-month follow-up, using multiple outcome measures, including the post-illumination pupil response (PIPR). The project seeks to confirm the effectiveness of TMS and the potential of RGCs\u002FipRGCs as predictors of treatment response, thereby facilitating the development of personalized treatment strategies for TRD patients undergoing rTMS therapy.",[164,63],"Depression - Major Depressive Disorder",[107,166,167,168,169],"Repetitive Transcranial Magnetic Stimulation","Retinal Ganglion Cells","ipRGCs","Treatment-resistant depression","2026-08-03",{"date":172,"type":39},"2026-08-06",{"date":174,"type":39},"2026-03-15",{"date":176,"type":23},"2027-07-31",{"name":178,"class":46},"Polytechnic Institute of Porto",{"id":180,"slug":181,"hasResults":12,"nctId":182,"briefTitle":183,"officialTitle":184,"acronym":185,"eligibilityCriteria":186,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":158,"enrollmentInfo":187,"targetDuration":4,"studyType":24,"phases":189,"briefSummary":190,"conditions":191,"keywords":193,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":194,"lastUpdatePostDateStruct":195,"startDateStruct":197,"completionDateStruct":199,"leadSponsor":200,"locationsCount":124},"100555948","phase-2-treatment-with-psilocybin-for-chronic-neuropathic-pain-and-depression-transcend-100555948","NCT06518720","Treatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND)","Treatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND): An Open-Label Clinical Trial","TRANSCEND","Inclusion Criteria:\n\n1. Adults 18 to 65 years old;\n2. Are outpatients;\n3. Must be deemed to have capacity to provide informed consent;\n4. Must sign and date the informed consent form;\n5. Stated willingness to comply with all study procedures;\n6. Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;\n7. Primary DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the Structured Clinical Interview for DSM-5 (SCID-5) administered at the first screening visit;\n8. Participants diagnosed with treatment-resistant depression defined as individuals with a baseline HamD-17 score \\> 14 and that have not responded to two or more separate trials of antidepressants at an adequate dosage and duration (an antidepressant resistance rating score of three or more is considered an adequate trial) based on the Antidepressant Treatment History Form (ATHF) (Sackeim \\& Sackeim, 2001); there is no upper limit on the number of treatment failures;\n9. Diagnosis of chronic neuropathic pain as determined by a pain specialist and confirmed with the standardized Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire\n10. Moderate-to-severe neuropathic pain determined by Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference score of ≥ 60, as well as mean pain intensity scores ≥ 5 on a numeric rating scale\n11. Previous trials of at least two medications recommended in the Canadian consensus guidelines on the management of neuropathic pain with no self-reported meaningful improvement in symptoms\n12. Ability to take oral medication;\n13. Individuals with an eGFR above 40mL\u002Fmin\u002F1.73m² and all blood work on clinical laboratory tests assessed as not clinically significant by study delegate physician at Screening (V1)\n14. Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation;\n15. Individuals who are willing to taper off current antidepressant and antipsychotic medications for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so; and\n16. Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration.\n\nExclusion Criteria:\n\n1. Pregnant as assessed by a urine pregnancy test at Screening (V1) or individuals that intend to become pregnant during the study or are breastfeeding;\n2. Treatment with another investigational drug or other intervention within 30 days of Screening (V1);\n3. Have initiated psychotherapy in the preceding 12 weeks prior to Screening (V1);\n4. Have a DSM-5 diagnosis of substance use disorder (recreational use of tobacco, alcohol, cannabis and prescribed opioids are permitted) within the preceding 6 months;\n5. Have active suicidal ideation with intent and plan as determined by item 3 of the HamD-17;\n6. Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; obsessive-compulsive disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview;\n7. Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant;\n8. Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment.\n9. Presence of baseline prolonged QTc or Torsade de Pointes as measured by the ECG or a history of long QTc syndrome or related risk factors;\n10. Individuals who are currently taking methadone, buprenorphine or \\> 100 milligrams of morphine (or morphine equivalents).\n11. Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.",{"count":188,"type":23},16,[26],"Psilocybin, the chemical component of \"magic mushrooms\", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects.\n\nThe purpose of this study is to assess the feasibility, tolerability, and preliminary efficacy of psilocybin therapy for adults with chronic neuropathic pain and co-morbid treatment resistant depression.",[63,192],"Chronic Pain",[31,32,34,192,63],"2026-07-29",{"date":196,"type":39},"2026-07-30",{"date":198,"type":39},"2025-04-01",{"date":73,"type":23},{"name":45,"class":46},{"id":202,"slug":203,"hasResults":12,"nctId":204,"briefTitle":205,"officialTitle":205,"acronym":206,"eligibilityCriteria":207,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":158,"enrollmentInfo":208,"targetDuration":4,"studyType":24,"phases":210,"briefSummary":211,"conditions":212,"keywords":213,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":194,"lastUpdatePostDateStruct":216,"startDateStruct":217,"completionDateStruct":219,"leadSponsor":221,"locationsCount":124},"100555448","phase-2-imaging-the-effects-of-serotonin-2a-receptor-modulation-on-synaptic-density-in-treatment-resistant-depression-synvest-100555448","NCT06512220","Imaging the Effects of Serotonin 2A Receptor Modulation on Synaptic Density in Treatment-resistant Depression (SYNVEST)","SYNVEST","Inclusion Criteria:\n\n1. Adults 18 to 65 years old;\n2. Must be deemed to have capacity to provide informed consent;\n3. Must sign and date the informed consent form;\n4. Stated willingness to comply with all study procedures;\n5. Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;\n6. Primary DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the Structured Clinical Interview for DSM-5 (SCID-5) administered at the first screening visit;\n7. Participants diagnosed with treatment-resistant depression defined as individuals with a baseline HamD-17 score \\> 14 and that have not responded to two or more separate trials of antidepressants at an adequate dosage and duration (an antidepressant resistance rating score of three or more is considered an adequate trial) based on the Antidepressant Treatment History Form (ATHF); there is no upper limit on the number of treatment failures;\n8. Ability to take oral medication;\n9. Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 3 months prior to screening and agreement to use such a method during study participation;\n10. Individuals who are willing to taper off current antidepressant and antipsychotic medications for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and whose physician confirms that it is safe for them to do so; and\n11. Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration.\n\nExclusion Criteria:\n\n1. Pregnant as assessed by a urine pregnancy test at Screening (V1) or individual's that intend to become pregnant during the study or are breastfeeding;\n2. Treatment with another investigational drug or other intervention within 30 days of Screening (V1);\n3. Have initiated psychotherapy in the preceding 12 weeks prior to Screening (V1);\n4. Have a DSM-5 diagnosis of substance use disorder (use of tobacco is permitted) within the preceding 6 months;\n5. Have active suicidal ideation with intent and plan as determined by item 3 of the HamD-17;\n6. Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; obsessive-compulsive disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview;\n7. Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I disorder as determined by the family medical history form and discussions with the participant;\n8. Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment.\n9. Presence of baseline prolonged QTc or Torsade de Pointes as measured by the ECG or a history of long QTc syndrome or related risk factors;\n10. History of allergy or contraindication to risperidone\n11. Current or past traumatic brain injury or other neurological\u002Fneurodegenerative disorder\n12. Unable or unwilling to undergo PET or MRI scanning (e.g. claustrophobia, pacemaker);\n13. Blood disorders, disorders of coagulation, or ongoing use of anticoagulant medication\n14. Any disability that may prevent the participant from completing study requirements (e.g., non-correctable clinically significant sensory impairment such as not hearing well enough to communicate with study personnel during scans, or physical disability that does not allow them to lie still on the scanner bed for 1-2 hours);\n15. Participant exceeds the annual or lifetime amount of radiation\n16. Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.",{"count":209,"type":23},12,[26],"Psilocybin, the chemical component of \"magic mushrooms\", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. In healthy volunteers, the psychedelic effects of psilocybin have been shown to be blocked by administration of certain medications such as risperidone.\n\nThe purpose of this study is to use an established SV2A radiotracer produced at our Centre to determine the feasibility of integrating PET imaging in to psilocybin trials. The preliminary imaging data will assess whether psilocybin's antidepressant effects are related to changes in synaptic density in adults with TRD, and whether any changes in synaptic density are associated with psilocybin's actions on the 5-HT2AR.",[63],[31,32,34,214,63,215],"Positron-Emission Tomography","Neurophysiology Testing",{"date":196,"type":39},{"date":218,"type":39},"2025-04-21",{"date":220,"type":23},"2027-09",{"name":45,"class":46},{"id":223,"slug":224,"hasResults":12,"nctId":225,"briefTitle":226,"officialTitle":227,"acronym":228,"eligibilityCriteria":229,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":4,"targetDuration":4,"studyType":230,"phases":4,"briefSummary":231,"conditions":232,"keywords":233,"overallStatus":238,"whyStopped":4,"lastUpdateSubmitDate":239,"lastUpdatePostDateStruct":240,"startDateStruct":4,"completionDateStruct":4,"leadSponsor":242,"locationsCount":124},"100499131","nrx-101-expanded-access-100499131","NCT05779267","NRX-101 Expanded Access","NRX-101 for Treatment-Resistant Depression in Patients Receiving Transcranial Magnetic Stimulation Who Do Not Qualify for NRX101-011 (MIND1): Expanded Access Program","NRX-101 EAP","Inclusion Criteria:\n\n\\-\n\nEligible for inclusion in this EAP only if all the following criteria apply:\n\n1. 