Projected mortality impact of increasing second-generation long-acting injectable antipsychotic exposure in Italy: A scenario-based population model.

BACKGROUND: In Italy, 165,846 adults receive specialist mental-health care for schizophrenia and other functional psychoses. People with schizophrenia have excess mortality, and long-acting injectable antipsychotics (LAIs) may reduce treatment discontinuity; however, the population impact of increasing second-generation LAI (SGA-LAI) exposure is unknown. METHODS: We developed a scenario-based closed-cohort model using the 2024 Italian Mental Health Information System denominator, SISM age-specific treated rates, and ISTAT 2024 age- and sex-specific mortality rates. Schizophrenia excess mortality was parameterized from meta-analytic evidence (standardized mortality ratio 2.523). The LAI-versus-oral mortality parameter came from a recent systematic review and meta-analysis (odds ratio 0.79). Scenarios evaluated 5-, 10-, 15- and 20-percentage-point absolute increases in SGA-LAI exposure. RESULTS: A 10-percentage-point absolute increase, equivalent to 16,585 additional SGA-LAI-treated patients, was projected to avert 384 all-cause deaths over 10 years and 643 over 20 years, generating 2042 and 7342 within-horizon life-years, respectively. A 20-percentage-point absolute increase was projected to avert 772 deaths over 10 years and 1295 over 20 years. An open-cohort scope analysis including treated incident entries raised the 20-year estimate for the 10-percentage-point scenario to 1413 deaths avoided. Results were most sensitive to the LAI mortality parameter, source of new uptake, eligibility assumptions and diagnostic restriction. CONCLUSIONS: Increasing appropriate SGA-LAI exposure could potentially generate mortality and life-year benefits in the Italian specialist-care psychosis population under explicit assumptions. Estimates are population-impact projections, not observed Italian causal effects.