Simulated long‐term outcomes of early use of long‐acting injectable antipsychotics in early schizophrenia

Aim Duration of untreated psychosis in early schizophrenia impacts long‐term outcomes. Because long‐acting injectable (LAI) antipsychotic drugs improve adherence in early‐stage patients, they could reduce additional time in uncontrolled psychosis (TUP) during the critical period of the illness. However, the long‐term benefit of early LAI use over oral formulations has not been quantified. This study explores the potential magnitude of the benefit with a simulation approach. Methods A microsimulation models the effects of 11 treatment pathways reflecting alternative decisions on whether and when LAI agents are used during a “calibration phase” that starts at treatment entry and lasts until the end of the 3‐year critical period. Treatment failure prolongs time in psychosis. Long‐term outcomes are predicted over the ensuing 7‐year period as a function of TUP. Results An “early LAI” pathway where LAI treatment follows the second oral treatment failure is compared to an oral‐only pathway. Under these pathways, 69% and 46% of patients, respectively, are estimated to exit the calibration phase with adequate symptom control (total positive and negative syndrome scale score below 68). Relative to the oral‐only pathway, the early LAI pathway is predicted to increase competitive employment by 39% (25% vs 18%) and independent or family living by 22% (71% vs 58%), and to decrease receipt of disability benefits by 36% (42% vs 66%) and hospital admissions per 1000 patient‐years by 15% (249% vs 294%). Conclusions While these simulation results need to be confirmed empirically, they suggest that earlier use of LAI antipsychotics can meaningfully improve patient outcomes.