Effect of Adjunctive Brexpiprazole on Sexual Functioning in MDD According to Concomitant Antidepressant: Post Hoc Analysis of Four Short-Term Studies

Background: We aimed to determine the effects of adjunctive brexpiprazole on sexual functioning in adults with major depressive disorder (MDD), according to antidepressant treatment (ADT).

Methods: Pyxis (NCT01360645), Polaris (NCT01360632), Sirius (NCT02196506) and Delphinus (NCT01727726) were randomized, double-blind, placebo-controlled studies in outpatients with MDD (DSM-IV-TR) and inadequate response to 1–3 prior ADTs. Following prospective ADT treatment, patients with inadequate response continued on ADT and were randomized to 6 weeks of adjunctive brexpiprazole, quetiapine extended-release (XR) (one study, data not shown), or placebo. Change in Massachusetts General Hospital Sexual Functioning Questionnaire (MSFQ), and MADRS Total score were calculated post hoc for ADT+brexpiprazole 2–3 mg and ADT+placebo groups, and for ADT subgroups.

Results: 1,574 patients were randomized to ADT+brexpiprazole 2–3 mg (n=782) or ADT+placebo (n=792). On the MSFQ, mean overall sexual satisfaction score changed (improved) by -0.37 from baseline to Week 6 for ADT+brexpiprazole and by -0.22 for ADT+placebo, p=0.014; range -0.67 (venlafaxine XR) to -0.09 (paroxetine CR). Similar mean changes were observed for interest in sex, sexually aroused, and achieve orgasm. For ‘maintain erection’, changes in ADT subgroups varied from -0.57 (improvement) with venlafaxine XR to 0.20 (worsening) with paroxetine CR. In the ADT+brexpiprazole group, MADRS Total score improved compared with the ADT+placebo group (p<0.0001); small differences between ADT subgroups.

Conclusion: In short-term MDD studies, adjunctive brexpiprazole did not adversely affect sexual functioning. ADT selection appeared to have little impact on sexual functioning, although patients receiving paroxetine CR appeared to fare worse than those receiving other concomitant ADTs.