[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"bipolar-depression\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:bipolar-depression":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,22,0,[8,41,74,97,119,148,174,205,234,254,275,300,324,354,375,404,428,448,472,493,522,554],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":40},"100613434","phase-4-rna-editing-as-a-biomarker-of-antidepressant-response-in-unipolar-and-bipolar-depression-edit-andre-100613434",false,"NCT07266545","RNA Editing as a Biomarker of Antidepressant Response in Unipolar and Bipolar Depression (EDIT-ANDRE)","Inclusion Criteria\n\nParticipants must meet all the following criteria to be eligible for the study:\n\n1. Adult females and males, aged 18-65 years\n2. Must have the capacity to understand study procedures, to comply with them for the entire length of the study, and to provide informed consent.\n3. Current major depressive episodes associated with MDD, BD-I, or BD-II, confirmed using the SCID-IV-CV. If a participant has already completed a structured diagnostic interview within the last 2 years or participated in any of the following studies and provided consent to use their information in future studies: (IRB 19-001722, IRB: 23-004500, IRB: 24-013228, IRB: 25-005856, IRB: 25-007244), those SCID results can be used for the EDIT-ANDRE study.\n4. Symptom severity score on the Quick Inventory for Depressive Symptomatology - Clinician (QIDS-C16) \\> 10.\n5. Ability to travel for assessment visits.\n6. Negative urine pregnancy test for people of childbearing potential\n7. People of childbearing potential must be using an acceptable method of birth control during the study, such as hormonal contraception, intrauterine device, bilateral tubal ligation, partner's documented vasectomy, or complete abstinence from intercourse with childbearing potential, with barrier methods permitted only when used in combination with one of these primary methods.\n8. BD-I patients must be on stable dose of at least one mood stabilizer (i.e., lithium, valproate, or a mood-stabilizing atypical antipsychotic at least for one month) at the time of enrollment.\n\nPatients with BD-II who enroll in the study while currently taking a mood stabilizer (including lithium, valproate, or lamotrigine) must have been on a stable dose of that medication for a minimum of one month before enrollment.\n\nExclusion Criteria\n\nAll candidates meeting any of the following criteria at baseline will be excluded from study participation:\n\n1. Individuals who cannot understand English will not be enrolled because informed consent, study procedures, and interviews require comprehension of English.\n2. Inability to provide written, voluntary informed consent due to but not limited to being under conservatorship, guardianship, commitment, or currently undergoing involuntary psychiatric hospitalization.\n3. Failure to score at least 75% on a 4-item comprehension assessment related to study goals, risks, and benefits\n4. For BD-I: not having used at least one mood stabilizer (e.g., lithium, valproate, or mood-stabilizing antipsychotics) at a stable dose and within a therapeutically effective antimanic range for a minimum of one month.\n5. History of treatment-refractory depression, defined as non-response to two or more antidepressant or mood-stabilizing regimens despite adequate dose, duration, and adherence during the current episode.\n6. Participants with active suicidal ideation, defined as a MADRS item #10 score greater than 4 or a \"yes\" response to item #4 (ideation with intent) or item #5 (ideation with plan) on the C-SSRS, will be excluded\n7. A medically serious suicide attempt within the past 6 months, defined as requiring emergency department evaluation, a medical procedure, or admission to a hospital (e.g., internal medicine, cardiology, or ICU)\n8. Current use of monoamine oxidase inhibitors or use within 14 days following discontinuation of a monoamine oxidase inhibitor\n9. Presence of mixed symptoms of depression, defined as a YMRS score ≥12\n10. Current use of any of the study medications (e.g., vortioxetine, or cariprazine) at the time of enrollment (previous use of these medications is acceptable)\n11. Prior hypersensitivity reaction to any of the study medications or documented non-response to any of the study medications at the maximum therapeutic dose\n12. A history of seizure disorder\n13. Recent use of long half-life psychotropic medications, including fluoxetine (in patients with BD and MDD) and long acting injectable forms of antipsychotics (mainly in BD II and MDD) within the past 4 weeks.\n14. Active psychosis, defined as a YMRS item #8 score \\>4 or diagnosis of schizophrenia, schizoaffective disorder, delusional disorder, or schizophreniform disorder as determined by structured clinical interview\n15. Current drug or alcohol use disorder (excluding nicotine); full remission for at least 3 months is required for eligibility\n16. Positive toxicology screen for illicit substances (e.g., cocaine, methamphetamine, illegal opiates). Participants who use cannabis for recreational or medicinal purposes and fail the toxicology screen can potentially be included in the study only if they take the CUDIT-R and score a 12 or less.\n17. Individuals who are pregnant, lactating, trying to conceive, or not using adequate contraception (e.g., hormonal contraception, intrauterine device, tubal ligation, or condoms)\n18. Any active or unstable medical condition judged by the principal investigator to confer excessive risk\n19. Clinically significant laboratory abnormality, uncontrolled hypertension (blood pressure \\>160\u002F100 mmHg), or tachycardia (heart rate \\>110 bpm)\n20. Significant renal, hepatic, or cardiac disease; malignancy; autoimmune disease; or chronic kidney disease \\> stage IIIa (estimated GFR \\\u003C 60 mL\u002Fmin\u002F1.73 m²)\n21. History of traumatic brain injury defined as loss of consciousness for 5 minutes and related to a trauma event\n22. Gastric bypass, specifically Roux-en-Y\n23. Clinical current diagnosis of delirium, encephalopathy, intellectual disability or cognitive disorder (mild or major neurocognitive disorder)\n24. Currently receiving electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), or deep brain stimulation (DBS) as acute or maintenance treatment\n25. Current use of systemic steroids, chemotherapy, and radiotherapy\n26. Daily use of lorazepam (Ativan) \\>4 mg\u002Fday, or equivalent doses of other benzodiazepines (e.g., clonazepam \\>1 mg, alprazolam \\>2 mg, diazepam \\>20 mg)\n27. No access to smartphones, internet\n28. Other Axis I or II diagnoses, by clinical judgments that are the current reason for treatment evaluation or play a large part of the current symptom presentation\n29. Ongoing treatment with opioid agonists will constitute an exclusion criterion. In contrast, other ongoing treatments, such as alcohol relapse prevention agents or ADHD pharmacotherapy, will not be considered exclusion criteria, provided that no treatment initiation or significant dose adjustment has occurred within the past 4 weeks.\n\nAll candidates meeting any of the following criteria at baseline will be excluded from the Phase 2 (cariprazine add-on) of the study:\n\n1. Meeting symptomatic remission criteria based on MADRS (≤ 10).\n2. Current use of a strong or moderate CYP3A4 inhibitor (e.g., ketoconazole, clarithromycin, fluconazole, or verapamil) strong or moderate CYP3A4 inducer (e.g., carbamazepine, rifampin, phenytoin, or St. John's Wort), due to potential pharmacokinetic interactions with cariprazine.\n3. Diagnosis of BD-I with concurrent use of an antipsychotic agent as a mood stabilizer.","ALL","18 Years","65 Years",{"count":19,"type":20},120,"ESTIMATED","INTERVENTIONAL",[23],"PHASE4","The purpose of this research is to understand how changes in RNA editing relate to treatment response in unipolar and bipolar depression.",[26,27],"Unipolar Depression","Bipolar Depression","RECRUITING","2026-06-17",{"date":31,"type":32},"2026-06-22","ACTUAL",{"date":34,"type":32},"2026-02-17",{"date":36,"type":20},"2030-12-31",{"name":38,"class":39},"Mayo Clinic","OTHER",1,{"id":42,"slug":43,"hasResults":11,"nctId":44,"briefTitle":45,"officialTitle":46,"acronym":47,"eligibilityCriteria":48,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":49,"enrollmentInfo":50,"targetDuration":4,"studyType":21,"phases":52,"briefSummary":54,"conditions":55,"keywords":59,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":63,"lastUpdatePostDateStruct":64,"startDateStruct":66,"completionDateStruct":68,"leadSponsor":70,"locationsCount":73},"100606204","phase-3-a-randomized-study-of-azetukalner-versus-placebo-in-depressive-episodes-associated-with-bipolar-i-or-ii-disorder-bipolar-depression-100606204","NCT07172516","A Randomized Study of Azetukalner Versus Placebo in Depressive Episodes Associated With Bipolar I or II Disorder (Bipolar Depression)","A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Azetukalner in Depressive Episodes Associated With Bipolar I or II Disorder (Bipolar Depression)","X-CEED","Key Inclusion Criteria:\n\n* Adults ≥18 and ≤74 years of age who experienced their first major depressive episode (MDE) prior to 50 years of age.\n* Body Mass Index (BMI) ≥18 kg\u002Fm2 and ≤40 kg\u002Fm2.\n* Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria for bipolar I or II disorder and is currently in a MDE, confirmed using the Mini International Neuropsychiatric Interview (MINI).\n* Current MDE must has a duration of ≥4 weeks and ≤12 months.\n\nKey Exclusion Criteria:\n\n* Participant has any type of major depressive disorder (MDD) diagnosis, including MDD with psychotic features, MDD with catatonia, MDD with seasonal pattern, or postpartum depression.\n* Participant has any nonbipolar psychiatric diagnosis.\n* Participant has a substance use disorder (excluding tobacco) within the 6 months prior to screening visit.\n* Participant has a symptomatic eating disorder within the 12 months prior to screening visit.\n* Participant has a Young Mania Rating Scale (YMRS) score \\>12 points at screening visit or randomization.\n* Participant has been hospitalized for mania within the 30 days prior to screening visit.\n* Participant is considered treatment-resistant in the current bipolar depressive episode, defined as having treatment resistance (no remission) to ≥2 different medications approved by the regional regulatory authority at an adequate dose (per regulatory approved label) and for an adequate duration (at least 6 weeks).\n* Participant has had an active suicidal plan\u002Fintent within the 6 months prior to screening, presence of suicidal behavior in the last 12 months.\n* Participant has self-injurious behavior without intent to die in the 12 months prior to screening.\n* Participant has used antidepressants, mood stabilizers, anticonvulsants, antipsychotics, or other prohibited medications within the 1 week or within a period less than 5 times the drug's half-life, whichever is longer prior to randomization.\n* Participants with medical conditions that may interfere with the purpose or conduct of the study.\n* Participant is pregnant, breastfeeding, or planning to become pregnant.","74 Years",{"count":51,"type":20},400,[53],"PHASE3","X-CEED is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of azetukalner in adult participants diagnosed with bipolar I or II disorder who are currently in a depressive episode (bipolar depression).",[56,27,57,58],"Bipolar Disorder","Bipolar I Disorder","Bipolar II Disorder",[60,61,62],"Bipolar","XEN1101","Azetukalner","2026-06-01",{"date":65,"type":32},"2026-06-03",{"date":67,"type":32},"2025-08-08",{"date":69,"type":20},"2028-08",{"name":71,"class":72},"Xenon Pharmaceuticals Inc.","INDUSTRY",28,{"id":75,"slug":76,"hasResults":11,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":4,"eligibilityCriteria":80,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":81,"enrollmentInfo":82,"targetDuration":4,"studyType":21,"phases":84,"briefSummary":86,"conditions":87,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":88,"lastUpdatePostDateStruct":89,"startDateStruct":91,"completionDateStruct":93,"leadSponsor":95,"locationsCount":40},"100594596","efficacy-and-safety-assessment-of-temporal-interference-stimulation-to-improve-bipolar-depression-100594596","NCT07021508","Efficacy and Safety Assessment of Temporal Interference Stimulation to Improve Bipolar Depression","Efficacy and Safety Assessment of Temporal Interference Stimulation to Improve Bipolar Depression: a Randomized Controlled Study","Inclusion Criteria:\n\n* right-handed, and have completed nine years of compulsory education;\n* Meet the diagnostic criteria for bipolar depression in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5);\n* ≥18 points on the Hamilton Depression Inventory (HAMD- 17);\n* ≤8 points on the Young's Mania Rating Scale (YMRS);\n* Subjects who have not been treated with psychiatric medication, or those who have been treated with medication are required to undergo medication washout within 2 weeks before randomization;\n* Subjects\u002Flegal guardians are willing to cooperate with the treatment and sign an informed consent form after they have fully understood the Temporal Interference Stimulation (TI).