18 years of age or older\n2. Able to understand the study procedures and risks and able to provide written and dated informed consent before any protocol-specific procedure.\n3. In the investigator's judgment, likely to comply with the Expanded Access Protocol, including transcranial magnetic stimulation visits, NRX-101 dosing instructions, scheduled assessments, and prompt communication of adverse events and other clinically important information.\n4. Under the care of a board-certified psychiatrist or other qualified psychiatric prescriber who has completed protocol-specific training, is registered as an investigator for this Expanded Access Protocol, and agrees to direct and document the patient's psychiatric care according to standard of care.\n5. Diagnosed with treatment resistant depression (TRD) according to the criteria defined in the DSM-5. This diagnosis must be made by a psychiatrist or other qualified licensed psychiatric provider.\n6. History of inadequate response, intolerance, or loss of effect to at least one prior adequate pharmacologic treatment for the current depressive episode with a medication indicated for treatment-resistant depression in the investigator's judgment.\n7. Planned course of theta burst transcranial magnetic stimulation as part of standard clinical care for the current depressive episode, to be delivered at a site with appropriate experience and safety procedures for transcranial magnetic stimulation.\n8. No uncontrolled or unstable medical condition that, in the investigator's judgment, creates an unacceptable risk with theta burst transcranial magnetic stimulation in combination with NRX-101 or prevents adequate assessment of safety.\n9. 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 treatment with NRX-101:\n\n   1. Non-childbearing potential: physiologically incapable of becoming pregnant (i.e., permanently sterilized \\[status post-hysterectomy, bilateral tubal ligation\\], or post-menopausal with last menses at least one year prior to Screening); or\n   2. Childbearing potential, and meets the following criteria:\n\n   i. Use of any form of hormonal birth control for at least 2 months prior to Screening, on hormone replacement therapy that started prior to 12 months of amenorrhea, using an intrauterine device (IUD) for at least 1 month prior to Screening, in a monogamous relationship with a partner who has had a vasectomy, or sexually abstinent.\n\n   ii. Negative urinary pregnancy test at Screening, confirmed by a second negative urinary pregnancy test at Day 1, prior to receiving treatment with NRX-101.\n10. Sufficient stability of residence and contact information to allow appropriate follow up and emergency contact during participation in the Expanded Access Protocol, in the investigator's judgment.\n11. The patient is not participating in and cannot reasonably enroll in the concurrent Phase IIb trial NRX101-011, because the patient does not meet at least one inclusion criterion for NRX101-011, meets at least one exclusion criterion for NRX101-011, or faces distance, transportation, schedule, or other practical barriers that prevent trial participation despite interest. The investigator must document the specific reason in the source record.\n\nExclusion Criteria:\n\n1. Heterosexual female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.\n2. Female who is pregnant (positive pregnancy test at Screening) or breastfeeding.\n3. Active suicidality (without the intention to act) as evidenced by a score of \\>3 on the Columbia Suicide Severity Rating Scale.\n4. 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).\n5. Current DSM-5 diagnosis of alcohol use disorder\n6. A lifetime history of phencyclidine (PCP)\u002Fketamine drug abuse\n7. History of schizophrenia or schizoaffective disorder\n8. 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.\n9. Has dementia, delirium, amnestic, or any other cognitive disorder.\n10. Renal impairment defined as estimated glomerular filtration rate (eGFR) \\\u003C 60 mL\u002Fmin, calculated using the 2021 CKD-EPI creatinine equation (race-free).\n11. 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.\n12. 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.\n13. Risk factors for neurocardiogenic syncope including history of syncope\u002F presyncope related to noxious stimuli, anxiety, micturation, or posture.\n14. 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.\n15. Diagnosis of moderate to severe heart disease or current episode of:\n\n    1. Myocardial infarction within 1 year of Screening.\n    2. Diagnosis of angina pectoris.\n    3. 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.\n16. Diagnosis of chronic lung disease, excluding asthma.\n17. 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.\n18. History of epilepsy, personal history of seizure, family history of epilepsy or seizure in a first degree relative.\n19. Diagnosis of parenchymal or leptomeningeal cancer.\n20. Diabetes mellitus fulfilling any of the following criteria:\n\n    1. Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) \\>8.0 percent at Screening.\n    2. Admitted to the hospital for treatment of diabetes mellitus or diabetes mellitus-related illness in the past 12 weeks.\n    3. Not under physician care for diabetes mellitus.\n    4. Not on the same dose of oral hypoglycemic drug(s) and\u002For diet for the 4 weeks prior to Screening.\n    5. Not on the same dose of oral thiazolidinediones (glitazones) for the 8 weeks prior to Screening.\n21. 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.\n22. On exclusionary concomitant psychotropic and non-psychotropic medications (see Section 9.5)\n23. Prescribed more than one agent in each of the following categories at randomization:\n\n    1. Approved SSRIs.\n    2. Approved serotonin and norepinephrine reuptake inhibitors (SNRIs).\n    3. Approved tetracyclic antidepressants (TeCAs).\n24. Currently prescribed oxcarbazepine or carbamazepine.\n25. 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.\n26. Known allergies to lurasidone or Latuda®, cycloserine or Seromycin®, or the following excipients: mannitol, croscarmellose sodium, magnesium stearate, silicon dioxide, and\u002For hydroxypropylmethylcellulose (HPMC).\n27. Participation in any clinical trial with an investigational drug or device within the past 3 months or planned concurrent study participation.\n28. 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.\n29. Positive urine toxicity screening for use of any cocaine, opiates, non-prescribed amphetamines, or non-prescribed barbiturates. (Note: cannabinoids or marijuana use is not exclusionary, unless patient meets the DSM-5 criteria for cannabis withdrawal).\n30. Patients with pacemakers and\u002For any implants including metal in the head except the mouth (cochlear implant, implanted brain stimulators, aneurysm clips)\n31. Individuals with an intracranial lesion or increased intracranial pressure","EXPANDED_ACCESS","The purpose of this Expanded Access Treatment Protocol is to make NRX-101 available to patients who have treatment-resistant depression and who are unable to participate in, or do not have access to, the ongoing NRX-101 clinical trial. The objective of the program is to provide treatment access while monitoring safety in the context of NRX-101 administration paired with theta burst transcranial magnetic stimulation..",[29],[234,235,236,237],"cycloserine","NMDA antagonist","NRX-101","transcranial magnetic stimulation","AVAILABLE","2026-07-16",{"date":241,"type":39},"2026-07-20",{"name":243,"class":244},"NeuroRx, Inc.","INDUSTRY",{"id":246,"slug":247,"hasResults":12,"nctId":248,"briefTitle":249,"officialTitle":250,"acronym":4,"eligibilityCriteria":251,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":252,"targetDuration":254,"studyType":86,"phases":4,"briefSummary":255,"conditions":256,"keywords":257,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":261,"lastUpdatePostDateStruct":262,"startDateStruct":264,"completionDateStruct":266,"leadSponsor":268,"locationsCount":124},"100647217","working-mechanisms-and-effectiveness-of-iv-ketamine-assisted-psychotherapy-on-depression-in-trd-clients-100647217","NCT07706478","Working Mechanisms and Effectiveness of IV Ketamine-assisted Psychotherapy on Depression in TRD Clients","Effectiveness and Underlying Mechanisms of an Innovative Treatment Program for Persistent Mood and Anxiety Conditions","Inclusion Criteria:\n\n* Adults (18 years and older)\n* TRD\n* A MADRS score above the established clinical cut-off, indicating clinically significant depressive symptoms\n* Insufficient response to at least two adequate antidepressant treatment trials and one evidence-based psychotherapy, or failure to achieve adequate improvement following at least three consecutive treatment steps in accordance with the Dutch Multidisciplinary Guideline for Depression\n\nExclusion Criteria:\n\n* Current substance use disorder or recent illicit drug use\n* Substance use disorder not in remission for at least 3 months\n* Inability to abstain from alcohol for 24 hours before and after treatment\n* Acute suicidality\n* Current or past psychotic disorder\n* Significant neurological disorders (e.g., epilepsy, elevated intracranial pressure)\n* Uncontrolled hypertension or medical conditions associated with increased cardiovascular or cerebrovascular risk (e.g., aneurysms, recent myocardial infarction or intracerebral hemorrhage)\n* Significant bladder disease (e.g., cystitis)\n* Severe hepatic impairment\n* Pregnancy, breastfeeding, or ongoing IVF treatment\n* Extreme underweight or obesity where treatment is deemed medically unsafe Inability to arrange an accompanying adult for transport and support after treatment",{"count":253,"type":23},120,"12 Months","Ketamine-Assisted Psychotherapy (KAP) is an innovative treatment that combines intravenous ketamine with psychotherapy in a carefully monitored clinical setting. At Senz, this treatment is being evaluated in an open-label clinical trial for individuals with persistent