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

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.

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.

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.

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.