\n\nExclusion Criteria:\n\n* Contraindications to magnetic resonance scanning (MRI) or time-interference stimulation (TI), such as the presence of metallic or electronic devices in the body (intracranial metallic foreign bodies, cochlear implants, pacemakers and stents, and other metallic foreign bodies);\n* Prior or current electroconvulsive therapy (ECT), modified electroconvulsive therapy (MECT), transcranial magnetic stimulation (TMS), transcranial direct current therapy (tDCS), transcranial alternating current stimulation (tACS), or other neurostimulation;\n* Pregnant and lactating women, and women of childbearing age with a positive urine pregnancy;\n* Possesses a diagnosis of another major psychiatric disorder that has been assessed by the study investigator as a major disorder that results in more impairment than a diagnosis of bipolar disorder;\n* Co-morbid other psychiatric disorders, including obsessive-compulsive disorder, personality disorders, anxiety spectrum disorders, mental retardation, substance dependence (abuse), etc.; Has active suicidal ideation (≥ 4 points on item 10 of the MADRS);\n* Risk of serious injury to self or others;\n* History of serious physical illness or disease that may affect the central nervous system;\n* Risk of neurologic disorders or seizures, such as previous craniosynostosis, cranial trauma, abnormal electroencephalograms, magnetic resonance evidence of structural abnormalities of the brain, or family history of epilepsy.","45 Years",{"count":83,"type":20},160,[85],"NA","The aim of this study was to explore the efficacy and safety of temporal interference stimulation to improve bipolar depression, as well as to explore the corresponding neuroimaging mechanisms using magnetic resonance and electroencephalogram to provide novel intervention protocols and objective indicators of efficacy prediction for depressive episodes in bipolar disorder.",[27],"2026-05-25",{"date":90,"type":32},"2026-05-27",{"date":92,"type":32},"2025-05-20",{"date":94,"type":20},"2026-12",{"name":96,"class":39},"First Affiliated Hospital of Zhejiang University",{"id":98,"slug":99,"hasResults":11,"nctId":100,"briefTitle":101,"officialTitle":102,"acronym":4,"eligibilityCriteria":103,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":104,"enrollmentInfo":105,"targetDuration":4,"studyType":21,"phases":107,"briefSummary":108,"conditions":109,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":110,"lastUpdatePostDateStruct":111,"startDateStruct":113,"completionDateStruct":115,"leadSponsor":117,"locationsCount":40},"100559194","synced---synchronized-eating-in-bipolar-depression-study-100559194","NCT06560957","SYNCED - SYNChronized Eating in Bipolar Depression Study","Feasibility and Acceptability of Adjunctive Time Restricted Eating in Bipolar Disorder: A Pilot Randomized Controlled Trial.","Inclusion Criteria:\n\n1. Be 18-55 years old\n2. Have a diagnosis of bipolar I or bipolar II disorder, confirmed by the Quick Structured Clinical Interview for DSM-5® Disorders, QuickSCID-5.\n3. Have depression symptoms as indicated by a score of ≥12 on MADRS and ≤12 on YMRS.\n4. Females of childbearing potential are willing to follow highly effective methods of contraception (mentioned below) for the duration of study\\*\n5. Participants must be able to speak, read, write and understand English or French.\n6. Be willing and able to provide informed consent.\n\nExclusion Criteria:\n\n1. Have any catatonic symptoms or eating disorder(s) as measured by the Quick Structured Clinical Interview for DSM-5® Disorders, QuickSCID-5.\n2. Have any unstable or inadequately treated neurological and medical conditions.\n3. Have had prior bariatric surgery. 4 Be taking hypoglycemia inducing medications.\n\n5\\. Be pregnant or lactating. 6. Currently taking any stimulant medications. 7. Be participating in any other diet or weight management program for the duration of the trial.\n\n8\\. Have any contraindication to fasting as judged by the assessing clinician. 9. Recently (i.e. within the past 8 weeks) began structured psychotherapy (i.e. cognitive-behavioral therapy, interpersonal psychotherapy, family-focused therapy, or interpersonal and social rhythm therapy).\n\n10\\. Have any other medical condition, substance use disorder or suicidal ideation for which physician or investigator team expresses concern about safety or ability to participate in the study.","55 Years",{"count":106,"type":20},40,[85],"Bipolar disorders (BD) are a group of complex disorders that impact mood, behaviour and cognition and are known to cause significant suffering and impairment. Circadian rhythm (your internal day\u002Fnight \"clock\") disruption, which can involve changes in sleep-wake cycles, frequently occurs in BD. Both depression and mania are accompanied by circadian disruption. These disruptions are hypothesized to lead to mood worsening, metabolic dysfunction and inflammation. If circadian dysfunction plays a significant role in the symptoms and trajectory of BD, then treatment approaches that target these functions may lead to better outcomes. One such approach is dietary interventions. Time restricted eating (TRE) is a dietary tool that restricts the eating to an 8-12 hour window, without changing diet quality or caloric intake. Studies involving time restricted eating have been done in other conditions with promising results. There have been no studies done for mood disorders in general or bipolar disorder specifically. In this proposal, the investigators will assess two dietary interventions (TRE and nutritional counselling) to examine how TRE may represent a safe and viable adjunct to traditional treatments. The investigators aim to compare TRE with nutritional counselling, while all participants continue to receive usual care. Participants will receive support from a registered dietician and will be instructed on dietary habits. Half of participants will receive nutritional counselling and half will be asked to do TRE. Those in the TRE group will be asked to select a 10-hour window to consume all food and non-water beverages for the 8-week period. Participants will be asked to complete a screening visit to determine eligibility, and then will complete questionnaires at baseline, week 4 and week 8 examining symptoms of their illness and cognition. Participants will also provide a blood sample at baseline and week 8 for standard biochemistry tests, pregnancy testing (if applicable), and to examine inflammatory markers. Participants will also wear an actigraphy watch which provides wireless continuous monitoring of movements and ambient light. The primary outcome is feasibility and acceptability (do people agree to participate, complete the study, and follow the intervention; what do they think of the intervention). Secondary outcomes include changes in depression, anxiety, sleep, and cognition. Exploratory outcomes include inflammatory markers and circadian disruption.",[27,57,58],"2026-04-27",{"date":112,"type":32},"2026-05-01",{"date":114,"type":32},"2025-07-10",{"date":116,"type":20},"2027-02-26",{"name":118,"class":39},"University of Ottawa",{"id":120,"slug":121,"hasResults":11,"nctId":122,"briefTitle":123,"officialTitle":123,"acronym":124,"eligibilityCriteria":125,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":126,"targetDuration":4,"studyType":21,"phases":128,"briefSummary":129,"conditions":130,"keywords":133,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":138,"lastUpdatePostDateStruct":139,"startDateStruct":141,"completionDateStruct":143,"leadSponsor":145,"locationsCount":147},"100544599","theta-burst-stimulation-for-bipolar-depression-100544599","NCT06370988","Theta-Burst Stimulation for Bipolar Depression","TRIBE","Inclusion Criteria\n\nThe participant must meet all of the inclusion criteria to eligible for this clinical trial:\n\n1. Must be deemed to have capacity to provide informed consent;\n2. Must be an outpatient\n3. Have a DSM 5 diagnosis of bipolar disorder (type I or II), current episode depressed confirmed by Mini-International Neuropsychiatric Interview version 7.0.2 (MINI);\n4. Age 18-65;\n5. failure to achieve a clinical response to ≥1 adequate treatment trial for bipolar depression based on the Antidepressant Treatment History Form - Short Form (ATHF-SF) OR unable to tolerate at least 2 separate inadequate treatment trials for bipolar depression;43\n6. moderately severe depression with a score ≥ 15 on the PHQ-9;44\n7. not currently experiencing a mixed or manic episode (YMRS ≤10);\n8. no increase or initiation of psychotropic medication with intention of treating depressive symptoms in the 4 weeks prior to screening. This excludes targeted treatment of insomnia with trazodone, melatonin, low-dose doxepin \\[3-6mg\\], low-dose benzodiazepines \\[≤2mg lorazepam daily equivalent\\], non-benzodiazepine benzodiazepine receptor agonists, or orexin antagonists;\n9. able to adhere to the treatment schedule;\n10. pass the TMS adult safety screening questionnaire.45\n\nExclusion Criteria\n\nAn individual who meets any of the following criteria will be excluded from participation in this clinical trial:\n\n1. have a history of MINI diagnosis of a substance use disorder (other than nicotine and\u002For caffeine) within the last 3 months;\n2. have a concomitant major unstable medical illness;\n3. have active suicidal intent (assessed during HRSD-17 Item 3 and SSRS as imminent intent to act on specific plan, confirmed by psychiatric staff);\n4. are pregnant or intend to get pregnant during the study;\n5. have a lifetime MINI diagnosis of schizophrenia or schizoaffective disorder;\n6. have psychotic symptoms within the current episode;\n7. have a MINI anxiety disorder, trauma-related disorder, obsessive compulsive disorder, or personality disorder assessed by a study investigator to be primary and\u002For causing greater impairment than BD-DE;\n8. failure of an adequate acute course of ECT as defined by ATHF-SF during the current episode;\n9. have received any rTMS before due to potential to compromise blinding of treatment allocation;\n10. have any clinically significant neurological disorder (e.g., recent major cerebrovascular accident), or any history of seizure except those therapeutically induced by ECT or with clear precipitant (e.g., febrile seizure of childhood, alcohol withdrawal, etc.);\n11. have any intracranial implant (e.g., aneurysm clips, shunts, stimulators,) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;\n12. are participating in psychotherapy for less than 3 months. Patients will be permitted if they have been in stable treatment for at least 3 months prior to study entry, with no anticipated change in the frequency of therapeutic sessions, or focus of therapeutic sessions over the duration of the study;\n13. are currently taking lorazepam \\>2 mg daily (or equivalent) due to the potential to limit rTMS efficacy;\n14. are currently taking any dose of an anticonvulsant due to the potential to limit rTMS efficacy. If anticonvulsants have been discontinued prior to screening, at least 5 half-lives have elapsed until screening to allow sufficient drug clearance;\n15. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).",{"count":127,"type":20},124,[85],"The purpose of this trial is to determine if intermittent theta-burst stimulation (iTBS) can reduce the symptoms of depression in treatment-resistant bipolar disorder. To do this, some of the participants in this study will receive treatment with active iTBS stimulation, while others will receive sham iTBS stimulation. Participants will come for 30 days of either active iTBS or sham iTBS, with a 6-week follow-up period. Symptoms of depression (for determining treatment efficacy) and mania (for determining treatment safety) will be assessed using the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Young Mania Rating Scale (YMRS) every five treatments during the treatment course, and at 1 week and 6 week after treatment completion.",[27,56,131,132],"Treatment- Resistant Bipolar Disorder","Type 2 Bipolar Disorder",[134,135,136,137],"Transcranial Magnetic Stimulation","Repetitive Transcranial Magnetic Stimulation","rTMS","iTBS","2026-03-16",{"date":140,"type":32},"2026-03-18",{"date":142,"type":32},"2024-05-15",{"date":144,"type":20},"2029-05",{"name":146,"class":39},"Centre for Addiction and Mental Health",2,{"id":149,"slug":150,"hasResults":11,"nctId":151,"briefTitle":152,"officialTitle":153,"acronym":154,"eligibilityCriteria":155,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":156,"targetDuration":4,"studyType":21,"phases":158,"briefSummary":159,"conditions":160,"keywords":162,"overallStatus":166,"whyStopped":4,"lastUpdateSubmitDate":167,"lastUpdatePostDateStruct":168,"startDateStruct":169,"completionDateStruct":171,"leadSponsor":172,"locationsCount":40},"100629303","empagliflozin-adjunctive-therapy-in-bipolar-depression-100629303","NCT07472920","Empagliflozin Adjunctive Therapy in Bipolar Depression","Empagliflozin as an Adjunctive Strategy for Treating Bipolar Depression in Patients With Insulin Resistance: A Proof-of-Concept Study (EMPA-BD)","EMPA-BD","Inclusion Criteria:\n\n1. Adults aged 18 to 65 years.\n2. Diagnosis of Bipolar Disorder type I or II according to DSM-5 criteria, confirmed by the MINI International Neuropsychiatric Interview.\n3. Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 15 at screening.\n4. Currently receiving stable pharmacological treatment for bipolar disorder, with no medication changes (addition or withdrawal) in the past 4 weeks.\n5. Ability to provide informed consent.\n6. Insulin resistance, defined as HOMA-IR ≥ 1.8.\n\nExclusion Criteria:\n\n1. History of hypersensitivity to empagliflozin or any SGLT2 inhibitor.\n2. Type 1 or type 2 diabetes mellitus or HbA1c ≥ 6.5% at screening.\n3. Known pancreatic disease (pancreatitis or pancreatic surgery).\n4. Chronic kidney disease (eGFR \\\u003C 30 mL\u002Fmin\u002F1.73m²).\n5. Recurrent genital fungal infections.\n6. Pregnant or breastfeeding.\n7. Alcohol abuse or dependence within the past 12 months.\n8. YMRS score ≥ 12 (presence of manic or hypomanic symptoms).",{"count":157,"type":20},20,[85],"Bipolar disorder is a long-term mental health condition that causes mood changes, with depressive episodes being the most frequent and disabling. Many people do not fully recover with current treatments, showing the need for new therapeutic options.\n\nRecent research shows that insulin resistance (IR), a condition in which the body does not respond well to insulin, is common in people with bipolar disorder. It is linked to more severe mood symptoms, poorer treatment response, and higher risk of heart disease. IR may raise inflammation and affect how the brain uses energy, which can influence mood regulation.\n\nEmpagliflozin is a medicine approved for type 2 diabetes. In addition to its metabolic and heart benefits, studies suggest that it may also protect the brain and reduce inflammation, possibly helping to improve mood.\n\nThis open-label, proof-of-concept clinical trial will test how well empagliflozin works and how safe it is as an add-on treatment for people with bipolar depression and insulin resistance. A total of 20 adults with bipolar disorder type I or II, currently in a depressive episode, will take part in the study over a 12-week period.