depression who have not responded sufficiently to previous treatments. The combination of ketamine, psychological support, and integration sessions aims to promote emotional processing, psychological flexibility, and lasting therapeutic change.",[63],[258,259,140,260],"KAP","TRD","IV ketamine","2026-07-13",{"date":263,"type":39},"2026-07-15",{"date":265,"type":39},"2025-06-01",{"date":267,"type":23},"2033-01",{"name":269,"class":46},"Senz",{"id":271,"slug":272,"hasResults":12,"nctId":273,"briefTitle":274,"officialTitle":274,"acronym":4,"eligibilityCriteria":275,"healthyVolunteers":12,"sex":18,"minAge":276,"maxAge":20,"enrollmentInfo":277,"targetDuration":4,"studyType":24,"phases":278,"briefSummary":279,"conditions":280,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":261,"lastUpdatePostDateStruct":282,"startDateStruct":283,"completionDateStruct":285,"leadSponsor":287,"locationsCount":124},"100358891","tractography-guided-subcallosal-cingulate-deep-brain-stimulation-for-treatment-resistant-depression-100358891","NCT03952962","Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression","Inclusion Criteria:\n\n* Men and women (non-pregnant) between ages 21 and 70;\n* DSM-5 diagnosis a current major depressive episode (MDE) for 10 years of less, recurrent or single episode with first episode after adulthood and did not start during childhood or adolescence, secondary to nonpsychotic unipolar major depressive disorder;\n* Current index MDE ≥24 months duration and\u002For recurrent illness with at least a total of 2 lifetime episodes (including current episode \\>12 months);\n* Treatment resistance (defined by criteria on the Antidepressant Treatment History Form (ATHF)28): Failure to respond to a minimum of four adequate depression treatments from different categories;\n* Symptom severity for Screening: Hamilton Depression Rating Scale-17 item (HDRS17) ≥20;\n* Symptom severity for Outcome: Montgomery Asberg Rating Scale (MADRS) ≥27 to be met at assessment one week pre-op;\n* Normal brain MRI within 3 months of surgery;\n* Antidepressant medication regimen has been held stable for ≥ 30 days prior to the study screening MADRS;\n* Remain on stable antidepressant medication throughout the study, unless there are safety concerns;\n* Montreal Cognitive Assessment (MoCA) \\>25;\n* Able and willing to give informed consent and agree to attend regular clinic visits for at least 12 months.\n\nExclusion Criteria:\n\n* DSM-5 Axis I Disorders: any lifetime history of psychotic disorder or bipolar disorder;\n* Alcohol or substance use disorder within 6 months, excluding nicotine;\n* History of childhood abuse (physical or sexual) 18\n* Personality disorders;\n* Seeking disability during the trial;\n* Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or made any suicide attempt within the last year; (MADRS ≥ 5 including the day of surgery);\n* No stable work history;\n* Neurological\u002FMedical condition that makes the patient, in the opinion of the surgeon, a poor candidate;\n\n  1. Pregnant or has plans to become pregnant in the next 36 months;\n  2. Unable\u002Funable to practice birth control through the period of randomization and withdrawal of therapy;\n* Subjects who have a history of a seizure disorder;\n* Subjects who will be exposed to diathermy;\n* Subjects who have any medical contraindications to undergoing DBS surgery (e.g. infection, coagulopathy, or significant cardiac or other medical risk factors for surgery);\n* Subjects with another implanted device such as a cardiac pacemaker, defibrillator or neurostimulator;\n* Subjects who have a history of hemorrhagic stroke;\n* Subjects who are unable to undergo MRI;\n* Subjects who are at increased risk of hemorrhage due to underlying medical conditions or medication.","21 Years",{"count":209,"type":23},[60],"Treatment resistant depression remains a major problem for individuals and society. Surgical procedures may provide relief for some of these patients. The most frequently considered surgical approach is deep brain stimulation (DBS) of a part of the brain called the subcallosal cingulate region. However, the effectiveness and safety is not well established. The investigators will use a novel approach using advanced imaging technique (magnetic resonance tractography) to evaluate the feasibility and safety of this surgical approach. An innovative method for the definition of DBS target will be applied that redefines the concept of targeting as one of targeting a symptomatic network rather than a structural brain region using subject-based brain anatomy to define the target location. The correlation between imaging findings at baseline with the mood score changes at different time points of the study will be investigated.",[63,281],"Undergoing Deep Brain Stimulation (DBS) Surgery",{"date":263,"type":39},{"date":284,"type":39},"2022-10-28",{"date":286,"type":23},"2027-07",{"name":288,"class":46},"Nader Pouratian",{"id":290,"slug":291,"hasResults":12,"nctId":292,"briefTitle":293,"officialTitle":294,"acronym":4,"eligibilityCriteria":295,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":296,"enrollmentInfo":297,"targetDuration":4,"studyType":24,"phases":299,"briefSummary":300,"conditions":301,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":302,"lastUpdatePostDateStruct":303,"startDateStruct":305,"completionDateStruct":307,"leadSponsor":309,"locationsCount":311},"100490016","phase-2-an-open-label-study-to-evaluate-the-safety-tolerability-and-pharmacodynamics-of-bpl-003-in-patients-with-treatment-resistant-depression-100490016","NCT05660642","An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients With Treatment Resistant Depression","An Open-Label, Phase 2a Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients With Treatment Resistant Depression","Inclusion Criteria:\n\n1. Diagnosed with Major Depressive Disorder.\n2. Diagnosed with TRD defined as failure to respond to an adequate dose and duration of at least 2 pharmacological treatments in the past 5 years prior to screening, at least one of which is during the current episode.\n3. Montgomery-Asberg Depression Rating Scale score ≥24 at Screening.\n4. Clinical Global Impression - Severity ≥4 at Screening.\n5. Willing and able to discontinue current pharmacological anti-depressant therapy.\n6. On current stable dose of pharmacological antidepressant therapy limited to one of 4 SSRIs (Arm B), i.e. either citalopram, escitalopram, sertraline or fluoxetine.\n\nExclusion Criteria:\n\n1. Current or history of schizophrenia, psychotic disorder including psychotic depression, bipolar disorder, delusional disorder, schizoaffective disorder, or any other severe psychiatric disorder.\n2. Current personality disorders.\n3. First-degree family history of schizophrenia, bipolar disorder, delusional disorder, personality disorders or schizoaffective disorder.\n4. Current alcohol or substance use disorder (other than caffeine or nicotine).\n5. A participant who at any time, has been unresponsive to ketamine, esketamine, an adequate course of treatment with electroconvulsive therapy, or has received vagal nerve stimulation or deep brain stimulation.\n6. Suicidal ideation with the intent to act or suicidal behaviour within the 12 months prior to the start of Screening or on Day 1 prior to dosing.\n7. Suicide attempt and\u002For self-injurious behaviour within the last 12 months prior to Screening.\n8. Uncontrolled medical conditions e.g. hypo\u002Fhyperthyroidism, diabetes, renal failure.\n9. Seizure disorder or history of seizures (including febrile seizures).\n10. Abnormal and clinically significant results on the physical examination, vital signs, electrocardiogram, or laboratory tests at Screening Baseline.\n11. Any nasal obstruction, blockage, or symptoms of congestion at the time of dosing, that in the Investigator's opinion may interfere with administration of the study drug.\n12. Currently receiving lithium, antipsychotics, serotonergic drugs (excluding the permitted SSRIs for arm B), psychostimulants, or any other prohibited medication.\n13. Female patients who are pregnant or lactating, or of childbearing potential and not willing to use adequate forms of contraception.\n14. Male patients who are sexually active and not willing to using adequate forms of contraception.","75 Years",{"count":298,"type":23},72,[26],"An open-label, multi-centre, Phase 2a study to evaluate the safety, tolerability, and pharmacodynamics of one and two doses of intranasal BPL-003 combined with psychological support, in patients with treatment resistant depression when administered as monotherapy or as adjunctive therapy with defined SSRIs (citalopram, escitalopram, sertraline or fluoxetine).",[63],"2026-07-02",{"date":304,"type":39},"2026-07-06",{"date":306,"type":39},"2023-02-10",{"date":308,"type":23},"2026-11",{"name":310,"class":244},"Beckley Psytech Limited",3,{"id":313,"slug":314,"hasResults":12,"nctId":315,"briefTitle":316,"officialTitle":316,"acronym":4,"eligibilityCriteria":317,"healthyVolunteers":318,"sex":18,"minAge":276,"maxAge":319,"enrollmentInfo":320,"targetDuration":4,"studyType":24,"phases":322,"briefSummary":324,"conditions":325,"keywords":327,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":330,"lastUpdatePostDateStruct":331,"startDateStruct":332,"completionDateStruct":334,"leadSponsor":336,"locationsCount":47},"100552985","phase-1-gamma-oscillations-as-a-prognostic-marker-for-ketamine-therapy-in-treatment-resistant-depression-100552985","NCT06480201","Gamma Oscillations as a Prognostic Marker for Ketamine Therapy in Treatment Resistant Depression","Inclusion Criteria:\n\n1. General\n\n   * The criteria for eligibility described here are intended to protect patient welfare where, for example, the administration of ketamine in the context of standardized research (i.e. pharmaco-EEG challenge) would be inadvisable or unsafe. An additional purpose is to decrease psychiatric co-morbidities that may affect the clinical phenomenology or treatment response and thus obscure findings. Further, by virtue of the eligibility criteria the investigators seek to limit variability due to demographic and other factors.\n2. All subjects Inclusion Criteria:\n\n   * Male or Female ages 21-45, inclusive.\n   * Level of understanding sufficient to agree to all tests and examinations required by the protocol.\n3. TRD patients\n\n   * Major depressive disorder (MDD) diagnosis confirmed by MINI, with major depressive episode of at least 4 weeks duration.\n   * MADRS score of 27 or greater.