Early Use of Third-Line Drug Treatments for Schizophrenia, Major Depressive Disorder, and Bipolar Depression After First Treatment Fails

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.

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