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.

Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure (NCT05603104) is a Phase 3 interventional studying Schizophrenia and Related Disorders and Major Depressive Disorder, sponsored by Dr. Inge Winter. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Schizophrenia and Related Disorders, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

A target enrollment of 1,254 participants makes this a sizable late-stage trial. Studies in this range typically have enough power to detect clinically meaningful differences from a comparator and to characterize less-common side effects.

Who May Be Eligible (Plain English)

Who May Qualify: 1\. 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.. Being willing and able to provide written willing to sign a consent form. Having a legal guardian to cosign is allowed. willing to sign a consent form will be signed at visit 1, before any study procedure. 3\. 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. 4\. 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). 5\. 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. 6\. 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. - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1\. 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.. 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. 3\. 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. 4\. 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). 5\. 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. 6\. 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. * 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. * The minimum symptom severity threshold for MDD is a score of ≥ 20 on the Montgomery Åsberg Depression Rating Scale (MADRS) * The minimum symptom severity threshold for BD is a score of ≥20 on the Montgomery Åsberg Depression Rating Scale (MADRS) * 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). Exclusion criteria: 1. Being pregnant or breastfeeding. 2. Subject has failed previously on the EIPT study medication (i.e. SZ: clozapine; MDD: esketamine intranasal/(es)ketamine IV) Treatment duration as ≥ 4 weeks within an efficacious dose range according to the SmPC. 3. Subject has a known intolerance to clozapine (SZ only), esketamine intranasal/ (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). 4. Meeting any of the contraindications of clozapine (SZ only), esketamine intranasal/ (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. 5. 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. 6. 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. 7. 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 8. 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/or cannabis use disorder (as defined by MINI v7.0.2). Severe alcohol and/or cannabis use disorder are not allowed. 9. Subjects have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities. 10. Subjects dependent on the sponsor, investigator or trial site must be excluded from participation in advance. 11. For the SZ sample only: schizophrenia subjects cannot meet the modified Andreasen criteria for remission. 12. For the SZ sample only: Subjects that have any clinically significant abnormal values on the local laboratory test (especially ANC/WBC and liver values), electrocardiogram (ECG) or physician examinations. 13. 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. 14. 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). 15. For the BD study sample only: Subjects with pre-existing severe liver damage (as tested within the local laboratory test at visit 1).

See arm description

DRUG

Bupropion

See arm description

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Sheba Medical Center

Ramat Gan, Israel

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05603104), the sponsor (Dr. Inge Winter), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05603104 clinical trial studying?

Who can participate in NCT05603104?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05603104?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05603104. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05603104. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.