This article is available to members only. Please enjoy the abstract for free. Subscribe for instant access to the full article.

This content is restricted to subscribers

Continue Reading...

Did you know members enjoy unlimited free PDF downloads as part of their subscription? Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.

Subscribe Now

Already a member? Login

Purchase PDF for $40

Members enjoy free PDF downloads on all articles. Join today

  1. Clinical Trials and Network Institute, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
  2. Clinical Trials and Network Institute, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
  3. Corresponding author: George I. Papakostas, MD, Clinical Trials and Network Institute, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, One Bowdoin Sq, 9th Floor, Boston, MA 02114 ([email protected]).
  4. Clinical Trials and Network Institute, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
  5. Clinical Trials and Network Institute, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
  6. Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, Texas
  7. Michael E. Debakey VA Medical Center Mental Health Care Line, Houston, Texas
  8. Clinical Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York
  9. Department of Psychiatry, New York University School of Medicine, New York, New York
  10. Depression and Anxiety Center for Discovery and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
  11. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
  12. Department of Psychiatry and Behavioral Neurobiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama
  13. Clinical Trials and Network Institute, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
  14. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
  15. Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, Dallas, Texas
  1. Papakostas GI, Jackson WC, Rafeyan R, et al. Inadequate response to antidepressant treatment in major depressive disorder. J Clin Psychiatry. 2020;81(3):OT19037COM5. PubMed
  2. Papakostas GI, Jackson WC, Rafeyan R, et al. Overcoming challenges to treat inadequate response in major depressive disorder. J Clin Psychiatry. 2020;81(3):OT19037BR4. PubMed
  3. Rafeyan R, Papakostas GI, Jackson WC, et al. Inadequate response to treatment in major depressive disorder: augmentation and adjunctive strategies. J Clin Psychiatry. 2020;81(3):OT19037BR3. PubMed CrossRef
  4. Jackson WC, Papakostas GI, Rafeyan R, et al. Recognizing inadequate response in patients with major depressive disorder. J Clin Psychiatry. 2020;81(3):OT19037BR2. PubMed CrossRef
  5. Trivedi MH, Papakostas GI, Jackson WC, et al. Implementing measurement-based care to determine and treat inadequate response. J Clin Psychiatry. 2020;81(3):OT19037BR1. PubMed CrossRef
  6. Trivedi MH. How can measurement-based care help improve treatment outcomes for major depressive disorder in primary care? J Clin Psychiatry. 2020;81(2):UT17042BR2C. PubMed CrossRef
  7. Trivedi MH. Major depressive disorder in primary care: strategies for identification. J Clin Psychiatry. 2020;81(2):UT17042BR1C. PubMed CrossRef
  8. Citrome L, Gaynes BN, Goldberg JF, et al. New mechanisms, new opportunities: integrating novel antidepressants in the treatment of major depressive disorder. J Clin Psychiatry. 2019;80(5):TK18061AS2C. PubMed CrossRef
  9. Thase ME. Current and emerging treatments to address unmet needs in MDD. J Clin Psychiatry. 2019;80(1):AL18009BR1C. PubMed
  10. Zhang J, Mathis MV, Sellers JW, et al. The US Food and Drug Administration’s perspective on the new antidepressant vortioxetine. J Clin Psychiatry. 2015;76(1):8–14. PubMed CrossRef
  11. Connolly KR, Thase ME. Vortioxetine: a new treatment for major depressive disorder. Expert Opin Pharmacother. 2016;17(3):421–431. PubMed CrossRef
  12. 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. PubMed CrossRef
  13. Jacobsen PL, Mahableshwarkar AR, Serenko M, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with major depressive disorder. J Clin Psychiatry. 2015;76(5):575–582. PubMed CrossRef
  14. Mahableshwarkar AR, Jacobsen PL, Serenko M, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of 2 doses of vortioxetine in adults with major depressive disorder. J Clin Psychiatry. 2015;76(5):583–591. PubMed CrossRef