\n\nThe main goal is to see whether empagliflozin can lower depressive symptoms, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). Other measures include changes in insulin resistance and incidence of adverse events.\n\nThe study aims to explore whether improving insulin resistance can help both mood and metabolic health in people with bipolar disorder, guiding future clinical research.",[56,27,161],"Insulin Resistance",[56,27,161,163,164,165],"Empagliflozin","SGLT2 Inhibitors","Metabolic Psychiatry","NOT_YET_RECRUITING","2026-03-11",{"date":138,"type":32},{"date":170,"type":20},"2026-03-09",{"date":94,"type":20},{"name":173,"class":39},"University of Sao Paulo",{"id":175,"slug":176,"hasResults":11,"nctId":177,"briefTitle":178,"officialTitle":178,"acronym":4,"eligibilityCriteria":179,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":180,"enrollmentInfo":181,"targetDuration":183,"studyType":184,"phases":4,"briefSummary":185,"conditions":186,"keywords":192,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":196,"lastUpdatePostDateStruct":197,"startDateStruct":199,"completionDateStruct":201,"leadSponsor":203,"locationsCount":40},"100399417","university-of-iowa-interventional-psychiatry-service-patient-registry-100399417","NCT04480918","University of Iowa Interventional Psychiatry Service Patient Registry","INCLUSION CRITERIA:\n\n1. 18-99 years of age\n2. English-speaker with a level of understanding sufficient to agree to clinical treatment with a treatment modality offered by the Interventional Psychiatry Service, all required research procedures, and sign an informed consent document\n3. Clinical diagnosis of a major depressive episode in the context of major depressive disorder or bipolar disorder or treatment-resistant OCD evaluated by a provider on the Interventional Psychiatry Service and felt to be an appropriate candidate for clinical treatment with a treatment modality offered by the Interventional Psychiatry Service.\n\nEXCLUSION CRITERIA:\n\n1. Age less than 18 years\n2. A primary neuropsychiatric diagnosis that is not either major depressive disorder or bipolar disorder\n3. Serious, unstable medical conditions\u002Fproblems including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, e.g. uncontrolled asthma, uncontrolled hyper\u002Fhypothyroidism or active cancer.\n4. Involuntary commitment to psychiatry inpatient units\n5. If patients have one or more of the following MRI Exclusion criteria, they will not be able to participate in those aspects of this study:\n\n   1. The presence of an implanted device including pacemaker, coronary stent, defibrillator, or neurostimulation device that is not MRI-compatible\n   2. The presence of ferromagnetic objects in the body, i.e. bullets, shrapnel, and\u002For metal slivers\n   3. Clinically-significant claustrophobia\n   4. Clinically-significant hearing loss\n   5. Pregnant or nursing women or women of child bearing potential not using at least one medically accepted means of contraception (to include oral, injectable, or implant birth control, condom or diaphragm with spermicide, intrauterine devices (IUD), tubal ligation, abstinence, or partner with vasectomy)\n   6. The presence of any medical illness likely to alter brain morphology and\u002For physiology (e.g., hypertension, diabetes) even if controlled by medications","99 Years",{"count":182,"type":20},1000,"2 Months","OBSERVATIONAL","The purpose of this study is to examine the effects of interventional\u002Fprocedural therapies for treatment-resistant depression (TRD) and Obsessive-Compulsive Disorder (OCD). These treatments include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), racemic ketamine infusion and intranasal esketamine insufflation. The investigators will obtain various indicators, or biomarkers, of a depressed individuals' state before, during, and\u002For after these treatments. Such biomarkers include neurobehavioral testing, neuroimaging, electroencephalography, cognitive testing, vocal recordings, epi\u002Fgenetic testing, and autonomic nervous system measures (i.e. \"fight-or-flight\" response). The results obtained from this study may provide novel antidepressant treatment response biomarkers, with the future goal of targeting a given treatment to an individual patient (\"personalized medicine\").",[187,188,189,190,56,27,191],"Treatment Resistant Depression","Major Depressive Episode","Major Depression","Major Depressive Disorder","Obsessive-Compulsive Disorder",[193,134,194,195],"Electroconvulsive Therapy","Ketamine","Esketamine","2026-02-27",{"date":198,"type":32},"2026-03-03",{"date":200,"type":32},"2020-11-02",{"date":202,"type":20},"2050-08",{"name":204,"class":39},"Mark Niciu",{"id":206,"slug":207,"hasResults":11,"nctId":208,"briefTitle":209,"officialTitle":210,"acronym":211,"eligibilityCriteria":212,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":213,"enrollmentInfo":214,"targetDuration":4,"studyType":21,"phases":216,"briefSummary":217,"conditions":218,"keywords":220,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":226,"lastUpdatePostDateStruct":227,"startDateStruct":229,"completionDateStruct":231,"leadSponsor":233,"locationsCount":40},"100553629","program-to-enhance-cardiovascular-risk-trough-an-intervention-of-nutrition-in-bipolar-disorder-100553629","NCT06488573","PROgram To Enhance Cardiovascular Risk Trough an Intervention of Nutrition in Bipolar Disorder","The Effect of a Nutritional Intervention Focused on Dietary Pattern in the Cardiovascular Risks of Individuals With Bipolar Disorder","PROTECTION-BD","Inclusion Criteria:\n\n* Clinical diagnosis of Bipolar disorder types I and II diagnosis\n* Adults of both genders, from 18 to 60 years old\n* In typical pharmacotherapy for BD, for at least one month\n* Agreement to participate in the study with signature of the consent form\n\nExclusion Criteria:\n\n* Patients with \"very good or excellent\" diet quality assessed by the diet quality scale (ESQUADA): \\>275 out of a score of 375\n* Patients in a state of hypomania or mania: score \\>8 (Young Mania Rating Scale - YMRS)\n* Patients with severe depression \\>21 Montgomery-Åsberg Depression Rating Scale\n* Patients at low cardiovascular risk (\\\u003C7 points for men or \\\u003C9 points for women on the Framingham Global Risk Score)\n* Low weight or eutrophic body mass index: \\\u003C25kg\u002Fm² as in similar studies\n* Pregnant or breastfeeding women\n* Patients diagnosed with anorexia and bulimia nervosa\n* Patientes diagnosed with Irritable Bowl Syndrome or other diagnosed conditions that affect the gastrointestinal function","60 Years",{"count":215,"type":20},88,[85],"Individuals with Bipolar Disorder (BD) have twice the risk of being affected by metabolic comorbidities and a 1.8-fold increased risk of mortality from cardiovascular diseases when compared to the general population. These factors are fundamental in the 14-year reduction in the life expectancy of people with TB reported in recent meta-analyses. This occurs mainly due to the increased inflammation associated with the disease, the adverse effects of pharmacological treatments and unhealthy lifestyle habits that are more common in people diagnosed with BD. Nutrition has been studied as an adjunctive treatment in other psychiatric disorders, but there is a lack of studies about the role of nutrition in TB. Considering that diet can impact metabolic health, this randomized controlled study aims to evaluate the effect of a nutritional intervention on cardiovascular risk in patients with TB. The intervention is based on the dietary pattern recommended in the Dietary Guidelines for the Brazilian Population and will be applied by a registered dietitian. According to the literature, the sample size will be 72 individuals with TB (36 in the control group with usual treatment + 36 in the intervention group added to the usual treatment). The intervention will be carried out in 7 individual sessions and 8 group sessions with specific themes. The primary aim of this protocol will be an intervention to contribute to cardiovascular health - verified by serum markers, anthropometric measurements and the Framingham Cardiovascular Risk Score (algorithm used to estimate an individual's 10-year cardiovascular risk). The secondary stages will be the adherence of the intervention and the impact on the quality of life of the participants. The possible positive results of this nutritional intervention can open new clinical perspectives. Meaning that might show that better food choices can protect the cardiovascular health of individuals with TB, leading to a reduction in morbidity and mortality associated with the disease.",[27,219],"Bipolar Disorder (BD)",[221,222,223,224,225],"nutrition intervention","nutritional psychiatry","bipolar disorder","dietary intervention","brazilian dietary guideline","2026-02-26",{"date":228,"type":32},"2026-03-02",{"date":230,"type":20},"2026-04",{"date":232,"type":20},"2027-12",{"name":173,"class":39},{"id":235,"slug":236,"hasResults":11,"nctId":237,"briefTitle":238,"officialTitle":239,"acronym":4,"eligibilityCriteria":240,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":241,"targetDuration":4,"studyType":21,"phases":243,"briefSummary":244,"conditions":245,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":246,"lastUpdatePostDateStruct":247,"startDateStruct":248,"completionDateStruct":250,"leadSponsor":252,"locationsCount":40},"100556392","efficacy-tolerability-and-cognitive-effects-of-deep-transcranial-magnetic-stimulation-for-bipolar-depression-100556392","NCT06524505","Efficacy, Tolerability, and Cognitive Effects of Deep Transcranial Magnetic Stimulation for Bipolar Depression","Efficacy, Tolerability, and Cognitive Effects of Deep Transcranial Magnetic Stimulation for Bipolar Depression: a Double-blind, Randomized Controlled Trial","Inclusion Criteria:\n\nConfirmed diagnosis of bipolar depression;\n\n* age between 18 and 65 years;\n* a 17-item Hamilton Depression Rating Scale (HDRS-17) score \\>= 17,\n* a stable pharmacological regimen maintained for at least 4 weeks prior to the beginning of the treatment phase ;\n* for participants who had previously received antidepressant therapy, a minimum 4-week washout period followed by re-evaluation.\n\nExclusion Criteria:\n\n* a lifetime history of other psychiatric disorders, neurological diseases, or severe brain injury;\n* receipt of electroconvulsive therapy, rTMS, transcranial direct current stimulation, transcranial alternating current stimulation, or other neurostimulation treatments within the previous 3 months;\n* contraindications to magnetic stimulation, including epilepsy, cardiovascular disorders, or metallic implants in the head;\n* the presence of hypomanic\u002Fmanic symptoms at baseline or a score greater than 12 on the Young Mania Rating Scale (YMRS);\n* pregnancy or lactation.",{"count":242,"type":20},100,[85],"The aim of this study is to evaluate the feasibility and efficacy of deep transcranial magnetic stimulation (dTMS) as an add-on treatment for bipolar depression. Meanwhile, we aim to evaluate the effect of dTMS on cognitive function of bipolar depressive patients. We hypothesize dTMS would improve depressive symptoms and cognitive function in bipolar disorder.",[27],"2026-02-24",{"date":196,"type":32},{"date":249,"type":32},"2024-08-01",{"date":251,"type":20},"2026-02",{"name":253,"class":39},"Tianjin Anding Hospital",{"id":255,"slug":256,"hasResults":11,"nctId":257,"briefTitle":258,"officialTitle":259,"acronym":4,"eligibilityCriteria":260,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":261,"enrollmentInfo":262,"targetDuration":4,"studyType":21,"phases":264,"briefSummary":265,"conditions":266,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":267,"lastUpdatePostDateStruct":268,"startDateStruct":270,"completionDateStruct":272,"leadSponsor":274,"locationsCount":40},"100602314","ketogenic-intervention-for-bipolar-depression-100602314","NCT07121894","Ketogenic Intervention for Bipolar Depression","Ketogenic Intervention for Bipolar Depression: An Open-Label Trial Guiding Clinical Implementation (KETO-MAYO)","Inclusion Criteria\n\n* Age 18-50 years\n* Willingness to change the current diet to a high fat, low carbohydrate diet\n* Diagnosis of bipolar I or II disorder, or BP schizoaffective Disorder by DSM-IV (SCID- confirmed). If a participant has already completed a structured diagnostic interview within the last 2 years or in any of the Department of Psychiatry and Psychology Mood Unit studies, existing SCID results can be used for this study; thus, they will not be required to repeat the SCID assessment. If a structured diagnostic interview was completed more than 2 years ago, the current mood state sections of the SCID must be repeated to ensure accuracy of current mood state assessment.\n* Depressive symptom severity of at least mild (MADRS \\> 6) with steady and stable (ie, at least 2 weeks) mood stabilization (eg, lithium, valproate, lamotrigine, carbamazepine\u002Foxcarbamazepine, and\u002For atypical antipsychotic therapy) and non-psychotropic medication.\n* Urine drug screen is negative except for allowable drugs that they have been prescribed, such as benzodiazepines.\n* Pregnancy test is negative.\n* Established birth control practice for sexually active individuals.\n* Medical comorbidity is stable (hypertension, T2D, gout - uric acid in normal limits).\n\nExclusion Criteria:\n\n* No access to smartphone or internet (unless provided by sponsor)\n* Inability to provide written, voluntary, informed consent and pass (80%) comprehension assessment related to study goals, risks, and benefits.\n* Structured clinical interview confirmation of schizophrenia or presence of psychotic symptoms (both SCID and YMRS question 8\\>5).\n* Clinical diagnosis of personality disorder that, upon review by the study psychiatrist, of all available information (SCID, electronic health record), is the primary psychiatric diagnosis.\n* Mixed symptoms of depression defined as a YMRS ≥12 (i.e., hypomania).