Vortioxetine improves symptomatic and functional outcomes in major depressive disorder: a novel dual outcome measure in depressive disorders
Abstract
Summary. With symptomatic remission and functional recovery as the overarching therapeutic objectives of antidepressant therapy, composite endpoint measures that conjointly consider both aspects of treatment are needed. This analysis evaluated the combined effect of vortioxetine on depressive symptoms and functional capacity in adults with MDD.
Methods: NCT01564862, a multinational, double-blind, placebo-controlled, duloxetine-referenced study, con-ducted between April 2012 and February 2014, in 602 adult outpatients (18–65 years) with moderate-tosevere MDD (Montgomery-Asberg Depression Rating Scale (MADRS) ≥ 26), a major depressive episode of ≥ 3 months’ duration, and self-reported cognitive symptoms were randomized to once-daily vortioxetine (10 or 20 mg), duloxetine (60 mg), or placebo for 8 weeks. Assessments included the University of California San Diego Performance-based Skills Assessment (UPSA) and the MADRS. Two versions of UPSA were utilized; UPSA ‒Validation of Intermediate Measures and UPSA Brief form. An aligned UPSA-B (communication and finance items) was examined for sensitivity analysis. Efficacy was analyzed versus placebo according to the dualresponse (change from baseline in UPSA ≥ 7 and ≥ 9 and reduction in MADRS total score from baseline ≥ 50%).
Results: Significantly more vortioxetine-treated patients were classified as dual responders for change in MADRS total score and UPSA score of ≥ 7 (clinically important difference [CID]) (27.4% vs 14.5%; P = 0.004), and change above CID (≥ 9) (23.4% vs 13.9%; P = 0.025). Duloxetine did not differ significantly from placebo for these dual response criteria. Sensitivity analysis using the aligned UPSA-B confirmed these results for vortiox-etine.
References
1. Adler D.A., McLaughlin T.J., Rogers W.H., Chang H., Lapitsky L., Lerner D. Job performance deficits due to depression. Am. J. Psychiatry. — 2006. — Vol.163. — P.1569–1576.
2. Bang-Andersen B., Ruhland T., Jorgensen M., Smith G., Frederiksen K., Jensen K.G., Zhong H., Nielsen S.M., Hogg S., Mork A., Stensbol T.B. Discoveryof 1-[2-(2,4-dimethylphenylsulfanyl) phenyl]piperazine (Lu AA21004): a novelmultimodalcompoundforthetreatmentofmajordepressivedisorder. J. Med. Chem. — 2011. — Vol.54. — P.3206–3221.
3. Bortolato B., Carvalho A.F., McIntyre R.S. Cognitive dysfunction in major de-pressive disorder: a state-of-the-art clinical review. CNS Neurol. Disord. DrugTargets. — 2014. — Vol.13. — P.1804– 1818.
4. Buist-Bouwman M.A., Ormel J., de Graaf, R., de Jonge, P., van Sonderen, E., Alonso, J., Bruffaerts, R., Vollebergh, W.A. Mediators of the association between depression and role functioning. ActaPsychiatr. Scand. — 2008. — Vol.118 — P.451– 458.
5. Ferrari, A.J., Charlson, F.J., Norman, R.E., Patten, S.B., Freedman, G., Murray, C.J., Vos, T., Whiteford, H.A. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoSMed. — 2013. — Vol.10. — e100-1547.
6. Gualtieri, C.T., Johnson, L.G., Benedict, K.B. Neurocognition in depression: patients on and off medication versus healthy comparison subjects. J. NeuropsychiatryClin. Neurosci. — 2006. — Vol.18. — P.217–225.
7. Gualtieri, C.T., Morgan, D.W. The frequency of cognitive impairment in patients with anxiety, depression, and bipolar disorder: an unaccounted source of variance in clinical trials. J. Clin. Psychiatry — 2008. — Vol.69. — P. 1122–1130.
8. Harvey, P.D., Jacobson, W., Zhong, W., Nomikos, G., Christensen, M.C., Kurre Olsen, C., Merikle, E. Determination of a clinically important difference and definition of a responder threshold for the UCSD performance-based skills assessment (UPSA) in patients with major depressive disorder. J. Affect. Disord. — 2017. — Vol.15. — P.105– 111.
9. Harvey, S.B., Glozier, N., Henderson, M., Allaway, S., Litchfield, P., Holland-Elliott, K., Hotopf, M. Depression and work performance: an ecological study using web-based screening. Occup. Med. — 2011. — Vol.61. — P.209–211.
10. Hays, R.D., Wells, K.B., Sherbourne, C.D., Rogers, W., Spritzer, K., Functioning and well-being outcomes of patients with depression compared with chronic general medical illnesses. Arch. Gen. Psychiatry. — 1995. — Vol.52. — P.11–19.
11. Jacobson, W., Harvey, P.D., Merikle, E., Zhong, W., Nomikos, G., Olsen, C.K., Christensen, M.C., 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. Int. J. Neuropsychopharmacol. — 2016. — Vol.19 (Issue Suppl_1) — P.28. Doi: 10.1093/ijnp/pyw043.08.
12. Jaeger, J., Berns, S., Uzelac, S., Davis-Conway, S. Neurocognitive deficits and disability in major depressive disorder. PsychiatryRes. — 2006. — Vol.145. — P.39–48.
