Patient Life Engagement and Metabolic Profile Improve After Switching from First-/Second-Generation Antipsychotics to Brexpiprazole: A Real-World Study in Patients with Schizophrenia

<b>Background:</b> Schizophrenia is a chronic disorder requiring long-term pharmacological treatment. Many patients experience inadequate response and adverse effects, often leading to poor adherence and need for antipsychotic switch or polypharmacotherapy. In this context, brexpiprazole, an atypical antipsychotic with favorable tolerability profile, may offer clinical benefits following previous treatment failure or intolerance. However, real-world evidence after treatment switch remains limited. <b>Methods</b>: This retrospective, observational study included 50 outpatients with schizophrenia switched to brexpiprazole (2-4 mg/day) via cross-titration and evaluated over 12 weeks. Primary outcomes were changes in <i>Patient Life Engagement</i>, assessed through a 14-item subset of the Positive and Negative Syndrome Scale (PANSS), along with response/remission rates. Secondary outcomes included changes in subjective well-being, quality of life, sexual functioning (based on Subjective Well-being under Neuroleptics-Short Form [SWN-S], WHO-5 Well-Being Index [WHO-5], and Arizona Sexual Experience Scale [ASEX] scores, respectively), metabolic parameters, and prolactin levels. <b>Results</b>: Life engagement improved significantly (<i>p</i> < 0.001) across all domains, and clinical response was achieved in 40% of patients. Significant improvements were observed in SWN-S and WHO-5 scores (both <i>p</i> < 0.001). Weight and BMI significantly decreased (-2.64 kg, <i>p</i> = 0.013, and -0.91 kg/m², <i>p</i> = 0.006, respectively). Numerical non-significant reductions were found in ASEX (<i>p</i> = 0.067) and prolactin levels (-30.7 ng/mL, <i>p</i> = 0.077). Overall, treatment was well-tolerated. <b>Conclusions</b>: Switching to brexpiprazole was associated with improvements in psychopathological, functional, and physical health domains. These findings support its potential role in real-world, personalized therapeutic strategies for patients with schizophrenia following suboptimal outcomes with prior antipsychotic treatments.