[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Dr. Inge Winter\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":113},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,44,74,96],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100485594","phase-3-intensified-pharmacological-treatment-for-schizophrenia-major-depressive-disorder-and-bipolar-depression-after-a-first-time-treatment-failure-100485594",false,"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).","ALL","18 Years","70 Years",{"count":21,"type":22},1254,"ESTIMATED","INTERVENTIONAL",[25],"PHASE3","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.",[28,29,30],"Schizophrenia and Related Disorders","Major Depressive Disorder","Bipolar Depression","RECRUITING","2026-01-19",{"date":34,"type":35},"2026-01-22","ACTUAL",{"date":37,"type":35},"2025-04-27",{"date":39,"type":22},"2028-06-30",{"name":41,"class":42},"Dr. Inge Winter","OTHER",1,{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":50,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":52,"targetDuration":4,"studyType":23,"phases":54,"briefSummary":56,"conditions":57,"keywords":59,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":66,"lastUpdatePostDateStruct":67,"startDateStruct":69,"completionDateStruct":71,"leadSponsor":72,"locationsCount":73},"100512932","phase-4-the-effect-of-a-six-week-intensified-pharmacological-treatment-for-schizophrenia-compared-to-treatment-as-usual-in-subjects-who-had-a-first-time-treatment-failure-on-their-first-line-treatment-100512932","NCT05958875","The Effect of a Six Week Intensified Pharmacological Treatment for Schizophrenia 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 Schizophrenia Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.","INTENSIFY SZ","Inclusion Criteria:\n\n1. In- or out patients, at least 18 years of age up until 70.\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; section 8.2).\n4. Meeting diagnostic criteria for a primary diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder, 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 level; see below) and subject needs to experience functional impairment.\n\n   * The minimum symptom severity threshold 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   * 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 used clozapine in the past.\n3. Subject has a known intolerance to clozapine or to all TAU medication options.\n4. Meeting any of the contraindications of clozapine or to all TAU medication options, 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. 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 who meet the modified Andreasen criteria for remission.\n11. Subjects that have any clinically significant abnormal values on the local laboratory test (especially ANC\u002FWBC and liver values), electrocardiogram (ECG) or physician examinations.\n12. Subjects dependent on the sponsor, investigator or trial site must be excluded from participation in advance",{"count":53,"type":22},418,[55],"PHASE4","Schizophrenia (SZ) affects approximately 4.5 million people across the European Union (EU) and is associated with annual healthcare and societal costs of 29 billion Euros. The impact on the daily life of patients is huge, ranging from frequent relapses and hospitalisations, the inability to maintain a job or continue scholing, to a low quality of life, impaired cognitive functioning, suicidal ideation and an increase morbidity rate, next to the large burden for carers 1. When diagnosed with schizophrenia or related disorder, patients are commonly prescribed antipsychotics. One-third of the schizophrenia patients are regarded treatment-resistant (TR), meaning that at least two antipsychotic trials have failed. Typically, clozapine is prescribed for TR patients, which is effective for approximately 40% of patients. Clozapine is among the most effective treatments, with the lowest all-cause mortality. Although it is among the most effective antipsychotics, it is generally not used earlier in the illness course due to a small risk of severe neutropenia\u002Fagranulocytosis, which is why patients treated with clozapine are intensely monitored. However, this small risk outweighs the burden of not receiving an effective treatment.\n\nSince clozapine is among the most effective treatments, this leads to the research question whether earlier initiation of third-line treatment ('early intensified' pharmacological treatment; EIPT) would be more beneficial than the current second-line treatments (treatment as usual; TAU). If this is indeed the case, this could lead to the prevention of unnecessary trials of ineffective treatments, hospitalisations, and recommendations for adaptations of worldwide guidelines as well as a reduction of healthcare and societal costs The INTENSIFY-Schizophrenia trial is part of the larger Horizon 2021 project Psych-STRATA, 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, the inestigators 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. The current protocol focuses on the sample of schizophrenia patients.",[28,58],"Early Treatment-Resistance",[60,61,62,63,64,65],"Schizophrenia","Schizoaffective disorder","Schizophreniform disorder","Clozapine","Treatment as usual","Early