  15. Baune BT, Brignone M, Larsen KG. A network meta-analysis comparing effects of various antidepressant classes on the Digit Symbol Substitution Test (DSST) as a measure of cognitive dysfunction in patients with major depressive disorder. Int J Neuropsychopharmacol. 2018;21(2):97–107. PubMed CrossRef
  16. Inoue T, Sasai K, Kitagawa T, et al. Randomized, double-blind, placebo-controlled study to assess the efficacy and safety of vortioxetine in Japanese patients with major depressive disorder. Psychiatry Clin Neurosci. 2020;74(2):140–148. PubMed CrossRef
  17. Papakostas GI. Antidepressants and their effect on cognition in major depressive disorder. J Clin Psychiatry. 2015;76(8):e1046. PubMed CrossRef
  18. Papakostas GI, Culpepper L. Understanding and managing cognition in the depressed patient. J Clin Psychiatry. 2015;76(4):418–425. PubMed CrossRef
  19. Berhan A, Barker A. Vortioxetine in the treatment of adult patients with major depressive disorder: a meta-analysis of randomized double-blind controlled trials. BMC Psychiatry. 2014;14(1):276. PubMed CrossRef
  20. Meeker AS, Herink MC, Haxby DG, et al. The safety and efficacy of vortioxetine for acute treatment of major depressive disorder: a systematic review and meta-analysis. Syst Rev. 2015;4(1):21. PubMed CrossRef
  21. Pae CU, Wang SM, Han C, et al. Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder. J Psychiatry Neurosci. 2015;40(3):174–186. PubMed CrossRef
  22. Baldwin DS, Florea I, Jacobsen PL, et al. A meta-analysis of the efficacy of vortioxetine in patients with major depressive disorder (MDD) and high levels of anxiety symptoms. J Affect Disord. 2016;206:140–150. PubMed CrossRef
  23. 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. PubMed CrossRef
  24. Koesters M, Ostuzzi G, Guaiana G, et al. Vortioxetine for depression in adults. Cochrane Database Syst Rev. 2017;7(7):CD011520. PubMed
  25. Nomikos GG, Tomori D, Zhong W, et al. Efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients aged 55 years or older. CNS Spectr. 2017;22(4):348–362. PubMed CrossRef
  26. Christensen MC, Florea I, Lindsten A, et al. Efficacy of vortioxetine on the physical symptoms of major depressive disorder. J Psychopharmacol. 2018;32(10):1086–1097. PubMed CrossRef
  27. Zheng J, Wang Z, Li E. The efficacy and safety of 10 mg/day vortioxetine compared to placebo for adult major depressive disorder: a meta-analysis. Afr Health Sci. 2019;19(1):1716–1726. PubMed CrossRef
  28. Papakostas GI, Charles D, Fava M. Are typical starting doses of the selective serotonin reuptake inhibitors sub-optimal? a meta-analysis of randomized, double-blind, placebo-controlled, dose-finding studies in major depressive disorder. World J Biol Psychiatry. 2010;11(2 pt 2):300–307. PubMed CrossRef
  29. Papakostas GI, Fava M. Does the probability of receiving placebo influence clinical trial outcome? a meta-regression of double-blind, randomized clinical trials in MDD. Eur Neuropsychopharmacol. 2009;19(1):34–40. PubMed CrossRef
  30. Iovieno N, Nierenberg AA, Parkin SR, et al. Relationship between placebo response rate and clinical trial outcome in bipolar depression. J Psychiatr Res. 2016;74:38–44. PubMed CrossRef
  31. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134(4):382–389. PubMed CrossRef
  32. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50–55. PubMed CrossRef
  33. Jaeger J. Digit symbol substitution test: the case for sensitivity over specificity in neuropsychological testing. J Clin Psychopharmacol. 2018;38(5):513–519. PubMed CrossRef
  34. Lenze EJ, Stevens A, Waring JD, et al. Augmenting computerized cognitive training with vortioxetine for age-related cognitive decline: a randomized controlled trial. Am J Psychiatry. 2020;177(6):548–555. PubMed CrossRef
  35. Vieta E, Florea I, Schmidt SN, et al. Intravenous vortioxetine to accelerate onset of effect in major depressive disorder: a 2-week, randomized, double-blind, placebo-controlled study. Int Clin Psychopharmacol. 2019;34(4):153–160. PubMed CrossRef
  36. Nierenberg AA, Loft H, Olsen CK. Treatment effects on residual cognitive symptoms among partially or fully remitted patients with major depressive disorder: a randomized, double-blinded, exploratory study with vortioxetine. J Affect Disord. 2019;250:35–42. PubMed CrossRef
  37. Smith J, Browning M, Conen S, et al. Vortioxetine reduces BOLD signal during performance of the N-back working memory task: a randomised neuroimaging trial in remitted depressed patients and healthy controls. Mol Psychiatry. 2018;23(5):1127–1133. PubMed CrossRef