\n   * Meet criteria for treatment resistance, defined as 2+ unsuccessful trials of antidepressants at an adequate dose for at least 6 weeks.\n   * On a stable dose of all psychotropic medications (including antidepressant, antipsychotic, lithium, hypnotic, etc) for a minimum of 4 weeks prior to the Screening period.\n4. MDD patients\n\n   * MDD diagnosis confirmed by the Mini International Neuropsychiatric Interview (MINI), with major depressive episode of at least 4 weeks duration.\n   * MADRS score of less than or equal to 12.\n   * On a stable dose of all psychotropic medications (including antidepressant, antipsychotic, lithium, hypnotic, etc) for a minimum of 4 weeks prior to the Screening period.\n\nExclusion Criteria:\n\n* History of MDD with psychotic features, bipolar disorder, schizophrenia spectrum and other psychotic disorders, currently exhibiting psychotic features, or a first-degree relative with a psychotic disorder.\n* Diagnosed with intellectual disability.\n* Current major medical problems that affect brain anatomy, neurochemistry, or function, e.g., liver insufficiency, kidney insufficiency, cardiovascular problems, (unstable Arrhythmias, Chronic Heart Failure, Myocardial Infarction (MI) cardiac pacemaker), systemic infections, cancer, active upper respiratory infections, respiratory depression and any brain disorder (seizure disorder, stroke, dementia, degenerative neurologic diseases), and head injury with loss of consciousness for any period of time.\n* Pregnancy or Breast-feeding. All female participants in reproductive age will undergo pregnancy tests. Female participants will be required to provide evidence of use of contraceptives during the course of the study.\n* Unable to understand the design and requirements of the study.\n* Unable to sign the informed consent for any reason.\n* Patients with a severe personality disorder, including risk for homicide or aggressive behavior, which in the opinion of the investigator has a major impact on the patients' current psychiatric status and would preclude safe study participation.\n* Patients at serious and imminent risk of suicide and not suitable for an outpatient study, in the judgment of the investigators.\n* Patients taking medications with known activity at the N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) glutamate receptor \\[eg, riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, D-cycloserine\\], or the mu-opioid receptor.\n* Previous exposure to ketamine or esketamine.\n* Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to screening.\n* Patients with no regular contact with at least one adult. Patients who are un-domiciled are excluded.\n* Body mass index (BMI) \\>=40 kg\u002Fm2.\n* Active eating disorder or cognitive deficit affecting the regulation of food intake.\n* Current or recent course of electroconvulsive therapy (ECT) (past month).\n* History of deep brain stimulation (DBS), vagal nerve stimulation (VNS) implantation, or other form of psychosurgery\n* Recently started cognitive behavioral therapy (CBT) (past month).\n* Patients taking \\>6mg\u002Fday lorazepam (benzodiazepine)-equivalents. Patients with lower and\u002For infrequent use of benzodiazepines will be required to discontinue their dose on the morning (noting that this is already per protocol at the partner ketamine clinic).\n* Patients taking prescription opioids. Over the counter pain medications are proscribed on infusion days.\n* Dietary supplements affecting central nervous system (CNS) function will be discontinued before the study start. This will include supplementation of glutamate, serotonin (e.g. 5-hydroxytryptophan(HTP), St. John's Wort), creatine, γ-Aminobutyric acid (GABA).\n* Patients habitually consuming legal cannabis products containing cannabidiol (CBD) or delta-8-tetrahydrocannabinol (THC).\n* The participant has a known ketamine allergy or is taking any medication that may interact with ketamine.",true,"45 Years",{"count":321,"type":23},100,[323],"PHASE1","The core objective of this study is to enhance the translational potential of this electroencephalogram (EEG) biomarker by using ketamine(KET)-induced gamma potentiation as a prognostic marker of 4-week treatment outcome. Previous research focused exclusively on KET-induced gamma band potentiation (GBP) in the context of a single infusion. Our study design captures the clinical variation associated with real-world treatment resistant depression (TRD) patients and allows us to analyze the relative importance of GBP to antidepressant symptom reduction across the induction phase of treatment. If successful, it provides a compelling rationale for a larger prospective investigation of gamma dynamics as a moderator of outcome to varied TRD therapies which impact the balance of cortical excitation and inhibition.",[326,107,63],"Healthy",[328,329],"depression","ketamine","2026-07-01",{"date":304,"type":39},{"date":333,"type":39},"2024-01-01",{"date":335,"type":23},"2026-12-31",{"name":337,"class":46},"Texas A&M University",{"id":339,"slug":340,"hasResults":12,"nctId":341,"briefTitle":342,"officialTitle":343,"acronym":185,"eligibilityCriteria":344,"healthyVolunteers":12,"sex":18,"minAge":345,"maxAge":20,"enrollmentInfo":346,"targetDuration":4,"studyType":24,"phases":347,"briefSummary":348,"conditions":349,"keywords":350,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":356,"lastUpdatePostDateStruct":357,"startDateStruct":359,"completionDateStruct":361,"leadSponsor":363,"locationsCount":365},"100548625","treatment-resistant-depression-subcallosal-cingulate-network-dbs-transcend-100548625","NCT06423430","Treatment ResistAnt Depression Subcallosal CingulatE Network DBS (TRANSCEND)","Treatment ResistAnt Depression Subcallosal CingulatE Network DBS","Inclusion Criteria:\n\n1. The patient must be diagnosed with non-psychotic unipolar Major Depressive Disorder.\n2. The patient must be in a major depressive episode for ≥12 months or have had at least 3 lifetime depressive episodes.\n3. The patient has tried and failed a minimum of four different types of antidepressant treatments as measured by a tool designed for this purpose.\n4. Depression medication and treatment regimen must be stable for a minimum of 4 weeks before the first baseline visit\n\nExclusion Criteria:\n\n1. Pregnant or those who plan to become pregnant during study\n2. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that could limit participation in the study or interfere with adherence to the study protocol.\n3. Current or lifetime history of psychotic features in any Major Depressive Episode.\n4. Has an intracranial Central Nervous System disease that impairs motor, sensory or cognitive function or that requires intermittent or chronic medication.\n5. Significant acute suicide risk.\n6. Diagnosis of Substance Use Disorder or Alcohol Use Disorder without sustained remission (12 months or longer).\n7. Current and ongoing use of neurostimulation treatment that may interfere with DBS therapy\u002Fsystem.\n8. Treatment with another investigational device or investigational drugs.","22 Years",{"count":321,"type":23},[60],"The goal of this clinical trial is to evaluate the effectiveness and safety of bilateral stimulation of the subcallosal cingulate white matter (SCCwm) using Deep Brain Stimulation (DBS) as an adjunctive treatment of non-psychotic unipolar Major Depressive Disorder (MDD) in adults.",[63],[351,107,352,353,354,355],"DBS","Bilateral Stimulation","Antidepressant Treatment","neurostimulation","ABT-CIP-10494","2026-06-25",{"date":358,"type":39},"2026-06-29",{"date":360,"type":39},"2024-09-11",{"date":362,"type":23},"2029-04",{"name":364,"class":244},"Abbott Medical Devices",24,{"id":367,"slug":368,"hasResults":12,"nctId":369,"briefTitle":370,"officialTitle":371,"acronym":372,"eligibilityCriteria":373,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":374,"enrollmentInfo":375,"targetDuration":4,"studyType":24,"phases":377,"briefSummary":378,"conditions":379,"keywords":381,"overallStatus":386,"whyStopped":4,"lastUpdateSubmitDate":387,"lastUpdatePostDateStruct":388,"startDateStruct":390,"completionDateStruct":392,"leadSponsor":394,"locationsCount":311},"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":376,"type":23},400,[26,136],"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.",[63,380],"Treatment Resistant Depression (TRD)",[140,259,382,65,383,234,384,236,385],"Transcranial Magnetic Stimulation","neuronavigation","D-cycloserine","NMDA","NOT_YET_RECRUITING","2026-06-21",{"date":389,"type":39},"2026-06-24",{"date":391,"type":23},"2026-09-01",{"date":393,"type":23},"2028-03-31",{"name":243,"class":244},{"id":396,"slug":397,"hasResults":12,"nctId":398,"briefTitle":399,"officialTitle":400,"acronym":401,"eligibilityCriteria":402,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":296,"enrollmentInfo":403,"targetDuration":4,"studyType":24,"phases":405,"briefSummary":406,"conditions":407,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":408,"lastUpdatePostDateStruct":409,"startDateStruct":411,"completionDateStruct":413,"leadSponsor":415,"locationsCount":124},"100522694","transcranial-ultrasonic-stimulation-in-treatment-resistant-depression--an-open-label-pilot-trial-100522694","NCT06085950","Transcranial Ultrasonic Stimulation in Treatment-resistant Depression : an Open-label Pilot Trial","Transcranial Ultrasonic Stimulation in Treatment-resistant Depression: an Open-label Pilot Trial","StimulUS","Inclusion Criteria:\n\n* Age between 18 and 75 years,\n* Diagnosis of major depressive episode (MDE) as part of major depressive disorder as defined by DSM-5 criteria\n* Severe MDE (HDRS-17\\> 20)\n* Drug resistance to at least two well-conducted antidepressant treatment lines\n* With stable antidepressant treatment for at least 4 weeks before inclusion\n* Benefiting from a social security scheme\n* Having given their consent to participate\n\nExclusion Criteria:\n\n* Psychiatric history other than a mood disorder\n* Neurological history, including epilepsy and intracerebral calcifications\n* History of substance use disorder other than tobacco\n* Contraindication to brain MRI (pacemaker, neurostimulator, injury from metallic shine, …)\n* Compulsory psychiatric care\n* Protected adults, people under legal safeguard\n* Pregnant or breastfeeding woman\n* Women of childbearing age who do not have a negative pregnancy test and are not using contraception",{"count":404,"type":23},32,[60],"The primary objective of this study is to optimize the protocol for the TUS administration in patients with TRD while gaining an initial impression of treatment efficacy.",[63],"2026-06-18",{"date":410,"type":39},"2026-06-22",{"date":412,"type":39},"2023-05-09",{"date":414,"type":23},"2028-06",{"name":416,"class":46},"Centre Hospitalier St Anne",{"id":418,"slug":419,"hasResults":12,"nctId":420,"briefTitle":421,"officialTitle":422,"acronym":4,"eligibilityCriteria":423,"healthyVolunteers":12,"sex":18,"minAge":424,"maxAge":20,"enrollmentInfo":425,"targetDuration":4,"studyType":24,"phases":427,"briefSummary":428,"conditions":429,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":430,"lastUpdatePostDateStruct":431,"startDateStruct":432,"completionDateStruct":434,"leadSponsor":435,"locationsCount":124},"100498707","dbs-for-trd-with-the-medtronic-percept-pc-100498707","NCT05773755","DBS for TRD With the Medtronic Percept PC","Deep Brain Stimulation for Treatment Resistant Depression: Exploration of Local Field Potentials (LFPs) With the Medtronic Percept PC System","Inclusion Criteria:\n\n* Age 25-70 years old.