Abstract
Background: Post-hoc analyses of study NCT01564862 evaluated the effect of flexible-dose vortioxetine (10-20mg) on functional capacity in adults with MDD using the UCSD Performance-Based Skills Assessment (UPSA).
Methods: Adults with MADRS≥26 who self-reported symptoms of cognitive dysfunction were enrolled in this double-blind, placebo-controlled, active-reference study. Change from baseline to Week 8 in both UPSA and MADRS were compared to placebo (ANCOVA, modified intent-to-treat). Analyses were performed in patient subgroups based on severity of functional impairment (baseline UPSA≤75, ≤70). Clinically relevant improvements in functional capacity were evaluated using pre-defined cutoffs for UPSA improvement (≥5, ≥7, ≥10). Path analysis determined the proportion of direct versus indirect effects of vortioxetine on UPSA. Analyses of remission from depressive symptoms and functional improvement (MADRS total score ≤10 and UPSA ≥75) were also conducted.
Results: 602 patients were randomly assigned to treatment. Statistically significant increases in functional capacity for vortioxetine versus placebo in the UPSA composite score, were seen in all patients (vortioxetine, n=175, ∆+8.0; placebo, n=166, ∆+5.1: p<0.001), in patients with baseline UPSA≤75 (n=62, ∆+14.9; n=73, ∆+9.9, p=0.003) and UPSA≤70 (n=41, ∆+16.7; n=46, ∆+10.8: p=0.010). Patients treated with duloxetine showed no significant improvement in functional capacity (p=0.637). More vortioxetine patients were responders: ΔUPSA≥7 (n=85, 48.6%; n=59, 35.5%: p=0.015) and ΔUPSA≥10 (n=66, 37.7%; n=46, 27.7%: p=0.049). Both vortioxetine and duloxetine significantly improved depressive symptoms versus placebo based on the MADRS (p<0.05; p<0.001, respectively). Path analysis of UPSA revealed that 96.9% of the effect of vortioxetine was direct and not due to improvement in depressive symptoms. For composite efficacy analysis (MADRS≤10 and UPSA≥75), vortioxetine was significantly superior to placebo (22.3% versus 10.2%, p=0.005), but duloxetine (16.0%) was not (p=0.124).
Conclusion: Vortioxetine, but not duloxetine, significantly improved functional capacity versus placebo on the UPSA. These results emphasize the distinct profile of vortioxetine in MDD patients with cognitive dysfunction.
Funding: This study was funded by H. Lundbeck A/S and Takeda Pharmaceutical Company, Ltd.