Long-Term Real-World Outcomes Among Patients with Major Depressive Disorder with Anxiety-Related Diagnosis Taking Brexpiprazole as Augmentation with Antidepressant Treatment

Patients with major depressive disorder (MDD) often experience comorbid anxiety diagnoses, associated with poorer treatment responses. Although adjunctive therapies show efficacy in patients with comorbid anxiety in randomized controlled trials, evidence supporting their effectiveness in real-world settings remains limited. This study characterized real-world clinical outcomes in patients with MDD with and without evidence of an anxiety-related diagnosis who were treated with adjunctive brexpiprazole. This analysis considered subsets of patients with MDD with and without comorbid anxiety from a retrospective study of linked electronic medical records and claims data. Patients with MDD using adjunctive brexpiprazole were included if they had ≥ 12 months of continuous data before and after brexpiprazole initiation. Anxiety status was determined from clinical records or claims diagnoses. Clinical outcomes included depressive symptom severity [9-item Patient Health Questionnaire (PHQ-9)] anxiety symptom severity [7-item Generalized Anxiety Disorder scale (GAD-7)] and clinician-rated improvement [Clinical Global Impression-Improvement (CGI-I)]. Changes from baseline to follow-up were analyzed separately for patients with and without anxiety-related diagnoses. Clinical improvement was further evaluated using standard thresholds for remission (PHQ-9 score < 5) and response (CGI-I score ≤ 2). Among 1073 patients with MDD, 653 had anxiety-related diagnoses, and 420 did not. Patients with anxiety-related diagnoses had a PHQ-9 score mean change of − 2.6 (95% CI: − 3.1 to − 2.2; p < 0.001); those without evidence of an anxiety-related diagnosis had a mean change of − 3.0 (95% CI: − 3.6 to − 2.4; p < 0.001). For patients with evidence of anxiety-related diagnoses, GAD-7 scores improved with brexpiprazole (mean change: − 2.7; 95% CI: − 3.7 to − 1.7; p < 0.001). PHQ-9 remission was achieved by 17.2% and 21.4% of patients with and without evidence of anxiety-related diagnoses, and CGI-I response was observed in 18.1% and 16.2% of patients, respectively. This real-world study provides evidence on clinical outcomes following initiation of adjunctive brexpiprazole in adults with MDD with and without anxiety-related diagnoses. The observed improvements support the value of evaluating adjunctive therapies in patient populations that reflect routine clinical practice.