Stability of psychotic symptoms and safety in switching to aripiprazole once-monthly according to prior oral antipsychotic drugs

Abstract

Long-acting injectable aripiprazole has substantiated safety and efficacy in treating schizophrenia. However, interindividual variability in clinical response to aripiprazole, possibly linked to its D2 partial agonism and D2 upregulation due to prior antipsychotics, has been reported. This study assessed whether there would be symptomatic aggravations or adverse events in clinically stable patients with schizophrenia when switching from oral antipsychotics to aripiprazole once-monthly (AOM), considering prior antipsychotics: oral aripiprazole (Group I) or other D2 antagonists (Group II). This was a 20-week, prospective, open-label, multicenter trial. Clinically stable patients with schizophrenia were assigned to two groups based on their oral antipsychotic medication and received AOM every 4 weeks. The primary endpoint was a change from baseline in the total Positive and Negative Syndrome Scale (PANSS) score. Treatment-emergent adverse events (TEAEs) were monitored. Altogether, 100 patients in Group I and 101 in Group II completed the study. The mean changes (±SD) from baseline in PANSS total score after switching to AOM were − 9.43 ± 9.79 in Group I (p < 0.0001) and − 4.04 ± 8.72 in Group II (p = 0.0102). Compared to Group I, in Group II, more sleep disturbance (p = 0.0243) and psychotic symptoms (p = 0.0042) TEAE emerged after AOM initiation, with both TEAEs resolving during the study. Psychotic symptoms TEAE was associated with faster tapering of the prior oral antipsychotics (p = 0.0269). Initiating AOM did not aggravate symptoms. Furthermore, AOM ameliorated psychotic symptoms without any significant adverse effect, regardless of their prior oral antipsychotics. However, patients previously treated with D2 antagonists may experience transient psychiatric TEAEs that can be minimized with longer cross-titration. © 2025 Elsevier B.V., All rights reserved.