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.