treatment-Resistance","2025-09-24",{"date":68,"type":35},"2025-09-26",{"date":70,"type":35},"2024-08-01",{"date":39,"type":22},{"name":41,"class":42},13,{"id":75,"slug":76,"hasResults":11,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":80,"eligibilityCriteria":81,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":82,"enrollmentInfo":83,"targetDuration":4,"studyType":23,"phases":84,"briefSummary":85,"conditions":86,"keywords":88,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":66,"lastUpdatePostDateStruct":90,"startDateStruct":91,"completionDateStruct":93,"leadSponsor":94,"locationsCount":95},"100514082","phase-3-the-effect-of-a-six-week-intensified-pharmacological-treatment-for-major-depressive-disorder-compared-to-treatment-as-usual-in-subjects-who-had-a-first-time-treatment-failure-on-their-first-line-treatment-100514082","NCT05973851","The Effect of a Six Week Intensified Pharmacological Treatment for Major Depressive Disorder 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 Sixweek Intensified Pharmacological Treatment for Major Depressive Disorder Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.","INTENSIFY MDD","Inclusion Criteria:\n\n1. In- or outpatients, at least 18 years of age up until 65.\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).\n4. Meeting diagnostic criteria for a primary diagnosis of major depressive disorder (without psychotic features), 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; perferably, 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).\n6. Subject and clinician intend to change pharmacotherapeutic treatment. However, other lines of treatment are allowed as well.\n7. 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 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 used (es)ketamine previously for the treatment of depressive symptoms.\n3. Subject has a known intolerance to (es)ketamine or to all TAU medication.\n4. Meeting any of the contraindications for (es)ketamine, 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.\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. 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.","65 Years",{"count":53,"type":22},[25],"Over 28 million people suffer from current depressive disorder in the European Union. Major depressive disorder (MDD) is one of the most common psychiatric illnesses. The symptoms cause clinically significant distress or impairment in social, occupational, and other important areas of functioning. To treat MDD, there are several antidepressants available and prescribing medication is a process of trial-and-error. Guidelines do not explicitly advise on the order in which antidepressant medication should be prescribed. The choice of antidepressant should be tailored to the patient, while involving the patient in the decision-making process. In general, the choice for the first- and second-line treatment will be a second-generation antidepressant. Recently, esketamine nasal spray (intranasal (IN) administration) was approved for patients with treatment-resistant MDD (TRD). A patient is diagnosed with TRD when having used two antidepressants in sufficient duration and adequate dose without sufficient effect. TRD is associated with a negative impact on quality of life, higher risk for hospitalisations and suicide, comorbidities, poorer social and occupational functioning and a high carer burden. The efficacy of intranasal use of esketamine has been demonstrated in MDD subjects with treatment-resistant symptoms but also in subjects with non-treatment resistant depression, and is approved by the FDA and EMA as a third-line treatment. Besides the registered esketamine nasal spray, which is not available in all countries to all patients because of the high costs, off-label utilization of (es)ketamine infusions (IV) is growing extensively over time to treat TRD. Research conducted so far indicates an unequivocal initial substantial response to (es)ketamine IV in MDD populations, regardless of whether or not patients suffer from treatment resistant MDD. However, until now, there has not been a study investigating this in a sufficiently large population. This may be a unique opportunity to potentially prevent patients progressing into a treatment resistant illness stage. The potential implications of the results of the current study are the prevention of unnecessary trials of ineffective treatments, reducing subject burden substantially, as well as a reduction of healthcare and societal costs.",[29,87],"Treatment Resistant Depression",[29,64,89],"Early treatment-resistance",{"date":68,"type":35},{"date":92,"type":35},"2024-08-31",{"date":39,"type":22},{"name":41,"class":42},12,{"id":97,"slug":98,"hasResults":11,"nctId":99,"briefTitle":100,"officialTitle":101,"acronym":102,"eligibilityCriteria":103,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":104,"targetDuration":4,"studyType":23,"phases":105,"briefSummary":106,"conditions":107,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":66,"lastUpdatePostDateStruct":108,"startDateStruct":109,"completionDateStruct":111,"leadSponsor":112,"locationsCount":73},"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":53,"type":22},[25],"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.",[30],{"date":68,"type":35},{"date":110,"type":35},"2025-02-11",{"date":39,"type":22},{"name":41,"class":42},""]