PS83. Impact of Vortioxetine on Functional Capacity in MDD Patients with Subjective Cognitive Dysfunction: A Post-hoc Analysis of the University of California San Diego Performance-Based Skills Assessment

Objective: Recent studies demonstrated changes of serum and plasma amyloid ß-protein (Aβ) levels in patients with depression. Although the change of serum levels of Aβ has been suggested as a risk factor for future onset of Alzheimer’s disease, the relationship between Aβ levels and treatment response in patients with depression is still unclear. Our objective of this study is to assess whether serum levels of Aβ may predict the response to antidepressant treatment in patients with major depression. Methods: Serum Aβ40 and Aβ42 levels at admission were evaluated in 120 patients with major depressive disorder. All patients were treated with antidepressant. Depressive symptoms were assessed using the Hamilton rating scale for depression at admission, 4-weeks after treatment and at the time of clinical remission. The relationship between serum levels of Aβ and 4-weeks response rate was analyzed using multiple regression analysis controlling age, gender, severity of depression and number of depressive episodes. Results: Serum levels of Aβ40 (β=-0.147, p=0.143), Aβ42 (β=-0.003, p=0.977) and Aβ40/42 ratio (β=0.085, p=0.396) were not significantly associated with 4-weeks response rate. Similar results were shown in elderly patients (>60 years). Conclusions: Serum levels of Aβ may not predict the response to antidepressant treatment in patients with major depression. Further studies which controlled antidepressant type and dose will be needed. PS83 Impact of Vortioxetine on Functional Capacity in MDD Patients with Subjective Cognitive Dysfunction: A Post-hoc Analysis of the University of California San Diego Performance-Based Skills Assessment William Jacobson1, Philip D. Harvey2, Elizabeth Merikle1, Wei Zhong1, George Nomikos1, Christina Kurre Olsen3, Michael Cronquist Christensen3 1Takeda Development Center, Americas, Deerfield, IL, USA 2University of Miami Miller School of Medicine, Miami, FL, USA 3 H. Lundbeck A/S, Copenhagen, Denmark 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.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. PS84 Comparison of risk for development of mania or hypomania between Venlafaxine monotherapy group and Olanzapine augmentation group with Originally diagnosed as Unipolar depressive disorder during 7-year follow up: naturalistic study, retrospective review. Sae-Heon Jang, MD. Young-Myo Jae, MD, Ph.D. Chin-Hyuk Choi, MD Department of Psychiatry, Bongseng memorial Hospital, Busan, South