Switching to aripiprazole reverses a high-risk metabolic syndrome subtype in schizophrenia: a 6-month prospective study

This study aimed to investigate the reversal of a high-risk metabolic syndrome (MetS) subtype (characterized by central obesity, hypertriglyceridemia, and low high-density lipoprotein cholesterol) following a switch from olanzapine (OLZ) to aripiprazole (ARI) in young patients with schizophrenia (SCZ). In this 6-month, prospective, single-arm study, 87 clinically stable patients with SCZ and the specified MetS subtype underwent a cross-titration from OLZ to ARI. 75 participants completed the protocol. Metabolic and psychiatric assessments were conducted at baseline and endpoint. Following the switch, significant reductions were observed in body weight ( p < 0.001), waist circumference ( p < 0.001), fasting blood glucose ( p = 0.002), and triglycerides ( p = 0.006). Psychiatric symptom severity remained stable ( p = 0.635), while the Global Assessment of Functioning score improved significantly ( p = 0.005) and treatment-emergent symptoms decreased ( p = 0.044). A total of 31 participants (41.33%) achieved a qualitative reversal of MetS diagnosis. Scheirer-Ray-Hare analysis revealed significant interaction effects between the intervention and metabolic diagnosis subgroups. Triglyceride levels decreased significantly in converters but paradoxically increased in non-converters (H = 19.42, p < 0.001), highlighting the heterogeneous metabolic response to this switching strategy. Switching from OLZ to ARI was associated with the reversal of a high-risk MetS subtype in a substantial proportion (41.33%) of patients without compromising psychiatric stability in this clinically pre-stabilized cohort. The marked heterogeneity in treatment response, however, indicates that this switch constitutes a foundational intervention. Early identification of patients less likely to respond is essential to guide adjunctive therapies for optimal cardiovascular risk reduction.