Efficacy of Vortioxetine on Anhedonia: Results from a Pooled Analysis of Short-Term Studies in Patients with Major Depressive Disorder

Roger S McIntyre,¹ Henrik Loft,² Michael Cronquist Christensen<sup>3

1</sup>Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada; ²Department of Biostatistics and Programming, H. Lundbeck A/S, Valby, Denmark; ³Department of Psychiatry Products, H. Lundbeck A/S, Valby, Denmark

Correspondence: Michael Cronquist Christensen
H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark
Tel +45 30835168
Email MCRC@lundbeck.com

Purpose: Anhedonia is a core symptom of major depressive disorder (MDD), which has important functional consequences for the patient. This post hoc analysis investigated the relationship between anhedonia and functioning in patients with MDD treated with vortioxetine.
Patients and Methods: We conducted a pooled analysis of all 11 short-term, double-blind, randomized, placebo-controlled studies of vortioxetine (fixed dose, 5– 20 mg/day) in patients with MDD which included Montgomery–Åsberg Depression Rating Scale (MADRS) and Sheehan Disability Scale (SDS) assessments. A short-term, randomized, active-controlled trial of flexible-dose treatment with vortioxetine (10– 20 mg/day) versus agomelatine (25– 50 mg/day) was also analyzed. Mean changes from baseline to study endpoint in MADRS total, MADRS anhedonia subscale, SDS total, and SDS social-functioning scores were analyzed by a mixed model for repeated measures. The relationship between treatment effects on anhedonia and functioning was investigated using path analysis.
Results: A total of 4988 patients with MDD were included in the placebo-controlled studies and 495 in the active-comparator study. Significant dose-dependent improvements in overall depressive symptoms, anhedonia, and measures of functioning were seen in vortioxetine-treated patients compared with those who received placebo or agomelatine. Results of the path analysis for the placebo-controlled studies suggested that the effect on functioning was mostly driven by the effect of treatment on MADRS anhedonia factors.
Conclusion: Vortioxetine showed significant short-term efficacy against anhedonia in this large population of patients with MDD. In the placebo-controlled studies, improvements in functioning associated with vortioxetine appeared to be mostly driven by the effect of treatment on MADRS anhedonia factors.

Keywords: anhedonia, functioning, major depressive disorder, vortioxetine