Actively Recruiting
Randomized Controlled Trial of Early-Intensified Pharmacological Treatment Compared to Treatment as Usual for Schizophrenia, Major Depressive Disorder, and Bipolar Depression After First-Line Treatment Failure
Led by Dr. Inge Winter · Updated on 2026-01-22
1254
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
D
Dr. Inge Winter
Lead Sponsor
U
Universität Münster
Collaborating Sponsor
AI-Summary
What this Trial Is About
Schizophrenia, bipolar depression, and major depressive disorder affect over 10 million people in the European Union and lead to high healthcare and societal costs. Researchers are studying whether using third-line treatments earlier in these disorders can improve symptom response compared to the usual second-line treatments. This trial aims to establish evidence-based criteria for early intensified treatment to reduce ineffective treatment trials, improve patient outcomes, and lower costs. Participants are randomized into two groups within each disorder category: treatment as usual or early-intensified pharmacological treatment. For schizophrenia, usual treatment involves switching to a second-line antipsychotic, while early-intensified treatment switches to clozapine. For major depressive disorder, usual treatment is a second-line antidepressant, whereas early-intensified treatment adds esketamine nasal spray or ketamine infusion. For bipolar depression, usual treatment involves quetiapine plus lithium or valproate acid, and early-intensified treatment involves combinations of antidepressants and mood stabilizers. Treatments are administered according to clinical guidelines, with treatment lasting six weeks. Participants undergo assessments at baseline and after six weeks, including symptom severity measured by PANSS for schizophrenia and MADRS for depression and bipolar disorder. Secondary measures include clinical global impression, anxiety and depression scales, cognitive tests, quality of life, side effects, medication use, treatment discontinuation, remission rates, and suicidal ideation. Safety monitoring follows usual clinical practice, with optional blood samples. The total participation time spans the six-week treatment period, with careful monitoring of symptoms and side effects to evaluate treatment responses.
CONDITIONS
Brief Title
Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 to 70 years (schizophrenia sample), up to 65 years (major depressive disorder sample), no age limit for bipolar depression
- Willing and able to provide written informed consent; legal guardian may cosign
- Female subjects of childbearing potential must use effective contraception during the trial; male subjects using valproate acid must also use contraception
- Diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, major depressive disorder (without psychotic features), or bipolar depression (bipolar I or II currently in depressive episode) confirmed by DSM-5 and MINI v7.0.2
- Experienced treatment failure due to lack of efficacy in the current episode, preferably first-line treatment prescribed for at least 4 weeks within effective dose range
- Intent to change pharmacological treatment with clinician agreement
- Minimum symptom severity threshold met (specific PANSS or MADRS scores) and functional impairment present (SDS score 5 or higher)
You will not qualify if you...
- Pregnant or breastfeeding
- Previous failure on early-intensified pharmacological treatment (e.g., clozapine, esketamine, quetiapine) with treatment duration of at least 4 weeks
- Known intolerance or contraindications to study medications as specified in SmPCs
- Participation in another experimental drug trial within 30 days before visit 1
- Significant disease or disorder that poses risk or affects participation or results
- Active suicidal ideation with intent or plan as assessed by C-SSRS and clinician
- Current severe substance use disorder; nicotine dependency and mild/moderate alcohol or cannabis use disorder allowed
- Institutionalization by judicial or administrative order
- Dependence on sponsor, investigator, or trial site
- For schizophrenia sample: meeting remission criteria or clinically significant abnormal labs or ECG
- For bipolar depression sample: Young Mania Rating Scale score of 12 or higher, history of antidepressant-induced mania or recent rapid cycling, severe liver damage
AI-Screening
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Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 6 weeks
Participants receive either early-intensified pharmacological treatment or treatment as usual for schizophrenia, major depressive disorder, or bipolar depression. The treatment involves medication changes such as switching to clozapine, esketamine nasal spray or ketamine infusions, or various antidepressant and mood stabilizer combinations depending on the diagnosis.
Multiple visits during 6-week treatment period
Trial Site Locations
Total: 1 location
1
Sheba Medical Center
Ramat Gan, Israel
Actively Recruiting
Research Team
I
Inge Winter, Dr.
C
Cynthia Okhuijsen-Pfeifer, Dr.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
6
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