\n* Ability to provide written informed consent.\n* Primary psychiatric diagnosis of Major Depressive Disorder (MDD), either single episode or recurrent type, without psychotic features, currently experiencing a Major Depressive Episode (MDE), as diagnosed by Structured Clinical Interview for DSM IV-TR or DSM-5 (SCID-IV or SCID-5). Two independent psychiatrists will confirm the diagnosis, as well.\n* Current depressive episode of at least two years duration OR a history of more than 3 lifetime depressive episodes.\n* Minimum score at study entry of 20 on the 17-item Hamilton Depression Rating Scale\n* Average pre-operative HDRS-17 score of 20 or greater (averaged over four weekly pre-surgical evaluations during the four weeks prior to surgery)\n* A maximum Global Assessment of Functioning of 50 or less.\n* Confirmed to have treatment-resistant depression (TRD). Treatment-resistance will be defined as failure to respond to at least four adequate antidepressant treatments (assessed with the Antidepressant Treatment History Form \\[ATHF-SF\\] and verified through medical records) during the current episode. Treatments which support study inclusion include antidepressive medications, certain augmentation agents, evidenced-based psychotherapy, and neuromodulation (ECT, transcranial magnetic stimulation (TMS)). For those patients who have not received ECT, patients may be considered eligible for study participation if they have received adequate trials of an SSRI, SNRI, augmentation agent (certain atypical antipsychotic medications, Lithium), and TMS and\u002For ketamine.\n* ability comply with study and device management procedures.\n\nExclusion criteria:\n\n* Other primary Axis I conditions\n* Active suicidal ideation with intent, suicide attempt within the last six months, more than three suicide attempts within the last two years, or serious suicide risk as determined by the study psychiatrists\n* Other primary neurological disorders or unstable medical illness\n* Conditions requiring anticoagulant therapy which cannot be discontinued for the perioperative period, as required\n* Pregnancy or plan to come pregnant during the study\n* Contraindications for general anesthesia, neurosurgery, or an MRI scan\n* Currently implanted with a cardiac pacemaker \u002F defibrillator or other implanted electrical device which may interfere with DBS stimulator or the function of which may be impacted by its implantation.","25 Years",{"count":426,"type":23},20,[60],"Of the estimated 30 million Americans who suffer from Major Depressive Disorder, approximately 10% are considered treatment resistant. Deep brain stimulation (DBS) to a region of the brain called the subcallosal cingulate (SCC) is an emerging strategy for treatment resistant depression (TRD), which involves placement of electrodes in a specific region of the brain and stimulating that area with electricity. This is believed to reset the brain network responsible for symptoms and results in a significant antidepressant response. A series of open-label studies have demonstrated sustained, long-term antidepressant effects in 40-60% of patients who received this treatment. A challenge to the effective dissemination of this fledgling treatment is the absence of biomarkers (objective, measureable indications of the state of the body and brain) to guide device placement and select stimulation parameters during follow-up care.\n\nBy using a DBS device called the Percept PC (Medtronic, Inc) which has the ability to both deliver stimulation to and record electrical signals directly from the brain, this study aims to identify changes in local field potentials (LFPs), specific electrical signals that are thought to represent how the brain communicates information from one region to another, to see how this relates to DBS parameter settings and patient depressive symptomatology. The goal of this study is to study LFPs before and during active DBS stimulation to identify changes that correlate with the antidepressant effects of SCC DBS.\n\nThe study team will recruit 20 patients with TRD and implant them with the Percept PC system. Participants will be asked to complete short questionnaires and collect LFP data twice daily for the first year of the study, as well as have weekly in person research procedures and assessments with the study team for up to one year. These include meetings with the study psychiatrist, psychologist, symptom ratings, and movement, voice, and video recordings. A brief discontinuation experiment will be conducted after 6 months of stimulation, in which the stimulation will be turned off and patterns of LFP changes will be recorded. The entire study is expected to last about 5 years, parcellated into several study phases. All participants are required to live in the New York metropolitan area for the first several months of the study.",[107,63],"2026-06-17",{"date":410,"type":39},{"date":433,"type":39},"2023-03-01",{"date":147,"type":23},{"name":436,"class":46},"Helen Mayberg, MD",{"id":438,"slug":439,"hasResults":12,"nctId":440,"briefTitle":441,"officialTitle":441,"acronym":442,"eligibilityCriteria":443,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":444,"targetDuration":4,"studyType":24,"phases":446,"briefSummary":447,"conditions":448,"keywords":449,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":451,"lastUpdatePostDateStruct":452,"startDateStruct":454,"completionDateStruct":456,"leadSponsor":458,"locationsCount":460},"100353886","a-prospective-multi-center-randomized-controlled-blinded-trial-demonstrating-the-safety-and-effectiveness-of-vns-therapy-system-as-adjunctive-therapy-versus-a-no-stimulation-control-in-subjects-with-treatment-resistant-depression-100353886","NCT03887715","A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression","RECOVER","Inclusion Criteria:\n\nThe patient must be in a major depressive disorder (MDD) episode for ≥ two years or have had at least four episodes of MDD, including the current episode.\n\nThe patient's depressive illness meets a minimum criterion of four prior failed treatments of adequate dose and duration as measured by a tool designed for this purpose.\n\nThe patient is experiencing a major depressive episode (MDE) as measured by a guideline recommended depression scale assessment tool on two visits, within a 45-day span prior to implantation of the VNS device.\n\nPatients must maintain a stable medication regimen for at least four weeks before device implantation.\n\nExclusion Criteria:\n\nCurrent or lifetime history of psychotic features in any MDE;\n\nCurrent or lifetime history of schizophrenia or schizoaffective disorder;\n\nCurrent or lifetime history of any other psychotic disorder;\n\nCurrent or lifetime history of rapid cycling bipolar disorder;\n\nCurrent secondary diagnosis of delirium, dementia, amnesia, or other cognitive disorder;\n\nCurrent suicidal intent; or\n\nTreatment with another investigational device or investigational drugs.",{"count":445,"type":23},6800,[60],"Objectives of this study are to determine whether active VNS Therapy treatment is superior to a no stimulation control in producing a reduction in baseline depressive symptom severity, based on multiple depression scale assessment tools at 12 months from randomization.",[63],[450,140,259],"VNS","2026-06-11",{"date":453,"type":39},"2026-06-15",{"date":455,"type":39},"2019-09-26",{"date":457,"type":23},"2030-12-31",{"name":459,"class":244},"LivaNova",101,{"id":462,"slug":463,"hasResults":12,"nctId":464,"briefTitle":465,"officialTitle":466,"acronym":4,"eligibilityCriteria":467,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":158,"enrollmentInfo":468,"targetDuration":4,"studyType":24,"phases":469,"briefSummary":470,"conditions":471,"keywords":472,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":473,"lastUpdatePostDateStruct":474,"startDateStruct":476,"completionDateStruct":478,"leadSponsor":480,"locationsCount":124},"100523478","phase-1-dbs-for-depression-100523478","NCT06096207","DBS for Depression","Deep Brain Stimulation (DBS) Therapy for Treatment Resistant Depression","Inclusion Criteria:\n\n1. Major Depression Disorder (MDD) or Bipolar Disorder (I \u002FII) diagnosed by Structured Clinical Interview for DSM-V (SCID I\u002FDSM-V)\n2. Age 18 - 65 years.\n3. 24-item Hamilton Depression Rating Scale (HDRS) score of at least 21 on the first 17 items and\u002For Montgomery-Asburg Depression Rating Scale (MADRS) score of at least 21.\n4. World Health Organization Disability Assessment Scale 2.0(WHODAS2.0) score of 19 or more\n5. A recurrent (equal or \\>4 episodes) or chronic (episode duration equal or higher \\>2 years) course AND a minimum of 5 years since the onset of the first depressive episode. Major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior) over lifetime history as determined by an investigator\n6. As determined by the study psychiatrist\u002Finvestigator, has treatment resistant depression defined as failure to respond to: 6.1. Adequate trials (equal or \\>6 weeks at an adequate dose) of primary antidepressants from at least 3 different classes AND; 6.2. adequate trials (equal\\>4 weeks at an adequate dose) of augmentation\u002Fcombination of a primary antidepressant using at least 2 different augmenting\u002Fcombination agents (lithium, T3, stimulants,neuroleptics, anticonvulsants, buspirone, or a second primary antidepressant) AND; 6.3 An adequate trial of ECT (\\>6 bilateral treatments), or inability to tolerate an adequate ECT trial, AND; 6.4 An adequate trial of individual psychotherapy (\\>20 sessions with an experienced psychotherapist).