13. Katona, C., Hansen, T., Olsen, C.K., A randomized, double-blind, placebo-controlled, duloxetinereferenced, fixed-dose study comparing the effcacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int. Clin. Psychopharmacol. — 2012. — Vol.27. — P.215– 223.
14. Kiosses, D.N., Klimstra, S., Murphy, C., Alexopoulos, G.S., Executive dysfunction and disability in elderly patients with major depression. Am. J. Geriatr. Psychiatry. — 2001. — Vol.9. — P.269– 274.
15. Lam, R.W., Parikh, S.V., Michalak, E.E., Dewa, C.S., Kennedy, S.H. Canadiannetwork for mood and anxiety treatments (CANMAT) consensus recommendations for functional outcomes in major depressive disorder. Ann. Clin. Psychiatry. — 2015. — Vol.27. — P.142–149.
16. Lam, R.W., Filteau, M.J., Milev, R. Clinical effectiveness: the importance of psy-chosocial functioning outcomes. J. Affect. Disord. — 2011. — Vol.132 (Suppl 1). — P.9–13.
17. Mahableshwarkar, A.R., Zajecka, J., Jacobson, W., Chen, Y., Keefe, R.S.. A ran-domized, placebo-controlled, active-reference, doubleblind, flexible-dose study of the effcacy of vortioxetine on cognitive function in major depressive disorder. Neuropsychopharmacology. — 2015. — Vol.22 — P.2025–2037.
18. McIntyre, R.S., Florea, I., Tonnoir, B., Loft, H., Lam, R.W., Christensen, M.C. Effcacy of vortioxetine on cognitive functioning in working patients with major depressive disorder. J. Clin. Psychiatry. — 2017. — Vol.78 (1). — P.115–121.
19. McIntyre, R.S., Xiao, H.X., Syeda, K., Vinberg, M., Carvalho, A.F., Mansur, R.B., Maruschak, N., Cha, D.S. Theprevalence, measurement, andtreatmentofthecognitivedimension/ domaininmajordepressivedisorder. CNS Drugs. — 2015a. — Vol.29. — P.577–589.
20. McIntyre, R.S., Soczynska, J.Z., Woldeyohannes, H.O., Alsuwaidan, M.T., Cha, D.S., Carvalho, A.F., Jerrell, J.M., Dale, R.M., Gallaugher, L.A., Muzina, D.J., Kennedy, S.H. Theimpactofcognitiveimpairmentonperceivedworkforceperformance: resultsfromtheInternationalmooddisorderscollaborativeproject. Compr. Psychiatry. — 2015. — Vol.56. — P.279–282.
21. McIntyre, R.S., Lophaven, S., Olsen, C.K. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int. J. Neuropsychopharmacol. — 2014. — Vol.17. — P.1557–1567.
22. Moussavi, S., Chatterji, S., Verdes, E., Tandon, A., Patel, V., Ustun, B. Depression, chronic diseases, and decrements in health: results from the world health surveys. Lancet. — 2007. — Vol.370. — P.851–858.
23. Olesen, J., Gustavsson, A., Svensson, M., Wittchen, H.U., Jonsson, B. The economic cost of brain disorders in Europe. Eur. J. Neurol. — 2012. — Vol.19. — P.155–162.
24. Patterson, T.L., Goldman, S., McKibbin, C.L., Hughs, T., Jeste, D.V., UCSD perfor-mance-based skills assessment: development of a new measure of everyday func-tioning for severely mentally ill adults. Schizophr. Bull. — 2001. — Vol. 27 (2). P. 235–245.
25. Reppermund, S., Ising, M., Lucae, S., Zihl, J. Cognitive impairment in unipolar depression is persistent and non-specific: further evidence for the final common pathway disorder hypothesis. Psychol. Med. — 2009. — Vol.39. — P.603–614.
26. Sanchez, C., Asin, K.E., Artigas, F. Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol. Ther. — 2015. — Vol.145. — P.43–57.
27. Wells, K.B., Stewart, A., Hays, R.D., Burnam, M.A., Rogers, W., Daniels, M., Berry, S., Greenfield, S., Ware, J. The functioning and well-being of depressed patients. Resultsfromthe Medical outcomesstudy. JAMA. — 1989. — Vol.262. — P.914– 919.
28. Withall, A., Harris, L.M., Cumming, S.R. The relationship between cognitive function and clinical and functional outcomes in major depressive disorder. Psychol. Med. — 2009. — Vol 39. — P.393–402.
29. World Health Organisation, 2017. Depression — fact sheet. http://www.who.int/mediacentre/factsheets/fs369/en/ (Accessed 25 September 2017).
30. Woo, J.M., Kim, W., Hwang, T.Y., Frick, K.D., Choi, B.H., Seo, Y.J., Kang, E.H., Kim, S.J., Ham, B.J., Lee, J.S., Park, Y.L. Impact of depression on work productivity and its improvement after outpatient treatment with antidepressants. ValueHealth. — 2011. — Vol.14. — P.475–482.
Review
For citations:
Christensen М.С., Loft Н., McIntyre R.S. Vortioxetine improves symptomatic and functional outcomes in major depressive disorder: a novel dual outcome measure in depressive disorders. V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY. 2019;(2):69-74. (In Russ.)
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