Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC): primary analysis from a Canadian open-label study of vortioxetine in patients with major depressive disorder (MDD)

Pratap Chokka, Joanna Bougie, Emmanouil Rampakakis, Jean Proulx, Pratap Chokka, Joanna Bougie, Emmanouil Rampakakis, Jean Proulx

Abstract

Objective: The Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC) study aimed to assess the association between cognitive symptoms and work productivity in gainfully employed patients receiving vortioxetine for a major depressive episode (MDE).

Methods: Patients diagnosed with major depressive disorder (MDD) and treated with vortioxetine independently of study enrollment were assessed over 52 weeks at visits that emulated a real-life setting. Patients were classified as those receiving vortioxetine as the first treatment for their current MDE (first treatment) or having shown inadequate response to a previous antidepressant (switch). The primary endpoint was the correlation between changes in patient-reported cognitive symptoms (20-item Perceived Deficits Questionnaire [PDQ-D-20]) and changes in work productivity loss (Work Limitations Questionnaire [WLQ]) at week 12. Additional assessments included changes in symptom and disease severity, cognitive performance, functioning, work loss, and safety.

Results: In the week 12 primary analysis, 196 eligible patients at 26 Canadian sites were enrolled, received at least one treatment dose, and attended at least one postbaseline study visit. This analysis demonstrated a significant, strong correlation between PDQ-D-20 and WLQ productivity loss scores (r=0.634; p<0.001), and this correlation was significant in both first treatment and switch patients (p<0.001). A weaker correlation between Digit Symbol Substitution Test and WLQ scores was found (r=-0.244; p=0.003).

Conclusion: At 12 weeks, improvements in cognitive dysfunction were significantly associated with improvements in workplace productivity in patients with MDD, suggesting a role for vortioxetine in functional recovery in MDD.

Keywords: Cognitive dysfunction; functional impairment; major depressive disorder; real life; vortioxetine; work productivity.

Figures

Figure 1
Figure 1
Study design of the AtWoRC study. MDE=major depression episode
Figure 2
Figure 2
Patient disposition. *“Completed” refers to those who attended the Week 12 visit. “Discontinued” refers to treatment discontinuation before Week 12. †Ongoing analysis. APTS=all patients treated set; FAS=full analysis set
Figure 3
Figure 3
Response and remission rates at Week 12 (OC). FAS=Full Analysis Set; OC=observed cases