\n7. Able to comply with the operational and administrative requirements of participation in the study.\n8. Able to give written informed consent\n9. Major Depressive Disorder (MDD) or Bipolar Disorder (I\u002FII) is the primary psychiatric diagnosis in the medical opinion of an investigator.\n10. On a stable psychiatric medication regimen beginning at least 6 weeks prior to enrollment and continuing through the first 6 months of the study, as determined by the investigator. Psychiatric medication changes can be made during the entirety of the subject's study participation but would be limited to the clinical judgment of the PI\u002Fstudy psychiatrist.\n11. At enrollment, provides the following information from at least two (2) verifiable contacts who reside within a 10-mile radius of the patient: name, relationship to patient, address (email mail); and telephone (mobile, home, work as applicable).\n12. Agrees to allow medical records requests and communications of any type to any and all health care providers who have seen the patient within five years of screening or enrollment.\n13. For the duration of study participation, agrees to be followed by a licensed psychiatrist and\u002For other licensed mental health practitioner on a regularly scheduled basis.\n14. FOR AGES 18-21: An average of at least 3 in the following subdomains on the Psychological Maturity Scale (PMS): questions 1-6, \"Ego Resilience\"; questions 7-13, \"Self-Awareness\"; questions 14-17, \"Autonomy\"; questions 18-21, Flexibility\".\n15. FOR AGES 18-21: Residing with a caretaker or having oversight of a caretaker.\n\nExclusion Criteria\n\n1. Patients with any lifetime history of psychosis or psychotic disorder, according to DSM-V diagnostic criteria, or in the medical opinion of the PI\u002Fstudy psychiatrist.\n2. Any finding on the preoperative magnetic resonance imaging (MRI) scan that, in the opinion of the principal investigator and after consultation with the neuroradiologist, is, or might be, considered clinically significant such that participation in the study: (a) seems likely to increase the medical risk to the subject sufficient to outweigh the potential benefit to study participation; (b) seems likely to jeopardize the subject's ability to complete the study or fulfill all study requirements per protocol; or (c) may impact he integrity of the data or the validity of the results.\n3. Any previous surgery to destroy the treatment target (superolateral MFB) rendering it either unilaterally or bilaterally damaged such that it cannot be effectively stimulated, as visualized by pre-operative MRI scans, in the medical opinion of the PI\n4. Any surgical contraindications to undergoing DBS, including labeled contraindications for DBS and\u002Forinability to undergo presurgical MRI (cardiac pacemaker, implantable defibrillator or other implantablestimulator, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy, inability to undergo an awake operation, significant cardiac or other medical risk factors for surgery. DBS contraindications include patients who are unable to properly operate the neurostimulator, and patientswho will be exposed to MRI or diathermy. MRI and diathermy (e.g., shortwave diathermy, microwave diathermy or therapeutic ultrasound diathermy) are contraindicated because the energy can be transferred through the implanted System (or any of the separate implanted components), which can cause tissue damage and can result in severe injury or death. Diathermy can damage parts of the neurostimulation system.\n5. Refusal of an adequate trial of ECT in the medical opinion of the study psychiatrist or PI following consultation with a study psychiatrist.\n6. History of stimulation intolerance in any area of the body.\n7. Within six (6) months of the enrollment date, has been diagnosed with, or has met the diagnostic criteria for, a substance abuse disorder (SUD) according to DSM-V criteria.\n8. Women of childbearing potential who, at enrollment or during the study: (a)have a positive urine pregnancy test; (b) are heterosexually active without the usage of a medically acceptable, highly effect contraceptive method\\* (≤1% pregnancy rate); or (c) are planning to become pregnant during the 60-month course of this study, as determined by the PI. \\*Examples include tubal ligation, vasectomized partner, IUD or IUS (intrauterine device or system), and long-acting reversible contraceptives (LARC).\n9. Active suicidal ideation with intent, suicide attempt within the last six months, more than three suicide attempts within the last two years, or serious suicide risk as determined by the study psychiatrists.\n10. Participation in another drug, device, or biologics trial within the preceding 30 days\n11. Presence of a condition requiring routine MRIs.\n12. Presence of a condition requiring diathermy.\n13. Subject is on anticoagulant medication.\n14. Prior to enrollment or during the course of the study and in the opinion of the PI, has a history of an medical, psychiatric, physical or non-physical disease, disorder, condition, injury, or disability; or has a non-medical reason (e.g., financial, logistical, personal, other) that: (a) may pose a significant risk to the patient; (b) may increase the possibility that the subject is unlikely to successfully complete all of the requirements of the study according to the study protocol; or (c) may adversely impact the integrity of the data or the validity of the study results.\n15. Subjects without a fixed home address or stable living situation, in the opinion of the Principal Investigator.\n16. Subjects involved in activities involving significant radiation exposure in the past year.\n17. Receiving TMS after DBS implantation\n18. Any mania or manic episodes within 5 years of enrollment according to DSM-V diagnostic criteria, or in the medical opinion of the PI\u002Fstudy psychiatrist",{"count":426,"type":23},[323],"The goal of this clinical trial is to demonstrate the feasibility and safety of deep brain stimulation in treatment resistant depression. The main questions it aims to answer are:\n\n* Is deep brain stimulation effective in treating treatment resistant depression?\n* Does deep brain stimulation improve overall clinical well-being and functioning?\n\nParticipants will be implanted with a deep brain stimulation device. They will then be monitored over a 5-year period by using multiple questionnaires to track their depression symptoms. The device will be turned off at certain time points, unbeknown to the participant, to show the efficacy of the device when it is turned on. The device will be ON for 8.5 months and OFF for 3.5 months during the first year.\n\nResearchers will compare questionnaire scores when the device is off versus on to see if the device is working in reducing depression.",[63],[259],"2026-06-02",{"date":475,"type":39},"2026-06-04",{"date":477,"type":39},"2023-10-18",{"date":479,"type":23},"2038-10-18",{"name":481,"class":46},"Northwell Health",{"id":483,"slug":484,"hasResults":12,"nctId":485,"briefTitle":486,"officialTitle":487,"acronym":488,"eligibilityCriteria":489,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":490,"targetDuration":4,"studyType":24,"phases":492,"briefSummary":494,"conditions":495,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":496,"lastUpdatePostDateStruct":497,"startDateStruct":499,"completionDateStruct":501,"leadSponsor":503,"locationsCount":505},"100537511","phase-4-comparative-effectiveness-study-of-two-forms-of-ketamine-for-treatment-resistant-depression-100537511","NCT06278779","Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression","Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-Resistant Depression: a Randomised, Rater-blinded Trial","TREK","Inclusion Criteria:\n\n* Adult with treatment-resistant depression (TRD: not responded adequately to at least two different antidepressants of adequate dose and duration) who has a current depressive episode (DSM 5)\n* Assessed and attested by clinic psychiatrist as appropriate to receive either racemic ketamine or Spravato® ketamine treatment for TRD\n* MADRS score of ≥20 at study baseline, assessed by certified study rater\n* Aged ≥18 years\n* Written informed consent for research study obtained\n\nExclusion Criteria:\n\n* Not able to give informed consent\n* Any physical or mental condition which, in the opinion of the investigator, could interfere with study participation including outcome assessments\n* Any treatment with ketamine or Spravato® within 4 weeks prior to written informed consent for the research study\n* Patients who require an interpreter\u002Ftranslator for the clinic consent process, due to the infeasibility of obtaining an interpreter for research assessments, including self-rated scales",{"count":491,"type":23},162,[493],"PHASE4","The goal of this study is to compare the effectiveness of two formulations of ketamine - Spravato® and racemic ketamine - in people with treatment-resistant depression (TRD). The main questions it aims to answer are:\n\n* How the two formulations compare in terms of their effectiveness in treating TRD.\n* How the two formulations compare in their acceptability to patients, safety, effects on patient quality of life and function, and cost effectiveness.