  38. Boulenger JP, Loft H, Florea I. A randomized clinical study of Lu AA21004 in the prevention of relapse in patients with major depressive disorder. J Psychopharmacol. 2012;26(11):1408–1416. PubMed CrossRef
  39. Baldwin DS, Loft H, Dragheim M. A randomised, double-blind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of Lu AA21004 in acute treatment of major depressive disorder (MDD). Eur Neuropsychopharmacol. 2012;22(7):482–491. PubMed CrossRef
  40. Mahableshwarkar AR, Jacobsen PL, Chen Y. A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder. Curr Med Res Opin. 2013;29(3):217–226. PubMed CrossRef
  41. Jain R, Mahableshwarkar AR, Jacobsen PL, et al. A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder. Int J Neuropsychopharmacol. 2013;16(2):313–321. PubMed CrossRef
  42. 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. PubMed CrossRef
  43. 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. PubMed CrossRef
  44. Alvarez E, Perez V, Dragheim M, et al. A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. Int J Neuropsychopharmacol. 2012;15(5):589–600. PubMed CrossRef
  45. Mahableshwarkar AR, Jacobsen PL, Chen Y, et al. A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015;232(12):2061–2070. PubMed CrossRef
  46. Nishimura A, Aritomi Y, Sasai K, et al. Randomized, double-blind, placebo-controlled 8-week trial of the efficacy, safety, and tolerability of 5, 10, and 20 mg/day vortioxetine in adults with major depressive disorder. Psychiatry Clin Neurosci. 2018;72(2):64–72. PubMed CrossRef
  47. Inoue T, Nishimura A, Sasai K, et al. Randomized, 8-week, double-blind, placebo-controlled trial of vortioxetine in Japanese adults with major depressive disorder, followed by a 52-week open-label extension trial. Psychiatry Clin Neurosci. 2018;72(2):103–115. PubMed CrossRef
  48. Baune BT, Sluth LB, Olsen CK. The effects of vortioxetine on cognitive performance in working patients with major depressive disorder: a short-term, randomized, double-blind, exploratory study. J Affect Disord. 2018;229:421–428. PubMed CrossRef
  49. McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014;17(10):1557–1567. PubMed CrossRef
  50. 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. 2016;41(12):2961. PubMed CrossRef
  51. Liebowitz MR, Careri J, Blatt K, et al. Vortioxetine versus placebo in major depressive disorder comorbid with social anxiety disorder. Depress Anxiety. 2017;34(12):1164–1172. PubMed CrossRef
  52. Thase M, Asami Y, Wajsbrot D, et al. A meta-analysis of the efficacy of venlafaxine extended release 75–225 mg/day for the treatment of major depressive disorder. Curr Med Res Opin. 2017;33(2):317–326. PubMed CrossRef
  53. Ball SG, Desaiah D, Zhang Q, et al. Efficacy and safety of duloxetine 60 mg once daily in major depressive disorder: a review with expert commentary. Drugs Context. 2013;2013:212245. PubMed
  54. Gopalakrishnan M, Zhu H, Farchione TR, et al. The trend of increasing placebo response and decreasing treatment effect in schizophrenia trials continues: an update from the US Food and Drug Administration. J Clin Psychiatry. 2020;81(2):19r12960. PubMed CrossRef
  55. Salloum NC, Fava M, Ball S, et al. Success and efficiency of phase 2/3 adjunctive trials for MDD funded by industry: a systematic review. Mol Psychiatry. 2020;25(9):1967–1974. PubMed CrossRef
  56. Papakostas GI, Østergaard SD, Iovieno N. The nature of placebo response in clinical studies of major depressive disorder. J Clin Psychiatry. 2015;76(4):456–466. PubMed CrossRef
  57. Trivedi MH, South C, Jha MK, et al. A novel strategy to identify placebo responders: prediction index of clinical and biological markers in the EMBARC Trial. Psychother Psychosom. 2018;87(5):285–295. PubMed CrossRef
  58. Zimmerman M, Balling C, Chelminski I, et al. Have treatment studies of depression become even less generalizable? applying the inclusion and exclusion criteria in placebo-controlled antidepressant efficacy trials published over 20 years to a clinical sample. Psychother Psychosom. 2019;88(3):165–170. PubMed CrossRef
  59. Iltis AS, McCall WV, Deria R. Suicidality, depression, and the FDA: health inequities and the ethical conduct of research. J Clin Psychiatry. 2020;81(2):19m13050. PubMed CrossRef
  60. Fava M, Rush AJ, Alpert JE, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry. 2008;165(3):342–351. PubMed CrossRef