\n* Active suicidal ideation as defined by MADRS score \\>4 on question #10 or Columbia Suicide Severity Scale (C-SSRS), yes response to Question #4 (ideation, intent, but no plan) or Question #5 (ideation, intent, and plan).\n* Any current drug and alcohol use disorder (excluding nicotine); complete (not partial) remission ≥3 months.\n* Positive toxicology screen for cannabis and cannabis use disorder by structured clinical interview. Participants who use cannabis for recreational or medicinal purposes and fail the toxicology screen can potentially be included if the Cannabis Use Disorder Identification Test (CUDIT-R) score is \\\u003C 12.\n* Currently undergoing ECT, transcranial magnetic stimulation, or deep brain stimulation as an acute or maintenance treatment. Maintenance vagal nerve stimulation is allowed if the placement of device is \\> 1 year.\n* Current involuntary psychiatric hospitalization.\n* Already in ketosis or on a medication that causes acidosis, such as carbonic anhydrase inhibitors (e.g., acetazolamide \"Diamox\" and topiramate).\n* BMI \\\u003C 18.5; (m) baseline LDL-c \\> 190.\n* Any active or unstable medical condition judged by the principal investigator as conferring significant medical risk to allow inclusion in the study, such as active severe infection.\n* Acute pancreatitis or history of lipid-associated pancreatitis.\n* Type I diabetes.\n* SGLT2 inhibitor use\n* Rare inborn errors of metabolism affecting fatty acid processing (typically diagnosed in infancy or, rarely, adolescence), such as Pyruvate carboxylase deficiency and Porphyria\n* Primary carnitine deficiency\n* Chronic renal failure, significant renal disease defined as creatinine clearance \\\u003C30 or in dialysis.\n* Severe vitamin D deficiency (serum levels of 25-hydroxyvitamin D \\[25(OH)D\\] \\\u003C 12 ng\u002FmL or 30 nMol\u002FL).\n* A diagnosis of osteopenia, defined as a bone mineral density (BMD) T-score between -1.0 and -2.5 on a dual-energy X-ray absorptiometry (DEXA) scan or with a history of fragility fractures\n* Clinically significant laboratory test abnormality\n* Anticipated elective surgical procedure within the next 18 weeks\n* Family history of premature coronary artery disease defined as atherosclerotic cardiovascular events (e.g., heart attack, stroke) before 55 and 65 years of age in male and female first-degree relatives, respectively.\n* History of familial hypercholesterolemia (note -current or start of statin or lipid-lowering drug as part of clinical care is not an exclusion provided managed by a primary care provider) or LDL-C\\>190 mg\u002Fdl (or LDL\\>160 mg\u002Fdl if on lipid lowering therapy) or triglycerides\\>500 mg\u002Fdl.\n* History of coronary disease or coronary calcifications or coronary stenosis found in invasive cardiac catheterization or imaging.\n* History of ischemic stroke or carotid plaque found on baseline common carotid intima-media thickness (IMT) ultrasound.\n* History of peripheral atherosclerotic arterial disease or any other form of clinical atherosclerosis.\n* History or current diagnosis of respiratory failure defined as a PaO₂ \\\u003C 60 mmHg or SpO₂ \\\u003C 90% on room air or any condition leading to clinically significant respiratory impairment\n* History or current diagnosis of liver failure or chronic liver disease with significant impairment, defined as ALT or AST \\> 5 times the upper limit of normal, or total bilirubin \\> 3 mg\u002FdL.","50 Years",{"count":263,"type":20},30,[85],"The purpose of this study is to assess the clinical correlates of therapeutic precision ketosis in bipolar depression and to evaluate the cardiometabolic correlates associated with therapeutic precision ketosis in bipolar depression.",[27],"2026-01-23",{"date":269,"type":32},"2026-01-26",{"date":271,"type":32},"2025-08-12",{"date":273,"type":20},"2029-05-01",{"name":38,"class":39},{"id":276,"slug":277,"hasResults":11,"nctId":278,"briefTitle":279,"officialTitle":280,"acronym":281,"eligibilityCriteria":282,"healthyVolunteers":11,"sex":15,"minAge":283,"maxAge":284,"enrollmentInfo":285,"targetDuration":4,"studyType":21,"phases":287,"briefSummary":288,"conditions":289,"keywords":290,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":267,"lastUpdatePostDateStruct":292,"startDateStruct":293,"completionDateStruct":295,"leadSponsor":297,"locationsCount":299},"100562125","deep-brain-stimulation-of-treatment-resistant-bipolar-depression-100562125","NCT06599099","Deep Brain Stimulation of Treatment-Resistant Bipolar Depression","Building Mood State Classifiers to Inform Deep Brain Stimulation of Treatment-Resistant Bipolar Depression","DBS in TRBD","Inclusion Criteria:\n\n1. Males and females ages 22-64, inclusive\n2. Diagnosis: Bipolar I disorder confirmed by SCID-5, currently in a major depressive episode (MDE).\n3. Symptom Severity: MADRS score of ≥27 at Screening and pre-operative baseline visit. CGI-S \\> 4 and YMRS \\\u003C12 at these visits.\n4. Failure to respond or maintain a response to a minimum of four evidence-based interventions for bipolar depression in the patient's lifetime, including at least two FDA-approved medications (olanzapine\u002Ffluoxetine, quetiapine, lurasidone, cariprazine, lumateperone), or ECT, administered at adequate doses and duration (adequately defined by the Antidepressant Treatment History Form (ATHF-Short Form). During the current episode, the patient must have failed to respond or maintain a response to a minimum of two FDA-approved interventions for bipolar depression. In addition, the patient is required to be currently taking at least one evidence-based medication for bipolar disorder (e.g., lithium, either alone or in combination with an atypical antipsychotic such as quetiapine), unless no evidence-based medications for bipolar disorder are tolerated.\n5. Initial mood episode occurred before the age of 40 - to minimize risk of enrolling patients with so atypical onset of initial mania\u002Fdepression.\n6. Must be on a stable dose of psychotropic medications for a minimum of four weeks prior to surgery.\n7. Minimum score on the Montreal Cognitive Assessment (MoCA).\n8. Able and willing to give informed consent and sign Treatment Contract that includes identification of a reliable informant.\n\nExclusion Criteria:\n\n1. Lifetime history of a psychotic disorder (e.g., schizophrenia, schizoaffective disorder, and other psychotic disorders), or any history of psychotic symptoms when not in a bipolar mood episode.\n2. Currently meets criteria for a manic or hypomanic episode or rapid cycling (4 or more mood episodes in the previous 12 months).\n3. Any psychiatric disorder which is the primary focus of treatment within the past 12 months (with bipolar disorder as the secondary focus of treatment).\n4. Alcohol\u002Fsubstance use disorder, moderate or severe, within the previous 12 months \\[excluding nicotine\\].\n5. Intellectual disability or neurocognitive disorder.\n6. Current major and\u002For unstable medical conditions. 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, endocrinopathies, and any major neurological disorder \\[e.g., seizure disorder, stroke, dementia, degenerative neurologic diseases, traumatic brain injury\\].\n7. Any medical contraindication to surgery or condition that makes the patient, in the opinion of the surgeon, a poor candidate.\n8. Female who is pregnant or breastfeeding or has plans to become pregnant in the next 24 months.\n9. Any contraindication for MRI.\n10. Patients with a clinically significant personality disorder, including risk for homicidal or aggressive behavior, which in the opinion of the investigator has a major impact on the patient's current psychiatric status and\u002For would preclude safe study participation.\n11. Patients at serious and imminent risk of suicide and not suitable for an outpatient study, in the judgment of the investigators.\n12. Participation in any investigational clinical trial within the preceding 30 days.\n13. Current implanted stimulation devices including cardiac pacemakers, defibrillators, and neurostimulators \\[including deep brain and spinal cord stimulators\\].\n14. Patients with no regular contact with at least one adult. Patients who are undomiciled are excluded.\n15. Body mass index (BMI) less than 16 and greater than 40 kg\u002Fm2\n16. Need for diathermy.\n17. Unable to sign the informed consent for any reason.\n18. Patients who are not under the care of a psychiatrist at Screening and throughout the duration of the study.","22 Years","64 Years",{"count":286,"type":20},10,[85],"This study is only enrolling at Baylor College of Medicine. The other research locations listed serve to support data analysis only.\n\nThis research study is to investigate the use of technology called Deep Brain Stimulation (DBS) to potentially improve Treatment-Resistant Bipolar Depression (TRBD) symptoms in patients with severe cases. DBS involves the surgical implantation of leads and electrodes into specific areas of the brain, which are thought to influence the disease. A pack implanted in the chest, called the neurotransmitter, keeps the electrical current coursing to the brain through a wire that connects the neurotransmitter and electrodes. It is believed DBS may restore balance to dysfunctional brain circuitry implicated in TRBD. The goal of this study is to enhance current approaches to DBS targeting in the brain and to use a novel approach to find a better and more reliable system for TRBD treatment.\n\nIts important for participants to understand that this is an investigational study where there could be a lack of effectiveness in improving TRBD symptoms. There may be no directly benefit from taking part in this study.\n\nThis study is expected to last 20 months and involves 3 main steps.\n\n1. Medical, psychiatric, and cognitive evaluations.\n2. Implantation of a brain stimulation system.\n3. Follow up after implantation of device, including programming, recording, and psychiatric testing.\n\nThere are risks and benefits to this study which need to be considered when deciding to participate or not. Some of the risks are from surgery, the DBS device and programming, the tests involved, and potential loss of confidentiality, as well as other unknown risks.\n\nSome of the more serious risks involved in this study and the percentage that they occur:\n\n1. Bleeding inside the Brain (1 to 2 percent).\n2. Infection from the procedures (3 percent)\n3. Seizure caused from the procedures (1.2 percent)\n\nHowever, the benefit of this study is that it may help relieve or decrease TRBD symptoms. This form of treatment has shown to reduce symptom severity in other cases. This could potentially improve quality of life and activities in daily routines. There is also a potential benefit to society in that the data the investigators will obtain from this study may help increase the understanding of the mechanisms underlying TRBD symptoms, as well as enhanced Deep Brain Stimulation techniques.\n\nStudy participation is expected to last 20 months from the time the DBS device is activated and should include approximately 23 visits. These visits also include 8 separate, 24 hour stays at the Menninger NeuroBehvaioral Monitoring Unit (NBU). These 24-hour sessions will occur at multiple points throughout the study (1 week prior to surgery, the week preceding device activation, the week following activation, then after 2 weeks, 4 weeks, 6 months, 9 months, and 12 months). Participants will need to stay locally for the week of the NBU stay (typically Monday through Friday).\n\nStudy visits will include clinician administered assessments and questionnaires, subject reported assessments, neuropsychological testing, and mobile behavioral assessments which will occur around 23 visits over the course of 20 months.",[27],[291],"Treatment Resistant Bipolar Depression",{"date":269,"type":32},{"date":294,"type":32},"2025-01-01",{"date":296,"type":20},"2030-05-30",{"name":298,"class":39},"Wayne Goodman MD",4,{"id":301,"slug":302,"hasResults":11,"nctId":303,"briefTitle":304,"officialTitle":305,"acronym":306,"eligibilityCriteria":307,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":308,"enrollmentInfo":309,"targetDuration":4,"studyType":21,"phases":311,"briefSummary":312,"conditions":313,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":315,"lastUpdatePostDateStruct":316,"startDateStruct":318,"completionDateStruct":320,"leadSponsor":322,"locationsCount":40},"100485594","phase-3-intensified-pharmacological-treatment-for-schizophrenia-major-depressive-disorder-and-bipolar-depression-after-a-first-time-treatment-failure-100485594","NCT05603104","Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure","A Randomised, Controlled Trial to Investigate the Effect of an Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.","INTENSIFY","Inclusion Criteria:\n\n1\\. In- or out patients, at least 18 years of age up until 70 (SZ study sample), 65 years (MDD study sample) and no limit for the BD study..\n\nBeing willing and able to provide written informed consent. Having a legal guardian to cosign is allowed. Informed consent will be signed at visit 1, before any study procedure.\n\n3\\. Female subjects of child bearing potential must be willing to ensure that they use effective contraception during the trial and as per the requirements in the protocol (section 8.2.1).Male subjects that will use valproate acid during the trial must use effective contraceptive measures during the trial.\n\n4\\. Meeting diagnostic criteria for a primary diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, major depressive disorder (without psychotic features) or bipolar depression (bipolar disorder type I and II currently in a depressive episode), according to DSM-5. The primary diagnosis will be confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2).\n\n5\\. Subject experiences a treatment failure due to lack of efficacy in the current episode, as confirmed by a CGI-I ≥3; preferably this treatment is a first-line pharmacotherapeutic agent for the primary DSM-5 diagnosis, and was prescribed for at least 4 weeks within an effective dose range as specified in the Summary of Product Characteristics (SmPCs). However, other lines of treatment are accepted as well.\n\n6\\. Subject and clinician intend to change pharmacotherapeutic treatment. 