Efficacy of Vortioxetine on Cognitive Functioning in Working Patients With Major Depressive Disorder

Abstract

Objective: This post hoc analysis investigates the effect of vortioxetine on cognitive functioning and depressive symptoms in working adults with major depressive disorder (MDD).Methods: Population data from FOCUS, a double-blind, randomized, placebo-controlled study investigating the efficacy of vortioxetine versus placebo on cognitive functioning and depression in patients with MDD, were used to analyze mean change from baseline scores for the Digit Symbol Substitution Test (DSST), Trail Making Test A/B (TMT-A/B), Stroop, and Perceived Deficits Questionnaire (PDQ). FOCUS, conducted from December 2011 through May 2013, included adult patients with recurrent MDD according to DSM-IV-TR criteria. Change in depression severity (Montgomery-Asberg Depression Rating Scale [MADRS] total score) was analyzed using data from 3 additional short-term placebo-controlled studies (2 of which included duloxetine) and 1 relapse prevention study. Analyses were done according to patients' working status at baseline and workplace position. All analyses were made versus placebo. Results:In FOCUS, the effect versus placebo on the DSST was 5.6 for 10 mg and 5.0 for 20 mg (P < .001 for both doses) in working patients; the effect was 4.0 (P < .001 for both doses) in total study population. The effect remained significant when adjusting for change in MADRS. In patients with "professional" positions, the effect was 9.2 for 10 mg (P = .006) and 9.0 for 20 mg (P = .001). A similar pattern of results was also observed for TMT-A/B, Stroop, PDQ, and MADRS total score. The efficacy of duloxetine was not different in working patients (MADRS). Conclusions:The beneficial effects of vortioxetine on objective and subjective measures of cognitive functioning are greater in working patients with MDD; the observed benefits were independent of improvement in depressive symptoms. 6 Evidence indicates that among adults with MDD, cognitive symptoms account for more variability in workplace performance than does total depressive symptom severity. 7 These observations support research underscoring the notion that cognitive dysfunction is a critical mediator of role impairment in MDD. 8Results from 2 double-blind, randomized, placebo-controlled studies demonstrated a clinical benefit of vortioxetine on cognitive functioning in adults with MDD, including objective neuropsychological tests of executive functioning, speed of processing, verbal learning, and memory.9-11 These studies confirm and extend the results from an earlier double-blind, randomized, placebo-controlled, duloxetine-referenced study with vortioxetine in elderly (≥ 65 years) patients with MDD. 12The beneficial effect observed on measures of cognitive functioning with vortioxetine is of particular importance for individuals with MDD who are working and/or engaged in activities that place high demands on cognition (eg, educational pursuit). Because depression is primarily a disorder affecting people of working age, 13 it is important to understand how the effect of vortioxetine on cognit...

Long-term functioning outcomes are predicted by cognitive symptoms in working patients with major depressive disorder treated with vortioxetine: results from the AtWoRC study

“…The significant improvements in both self-reported cognitive symptoms and cognitive performance assessed by the DSST seen in this study are consistent with results of previous studies of vortioxetine and reinforce these findings in a real-life setting. [33][34][35][36][37][38] The significant improvements in work productivity seen in the present study during treatment with vortioxetine are consistent with the findings of the Combined Medications to Enhance Depression Outcomes (CO-MED) trial, which demonstrated that work productivity outcomes improve significantly with antidepressant treatment and that early changes in work productivity are significant predictors of long-term clinical course. 52 In contrast to the results of the European PERFORM study, 43 patient-rated depression severity (QIDS-SR) scores were not found to significantly predict functioning outcomes (SDS or WLQ) when simultaneously adjusting for improvements in cognitive symptom severity (PDQ-D-20 score) at any subsequent timepoint in the current SEM analyses.…”

“…29,30 Vortioxetine has been shown to be effective not only for the treatment of MDD, 31,32 but also to improve cognitive symptoms in patients with depression. [33][34][35][36][37][38] A recent meta-analysis showed that vortioxetine also demonstrates efficacy in improving overall functioning and functional remission, as assessed by the Sheehan Disability Scale (SDS), in adults with MDD. 39 Assessment in Work productivity and the Relationship with Cognitive symptoms (AtWoRC) is an interventional, open-label, real-world study undertaken to examine the association between cognitive symptoms and workplace productivity in working Canadian patients with MDD treated with vortioxetine.…”

Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force

“…A recent preclinical study revealed that the EPO‐associated increase in hippocampal pyramidal neurons and oligodendrocytes was only maintained long‐term (≥6 months) in mice that also received continuous cognitive challenges . This finding is consistent with the demonstration in a cognition trial in unipolar depression that working patients displayed greater cognitive benefits of vortioxetine than those who were unemployed . Taken together, these observations are suggestive of stronger treatment effects on neuroplasticity and cognition in individuals who receive continuous cognitive challenges.…”

“…Given this legacy from schizophrenia research, cognition trials in bipolar disorder will need to make decisions about how to define their key secondary (if not co‐primary) measure of functional change. Inclusion of a functional measure would also enable assessment of the potential interaction between functional status and the cognition benefits of an intervention, which would be interesting in light of preliminary evidence for greater treatment‐related cognitive improvement in high‐ vs low‐functioning patients,…”

Quantum Analysis of the Interaction of Vortioxetine vs. Neurotransmitters.

“…[8] Vx significantly improves cognition, independent of depressive symptoms and is an important treatment for MDD-related cognitive dysfunction. [9,10] In patients with MDD the recommended dose range is 5-20 mg / day. [11] Scientists have found that Vx 5-20 mg over 6/8 weeks improves the overall functioning of patients with MDD.…”