\n\nParticipants will be randomised to receive either Spravato® or racemic ketamine treatment and asked to complete some questionnaires to assess the effects on mood, treatment acceptability, side effects, quality of life and function, and health economic outcomes.",[63],"2026-05-27",{"date":498,"type":39},"2026-05-29",{"date":500,"type":39},"2024-06-03",{"date":502,"type":23},"2027-04",{"name":504,"class":46},"The George Institute",7,{"id":507,"slug":508,"hasResults":12,"nctId":509,"briefTitle":510,"officialTitle":511,"acronym":512,"eligibilityCriteria":513,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":296,"enrollmentInfo":514,"targetDuration":4,"studyType":24,"phases":516,"briefSummary":517,"conditions":518,"keywords":521,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":529,"lastUpdatePostDateStruct":530,"startDateStruct":532,"completionDateStruct":534,"leadSponsor":536,"locationsCount":538},"100438987","a-comparison-of-two-psychotherapy-programs-in-persistently-depressed-treatment-resistant-inpatients-100438987","NCT04996433","A Comparison of Two Psychotherapy Programs in Persistently Depressed Treatment-Resistant Inpatients","Cognitive Behavioral Analysis System of Psychotherapy (CBASP) vs. Behavioral Activation (BA) in Persistently Depressed Treatment-resistant Inpatients: Efficacy, Moderators, and Mediators of Change","ChangePDD","Inclusion Criteria:\n\n* Primary DSM-5 diagnosis of PDD (300.4, 296.2x, 296.3x)\n* Total Hamilton Depression Rating Scale (HDRS-24) Score ≥ 20\n* Treatment-resistance (TR) (defined by the ATHF-SF or medication intolerance or one psychotherapy at least 25 sessions by a certified therapist in the current episode)\n* Sufficient knowledge of the German language\n* Written informed consent\n\nExclusion Criteria:\n\n* Bipolar I or II disorder\n* Active substance use disorders (abstinence shorter than 6 months)\n* Schizophrenia spectrum and other psychotic disorders\n* Antisocial personality disorder\n* Acute suicidality (HRSD item 3 \\> 2 or agreement with C-SSRS item 4 and\u002For item 5)\n* Previous CBASP or BA treatment within the last year\n* Inability to tolerate CBASP or BA (e.g., organic brain disorders, severe cognitive deficits)\n* Inability to participate in dayclinic or outpatient continuation treatment\n* Participation in another (psycho)therapeutic study of an interventional nature",{"count":515,"type":23},396,[60],"The purpose of this study is to compare the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) conducted over 16 weeks (acute and continuation treatment) with Behavioral Activation (BA; same dose and duration) in persistently depressed treatment-resistant inpatients regarding efficacy, moderators and mediators of change.",[519,520],"Persistent Depressive Disorder","Treatment-resistant Depression",[522,140,523,524,525,526,527,528],"Psychotherapy","Inpatient Treatment","Child Maltreatment","Epigenetic","Moderator","Mediator","Efficacy","2026-05-20",{"date":531,"type":39},"2026-05-26",{"date":533,"type":39},"2021-12-01",{"date":535,"type":23},"2028-04",{"name":537,"class":46},"University of Greifswald",8,{"id":540,"slug":541,"hasResults":12,"nctId":542,"briefTitle":543,"officialTitle":544,"acronym":4,"eligibilityCriteria":545,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":158,"enrollmentInfo":546,"targetDuration":4,"studyType":24,"phases":548,"briefSummary":549,"conditions":550,"keywords":551,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":560,"lastUpdatePostDateStruct":561,"startDateStruct":563,"completionDateStruct":565,"leadSponsor":567,"locationsCount":569},"100556417","phase-2-a-study-to-assess-the-efficacy-safety-and-tolerability-of-vls-01-buccal-film-compared-to-placebo-in-patients-with-treatment-resistant-depression-elumina-100556417","NCT06524830","A Study to Assess the Efficacy, Safety and Tolerability of VLS-01 Buccal Film, Compared to Placebo in Patients With Treatment Resistant Depression (ELUMINA)","A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled Trial to Assess the Efficacy, Safety, and Tolerability of Repeated Doses of VLS-01 Buccal Film in Participants With Treatment Resistant Depression","Inclusion Criteria:\n\n* Participant must be 18 to 65 years of age inclusive at the time of signing the Informed Consent.\n* Has a diagnosis of recurrent moderate or severe MDD without psychotic features or single- episode MDD with duration greater than or equal to 3 months without psychotic features and is currently experiencing a major depressive episode.\n* Onset of first episode of MDD occurred before age 55.\n* Has not responded to an adequate dose and duration of at least two and no more than five antidepressant medications for the current depressive episode, as determined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH- ATRQ).\n* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.\n\nExclusion Criteria:\n\n* Has a current or prior DSM-5-TR diagnosis of a schizophrenia spectrum and other psychotic disorder, substance\u002Fmedication-induced psychotic disorder, bipolar and related disorder, or any disorder with psychotic features.\n* Has a moderate or severe substance use disorder (drug, alcohol, or tobacco) within the 6 months before Screening and\u002For history of moderate or severe substance use disorder (drug alcohol) within the previous 1 year before Screening\n* Has a history of, or current signs and symptoms of, diseases or conditions that would make participation not be in the best interest (e.g., compromise the wellbeing) of the participant or that could prevent, limit, or confound the protocol-specified assessments.\n* Has suicidal ideation with some intent to act within 6 months before Screening or a history of suicidal behavior within the past 1 year before Screening.\n* Has a history of clinically significant cardiovascular, cerebrovascular, or peripheral vascular disease or condition, including but not limited to unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, valvular heart disease, obstructive coronary artery disease, hypertension, hypotension, bradycardia, tachycardia, or risk factors for long QT Syndrome.\n* Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years before Screening.\n* Has any known allergy or hypersensitivity to VLS-01 or to any of the excipients in the formulation.\n* Has recently initiated and is currently undergoing directive psychotherapy (e.g., cognitive behavioral therapy, interpersonal psychotherapy, psychodynamic psychotherapy) within the past 30 days before Screening. Participants planning to initiate individual or group therapy during the study are also not eligible.\n* Has received any prohibited therapies.\n* Has clinically significant laboratory abnormalities at Screening.",{"count":547,"type":23},142,[26],"This Phase 2 study (protocol number VLS-01-203) will determine the efficacy, safety, and tolerability of short-term treatment with a VLS-01 transmucosal buccal film (VLS-01-BU) in patients with treatment resistant Major Depressive disorder (TRD) and will characterize the onset and durability of antidepressant effects of VLS-01-BU versus placebo.",[63],[552,553,554,555,140,556,557,558,63,89,559],"Major Depression","Mood Disorders","Mental Disorders","Depressive Disorder","Depressive Disorder, Major","Antidepressive Agents","Psychotropic Drugs","Depressive Disorder, Treatment-Resistant","2026-05-08",{"date":562,"type":39},"2026-05-11",{"date":564,"type":39},"2024-12-30",{"date":566,"type":23},"2026-08-30",{"name":568,"class":244},"atai Therapeutics, Inc.",48,{"id":571,"slug":572,"hasResults":12,"nctId":573,"briefTitle":574,"officialTitle":575,"acronym":576,"eligibilityCriteria":577,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":578,"targetDuration":4,"studyType":24,"phases":580,"briefSummary":581,"conditions":582,"keywords":583,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":585,"lastUpdatePostDateStruct":586,"startDateStruct":587,"completionDateStruct":589,"leadSponsor":591,"locationsCount":124},"100599737","phase-3-ketamine-augmentation-of-ect-in-treatment-resistant-depression-100599737","NCT07088380","Ketamine Augmentation of ECT in Treatment-Resistant Depression","The Additive Effect of Ketamine in Combination With ElectroConvulsive Stimulation (ECS) in Major Depressive Disorder (MDD): a Translational Study","Ketamina","Inclusion Criteria:\n\n* Male and female subjects ages 18-70,\n* diagnosed with MDD (according to SCID5-CV interview)\n* treatment resistant (defined as at least 2 different antidepressant agents used without success),\n* ability to give informed consent,\n* adequacy of the score for anesthesia.\n\nExclusion Criteria:\n\n* Chronic neurological diseases,\n* Intellectual disability\n* Contraindications to the electroconvulsive therapy (severe aortic valve stenosis, implantable cardiac defibrillators, uncontrolled hypertension, clinically significant respiratory, renal or hepatic disease, abdominal aortic aneurysm, endocrine disorders, neuromuscular diseases, space occupying brain lesions, stroke in the last 6 months),\n* Patients with Alcohol Use Disorder or Substance Use Disorder or Substance Abuse history in the past year,\n* Pregnancy and lactation\n* Cardiovascular conditions,\n* Psychiatric Disorders,\n* Hepatic impairment,\n* Participants with a known hypersensitivity to ketamine or any of its excipients will be excluded from the study,\n* Participants with any contraindications to the use of ketamine, such as a history of severe cardiovascular conditions (e.g., uncontrolled hypertension, significant arrhythmias), intracranial hypertension, or severe liver impairment, will also be excluded to prevent potential adverse events.",{"count":579,"type":23},30,[136],"This is a randomized, double-blind, placebo-controlled phase 3 clinical trial evaluating the additive effect of intravenous ketamine in combination with electroconvulsive therapy (ECT) in patients with treatment-resistant major depressive disorder (MDD). The study aims to determine whether ketamine enhances the antidepressant efficacy of ECT and reduces associated cognitive side effects. Thirty hospitalized patients diagnosed with treatment-resistant MDD will be randomized to receive either ketamine or placebo (saline) during ECT sessions 2, 4, and 6. Primary outcome is the change in depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4 weeks.",[107,63],[329,259,328,584],"electroconvulsive therapy (ECT)","2026-05-05",{"date":562,"type":39},{"date":588,"type":39},"2025-07-10",{"date":590,"type":23},"2026-09",{"name":592,"class":46},"Università Vita-Salute San Raffaele",{"id":594,"slug":595,"hasResults":12,"nctId":596,"briefTitle":597,"officialTitle":598,"acronym":4,"eligibilityCriteria":599,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":158,"enrollmentInfo":600,"targetDuration":4,"studyType":24,"phases":601,"briefSummary":602,"conditions":603,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":604,"lastUpdatePostDateStruct":605,"startDateStruct":607,"completionDateStruct":608,"leadSponsor":610,"locationsCount":124},"100632330","phase-2-mindfulness-engaged-neurostimulation-for-depression-mend-ii-100632330","NCT07512284","Mindfulness Engaged Neurostimulation for Depression (MEND II)","Mindfulness Engaged Neurostimulation for Depression","Inclusion Criteria:\n\n* Diagnosis of major depressive episode (MDE, in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder.\n* At least one failed antidepressant medication trial at level 3 in the Antidepressant -Treatment History Form: Short Form (ATHF-SF) classification.\n* Montgomery-Åsberg Depression Rating Scale (MADRS) Score \\>19 (moderate - severe depression).\n* No increase or initiation of new antidepressant therapy in the four weeks prior to screening.