7. A minimum symptom severity threshold needs to be present (moderate level; see below) and subject needs to experience functional impairment.\n\n* The minimum symptom severity threshold for SZ subjects is at least 2 PANSS positive or negative items with a score of 4, or at least one PANSS positive or negative item with a score of 5.\n* The minimum symptom severity threshold for MDD is a score of ≥ 20 on the Montgomery Åsberg Depression Rating Scale (MADRS)\n* The minimum symptom severity threshold for BD is a score of ≥20 on the Montgomery Åsberg Depression Rating Scale (MADRS)\n* For all study samples: Functional impairment is defined as a score of 5 or higher on any of the three scales of the Sheehan Disability Scale (SDS).\n\nExclusion criteria:\n\n1. Being pregnant or breastfeeding.\n2. Subject has failed previously on the EIPT study medication (i.e. SZ: clozapine; MDD: esketamine intranasal\u002F(es)ketamine IV) Treatment duration as ≥ 4 weeks within an efficacious dose range according to the SmPC.\n3. Subject has a known intolerance to clozapine (SZ only), esketamine intranasal\u002F (es)ketamine IV (MDD only) or quetiapine (BD only) or to all medication options for a study sample (related to the TAU treatment arms) or all EIPT medications (BD study sample).\n4. Meeting any of the contraindications of clozapine (SZ only), esketamine intranasal\u002F (es)ketamine IV (MDD only) or quetiapine (BD only), or to all medication options for a study sample (related to the TAU treatment arms), or all EIPT medications (BD study sample), as specified within the applicable SmPC.\n5. Subject has participated in another clinical trial in which the subject received an experimental or investigational drug or agent within 30 days before visit 1.\n6. Subject experiences any other significant disease or disorder which, in the opinion of the investigator, may either put the subjects at risk because of participation in the trial, or may influence the result of the trial, or the subject's ability to participate in the trial.\n7. 7\\. Subjects with active suicidal ideation with some intent to act, without specific plan (\"Yes\" to question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS)) or active suicidal ideation with specific plan and intent (\"Yes\" to question 5 of the C-SSRS), followed by an assessment by the treating clinician who determines it is not safe for the subject to participate in the study\n8. Subject meets criteria for current substance use disorder, as confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2). Nicotine dependency is allowed, as well as mild and moderate alcohol and\u002For cannabis use disorder (as defined by MINI v7.0.2). Severe alcohol and\u002For cannabis use disorder are not allowed.\n9. Subjects have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.\n10. Subjects dependent on the sponsor, investigator or trial site must be excluded from participation in advance.\n11. For the SZ sample only: schizophrenia subjects cannot meet the modified Andreasen criteria for remission.\n12. For the SZ sample only: Subjects that have any clinically significant abnormal values on the local laboratory test (especially ANC\u002FWBC and liver values), electrocardiogram (ECG) or physician examinations.\n13. For the BD sample only: a score of 12 or higher on the Young Mania Rating Scale (YMRS) in order to exclude subjects with predominant manic symptoms or mixed symptoms.\n14. For the BD study sample only: Subjects with a history of antidepressant-induced mania or hypomania or recent rapid cycling (based on the medical file of the potential participant or the clinical judgment of the clinician).\n15. For the BD study sample only: Subjects with pre-existing severe liver damage (as tested within the local laboratory test at visit 1).","70 Years",{"count":310,"type":20},1254,[53],"Schizophrenia, bipolar and major depressive disorders collectively affect over 10 million people across the EU and are associated with annual healthcare and societal costs in excess of 100 billion Euros. When diagnosed with one of these disorders, patients are prescribed psychotropic medication such as antidepressants, mood stabilisers or antipsychotics. It is unknown whether this first-line treatment will be successful. After this first-line treatment fails, usually a second-line treatment is initiated, and when this is not successful either a third-line treatment is initiated. Third-line treatments are quite successful, especially when compared to second-line treatments. The research question is whether the third-line treatments (early-intensified treatments) when used earlier in the disease course for schizophrenia, bipolar and major depressive disorders. If this is indeed the case, this could lead to the prevention of unnecessary trials of ineffective treatments and adaptations of worldwide guidelines as well as a reduction of healthcare and societal costs.",[314,190,27],"Schizophrenia and Related Disorders","2026-01-19",{"date":317,"type":32},"2026-01-22",{"date":319,"type":32},"2025-04-27",{"date":321,"type":20},"2028-06-30",{"name":323,"class":39},"Dr. Inge Winter",{"id":325,"slug":326,"hasResults":11,"nctId":327,"briefTitle":328,"officialTitle":329,"acronym":4,"eligibilityCriteria":330,"healthyVolunteers":11,"sex":15,"minAge":331,"maxAge":16,"enrollmentInfo":332,"targetDuration":4,"studyType":21,"phases":333,"briefSummary":334,"conditions":335,"keywords":340,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":345,"lastUpdatePostDateStruct":346,"startDateStruct":348,"completionDateStruct":350,"leadSponsor":352,"locationsCount":40},"100611858","hd-tdcs-for-adolescent-bipolar-depression-targeting-s1-100611858","NCT07246044","HD-tDCS for Adolescent Bipolar Depression Targeting S1","High-Definition Transcranial Direct Current Stimulation (HD-tDCS) Targeting the Primary Somatosensory Cortex for Bipolar Depression in Adolescents: A Randomized Double-Blind Controlled Trial","Inclusion Criteria:\n\n* Between 12 and 18 years of age;\n* Participants fulfill the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria for bipolar disorder (BD). Participants are assessed by the Structured Clinical Interview for DSM-IV for Axis I Disorders (SCID-I, patients' age ≥18 years old), or the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K- SADS-PL, patients' age\\\u003C 18 years old);\n* A current moderate or severe depressive episode defined by HAMD≥17 and Young Mania Rating Scale (YMRS) \\\u003C12;\n* Participants receive a stable psychotropic medication regimen prior to randomization to the trial and are willing to remain on the stable regimen during the HD-tDCS treatment phase;\n* Participants and 1 or 2 parents (patients' age\\\u003C 18 years old) provide informed consent after the detailed description of the study.\n\nExclusion Criteria:\n\n* Prior rTMS or tDCS or electroconvulsive therapy (ECT) treatment or standard psychological therapy within 6 months prior to screening;\n* Comorbidity of other DSM-IV axis I disorders or personality disorders;\n* Judged clinically to be at serious suicidal risk;\n* Diabetes mellitus, hypertension, vascular and infectious diseases and other major medical comorbidities;\n* Unstable medical conditions, e.g., severe asthma;\n* Neurological disorders, e.g., history of head injury with loss of consciousness for ≥ five minutes, cerebrovascular diseases, brain tumors and neurodegenerative diseases;\n* Mental retardation or autism spectrum disorder;\n* Contraindications to MRI (e.g., severe claustrophobia, pacemakers, metal implants);\n* Contraindications to tDCS (e.g., metal in head, history of seizure, EEG test suggesting high risk of seizure, known brain lesion);\n* Current drug\u002Falcohol abuse or dependence;\n* Pregnant or lactating female.","12 Years",{"count":242,"type":20},[85],"This randomized, double-blind, sham-controlled clinical trial aims to evaluate the efficacy and underlying biological mechanisms of HD-tDCS targeting the primary somatosensory cortex in adolescents with bipolar depression. Participants will be randomly assigned to receive either active HD-tDCS or sham stimulation, in addition to routine clinical care. Biological data, including neuroimaging, blood biomarkers, voice and facial features, Photoplethysmography (PPG), Electroencephalography (EEG), and behavioral data, will be collected to explore potential predictors of treatment response.",[336,27,337,338,339],"Adolescent","tDCS","Primary Somatosensory Cortex","Bipolar Disorder Depression",[341,342,343,344],"primary somatosensory cortex","adolescent","bipolar depression","high-definition transcranial direct current stimulation","2025-11-17",{"date":347,"type":32},"2025-11-24",{"date":349,"type":32},"2025-09-16",{"date":351,"type":20},"2027-12-31",{"name":353,"class":39},"Jiangsu Province Nanjing Brain Hospital",{"id":355,"slug":356,"hasResults":11,"nctId":357,"briefTitle":358,"officialTitle":359,"acronym":360,"eligibilityCriteria":361,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":362,"targetDuration":4,"studyType":21,"phases":364,"briefSummary":365,"conditions":366,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":367,"lastUpdatePostDateStruct":368,"startDateStruct":370,"completionDateStruct":372,"leadSponsor":373,"locationsCount":374},"100514077","phase-3-the-effect-of-a-six-week-intensified-pharmacological-treatment-for-bipolar-depression-compared-to-treatment-as-usual-in-subjects-who-had-a-first-time-treatment-failure-on-their-first-line-treatment-100514077","NCT05973786","The Effect of a Six Week Intensified Pharmacological Treatment for Bipolar Depression Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.","A Randomised, Controlled Trial to Investigate the Effect of a Six Week Intensified Pharmacological Treatment for Bipolar Depression Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.","INTENSIFY BD","Inclusion criteria:\n\n1. In- or out patients, at least 18 years of age.\n2. Being willing and able to provide written informed consent. Having a legal guardian to cosign is allowed. Informed consent will be signed at visit 1, before any study procedure.\n3. Female subjects of child bearing potential must use effective contraception during the trial as per the requirements of the applicable SmPCs and should have a negative pregnancy test at visit 1 or 2 (before randomisation). Male subjects that will use valproate acid during the trial must use effective contraceptive measures during the trial (see section 8.2.1).\n4. Meeting diagnostic criteria for a primary diagnosis of bipolar depression (bipolar disorder type I and II currently in a depressive episode), according to DSM-5. The primary diagnosis will be confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2).\n5. Subject experiences a treatment failure due to lack of efficacy in the current episode, as confirmed by a CGI-I ≥3; preferably, this treatment is a first-line pharmacotherapeutic agent for the primary DSM-5 diagnosis, and was prescribed for at least 4 weeks within an effective dose range as specified in the Summary of Product Characteristics (SmPCs). However, other lines of treatment are accepted as well.\n6. Subject and clinician intend to change pharmacotherapeutic treatment.\n7. A minimum symptom severity threshold needs to be present (moderate leve) and subject needs to experience functional impairment.\n\n   * The minimum symptom severity threshold is a score of ≥20 on the Montgomery Åsberg Depression Rating Scale (MADRS)\n   * Functional impairment is defined as a score of 5 or higher on any of the three scales of the Sheehan Disability Scale (SDS).\n\nExclusion criteria\n\n1. Being pregnant or breastfeeding.\n2. Subject has a known intolerance to quetiapine or to all EIPT medication or to all TAU medication.\n3. Meeting any of the contraindications for quetiapine, or to all EIPT medication or to all TAU medication options, as specified within the applicable SmPC, supported by clinically significant abnormal values on local laboratory tests, electrocardiogram (ECG) or physical examinations.\n4. Subject has participated in another clinical trial in which the subject received an experimental or investigational drug or agent within 30 days before visit 1.\n5. Subject experiences any other significant disease or disorder which, in the opinion of the investigator, may either put the subjects at risk because of participation in the trial, or may influence the result of the trial, or the subject's ability to participate in the trial.\n6. Subjects with active suicidal ideation with some intent to act, without specific plan (\"Yes\" to question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS)) or active suicidal ideation with specific plan and intent (\"Yes\" to question 5 of the C-SSRS), followed by an assessment by the treating clinician who determines it is not safe for the subject to participate in the study.\n7. Subject meets criteria for current substance use disorder, as confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2). Nicotine dependency is allowed, as well as mild and moderate alcohol and\u002For cannabis use disorder (as defined by MINI v7.0.2). Severe alcohol and\u002For cannabis use disorder are not allowed.\n8. Subjects have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.\n9. A score of 12 or higher on the Young Mania Rating Scale (YMRS) in order to exclude subjects with predominant manic symptoms or mixed symptoms.\n10. Subjects dependent on the sponsor, investigator or trial site must be excluded from participation in advance.\n11. Subjects with pre-existing severe liver damage (as tested within the local laboratory test at visit 1).