Add-on of aripiprazole improves outcome in clozapine-resistant schizophrenia

Although clozapine proved effective in treating 30–50% of the cases of resistant schizophrenia, its clinical use is hampered by significant side effects. To overcome this problem, augmentation with other atypical antipsychotics has been attempted, with conflicting results. A clozapine–aripiprazole combination showed interesting properties, due to the favourable complementary pharmacodynamic receptor profile and to the negligible metabolic interactions. In this retrospective case series, we investigated the change in BPRS scores and metabolic features like BMI, fasting glucose, total and LDL cholesterol, triglycerides, functional outcome HoNOS Rome and PSP scores after aripiprazole augmentation in 16 persons with treatment-resistant schizophrenia who were already treated with clozapine. The results demonstrated a statistically significant improvement in metabolic indices, psychopathology and functional outcome measures from baseline to endpoint (6 weeks) after augmentation with aripiprazole. Statistically significant correlations were observed between psychopathological and behavioural measures at baseline and at endpoint. Linear regression analysis defined a tripartite model, in which item HoNOS Rome 11, measuring autonomy in everyday life, explained nearly half of functional outcome PSP score predictive variance, together with BPRS total psychopathology score and HoNOS Rome total social functioning score. Adequately conducted randomised double-blind studies should provide further specific data highlighting the role of a clozapine–aripiprazole combination in improving functional outcome of persons with treatment-resistant schizophrenia.

Research highlights
► The effectiveness of clozapine–aripiprazole association in resistant schizophrenia
► The efficacy of this drug combination on functional autonomy
► The study concerns real-world patients