Low-dose versus standard-dose antipsychotic treatment in first-episode schizophrenia: A secondary analysis of EUFEST data

OBJECTIVE: To compare clinical outcomes between low-dose and standard-dose antipsychotic treatment and to identify characteristics associated with low-dose treatment in first-episode schizophrenia. METHODS: We conducted a secondary analysis of the European First Episode Schizophrenia Trial (EUFEST), an open-label randomized study comparing several antipsychotics. Participants were classified into low-dose and standard-dose groups according to guideline-based dose thresholds. The primary outcome was time to any-cause study discontinuation. Kaplan-Meier curves and Cox proportional hazards models adjusted for country, age, sex, and antipsychotic-naïve status were used to compare groups. RESULTS: Among 421 eligible participants, 58 (13.8%) received lower doses and 363 (86.2%) received standard doses. The low-dose group included individuals who were more often employed or studying, less frequently hospitalized at baseline, more commonly antipsychotic-naïve, and had lower baseline PANSS scores and higher GAF scores. Kaplan-Meier analysis showed similar study discontinuation patterns across the groups (log-rank p = 0.106). In the adjusted Cox model, the hazard ratio for standard-dose versus low-dose treatment was 0.86 (95% CI 0.56-1.32). Symptom trajectories assessed by the PANSS total score did not differ between the groups over time. The low-dose group also showed significantly less longitudinal weight gain after adjustment for baseline characteristics and antipsychotic drug. CONCLUSIONS: These findings suggest that starting antipsychotic treatment at the lower end of the recommended dose range may be feasible for some individuals with first-episode schizophrenia without compromising treatment continuation while potentially reducing weight gain, although confirmation in randomized dose-strategy trials is required.