\n12. Subjects with a history of antidepressant-induced mania or hypomania or recent rapid cycling (based on the medical file of the potential participant or the clinical judgment of the clinician).",{"count":363,"type":20},418,[53],"Bipolar disorders affect approximately 4.5 million people across the European Union (EU) and are associated with high annual healthcare and societal costs. Bipolar disorder I and II represent disorders that cause extreme fluctuation in a person's mood, energy, and ability to function, in which symptoms of (hypo)mania and depression alternate. The depressive episodes of bipolar disorders are often referred to as bipolar depression (BD). In other words: it is a phase\u002Fstate of the disorder. For many patients with BD, the depressive polarity is often more pervasive and more debilitating than manic states, with estimates that depressed mood accounts for up to two-thirds of the time spent unwell, even with treatment. The burden of not received an effective treatment for BD is high: more severe psychopathology, higher rates of unemployment, more hospitalisations, lower quality of life, lower cognitive functioning, risk of suicide, comorbidities and poorer social and occupational functioning and thus more carer burden. For BD, the treatment guidelines are very heterogeneous, amongst other reasons because the disease is heterogeneous and treatments should be tailored to the patients. There is no clear treatment algorithm and it cannot yet be predicted which treatment will be effective. Especially the place of adjunctive antidepressants is under debate. Usually, for psychiatric disorders (including bipolar disorder), a patient is considered to be treatment-resistant is two medicinal treatments have been tried (in sufficient duration and dosage) without sufficient success. For BD, there is no consensus on when to consider a patient as treatment-resistant, but the most common definition is after one prior treatment failure. This raises the research question whether adjunctive antidepressants to treat BD should be introduced earlier in the treatment. Additionally, The INTENSIFY trial is part of the larger Horizon 2021 project, with the central goal of paving the way for a shift towards a treatment decision-making process tailored for the individual at risk for treatment resistance. To that end, we aim to establish evidence-based criteria to make decisions of early intense treatment in individuals at risk for treatment resistance across the major psychiatric disorders of schizophrenia, bipolar disorder and major depression.",[27],"2025-09-24",{"date":369,"type":32},"2025-09-26",{"date":371,"type":32},"2025-02-11",{"date":321,"type":20},{"name":323,"class":39},13,{"id":376,"slug":377,"hasResults":11,"nctId":378,"briefTitle":379,"officialTitle":380,"acronym":4,"eligibilityCriteria":381,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":382,"targetDuration":4,"studyType":21,"phases":383,"briefSummary":384,"conditions":385,"keywords":387,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":395,"lastUpdatePostDateStruct":396,"startDateStruct":398,"completionDateStruct":400,"leadSponsor":402,"locationsCount":40},"100601266","magnetic-resonance-guided-focused-ultrasound-bilateral-capsulotomy-for-the-treatment-of-refractory-bipolar-depression-100601266","NCT07108257","Magnetic Resonance-Guided Focused Ultrasound Bilateral Capsulotomy for the Treatment of Refractory Bipolar Depression","Phase I Trial of Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Bipolar Depression","Inclusion Criteria:\n\n1. Men and women ≥18 and ≤65 years of age, inclusive.\n2. Patients who are competent and willing to give consent and able to attend study visits, as determined by both study Psychiatrist and the surgeon.\n3. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of Bipolar Disorder, Type 1 or Type 2.\n4. A minimum score of 20 on the Hamilton Depression Rating Scale (HAMD) when depressed (at least 2 weeks of major depression at the time the HAMD is conducted).\n5. Treatment refractory bipolar depression indicated by at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. The minimum duration for being on either of these regimens should be 4 weeks.\n6. Ability to provide informed consent\u002Fcompetent to make medical decisions.\n\nExclusion Criteria:\n\nPatients with unstable cardiac status \\[e.g. Unstable angina pectoris on medication, Patients with documented myocardial infarction within six months, Congestive heart failure requiring medication (other than diuretic), Patients on anti-arrhythmic drugs, Severe hypertension (diastolic BP \\> 100 on medication)\\] 2. Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.\n\n3\\. Laboratory biochemical evidence of abnormal bleeding and\u002For coagulopathy, including risk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter or abnormal International Normalized Ratio) 4. Cerebrovascular disease (e.g. Cerebrovascular Accident within 6 months) or history of intracranial hemorrhage.\n\n5\\. Untreated, uncontrolled sleep apnea. 6. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure.\n\n7\\. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment.\n\n8\\. Are participating or have participated in another clinical trial in the last 30 days.\n\n9\\. Patients unable to communicate with the investigator and staff. 10. Presence of significant cognitive impairment 11. History of psychosis on clinical evaluation. 12. Catatonic or psychotic or actively suicidal on clinical evaluation. 12. Patients with brain tumors already known or revealed on pretreatment MRI. 13. Currently pregnant (as determined by history and serum Human Chorionic Gonadotropin) or lactating.\n\n14\\. Chemical abuse or dependence within the previous six months",{"count":286,"type":20},[85],"The goal of this clinical trial is to evaluate the safety and initial effectiveness of MR-guided focused ultrasound (MRgFUS) bilateral capsulotomy in patients with treatment-resistant bipolar depression (TRBD).",[386,27],"Treatment-Resistant Depression",[388,389,390,391,392,393,394],"TRBD","FUS","MRgFUS","capsulotomy","Focused Ultrasound","MR-guided Focused Ultrasound","refractory Bipolar Depression","2025-08-05",{"date":397,"type":32},"2025-08-06",{"date":399,"type":32},"2025-06-25",{"date":401,"type":20},"2028-07-16",{"name":403,"class":39},"Sunnybrook Health Sciences Centre",{"id":405,"slug":406,"hasResults":11,"nctId":407,"briefTitle":408,"officialTitle":409,"acronym":4,"eligibilityCriteria":410,"healthyVolunteers":11,"sex":15,"minAge":411,"maxAge":412,"enrollmentInfo":413,"targetDuration":4,"studyType":21,"phases":415,"briefSummary":416,"conditions":417,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":418,"lastUpdatePostDateStruct":419,"startDateStruct":421,"completionDateStruct":423,"leadSponsor":425,"locationsCount":427},"100544751","phase-3-multicenter-study-of-lumateperone-for-the-treatment-of-bipolar-depression-in-pediatric-patients-100544751","NCT06372964","Multicenter Study of Lumateperone for the Treatment of Bipolar Depression in Pediatric Patients","A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Lumateperone for the Treatment of Major Depressive Episodes (MDEs) Associated With Bipolar I or Bipolar II Disorder (Bipolar Depression) in Pediatric Patients Aged 10 to 17 Years","Inclusion Criteria:\n\n1. Able to provide consent as follows:\n\n   * The Legally Authorized Representative (LAR) must provide written, informed consent.\n   * The patient must provide written assent;\n2. Male or female patients 10 to 17 years of age, inclusive;\n3. Have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Text Revision (DSM-5-TR) primary diagnosis of bipolar I or bipolar II disorder with a current MDE without psychosis as confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL);\n4. Subject has a lifetime history of at least one manic or hypomanic episode.\n5. Subject's current major depressive episode is ≥ 4 weeks and less than 12 months in duration;\n6. CDRS-R total score ≥ 45 with ≥ 5 on Item 11 (depressed feelings) at Screening and Baseline;\n7. Young Mania Rating Scale (YMRS) score ≤ 15 (with YMRS Item 1 \\[elevated mood\\] score ≤ 2) at Screening and Baseline.\n\nExclusion Criteria:\n\n1. Has a primary psychiatric diagnosis other than bipolar I or bipolar II disorder. Exception includes:\n\n   * Attention deficit hyperactivity disorder (ADHD). If a subject is taking medications for ADHD, they must have been on a stable treatment regimen of these medication(s) for 30 days prior to screening and the treatment regimen is expected to remain stable throughout the study.\n2. Intellectual disability based on Investigator opinion and DSM-5 criteria\n3. Patient has been hospitalized for a bipolar manic episode within the 30 days prior to randomization;\n4. Demonstrates a ≥ 25% decrease (improvement) in the CDRS-R total score between Screening and Baseline visits, or the CDRS-R is below 45 at Baseline;\n5. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during his\u002Fher participation in the study or\n\n   1. At Screening, the patient scores \"yes\" on Suicidal Ideation Items 3, 4, or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening or, at Baseline, the patient scores \"yes\" on Suicidal Ideation Items 3, 4, or 5 since the Screening Visit;\n   2. At Screening, the patient has had 1 or more suicidal attempts within the 2 years prior to Screening; or\n   3. At Screening or Baseline, scores \\> 3 on Item 13 (suicidal ideation) on the CDRS-R; or\n   4. The patient is considered to be an imminent danger to him\u002Fherself or others.","10 Years","17 Years",{"count":414,"type":20},384,[53],"This is a multicenter, randomized, double-blind, placebo-controlled study in pediatric patients who are experiencing major depressive episodes (MDEs) associated with a primary diagnosis of bipolar I or bipolar II disorder as confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5).",[27],"2025-07-03",{"date":420,"type":32},"2025-07-08",{"date":422,"type":32},"2024-05-13",{"date":424,"type":20},"2027-05",{"name":426,"class":72},"Intra-Cellular Therapies, Inc.",59,{"id":429,"slug":430,"hasResults":11,"nctId":431,"briefTitle":432,"officialTitle":432,"acronym":4,"eligibilityCriteria":433,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":104,"enrollmentInfo":434,"targetDuration":4,"studyType":21,"phases":435,"briefSummary":438,"conditions":439,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":92,"lastUpdatePostDateStruct":440,"startDateStruct":442,"completionDateStruct":444,"leadSponsor":446,"locationsCount":40},"100522908","phase-1-effects-of-acute-exercise-and-ibuprofen-on-symptoms-immunity-and-neural-circuits-in-bipolar-depression-100522908","NCT06088732","Effects of Acute Exercise and Ibuprofen on Symptoms, Immunity, and Neural Circuits in Bipolar Depression","Inclusion Criteria:\n\n1. Provision of signed and dated informed consent form\n2. Has an established residence and phone\n3. Agrees to and is eligible for behavioral testing, magnetic resonance imaging, and blood draws.\n4. Stated willingness to comply with all study procedures and lifestyle considerations (see Section 5.3, Lifestyle Considerations) and availability for the duration of the study\n5. Males and females; Age 18-55 years\n6. DSM-V diagnosis of bipolar disorder\n7. Has a current major depressive episode\n8. Depression at enrollment of sufficient severity to score \\> 11 on the QIDS\n9. Be stably medicated for at least 4 weeks (a non-medicated subject may be included in the study if judged to be appropriate in the medical\u002Fpsychiatric opinion of the investigator)\n10. BMI between 18.5 and 35\n\nExclusion Criteria:\n\n1. Diagnosis of any other major psychiatric disorder such as schizoaffective disorder, schizophrenia, or current psychotic depression\n2. A history of bipolar disorder with rapid cycling\n3. Concurrent manic symptoms of sufficient severity to pose a substantial risk of the development of a manic episode (\\>19 on the YMRS)\n4. Current drug or alcohol or substance use disorder moderate or severe, except nicotine (within 6 months for severe use disorder; 2 months for moderate use disorder)\n5. Volunteers currently receiving more than 4 mood-relevant psychotropic medications in a daily regimen (since this may signify a more brittle or complex clinical state)\n6. Taking any of the following medications: medications with significant interactions with ibuprofen; immune-modulating medications (e.g. oral steroids); regular use of NSAIDs (\\> 3 times per week)\n7. Current or prior cardiac disease, cardiac arrhythmia (e.g. supraventricular tachycardia, atrial fibrillation, ventricular fibrillation), or history of cardiac ablation therapy\n8. Unstable medical condition, including significant respiratory disease (e.g., asthma, reactive airway disease (i.e., exercise induced asthma), or chronic obstructive pulmonary disease (COPD)), liver disease, hypothyroidism (i.e., condition not adequately stabilized for 3 months), or other conditions likely to require hospitalization or with a life expectancy of \\\u003C 6 months (e.g., cancer).\n9. History of claustrophobia that would prevent participation in imaging scans\n10. Actively suicidal, as defined by expressive ideation with a plan and intent for suicide or developing suicidal ideation that requires immediate medical or treatment intervention or a suicide attempt within the previous six months\n11. Participants who endorse a history of moderate to severe traumatic brain injury (\\>30 min. loss of consciousness or \\>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits\n12. Inadequate understanding of English\n13. Currently pregnant or breast-feeding; fecund women not using adequate contraceptive methods; plan to become pregnant within 12 months\n14. Metal in the body (e.g. history of working as a sheet metal worker) or pacemaker which is a contra-indication to magnetic resonance imaging\n15. Has epilepsy, a neuromuscular disorder, or tardive dyskinesia\n16. Has a chronic infectious illness\n17. Requires immediate hospitalization for psychiatric disorder\n18. Requires medications for a general medical condition that contraindicate any study medication\n19. Receiving or have received during the index episode vagus nerve stimulation, electroconvulsive therapy, transcranial magnetic stimulation, or other somatic treatments\n20. Allergy to, or other medical contraindication to ibuprofen (e.g. stomach ulcers)\n21. Symptoms of myalgic encephalomyelitis\u002Fchronic fatigue syndrome or \"long-COVID\".