Reducing re-hospitalization in schizophrenia: real-world comparison of first- vs. second-generation long-acting injectable antipsychotics

Long-acting injectable (LAI) antipsychotics represent a valid and effective option in the pharmacological treatment of schizophrenia, but the choice between first- (FGA) and second-generation (SGA) LAIs is not always clear. We aimed to evaluate differences in reducing the frequency and duration of hospitalizations, clinical relapses and suicide attempts in patients suffering from schizophrenia spectrum disorders (SSDs) by comparing introduction of FGA-LAIs vs. SGA-LAIs. We conducted a mirror-image study with a three-year retrospective observation and follow-up time in patients with SSDs switching from oral antipsychotics to LAI formulations. The sample included 133 predominantly male (69.2%), middle-aged (mean 50.3 years), single, caucasian patients with a long-standing course of SSDs illness (20.1 years) and antipsychotic treatment (17.1 years). Initiation of LAI treatment was associated with a significant reduction in hospital admissions from 53.4% to 6.0% over three years, consistently observed across all patient subgroups and treatment conditions. The average duration of hospitalization decreased markedly, dropping from 14.26 days (± 29.1) to 1.35 days (± 8.09) after LAI start. Both FGA-LAIs and SGA-LAIs were associated with significant reductions in hospitalization days, relapses, and suicide attempts. No statistically significant differences in improvement were detected between the two groups in this cohort. Treatment with LAI was associated with sustained medium- to long-term reductions in rehospitalizations, relapses, and suicide attempts in patients with SSD. However, because of the observational mirror-image design and the potential for residual confounding, the present findings should not be interpreted as establishing the comparative effectiveness of first- and second-generation LAIs. Treatment selection should therefore remain individualized, taking into account the overall clinical profile, tolerability, patient preferences, and clinician judgement. No significant differences were observed between FGA-LAI and SGA-LAI antipsychotics in reducing hospitalization rate. Both generations showed comparable effectiveness in preventing relapse over the three-year follow-up period. The incidence of suicide attempts did not differ significantly between patients treated with FGA-LAIs and SGA-LAIs. Clinical outcomes suggest similar real-world effectiveness of both LAI generations in SSDs population. Treatment choice between LAI generations may therefore be guided more by patient tolerability, side-effect profile, and clinical preference than by differences in efficacy.