DREAMSPHEN: a randomised controlled study comparing dose reduction of antipsychotics vs maintenance treatment in schizophrenia spectrum disorder after stratification based on patients’ psychotic phenotype – study protocol of a personalised medicine approach

Abstract

Introduction The DREAMSPHEN study (Dose REduction of Antipsychotics vs. Maintenance treatment in schizophrenia after Stratification based on psychotic PHENotype) aims to compare the benefits and risks of a hyperbolic tapering method for antipsychotics to the maintenance of antipsychotics in a sample of clinically stabilised patients with schizophrenia spectrum disorder.

Methods and analysis A sample of 288 patients will be recruited from 12 centres in France. Inclusion criteria are: diagnosis of schizophrenia spectrum disorder (according to the 5th version of the Diagnostic and Statistical Manual of mental disorders, DSM-5), minimum of 3 months remission of psychotic symptoms and in treatment with antipsychotic medication (except clozapine and long-acting antipsychotic injection). First, the psychotic phenotype of the patients (cycloid psychosis vs other psychotic phenotype) will be assessed. Then, patients will be randomised either to the maintenance of treatment (MT) or to the antipsychotics dose reduction (DR) arm. DR will follow a hyperbolic schema according to Horowitz protocol. Patients will be assessed at baseline, and every 2 months until 24 months follow-up regarding social functioning, psychotic and negative symptoms, side effects of antipsychotic medication, cognitive functioning, patient satisfaction, substance and alcohol use, and quality of life. The primary outcome will be a good social functioning after 24 months defined as a score at the Personal and Social Performance Scale >70. Secondary outcome measures will include: psychotic and negative symptoms, hospitalisation for psychotic episode, antipsychotic dose, antipsychotic side effects, withdrawal symptoms, cognitive functioning, patient’s well-being and quality of life. Safety measures will include death, admissions to psychiatric hospital, psychotic relapses and severe self-harm.

Ethics and dissemination The DREAMSPHEN trial aims to better identify patients with psychotic disorders who are most likely to benefit from antipsychotic tapering with an aim to inform future clinical treatment guidelines for antipsychotic treatment. DREAMSPHEN V2.0 of the 14 May 2025 has received ethical approval from Comité de protection des personnes Ile de France IV (N° 2023-509558-80-00) on 17 July 2025.