\n22. Current use of medications or dietary supplements for weight or appetite control, whether prescribed or not\n23. Ulcerative colitis, Crohn's disease or other autoimmune disorder (except treated hypothyroidism)\n24. Activity restrictions that limit the subject's ability to engage in intense physical activity\n25. Use of beta-blockers, calcium channel inhibitors, or other heart-modulating medications (e.g., amiodarone)\n26. Clinically significant abnormality on EKG\n27. Hypertension, hepatitis, renal dysfunction, and\u002For anemia of sufficient severity to pose a risk to the participant\n28. Moderate or heavy smoker based on Fagerstrom\n29. Resting heart rate \\>100 beats per minute, systolic blood pressure \\> 160 mmHg, diastolic blood pressure \\> 100 mmHg\n30. Clinically significant screening laboratory abnormalities not covered above\n31. Any reason not listed herein that would make participation in the study hazardous",{"count":157,"type":20},[436,437],"PHASE1","PHASE2","This is a 2x2, within-subjects, cross-over trial to test the anti-depressant effects of acute exercise in 20 participants with bipolar depression. Participants will complete four experimental sessions, two with an exercise challenge and two with a resting control condition in a counterbalanced order. Participants will receive either 800mg of ibuprofen or placebo before exercise or rest in order to test whether blocking the inflammatory response to exercise interferes with the neural and psychological effects of exercise.",[27],{"date":441,"type":32},"2025-05-23",{"date":443,"type":32},"2024-03-12",{"date":445,"type":20},"2026-12-31",{"name":447,"class":39},"Laureate Institute for Brain Research, Inc.",{"id":449,"slug":450,"hasResults":11,"nctId":451,"briefTitle":452,"officialTitle":453,"acronym":4,"eligibilityCriteria":454,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":455,"targetDuration":4,"studyType":21,"phases":456,"briefSummary":457,"conditions":458,"keywords":459,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":463,"lastUpdatePostDateStruct":464,"startDateStruct":466,"completionDateStruct":468,"leadSponsor":470,"locationsCount":40},"100517851","behavioural-activation-for-bipolar-depression-100517851","NCT06022913","Behavioural Activation for Bipolar Depression","Adjunctive Behavioural Activation for Bipolar Depression: A Case Series (BA-BD)","Inclusion Criteria:\n\n* scoring in the clinical range on a self-report measure of depression severity (the PHQ-9) meeting diagnostic criteria for depression based on a diagnosis on Diagnostic Interview for Anxiety, Mood, and OCD and Related Neuropsychiatric Disorders (DIAMOND)\n\nmeeting diagnostic criteria for Bipolar I or II Disorder DIAMOND) participants will require a working knowledge of written and spoken Icelandic, sufficient to make use of therapy and complete research assessments without the need for a translator.\n\nExclusion Criteria:\n\n* current\u002Fpast learning disability, organic brain change, substance dependence (drugs and alcohol) that would compromise the ability to use therapy\n* current marked risk to self (i.e., self-harm or suicide) that we deem could not be appropriately managed in the Bipolar outpatient clinic at Landspitali.\n* currently lacking the capacity to give informed consent\n* currently receiving other psychosocial therapy for depression or bipolar disorder\n* presence of another area of difficulty that the therapist and client believe should be the primary focus of intervention (for example, Post-Traumatic Stress Disorder, psychosis)",{"count":286,"type":20},[85],"Bipolar disorder (BD) affects between 1-3% of the world's population. People with BD experience episodes of mania or hypomania and in most cases, they experience periods of depression which can cause difficulties in daily life. Psychological therapies for people experiencing depression without mania or hypomania are widely available, but there is little research into how effective these therapies are for people with BD. Behavioral activation therapy (BA) is based on behavioral theory and has been proven to be an effective treatment for unipolar depression. It helps people re-establish healthier activity patterns and sleep regulation, especially in BD for mood stabilization. BA is theoretically and clinically well matched to the treatment of bipolar depression, but there is still very little research into offering BA to people with BD.\n\nThe first aim of the current research is to implement BA for people with depression in Bipolar Disorder and study if it is feasible for this patient group. The second aim is to do a pilot study on the effectiveness of the treatment for this patient group. The research will be implemented with people seeking treatment at the specialized service for bipolar disorder at Landspítali University Hospital in Iceland. The participants will receive treatment as usual and the BA will be adjunctive.\n\nAt least ten people, that are currently experiencing Bipolar Depression and are willing to take part, will receive up to 20 individual therapy sessions of BA that have been adapted for Bipolar Depression (BA-BD), and will complete regular questionnaires and interviews.\n\nThe study will be a replication study to validate the previous study's findings by Kim, W. et al., 2022 in another setting.",[27],[460,56,461,462],"Bipolar depression","Behavioural Activation","Depression","2025-04-11",{"date":465,"type":32},"2025-04-16",{"date":467,"type":32},"2023-11-22",{"date":469,"type":20},"2025-12-31",{"name":471,"class":39},"Reykjavik University",{"id":473,"slug":474,"hasResults":11,"nctId":475,"briefTitle":476,"officialTitle":477,"acronym":478,"eligibilityCriteria":479,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":480,"targetDuration":4,"studyType":21,"phases":481,"briefSummary":482,"conditions":483,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":484,"lastUpdatePostDateStruct":485,"startDateStruct":487,"completionDateStruct":489,"leadSponsor":491,"locationsCount":40},"100462030","phase-2-osu6162-in-bipolar-depression-obid-100462030","NCT05296356","OSU6162 in Bipolar Depression (OBID)","OSU6162 in Bipolar Depression: An Open-label, Flexible Dose Study (OBID)","OBID","Inclusion Criteria:\n\n1. Signed informed consent\n2. Voluntary admission to the psychiatric ward prior or directly after the screening point\n3. Age: 18-65 on the day of screening\n4. Meeting DSM-5 criteria for a depressive episode in Bipolar Disorder type I or type II, as confirmed by the Mini International Neuropsychiatric Interview (MINI)\n5. Displaying a sum score of ≥10 on the Bech 6-item subscale of the Hamilton Depression rating Scale.\n6. Treatment with a stable dose of a mood stabilizer since at least 4 weeks before screening: lithium s-conc\\> 0,45 mmol\u002FL; \\>lamotrigine dose 100 mg\u002Fd; \\>valproate dose \\> 900 mg\u002Fd, \\>carbamazepine concentration \\>20 mmol\u002FL\n7. In female patients of childbearing potential: negative result of a pregnancy test and a method of contraception with a failure rate of less than 1 %. Women of childbearing potential must, for inclusion, use a highly efficient method of contraception, i.e. a method with a failure rate of less than 1% (e.g. sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomy in partner).\n8. Male patients must agree to use condoms during the study and for 2 weeks after the end of the study\u002Flast dose of IMP, unless their partner is using a highly efficient method of contraception, as described above.\n\nExclusion Criteria:\n\n1. Ongoing compulsory care.\n2. Subject is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property.\n3. Previously diagnosed or meeting MINI criteria at interview for obsessive-compulsive disorder or post-traumatic stress disorder.\n4. A previous diagnosis of a personality disorder, autism, ADHD, or intellectual disability.\n5. A history of substance\u002Falcohol abuse within 2 years prior to screening.\n6. Any other previously diagnosed or suspected CNS disorder that according to the investigator renders the patient unsuitable for participation in the trial (such as dementia, brain injury, and epilepsy).\n7. Young Mania Rating Scale (YMRS) total score of \\>12 at screening or at any time during the trial.\n8. Any somatic illness that according to the investigator renders the patient unsuitable for participation in the trial.\n9. Any signs or symptoms of somatic illness resulting from assessment of vital signs, physical examination, clinical laboratory tests or 12- lead ECG that according to the investigator renders the patient unsuitable for participation for safety reasons, including a QTc-time on ECG exceeding 450 ms in men and 460 ms in women.\n10. Any factor that according to the investigator renders it unlikely that the patient will comply with the instructions regarding treatment, visits etc.\n11. Any change in medication (including dosage) of an antidepressant drug or a mood stabiliser within 4 weeks prior to screening or at any time during the trial.\n12. Ongoing treatment with potent cytochrome P450 enzyme inhibitors (e.g., bupropion, fluvoxamin, ketoconazol, itraconazole, telitromycin, clarithromycin, protease inhibitors, quinidine, and terbinafine).\n13. Ongoing treatment with drugs displaying a narrow therapeutic window - with the exception of lithium - where either reduced or increased serum levels are potentially harmful (including but not limited to warfarin, other anticoagulants, digoxin. other antiarrythmics, anticonvulsants when prescribed for treatment of epilepsy but not when prescribed for bipolar disorder, cyclosporine, and immunosuppressants).\n14. Ongoing treatment with drugs with dopaminergic synapses as primary site of action (e.g., antipsychotics, bupropion, central stimulants, and drugs for Parkinson's disease).\n15. No observed beneficial effect of treatment and a symptom severity that by the investigator's assessment would render continued participation unethical.\n16. Previous intake of OSU6162.\n17. Current participation in another clinical trial.\n18. Nursing women.",{"count":5,"type":20},[437],"An explorative, open label, single armed, flexible dose, single center, phase IIa study of 8 weeks, initiated in subjects with bipolar depression. The study will consist of 9 visits and 1 safety visit.\n\nSubjects with a primary diagnosis of bipolar disorder (type 1 or 2) currently in an acute depressive phase (i.e. bipolar depression) and being on stable medication with at least one mood stabilizer.",[27],"2025-03-19",{"date":486,"type":32},"2025-03-21",{"date":488,"type":32},"2021-10-25",{"date":490,"type":20},"2027-05-31",{"name":492,"class":39},"Göteborg University",{"id":494,"slug":495,"hasResults":11,"nctId":496,"briefTitle":497,"officialTitle":498,"acronym":499,"eligibilityCriteria":500,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":501,"targetDuration":4,"studyType":21,"phases":502,"briefSummary":503,"conditions":504,"keywords":505,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":513,"lastUpdatePostDateStruct":514,"startDateStruct":516,"completionDateStruct":518,"leadSponsor":520,"locationsCount":40},"100554971","phase-1-neurobiological-effects-of-psilocybin-in-treatment-resistant-bipolar-depression-100554971","NCT06506019","Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression","Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression: An Emotional-Processing fMRI Pilot Study","Psilo-BD","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 Bipolar II Disorder (BD-II) currently experiencing a Major Depressive Episode (MDE) without psychotic features as diagnosed by a mood disorder specialist and confirmed using the Mini-International Neuropsychiatric Interview (MINI);\n7. Current MDE must be moderate to severe, as determined by the Hamilton Depression Rating Scale (HDRS-17) score greater than 20 with inadequate response to two or more adequate evidence-based treatment trials for bipolar depression, as per the 2018 CANMAT Bipolar Disorder Guidelines. Treatment trials are specific to current MDE rather than lifelong trials;\n8. Ability to take oral medication;\n9. Must be currently taking lamotrigine or planning on starting lamotrigine outside of the trial for the duration of the study, including the 1-month follow-up period, without changes in the medication;\n10. 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;\n11. Individuals who are capable of fathering a child: use of condoms or other methods for the duration of study participation to ensure effective contraception with partner;\n12. Individuals who are willing to taper off current medications for a minimum of 1-month prior to Baseline (V3, Day -1) and whose physician confirms that it is safe for them to do so;\n13. 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 (Visit 1) 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 (Visit 1);\n3. Current symptoms of mania, hypomania or mixed features, as determined by the Young Mania Rating Scale (YMRS) score greater than 12;\n4. History of mania or hypomania in the past 6 months as determined by psychiatric history;\n5. Have a DSM-5 diagnosis of substance use disorder (excluding use of tobacco) within the preceding 12 months;\n6. Have active suicidal ideation as determined by the C-SSRS and\u002For clinical interview Significant suicide risk is defined by suicidal ideation as endorsed by items 4 or 5 of the C-SSRS, OR active suicidality requiring involuntary inpatient treatment or recent suicide attempts within the past 3 months;\n7. Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; psychotic disorder (including but not limited to during previous mood episodes or substance-induced psychosis), bipolar I disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history, the MINI clinical interview, and the International Personality Disorder Examination (IPDE) administered at V1;\n8. Have contraindications to fMRI as determined by the MRI questionnaire;\n9. Have a history of seizures;\n10. Are taking anticonvulsants (with the exception of lamotrigine) or benzodiazepines (lorazepam up to 2mg\u002Fday is acceptable);\n11. History of Steven-Johnson Syndrome (SJS) or suspected SJS as determined by medical history;\n12. 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;\n13. 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;\n14. 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;\n15. History of allergy to lamotrigine or psilocybin, or inability to tolerate lamotrigine during trial.