SwapIII: Clarifying the Role of D2 Receptor Occupancy in Psychosis and Movement Disorders

Objective We investigated the relationship between changes in estimated dopamine D2 receptor occupancy (D2RO), movement disorders, and psychotic symptoms in a sample of 111 long-term inpatients with schizophrenia. Methods Data were derived from a large 9-month randomized open trial in which patients receiving antipsychotic polypharmacy were randomly assigned to either maintain treatment or switch to antipsychotic monotherapy via a structured tapering protocol. Changes in D2RO were estimated non-invasively using a validated dose-occupancy model for antipsychotics based on Michaelis-Menten kinetics. Associations with movement disorders and psychotic symptoms were estimated using repeated measures correlations assessing intra-individual change. Results Reductions in D2RO during switching to antipsychotic monotherapy were associated with decreased severity of movement disorders and psychotic symptomatology. Conclusions These findings suggest that dose optimization should be prioritized over escalation or polypharmacy. Future research should validate D2RO estimates and explore their potential use in guiding personalized treatment.