Examining Depressive Symptoms Across Diagnostic and Statistical Manual Indications: Treatment Effects of Brexpiprazole in Patients With Major Depressive Disorder and Schizophrenia

Background: The NIMH Research Domain Criteria (RDoC) framework could be used to recategorize symptoms across the established DSM criteria for neuropsychiatric disorder indications. This post-hoc analysis combined data for MDD and schizophrenia to examine depressive symptoms across DSM indications.

Methods: Data were pooled from short-term, placebo-controlled studies of brexpiprazole adjunctive use in MDD (NCT01360645, NCT01360632, NCT02196506), and in schizophrenia (NCT01396421, NCT01393613). For MDD, MADRS Total scores were used. For schizophrenia, PANSS depressive symptom factor item scores were used – Anxiety (G2), Guilt feelings (G3) and Depression (G6). To combine data across indications, PANSS items data were normalized; all data were then expressed as percentage change from baseline. Differences between treatment groups were compared using MMRM analysis.

Results: Brexpiprazole 1–3 mg significantly improved depressive symptoms, compared with placebo, at all timepoints in the combined MDD studies (Week 6: brexpiprazole [n=742] 32.1% vs. placebo [n=555] 25.1%; p < 0.001), and at doses of 1–4 mg for the combined schizophrenia studies (Week 6: brexpiprazole [n=568] 48.8% vs. placebo [n=221] 41.0%; p < 0.05). When data were collapsed across MDD and schizophrenia indications, brexpiprazole 1–4 mg continued to demonstrate a significant treatment effect, compared with placebo (Week 6: brexpiprazole [n=1,310] 37.6% vs. placebo [n=776] 29.7%; p < 0.001).

Conclusions: These results suggest that combining existing clinical data sets to understand treatment effects for common symptomatology across DSM indications is feasible. This type of analysis opens the opportunity to further explore symptoms that are reflective of human behavior across symptom domains, rather than being restricted to discretely defined indications.