Effects of vortioxetine on functional capacity across different levels of functional impairment in patients with major depressive disorder: a University of California, San Diego Performance-based Skills Assessment (UPSA) analysis

TY - JOUR

T1 - Effects of vortioxetine on functional capacity across different levels of functional impairment in patients with major depressive disorder

T2 - a University of California, San Diego Performance-based Skills Assessment (UPSA) analysis

AU - Jacobson, William

AU - Zhong, Wei

AU - Nomikos, George G.

AU - Christensen, Michael Cronquist

AU - Kurre Olsen, Christina

AU - Harvey, Philip D.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: To evaluate the consistency of vortioxetine’s effects on functional capacity in adults with major depressive disorder (MDD) and self-reported cognitive symptoms at different levels of functional impairment. Methods: An exploratory analysis of data from a randomized, placebo-controlled, duloxetine-referenced study (NCT01564862) involving 529 patients with moderate to severe MDD treated once-daily with vortioxetine 10/20 mg, duloxetine 60 mg, or placebo for 8 weeks. Analysis of the University of California, San Diego Performance-based Skills Assessment (UPSA) composite scores stratified patients into subgroups by baseline functional impairment and assessed clinically important differences using several cutoffs for change from baseline (CFB) (least-square means) in UPSA composite score. A path analysis was also conducted to determine the proportion of direct versus indirect effects of vortioxetine on functional capacity. Results: Vortioxetine significantly separated from placebo across different baseline levels of functional impairment, particularly at the ≤70 cutoff (mean difference = 5.9, 95% confidence interval, 1.5–10.4). A greater proportion of patients treated with vortioxetine than placebo exhibited UPSA composite score response at each threshold analyzed and were classified as responders based on UPSA CFB of ≥7 (p = 0.006) or ≥9 (p = 0.016). No significant effects were observed for duloxetine versus placebo for any baseline levels of functional impairment or response thresholds. Path analysis demonstrated that 96.9% of the effects on functional capacity can be directly attributed to the treatment effect of vortioxetine and are not mediated by improvements in depressive symptoms as measured by MADRS. Conclusion: The effects of vortioxetine on functional capacity is robust across different level of functional impairment in patients with MDD. The effect on functional capacity was largely independent of the effect on depressive symptoms. Trial Registration: ClinicalTrials.gov identifier: NCT01564862: https://clinicaltrials.gov/ct2/show/NCT01564862; European Clinical Trials Database [EudraCT] Number 2011-005298-22: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005298-22/DE.

AB - Objective: To evaluate the consistency of vortioxetine’s effects on functional capacity in adults with major depressive disorder (MDD) and self-reported cognitive symptoms at different levels of functional impairment. Methods: An exploratory analysis of data from a randomized, placebo-controlled, duloxetine-referenced study (NCT01564862) involving 529 patients with moderate to severe MDD treated once-daily with vortioxetine 10/20 mg, duloxetine 60 mg, or placebo for 8 weeks. Analysis of the University of California, San Diego Performance-based Skills Assessment (UPSA) composite scores stratified patients into subgroups by baseline functional impairment and assessed clinically important differences using several cutoffs for change from baseline (CFB) (least-square means) in UPSA composite score. A path analysis was also conducted to determine the proportion of direct versus indirect effects of vortioxetine on functional capacity. Results: Vortioxetine significantly separated from placebo across different baseline levels of functional impairment, particularly at the ≤70 cutoff (mean difference = 5.9, 95% confidence interval, 1.5–10.4). A greater proportion of patients treated with vortioxetine than placebo exhibited UPSA composite score response at each threshold analyzed and were classified as responders based on UPSA CFB of ≥7 (p = 0.006) or ≥9 (p = 0.016). No significant effects were observed for duloxetine versus placebo for any baseline levels of functional impairment or response thresholds. Path analysis demonstrated that 96.9% of the effects on functional capacity can be directly attributed to the treatment effect of vortioxetine and are not mediated by improvements in depressive symptoms as measured by MADRS. Conclusion: The effects of vortioxetine on functional capacity is robust across different level of functional impairment in patients with MDD. The effect on functional capacity was largely independent of the effect on depressive symptoms. Trial Registration: ClinicalTrials.gov identifier: NCT01564862: https://clinicaltrials.gov/ct2/show/NCT01564862; European Clinical Trials Database [EudraCT] Number 2011-005298-22: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005298-22/DE.

KW - cognitive dysfunction

KW - functional capacity

KW - major depressive disorder

KW - serotonin reuptake inhibitor (SERT)

KW - UCSD Performance-based Skills Assessment

KW - Vortioxetine

UR - http://www.scopus.com/inward/record.url?scp=85071633407&partnerID=8YFLogxK

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U2 - 10.1080/03007995.2019.1657692

DO - 10.1080/03007995.2019.1657692

M3 - Article

C2 - 31422713

AN - SCOPUS:85071633407

JO - Current Medical Research and Opinion

JF - Current Medical Research and Opinion

SN - 0300-7995

ER -