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

William Jacobson, Wei Zhong, George G. Nomikos, Michael Cronquist Christensen, Christina Kurre Olsen, Philip D. Harvey

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalCurrent Medical Research and Opinion
DOIs
StateAccepted/In press - Jan 1 2019

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Major Depressive Disorder
Placebos
Depression
Neurobehavioral Manifestations
vortioxetine
Least-Squares Analysis
Clinical Trials
Databases
Confidence Intervals
Duloxetine Hydrochloride

Keywords

  • cognitive dysfunction
  • functional capacity
  • major depressive disorder
  • serotonin reuptake inhibitor (SERT)
  • UCSD Performance-based Skills Assessment
  • Vortioxetine

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{4a4dac2017b64abe95ad8ef37497e960,
title = "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",
abstract = "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.",
keywords = "cognitive dysfunction, functional capacity, major depressive disorder, serotonin reuptake inhibitor (SERT), UCSD Performance-based Skills Assessment, Vortioxetine",
author = "William Jacobson and Wei Zhong and Nomikos, {George G.} and Christensen, {Michael Cronquist} and {Kurre Olsen}, Christina and Harvey, {Philip D.}",
year = "2019",
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day = "1",
doi = "10.1080/03007995.2019.1657692",
language = "English (US)",
journal = "Current Medical Research and Opinion",
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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.

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KW - functional capacity

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KW - UCSD Performance-based Skills Assessment

KW - Vortioxetine

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