\n* Demonstrated capacity to give informed consent.\n\nExclusion Criteria:\n\n* Inability to provide informed consent.\n* Medically unstable patients.\n* Concomitant neurological disorder or a history of a seizure disorder.\n* Exhibiting current suicidal behavior rating on the Columbia Suicide Severity Rating Scale (C-SSRS)\n* Patients who are pregnant or breastfeeding.\n* Any psychotic disorder or current active psychotic symptoms.\n* Patients who have intracranial implants, other medical device or condition deemed unsafe for TMS.\n* Contraindication to MRI scanning.",{"count":253,"type":23},[26],"Repetitive Transcranial Magnetic stimulation (rTMS) is an FDA-approved therapy for treatment resistant depression (TRD) that involves brief magnetic stimulation pulses on the dorsolateral prefrontal cortex (DLPFC) brain region. But studies of rTMS alone show remission rates of \\~30%. Additionally, rTMS has not been shown to improve cognitive functioning that may be an independent factor predicting treatment success. This study will develop a novel multimodal treatment, which combines intermittent theta burst stimulation (iTBS) - a type of rTMS with digital mindfulness training to engage brain plasticity, enhance cognition and alleviate depression symptoms in individuals with TRD.",[140,63,107,555,106],"2026-05-01",{"date":606,"type":39},"2026-05-06",{"date":604,"type":23},{"date":609,"type":23},"2029-04-30",{"name":611,"class":46},"University of California, San Diego",{"id":613,"slug":614,"hasResults":12,"nctId":615,"briefTitle":616,"officialTitle":617,"acronym":618,"eligibilityCriteria":619,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":374,"enrollmentInfo":620,"targetDuration":4,"studyType":24,"phases":622,"briefSummary":623,"conditions":624,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":625,"lastUpdatePostDateStruct":626,"startDateStruct":628,"completionDateStruct":629,"leadSponsor":631,"locationsCount":311},"100588241","maintenance-rtms-for-depression-maitr-de-100588241","NCT06938841","Maintenance rTMS for Depression (Maitr-De)","Maintaining the Acute Therapeutic Effect of rTMS in Treatment-Resistant Depression (Maitr-De)","Maitr-De","Inclusion Criteria:\n\n1. They met criteria for a DSM-5 diagnosis of a Major Depressive Episode (MDE) during the index episode of depression for which they have received an acute rTMS treatment course.\n2. Meet criteria for either response or remission from their initial depressive illness. The MINI assessment timeline will be adjusted to allow scoring of illness symptoms prior to rTMS response. Response to acute course of treatment is defined as either a MADRS score of \\\u003C10, or a MADRS score of 10-19, plus evidence of having met response criteria on either the MADRS or another structured depression rating scale. The response is defined as a \\>50% reduction in the total score from the start to the end of treatment.\n3. Their initial rTMS treatment course must have consisted of at least 15 rTMS treatment sessions.\n4. People between the ages of 18 and 80 at the time of screening. A written statement from the referring physician will be required to confirm that the participant demonstrates the capacity to consent.\n5. Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires \u002F follow instructions during TMS-EEG assessments and iTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.\n6. In good general health, as evidenced by medical history.\n7. Agreement to adhere to Lifestyle Considerations throughout study duration.\n8. If a person of child-bearing potential is: must take a pregnancy test at the screening visit, with results confirmed as negative by study staff\n\nExclusion Criteria:\n\n* 1\\. Pregnancy 2. History of or current psychotic disorder or depression with psychotic features 3. Severe borderline personality disorder based on clinical assessment. 4. Diagnosis of Intellectual Disability or Autism Spectrum Disorder 5. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal 6. Clinically significant suicidal ideation with plan 7. Any history of ECT (greater than 8 sessions) without a clinical meaningful response in the current episode.\n\n  8\\. Recent (during the current depressive episode) or concurrent use of rapid-acting antidepressant agent (i.e., ketamine or a course of ECT) in the last 30 days 9. 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 10. Untreated or insufficiently treated endocrine disorder. 11. Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion) 12. Treatment with an investigational drug or other intervention within the study period 13. The patient experiences a relapse between baseline and screening, defined as a moderate depression (MADRS \\>=20) and a 25% increase from screening to baseline 14. Require a benzodiazepine with a dose \\> lorazepam 2 mg\u002Fday or equivalent or any anticonvulsant (with the exception of Gabapentin, pregabalin, and lamotrigine).",{"count":621,"type":23},75,[60],"Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising intervention for treatment-resistant depression (TRD), yet substantial uncertainties persist regarding its efficacy as a maintenance treatment. This prospective study seeks to investigate the efficacy of maintenance rTMS in individuals with TRD who have previously responded to an acute course of rTMS. In the R61 phase of the study, we will recruit 75 participants across three study sites, the University of California San Diego, Weill Cornell Medicine, and Australian National University, into a double-blind, three-arm maintenance treatment trial. In this trial, participants will be randomized to receive either standard maintenance rTMS, clustered maintenance rTMS, or sham maintenance rTMS for a duration of 6 months. Our primary aim is to examine the efficacy of maintenance rTMS on sustaining connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate cortex (SGC) measured through concurrent TMS and electroencephalography (TMS-EEG) at baseline and every six weeks throughout the 6-month treatment period. We will also assess changes in depressive symptom severity using clinical scales, including the Montgomery-Asberg Depression Rating Scale (MADRS) as a secondary outcome measure. It is hypothesized that stimulation with clustered maintenance rTMS will demonstrate superiority in sustaining DLPFC-SGC connectivity compared with standard maintenance rTMS and sham maintenance rTMS",[107,63],"2026-04-23",{"date":627,"type":39},"2026-04-29",{"date":198,"type":39},{"date":630,"type":23},"2027-03-31",{"name":611,"class":46},{"id":633,"slug":634,"hasResults":12,"nctId":635,"briefTitle":636,"officialTitle":637,"acronym":638,"eligibilityCriteria":639,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":640,"targetDuration":4,"studyType":86,"phases":4,"briefSummary":642,"conditions":643,"keywords":644,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":647,"lastUpdatePostDateStruct":648,"startDateStruct":650,"completionDateStruct":652,"leadSponsor":654,"locationsCount":124},"100483608","belief-updating-in-treatment-resistant-depression-100483608","NCT05577247","Belief Updating in Treatment Resistant Depression","How the Brain Encodes Beliefs: A Functional Magnetic Resonance Imaging Study of the Belief Updating in Treatment Resistant Depression.","KETABELIEF","Inclusion Criteria:\n\nDemographic criteria:\n\n* Age: 18 to 70 years\n* Male et female\n\nDiagnostic criteria, severity and clinical course:\n\n* Major depressive disorder (MDD) according to the DSM5 criteria\n* MADRS≥20,\n* Treatment resistant depression (TRD) defined by failure to respond to at least two trials of different antidepressant treatments\n* affiliation of a social security regime\n\nTreatments\u002Fstrategies\u002Fprocedures:\n\no At the start of new antidepressant treatment involving glutamate receptor modulators.\n\nExclusion criteria:\n\nCriteria relating to associated pathologies carrying specific risks:\n\n* Mental disorder other than MDD: personality disorder type borderline, schizophrenia\n* Inability to understand the task instructions and to perform the behavioral task\n* Mini Mental Score (MMS) ≤ 25\n* Antidepressant treatment involving dopaminergic agonists, and Monoamine oxidase inhibitors (MAOI)\n* Neurological comorbidities : epilepsy, brain tumor, non-corrected visual and\u002For auditory deficit\n\nCriteria associated with contraindications\u002Fprocedures\u002Finterventions added by the research:\n\no Contra-indications for an MRI exam (metallic implant, pacemaker, artificial heart valve, brain vascular malformation, aneurysm clips, exposed by metallic fragments, artificial implants, peripheral or neuronal stimulator, insulin pump, intravenous catheter, epilepsy, metallic contraceptive device, claustrophobia, unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly))\n\nCriteria relating to vulnerable populations:\n\n* Pregnancy\n* Patient on AME (state medical aid)\n* Patient under guardianship, curators or legal protection",{"count":641,"type":23},60,"Major depressive disorder (MDD) is characterized by a cognitive triad of negative beliefs about oneself, the future and the world. For example, depressed patients hold persistently negative expectations about the future, despite contradictory evidence, and these strong negative beliefs are thought to play an important role in the maintenance of depressive symptoms and potentially in treatment resistance. Indeed, one out of three patients with major depressive disorder does not respond to conventional, monoaminergic treatments, which has led to the concept of treatment resistant depression (TRD). It is unknown how the brain encodes the strong negative beliefs that are insensitive to positive disconfirming information in TRD patients, and how these neural underpinnings of maladaptive belief updating are altered by antidepressant treatment.\n\nThe principal objective of this study is to gain insight into the brain mechanisms of belief updating about the future in TRD patients before and after starting ketamine treatment. The results of this study are expected to provide a better understanding of the neurocognitive mechanisms of belief-updating in depressed patients, and how these mechanisms contribute to clinical improvement following ketamine antidepressant treatment.",[63],[33,645,646,329],"belief updating","fMRI","2026-04-08",{"date":649,"type":39},"2026-04-13",{"date":651,"type":39},"2024-05-13",{"date":653,"type":23},"2026-12-13",{"name":655,"class":46},"Assistance Publique - Hôpitaux de Paris"]