Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure

• Status: Not yet recruiting
• Trial end date: 2026-06-30
• Target enrollment: 0
• Participant gender: All

Summary

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) would be more efficacious than the current second-line treatments (treatment as usual) 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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dr. Inge Winter
• Collaborator: Westfälische Wilhelms-Universität Münster
• Treatments: Antidepressive Agents; Antipsychotic Agents; Citalopram; Clozapine; Duloxetine Hydrochloride; Esketamine; Lamotrigine; Quetiapine Fumarate; Sertraline; Valproic Acid; Venlafaxine Hydrochloride

Criteria

Inclusion Criteria:

1. In- or out patients, at least 18 years of age up until 70.

2. Being willing and able to provide written informed consent. If unable, having a legal guardian to provide written informed consent is allowed (participant's opinion will also be considered in these cases).

3. Female participants 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).

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 currently experiences his/her first treatment failure due to lack of efficacy; this treatment is a first-line pharmacotherapeutic agent for the primary DSM-5 diagnosis, and was prescribed for at least 4 weeks within the dose range as specified in the Summary of Product Characteristics (SmPCs).

6. Subject has failed (CGI-I ≥3) on current psychopharmacological treatment of current episode of SZ/MDD/BD.

7. Patient and clinician intend to change pharmacotherapeutic treatment.

8. 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 Positive and Negative Syndrome Scale (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. Patient has failed previously on the early-intesified study medication (i.e. schizophrenia: clozapine; major depressive disorder: esketamine intranasal) or the treatment as usual treatment for bipolar depression (quetiapine) due to inefficacy. The medication was tried in sufficient duration (≥ 4 weeks within an efficacious dose range according to the SmPC).

3. Patient has a known intolerance to clozapine (schizophrenia only), esketamine intranasal (major depressive disorder only) or quetiapine (bipolar depressiononly).

4. Meeting any of the contraindications of clozapine (schizophrenia only), esketamine intranasal (major depressive disorder only) or quetiapine (bipolar depression only), as specified within the applicable SmPC.

5. Subjects cannot meet criteria for current drugs dependency. This is to be confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2 ). Alcohol and nicotine dependency is allowed.

6. 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.

7. Subject currently uses more than the allowed concomitant medication and needs to stay on this medication during the study.

8. Subject experiences any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

9. Current active suicidal ideation within the last 2 weeks, defined as a score of 1 or higher on the Calgary Depression Scale for Schizophrenia question 8, followed by an assessment by the treating clinician who determines it is not safe for the patient to participate in the study.

10. Schizophrenia subjects cannot meet the modified Andreasen criteria for remission.

11. For the bipolar depression sample only: a score of 8 or higher on the Young Mania Rating Scale (YMRS) in order to exclude mixed subjects with predominant manic symptoms.