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.
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.
⁃ 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).