Effectiveness of amisulpride augmentation versus other antipsychotics in clozapine-treated adolescents: a real-world retrospective study.

backgroundIn this study, we compared the clinical response to clozapine-amisulpride augmentation versus clozapine augmentation with other antipsychotics among children and adolescents with schizophrenia spectrum disorders in clinical practice. Crucially, the comparative efficacy of specific augmentation strategies in this vulnerable, early-onset population remains a largely unanswered question in current literature.

methodsSeventy-six inpatients who were treated with clozapine between 2013 and 2023 years at a tertiary care psychiatric university teaching hospital in Turkey were included in this retrospective study. Patients were divided into clozapine+amisulpride (n = 22) and clozapine+others (n = 54) groups according to their treatment regimen. Clinical response was assessed by comparing baseline and discharge Positive and Negative Syndrome Scale (PANSS) scores and response rates defined as ≥20% and ≥30% improvement. The effect of group assignment on clinical response was examined by multiple linear regression analysis while controlling for clozapine dose, baseline PANSS scores, and adjunctive antipsychotic load standardized via the Defined Daily Dose (DDD) method.

resultsMean age of the patients was 15.9 ± 2.3 years. Baseline PANSS total scores were similar between groups (p = 0.977). Mean changes in PANSS total scores (-25.1±34.7 vs. -25.5±32.1; p = 0.968) and subscale scores were not significantly different between groups at discharge. Response rates according to 30% and 20% thresholds were similar between groups (38.1% vs. 51.1%; p = 0.324, p = 0.954). In the multiple linear regression analysis, clozapine dose (p = 0.026) and baseline PANSS score (p < 0.001) were significant predictors of change in PANSS total score. In the negative subscale model, higher clozapine doses predicted greater symptom reduction (p = 0.028), whereas higher standardized doses of adjunctive antipsychotics predicted poorer improvement (p = 0.031).

conclusionsClozapine augmentation with amisulpride was not superior to augmentation with other antipsychotics in our sample. Treatment response appears to be driven more by clozapine dose and baseline severity. In addition, high standardized doses of adjunctive agents may counterproductively limit negative symptom recovery, perhaps due to secondary negative symptoms caused by excessive D2 receptor blockade. CLINICAL TRIAL NUMBER: Not applicable.