This analysis evaluated potential differences in subjective well-being (SW) among patients with early-phase schizophrenia (SZ) randomized to treatment with either long-acting injectable (LAI) or oral aripiprazole or paliperidone within the “European Long-acting Antipsychotics in Schizophrenia Trial” (EULAST).

A total of 478 patients were followed for up to 19 months. SW was measured using the Subjective Well-being under Neuroleptic Treatment scale (SWN). Linear mixed-effects models assessed treatment differences. Comprehensive analyses included age, sex, symptomatology (Positive and Negative Syndrome Scale [PANSS]), and side effects (Systematic Monitoring of Adverse Events Related to Treatments [SMARTS] and St. Hans rating scale [SHRS] for extrapyramidal syndromes) on SWN changes.

Overall, SW improved over the course of the study. No significant differences emerged between LAI and oral administration (p = 0.1533) or between aripiprazole and paliperidone (p = 0.2008). Similarly, age and sex were not relevant in this regard. In contrast, negative, positive, and affective symptoms (all p < 0.0001) as well as the overall side effect burden (SMARTS sum-score, p < 0.0001) showed significant inverse associations with SW. Certain SHRS subscales correlated with SW in partial models, but associations disappeared in the fully adjusted model.

Patients with SZ initiating LAI or oral treatment with aripiprazole or paliperidone reported comparable SW improvements. Findings emphasize that treatment choice should be guided less by formulation or substance and more by individual patient needs, prioritizing symptom control while minimizing adverse effects. A patient-centered approach remains essential to optimize both clinical outcomes and subjective well-being in early-phase SZ.