References

    1. Rosenblat JD, Kakar R, McIntyre RS. The cognitive effects of antidepressants in major depressive disorder: A systematic review and meta-analysis of randomized clinical trials. International Journal of Neuropsychopharmacology. 2015; 19(2).
    1. Kessler RC, Akiskal HS, Ames M, et al. Prevalence and effects of mood disorders on work performance in a nationally representative sample of U.S. Workers. Am J Psychiatry. 2006; 163(9): 1561–1568.
    1. Patten SB, Williams JV, Lavorato DH, et al. Descriptive epidemiology of major depressive disorder in Canada in 2012. Can J Psychiatry. 2015; 60(1): 23–30.
    1. Lam RW, McIntosh D, Wang J, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 1. Disease burden and principles of care. Can J Psychiatry. 2016; 61(9): 510–523.
    1. Ostergaard SD, Jensen SO, Bech P. The heterogeneity of the depressive syndrome: when numbers get serious. Acta Psychiatr Scand. 2011; 124(6): 495–496.
    1. McIntyre RS, Cha DS, Soczynska JK, et al. Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress Anxiety. 2013; 30(6): 515–527.
    1. Evans VC, Iverson GL, Yatham LN, et al. The relationship between neurocognitive and psychosocial functioning in major depressive disorder: a systematic review. J Clin Psychiatry. 2014; 75(12): 1359–1370.
    1. McIntyre RS, Soczynska JZ, Woldeyohannes HO, et al. The impact of cognitive impairment on perceived workforce performance: results from the International Mood Disorders Collaborative Project. Compr Psychiatry. 2015; 56: 279–282.
    1. World Health Organization. Depression fact sheet. 2017. . Accessed October 5, 2017.
    1. Rizvi SJ, Cyriac A, Grima E, et al. Depression and employment status in primary and tertiary care settings. Can J Psychiatry. 2015; 60(1): 14–22.
    1. Evans-Lacko S, Knapp M. Global patterns of workplace productivity for people with depression: absenteeism and presenteeism costs across eight diverse countries. Soc Psychiatry Psychiatr Epidemiol. 2016; 51(11): 1525–1537.
    1. Greenberg PE, Fournier AA, Sisitsky T, et al. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry. 2015; 76(2): 155–162.
    1. Veiel HO. A preliminary profile of neuropsychological deficits associated with major depression. J Clin Exp Neuropsychol. 1997; 19(4): 587–603.
    1. Goeldner C, Ballard TM, Knoflach F, et al. Cognitive impairment in major depression and the mglu2 receptor as a therapeutic target. Neuropharmacology. 2013; 64: 337–346.
    1. Lee RS, Hermens DF, Porter MA, et al. A meta-analysis of cognitive deficits in first-episode major depressive disorder. J Affect Disord. 2012; 140(2): 113–124.
    1. Hasselbalch BJ, Knorr U, Kessing LV. Cognitive impairment in the remitted state of unipolar depressive disorder: a systematic review. J Affect Disord. 2011; 134(1–3): 20–31.
    1. Weisenbach SL, Boore LA, Kales HC. Depression and cognitive impairment in older adults. Curr Psychiatry Rep. 2012; 14(4): 280–288.
    1. Buist-Bouwman MA, Ormel J, de Graaf R, et al. Mediators of the association between depression and role functioning. Acta Psychiatr Scand. 2008; 118(6): 451–458.
    1. Jaeger J, Berns S, Uzelac S, et al. Neurocognitive deficits and disability in major depressive disorder. Psychiatry Res. 2006; 145(1): 39–48.
    1. Southerland G, Stonebridge C. Healthy Brains at Work: Estimating the Impact of Workplace Mental Health Benefits and Programs. Ottawa: The Conference Board of Canada; 2016.
    1. Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 3. Pharmacological treatments. Can J Psychiatry. 2016; 61(9): 540–560.
    1. McIntyre RS, Lee Y, Mansur RB. Treating to target in major depressive disorder: response to remission to functional recovery. CNS Spectr. 2015; 20(Suppl 1): 20–30; quiz 31.
    1. Campbell S, Macqueen G. The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci. 2004; 29(6): 417–426.
    1. Murrough JW, Iacoviello B, Neumeister A, et al. Cognitive dysfunction in depression: neurocircuitry and new therapeutic strategies. Neurobiol Learn Mem. 2011; 96(4): 553–563.
    1. Harmer CJ, Clark L, Grayson L, et al. Sustained attention deficit in bipolar disorder is not a working memory impairment in disguise. Neuropsychologia. 2002; 40(9): 1586–1590.
    1. Iosifescu DV. The relation between mood, cognition and psychosocial functioning in psychiatric disorders. Eur Neuropsychopharmacol. 2012; 22(Suppl 3): S499–S504.
    1. Fried EI, Nesse RM. The impact of individual depressive symptoms on impairment of psychosocial functioning. PLoS One. 2014; 9(2): e90311.
    1. Kim JM, Chalem Y, di Nicola S, et al. A cross-sectional study of functional disabilities and perceived cognitive dysfunction in patients with major depressive disorder in South Korea: the PERFORM-K study. Psychiatry Res. 2016; 239: 353–361.
    1. Francomano A, Bonanno B, Fuca L, et al. The role of antidepressant treatments on cognitive deficits. A review of recent literature. Clinical Neuropsychiatry. 2011; 8(6): 354–366.
    1. Garnock-Jones KP. Vortioxetine: a review of its use in major depressive disorder. CNS Drugs. 2014; 28(9): 855–874.
    1. Thase ME, Mahableshwarkar AR, Dragheim M, et al. A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults. Eur Neuropsychopharmacol. 2016; 26(6): 979–993.