\n16. Participants who are unwilling or unable to take their lamotrigine (as prescribed by their most responsible physician) throughout the duration of the study, including up to the four-week post-dose visit, will be excluded from the study.\n17. Use of classic psychedelic drugs (e.g., psilocybin, DMT, LSD, mescaline) within the previous 6 months of singing the informed consent form;\n18. Use of intravenous or oral steroids within one week of the administration of psilocybin;\n19. Use of S-Adenosyl methionine (SAM-e), 5-Hydroxytryptophan (5-HTP), L-tryptophan, and St. John's Wort one week prior to administration of psilocybin; and\n20. 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":263,"type":20},[436],"This study is an open-label, single-arm, proof-of-concept study, wherein treatment resistant bipolar depression (TRBD) participants will receive one 25 mg dose of oral psilocybin accompanied by preparatory, monitoring, and integration psychotherapy sessions (psilocybin-assisted psychotherapy, or PAP). Using fMRI (functional magnetic resonance imaging), the findings of this study will provide data on the neurobiological mechanism of psilocybin in TRBD.\n\nThe primary objective is to understand the dynamic role of amygdala activity by evaluating the neurobiological effects of a single psychedelic dose (25 mg) of oral psilocybin in individuals with a moderate to severe major depressive episode and a primary diagnosis of Bipolar II Disorder, with 2 or more failed treatment trials (i.e., treatment resistant bipolar depression \\[TRBD\\]). Neurobiological effects will be determined by evaluating the association between post-treatment right amygdala activity during the facial affect task (determined by fMRI one day after the psilocybin dose) and antidepressant effects (determined by changes in the Montgomery-Åsberg Depression Rating Scale \\[MADRS\\] scores over time, during the one-week period post-psilocybin dose). This is a single-arm, open-label clinical trial wherein all participants will receive the same study intervention.\n\nHypothesis: Increased right amygdala activity on fMRI with emotional stimuli one day after psilocybin treatment will be associated with greater antidepressant effects in the one-week period post-treatment in individuals with TRBD.",[27],[462,56,27,386,506,507,508,509,510,511,512],"Psilocybin","Psychedelics","Psychotherapy","fMRI","Bipolar Disorder II","Bipolar Disorder 2","Psilocybin-Assisted Psychotherapy","2024-10-16",{"date":515,"type":32},"2024-10-18",{"date":517,"type":32},"2024-10-09",{"date":519,"type":20},"2027-01-01",{"name":521,"class":39},"University Health Network, Toronto",{"id":523,"slug":524,"hasResults":11,"nctId":525,"briefTitle":526,"officialTitle":527,"acronym":4,"eligibilityCriteria":528,"healthyVolunteers":529,"sex":15,"minAge":16,"maxAge":530,"enrollmentInfo":531,"targetDuration":4,"studyType":21,"phases":533,"briefSummary":534,"conditions":535,"keywords":536,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":544,"lastUpdatePostDateStruct":545,"startDateStruct":547,"completionDateStruct":549,"leadSponsor":551,"locationsCount":553},"100406210","phase-3-brexpiprazole-treatment-for-bipolar-i-depression-100406210","NCT04569448","Brexpiprazole Treatment for Bipolar I Depression","Low-Dose Adjunctive Brexpiprazole in the Treatment of Bipolar I Depression: An Open-Label Study","Patient Inclusion Criteria:\n\n* Age: 18-75\n* Male or female\n* Bipolar Disorder type I or type II\n* Current treatment-resistant depressive episode (with MADRS \\>\u002F= 24 and item 2 (reported sadness) \\>\u002F= 3) for a minimum of 2 weeks but \\\u003C\u002F= 52 weeks at screening visit and baseline visit\n* Patients must have failed at least one other treatment for the current depressive episode\n* If female and of childbearing potential, is using an adequate method of contraception. Adequate methods of contraception include abstinence; oral contraceptive pill or surgically implanted device; intra-uterine device; condom plus spermicidal foam or jelly; or tubal ligation\n* Is treated with a mood stabilizer (lithium and\u002For valproate and\u002For lamotrigine and\u002For quetiapine \\\u003C\u002F= 100mg\u002Fday)\n* The following laboratory values are within normal limits at Screening: CBC with differential; ferritin; extended electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphate); thyroid function test(s); kidney function tests; hemoglobin A1c; lipid profile; prolactin\n* Normal EKG at Screening\n* Patient is able to give his(her) consent\n\nPatient Exclusion Criteria:\n\n* Is at high risk of suicide as defined by a score of \\>\u002F= 3 to item 10 of MADRS and\u002For in the clinical opinion of the investigator\n* Hypo(mania) episode with YMRS \\>\u002F= 8\n* Psychotic symptoms as defined by a score of \\>\u002F= 4 to item 8 (content) of YMRS and\u002For in the opinion of the investigator\n* Is treated with fluoxetine OR carbamazepine\n* Is treated with risperidone OR olanzapine OR quetiapine \\> 100mg\u002Fday OR ziprazidone OR any other antipsychotic\n* Is pregnant or lactating or absence of contraceptive treatment\n* Drug abuse or dependence as per DSM-V (MINI)\n* Unstable medical condition\n* Other unstable and\u002For untreated psychiatric condition, organic brain disorder, unstable and\u002For untreated medical condition such as hypothyroidism, hyperthyroidism, diabetes, cardiac condition, hypertension\n* Deficit in vitamin B12 or folate\n* Rapid cycling (more than 4 mood episodes per year)\n* Active or history of difficulty to swallow\n* Seizures not currently controlled with medications\n* Orthostatic hypotension defined as a drop in systolic blood pressure of at least 20 mmHg or of diastolic BP of at least 10 mmHg within 3 minutes of standing\n* A history of clinically significant cardiovascular disorders and cardiac arrhythmias\n* A low white blood cell count\n* Known eye disease\n* Involuntary, irregular muscle movements, especially in the face\n* Known hypersensitivity to Brexpiprazole and any components of its formulation\n* Known lactose intolerance or have hereditary galactose intolerance or glucose-galactose malabsorption, because Brexpiprazole and placebo tablets contain lactose (a disaccharide of glucose and galactose)\n* Active inflammatory disease including lupus, colitis, Crohn's disease, psoriasis, irritable bowel syndrome (IBS)\n* Mild or major neurocognitive disorder\n* Previous history of sensitivity\u002Flow tolerance to medications metabolized by CYP 2D6 inhibitors, or CYP 3A4 inducers\n\nControl Inclusion Criteria:\n\n* Age: 18-75\n* Male or female\n* No current or past history of any psychiatric disorder\n* Patients must have failed at least one other treatment for the current depressive episode\n* If female and of childbearing potential, is using an adequate method of contraception. Adequate methods of contraception include abstinence; oral contraceptive pill or surgically implanted device; intra-uterine device; condom plus spermicidal foam or jelly; or tubal ligation\n* The following laboratory values are within normal limits at Screening: CBC with differential; ferritin; extended electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphate); thyroid function test(s); kidney function tests; hemoglobin A1c; lipid profile; prolactin\n* Normal EKG at Screening\n* Patient is able to give his(her) consent\n\nControl Exclusion Criteria:\n\n* Alcohol or drug abuse\n* Deficit in vitamin B12 or folate\n* Seizures not currently controlled with medications\n* History of clinically significant cardiovascular disorders and cardiac arrhythmias\n* Mild or major neurocognitive disorder\n\nPatient\u002FControl Exclusion Criteria for MRI:\n\n* Pacemaker\n* Heart\u002Fvascular clip\n* Metal prosthesis\n* Metal fragments in body\n* Transdermal patch\n* Aneurysm clip\n* Prosthetic valve\n* Claustrophobia\n* Pregnant",true,"75 Years",{"count":532,"type":20},58,[53],"Bipolar disorder (BD) is a frequent and lifelong recurrent mood disorder with treatment-resistant depressive episodes. Importantly, depressive symptoms and cognitive decline are major determinants of functionality and quality of life in this clinical population. There is robust evidence that individuals with BD have neurocognitive deficits (especially in memory and executive functioning domains) compared to the healthy population. These deficits are present in all mood states and can greatly affect patients' functional capacity, often more so than mood symptoms themselves. Many pharmacological treatments for BD adversely affect cognition, and those that are beneficial can be difficult to use. There is thus a pressing need to identify a safe, easy-to-use medication that can target both cognitive deficits and depressive symptoms in BD. It is expected that Brexpiprazole adjunctive treatment will be efficacious in treating BD type I and type II depression by improving mood symptoms, as well as cognitive capacity and global functioning, and that such changes will be accompanied by concurrent alterations in associated brain structures.",[27],[537,538,539,540,541,542,543],"Brexpiprazole","Treatment-resistant depression","Cognition","Functioning","Rest-Activity rhythm","Hippocampus","CRP","2024-08-05",{"date":546,"type":32},"2024-08-07",{"date":548,"type":32},"2021-05-10",{"date":550,"type":20},"2025-02",{"name":552,"class":39},"Douglas Mental Health University Institute",3,{"id":555,"slug":556,"hasResults":11,"nctId":557,"briefTitle":558,"officialTitle":559,"acronym":4,"eligibilityCriteria":560,"healthyVolunteers":529,"sex":15,"minAge":331,"maxAge":4,"enrollmentInfo":561,"targetDuration":4,"studyType":21,"phases":562,"briefSummary":563,"conditions":564,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":565,"lastUpdatePostDateStruct":566,"startDateStruct":568,"completionDateStruct":570,"leadSponsor":572,"locationsCount":40},"100548164","phase-4-non-invasive-bci-and-application-verification-for-depressed-people-100548164","NCT06417437","Non-invasive BCI and Application Verification for Depressed People","New Non-invasive Brain-computer Interface: Theory, Technology and Application Demonstration - Studies on and Intervention for Depressed People Based on Non-invasive BCI and Application Verification","Inclusion Criteria:\n\n* ≥ 12 years old, male or female, right-handed, Han ethnicity\n* Meets the DSM-5 diagnostic criteria for depression, with HAMD-17 scores greater than 17 and YMRS scores less than 6;\n* Primary school education or above, able to understand the research content, willing to participate in this study and sign an informed consent form\n\nExclusion Criteria:\n\n* Concomitant or previous history of organic brain disease or severe traumatic brain injury, personal or family history of epilepsy;\n* Severe abnormalities in heart, liver, and kidney function;\n* Patients with severe physical illnesses;\n* History of substance dependence or abuse (alcohol, cocaine, drugs, etc.);\n* Patients with mental disorders caused by organic diseases, drug or alcohol induced mental disorders, and other mental disorders;\n* Pregnancy or lactation period;\n* Within six months, physical therapy such as MECT and TMS should be used;\n* Implants of vegetative nerve stimulation;\n* Individuals who have implanted electronic or metal instruments (such as pacemakers, defibrillators, stents, orthopedic plates, etc.) and undergo ventriculoperitoneal shunt surgery;\n* Obvious visual and auditory impairment, unable to cooperate in completing neuropsychological and scale assessments.",{"count":51,"type":20},[23],"Major Depressive Disorder (MDD) is a serious mental illness and public health problem that poses threat to both physical and mental health. According to statistics from WHO, it is estimated that more than 350 million people worldwide suffer from depression, with a prevalence rate of 2.1% in China, which is approximately 30 million people.\n\nAt present, due to the lack of neurobiological markers for screening and diagnosing depression, the identification and diagnosis of MDD are based on the judgment of professional doctors, and the treatment mostly relies on clinical symptoms.\n\nIn terms of treatment, medication remains the main stream for MDD. Although current methods have certain therapeutic effects, patients still suffer from various side effects and poor cognitive function.In current clinical practice, relying purely on symptomatic diagnosis and treatment is difficult to meet the needs of clinical practice, so there is an urgent need to search for neurobiological markers in depression and develop targeted non-invasive intervention technologies.\n\nThis study aims to combine advanced brain imaging technology, digital twin-brain models, multi-source information decoding technology, integrated detection and intervention technology. The target is to create two new types of non-invasive BCI systems that can regulate emotions. One is a intervention BCI system for MDD that is suitable for hospital settings with the purpose of precise physical stimulation, and the other one is an ecological BCI system that regulate emotions and intervene with depression which is suitable for both hospital settings and future family environments.\n\nThis study will collect a comprehensive collection of physiological and biochemical indicators from patients with depression and from healthy control groups, as well as multimodal information such as head surface electroencephalography, MRI, and eye movements under different brain states, to personalize the available BCI information of depression related brain regions, circuits, and networks. The study also tries to explore emotional-interactive games that can intervene with depression and build a game data base that is dedicated to MDD. Other goals include designing and establishing two new types of emotional regulation systems, which are precise external physical stimulation intervention and ecological intervention, constructing a BCI regulation system, and conducting application verification to evaluate the regulation effect.",[462,190,27],"2024-05-12",{"date":567,"type":32},"2024-05-16",{"date":569,"type":32},"2023-07-01",{"date":571,"type":20},"2027-07-31",{"name":573,"class":39},"Shanghai Mental Health Center"]