Brexpiprazole augmentation in treatment-resistant obsessive-compulsive disorder: a preliminary retrospective observational study

Obsessive-compulsive disorder (OCD) is a chronic illness associated with significant functional impairment. Monotherapy with serotonin reuptake inhibitors (SRIs) often leads to only partial improvement of symptoms. In such cases, a common, well established, treatment approach for most patients is the augmentation of SRI therapy with antipsychotic medications. Brexpiprazole is an atypical antipsychotic agent that acts as a partial agonist of 5-HT1A, D2, and D3 receptors. Purpose of this retrospective observational study was to evaluate the effectiveness and tolerability of brexpiprazole as augmentation to SRIs in patients with treatment-resistant OCD. This preliminary study included a sample of 10 patients diagnosed with treatment-resistant OCD who underwent a 12-week trial of augmentative brexpiprazole, starting at a dose of 1 mg/day, with dosage adjustments based on clinical judgment. Treatment response was assessed through changes in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score from baseline to the end of the 12-week observation period. Adverse events were systematically recorded. Significant improvement was observed after the 12-week period: at the endpoint, seven patients (70%) achieved a ≥25% reduction in Y-BOCS total score compared to baseline, with five of them (50% of the overall sample) showing a more robust clinical response (≥35% reduction). Mild adverse effects, such as sedation and weight gain, were reported by two participants (20% of the overall sample). These findings suggest that brexpiprazole may offer a promising effectiveness and tolerability profile in the management of treatment-resistant OCD. Int Clin Psychopharmacol XXX: XXXX–XXXX Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.