    1. Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of lu aa21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol. 2012; 27(4): 215–223.
    1. Harrison JE, Lophaven S, Olsen CK. Which cognitive domains are improved by treatment with vortioxetine? International Journal of Neuropsychopharmacology 2016.
    1. McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. International Journal of Neuropsychopharmacology. 2014; 17(10): 1557–1567.
    1. McIntyre RS, Florea I, Tonnoir B, et al. Efficacy of vortioxetine on cognitive functioning in working patients with major depressive disorder. J Clin Psychiatry. 2017; 78(1): 115–121.
    1. Mahableshwarkar AR, Zajecka J, Jacobson W, et al. A randomized, placebo-controlled, active-reference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in major depressive disorder. Neuropsychopharmacology. 2015; 40(8): 2025–2037.
    1. Trintellix(tm) (vortioxetine) product monograph. Montreal, QC, Canada: Lundbeck Canada Inc.; 2014.
    1. Boulenger JP, Loft H, Olsen CK. Efficacy and safety of vortioxetine (lu aa21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder. Int Clin Psychopharmacol. 2014; 29(3): 138–149.
    1. Henigsberg N, Mahableshwarkar AR, Jacobsen P, et al. A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of lu aa21004 in adults with major depressive disorder. J Clin Psychiatry. 2012; 73(7): 953–959.
    1. Jha MK, Minhajuddin A, Greer TL, et al. Early improvement in work productivity predicts future clinical course in depressed outpatients: findings from the CO-MED trial. Am J Psychiatry. 2016; 173(12): 1196–1204.
    1. Srisurapanont M, Suttajit S, Eurviriyanukul K, et al. Discrepancy between objective and subjective cognition in adults with major depressive disorder. Scientific Reports. 2017; 7(1): 3901.
    1. Lam RW, Iverson GL, Evans VC, et al. The effects of desvenlafaxine on neurocognitive and work functioning in employed outpatients with major depressive disorder. J Affect Disord. 2016; 203: 55–61.
    1. Cha DS, Carmona NE, Subramaniapillai M, et al. Cognitive impairment as measured by the thinc-integrated tool (thinc-it): Association with psychosocial function in major depressive disorder. J Affect Disord. 2017; 222: 14–20.
    1. Hudson JI, Perahia DG, Gilaberte I, et al. Duloxetine in the treatment of major depressive disorder: an open-label study. BMC Psychiatry. 2007; 7: 43.
    1. Wohlreich MM, Martinez JM, Mallinckrodt CH, et al. An open-label study of duloxetine for the treatment of major depressive disorder: comparison of switching versus initiating treatment approaches. Journal of Clinical Psychopharmacology. 2005; 25(6): 552–560.
    1. Lawrence C, Roy A, Harikrishnan V, et al. Association between severity of depression and self-perceived cognitive difficulties among full-time employees. Prim Care Companion CNS Disord. 2013; 15(3).
    1. Lam RW, Saragoussi D, Danchenko N, et al. Psychometric validation of Perceived Deficits Questionnaire–Depression (PDQ-D) in patients with major depressive disorder (MDD). Value in Health. 2013; 16(7): A330.
    1. Lerner D, Adler DA, Chang H, et al. The clinical and occupational correlates of work productivity loss among employed patients with depression. J Occup Environ Med. 2004; 46(6 Suppl): S46–S55.
    1. Tang K, Beaton DE, Boonen A, et al. Measures of work disability and productivity: Rheumatoid Arthritis Specific Work Productivity Survey (WPS-RA), Workplace Activity Limitations Scale (WALS), Work Instability Scale for Rheumatoid Arthritis (RA-WIS), Work Limitations Questionnaire (WLQ), and Work Productivity and Activity Impairment Questionnaire (WPAI). Arthritis Care Res (Hoboken). 2011; 63(Suppl 11): S337–S349.
    1. Rush AJ, Trivedi MH, Ibrahim HM, et al. The 16-item Quick Inventory Of Depressive Symptomatology (QIDS), Clinician Rating (QIDS-C), and Self-Report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. 2003; 54(5): 573–583.
    1. Ustun TB, Chatterji S, Kostanjsek N, et al. Developing the World Health Organization Disability Assessment Schedule 2.0. Bulletin of the World Health Organization. 2010; 88(11): 815–823.
    1. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993; 4(5): 353–365.
    1. Trivedi MH, Morris DW, Wisniewski SR, et al. Increase in work productivity of depressed individuals with improvement in depressive symptom severity. Am J Psychiatry. 2013; 170(6): 633–641.
    1. Arbuckle R, Frye MA, Brecher M, et al. The psychometric validation of the Sheehan Disability Scale (SDS) in patients with bipolar disorder. Psychiatry Res. 2009; 165(1–2): 163–174.
    1. Lowe B, Decker O, Muller S, et al. Validation and standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population. Med Care. 2008; 46(3): 266–274.
    1. Guy W. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US Department of Health, Education, and Welfare; 2014.
    1. Swan GE, Carmelli D, LaRue A. Performance on the Digit Symbol Substitution Test and 5-year mortality in the western collaborative group study. Am J Epidemiol. 1995; 141(1): 32–40.
    1. Rosano C, Newman AB, Katz R, et al. Association between lower Digit Symbol Substitution Test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults. J Am Geriatr Soc. 2008; 56(9): 1618–1625.

Source: PubMed

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