Antipsychotics in monotherapy and cross-sectional symptom burden: analysis adjusted for diagnosis, disease duration, and age

Introduction: Second-generation antipsychotics present differentiated pharmacological profiles that may translate into varying levels of residual symptom burden in patients with chronic psychotic disorders treated in monotherapy. However, comparative studies conducted under routine clinical practice conditions are scarce and rarely control simultaneously for relevant variables such as diagnosis, years of disease duration, or patient age. Evidence in this area could help guide therapeutic decision-making in a more individualized and clinically grounded manner, improving long-term outcomes and optimizing patient-centered care strategies.

Objectives: To analyze the association between the antipsychotic used in monotherapy and the total score on The Transdiagnostic Global Impression of DSM-V, and to determine whether this association remains independent after adjusting for diagnosis, years of disease duration, and age.

Methods: Cross-sectional observational study involving 43 adult outpatients on antipsychotic monotherapy. Variables collected included the antipsychotic used (aripiprazole, brexpiprazole, cariprazine, paliperidone, and olanzapine as groups with n≥3), ICD-10 diagnosis, years of disease duration, and age. The outcome variable was the total score on The Transdiagnostic Global Impression of DSM-V. Statistical analysis included: Kruskal-Wallis test for overall between-group comparison, post-hoc comparisons using Mann-Whitney with Bonferroni correction, Spearman correlation for continuous variables, and four multiple linear regression models with dummy variables to estimate the independent effect of the antipsychotic: unadjusted, adjusted for diagnosis, adjusted for years of disease duration, and adjusted for age.

Results: Statistically significant differences were observed in total scale scores across antipsychotic groups (Kruskal-Wallis H=12.79; p=0.025). Olanzapine showed the highest mean score (23.6±4.9) and cariprazine the lowest (13.8±3.1). In the adjusted models, cariprazine showed significantly lower scores than aripiprazole when controlling for diagnosis (β=−7.02; p=0.036) and for years of disease duration (β=−5.61; p=0.041), although it lost significance when adjusting for age. Olanzapine was consistently associated with higher symptom burden, reaching significance in the model adjusted for disease duration (β=+4.94; p=0.027). Age showed a positive and independent association with the total score (Spearman ρ=0.39; p=0.013) and was the most robust predictor in the full model (β=+2.53; p=0.022). Diagnosis and years of disease duration did not act as relevant confounders. In the subscale analysis, cognitive symptoms (H=16.73; p=0.005) and anxiety (H=13.04; p=0.023) showed significant differences between groups, with brexpiprazole associated with greater anxiety burden compared to aripiprazole (adjusted p=0.038).

Conclusions: The antipsychotic used in monotherapy is significantly associated with cross-sectional symptom burden as measured by the scale, independently of diagnosis and years of disease duration. Age acts as a relevant confounder and should be considered in future comparative studies. Cariprazine and olanzapine represent opposite ends of the symptomatic spectrum in this sample, with potential clinical implications for antipsychotic selection based on the predominant residual symptom profile. Limitations include the small sample size and the cross-sectional design, which precludes establishing causality and limits the generalizability of findings.

References

Correll CU, Dombi ZB, Barabássy A, Németh G, Brevig T, McIntyre RS. The Transdiagnostic Global Impression - Psychopathology scale (TGI-P): initial development of a novel transdiagnostic tool for assessing, tracking, and visualising psychiatric symptom severity in everyday practice. Eur Neuropsychopharmacol. 2024;88:31–39.