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

Abstract

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. 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. 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%). While these simulation results need to be confirmed empirically, they suggest that earlier use of LAI antipsychotics can meaningfully improve patient outcomes.