Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-25T16:09:06.940Z Has data issue: false hasContentIssue false
  • English
  • Français

Predictors of functional response and remission with desvenlafaxine 50 mg and 100 mg: a pooled analysis of randomized, placebo-controlled studies in patients with major depressive disorder

Published online by Cambridge University Press:  07 May 2019

Claudio N. Soares Open the ORCID record for Claudio N. Soares [Opens in a new window] ,
Dalia B. Wajsbrot  and
Matthieu Boucher
Claudio N. Soares*
Affiliation:
Queen’s University School of Medicine, Kingston, ON, Canada
Dalia B. Wajsbrot
Affiliation:
Pfizer Inc, New York, NY, USA
Matthieu Boucher
Affiliation:
Pfizer Canada Inc, Kirkland, QC, Canada McGill University, Montréal, QC, Canada
*
* Address correspondence to: Claudio N. Soares, MD, PhD, FRCPC, MBA, Professor of Psychiatry, Queen’s University School of Medicine, Department of Psychiatry c/o Providence Care Hospital, 752 King St W, Kingston, ON K7L 4X3, Canada. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective.

The value of early functional improvement at week 2 for predicting subsequent functional outcomes at week 8 was assessed in a pooled analysis of patients with major depressive disorder (MDD) treated with desvenlafaxine (50 or 100 mg/d) or placebo.

Methods.

Data were pooled from eight double-blind, placebo-controlled studies of desvenlafaxine 50 mg/d or 100 mg/d for the treatment of MDD. Optimal week-2 improvement thresholds in Sheehan Disability Scale (SDS) score, which best predicted week-8 treatment success, were determined using receiver operating characteristic (ROC) analysis. Four definitions of treatment success were established: (1) functional response, (2) functional/depression response, (3) functional remission, and (4) functional/depression remission. Odds ratios (ORs) of early improvement for prediction (based on thresholds determined in the ROC analysis) of week-8 treatment success were computed using logistic regression models.

Results.

Functional early improvement thresholds of 17%–32% were predictive of week-8 treatment success across treatment groups and definitions of treatment success. Optimal thresholds were higher for more stringent definitions. Negative predictive value exceeded positive predictive value, indicating that failure to achieve early functional improvement was more informative about later treatment success than was the achievement of early functional improvement. Early change in SDS was a highly significant predictor of functional response/remission (ORs, 4.981–8.737; all p < 0.0001); the interaction between treatment and early functional improvement was not significant.

Conclusion.

Early improvement in SDS total score was predictive of functional outcomes for patients treated with desvenlafaxine 50 mg, desvenlafaxine 100 mg, or placebo.

Keywords

Antidepressantsmajor depressive disorderpredictive value of teststreatment outcome
Type
Original Research
Information
CNS Spectrums , Volume 25 , Issue 3 , June 2020 , pp. 363 - 371
Copyright
© Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

This study was sponsored by Pfizer Inc. Medical writing support was provided by Kathleen M. Dorries, PhD, of Peloton Advantage, LLC, an OPEN Health Company, and was funded by Pfizer Inc. Xuemei Wang of Syneos Health wrote the Statistical Analysis Plan and oversaw programming activities. Statistical programming was performed by Eliassen Group.

References

World Health Organization. The global burden of disease. 2004 update. Available at: http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/index.html. Accessed: January 11, 2019.Google Scholar
World Health Organization. Depression. Fact sheet 369. 2017. Available at: http://www.who.int/mediacentre/factsheets/fs369/en/. Accessed: January 11, 2019.Google Scholar
Greer, TL, Kurian, BT, Trivedi, MH.Defining and measuring functional recovery from depression. CNS Drugs. 2010; 24(4):267–284.Google Scholar
American Psychiatric Association. Depressive Disorders. In: Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: American Psychiatric Association; 2013:155–188.Google Scholar
Gelenberg, AJ, Freeman, MP, Markowitz, JC, et al. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 2010. Available at: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed: January 11, 2019.Google Scholar
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.Google Scholar
Habert, J, Katzman, MA, Oluboka, OJ, et al.Functional recovery in major depressive disorder: focus on early optimized treatment. Prim Care Companion CNS Disord. 2016; 18(5).Google Scholar
Oluboka, OJ, Katzman, MA, Habert, J, et al.Functional recovery in major depressive disorder: providing early optimal treatment for the individual patient. Int J Neuropsychopharmacol. 2018; 21(2):128–144.Google Scholar
Machado, M, Iskedjian, M, Ruiz, I, Einarson, TR.Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials. Curr Med Res Opin. 2006; 22(9):1825–1837.Google Scholar
Rush, AJ, Trivedi, MH, Wisniewski, SR, et al.Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11):1905–1917.Google Scholar
Gormley, N, O’Leary, D, Costello, F.First admissions for depression: is the ‘no-treatment interval’ a critical predictor of time to remission? J Affect Disord. 1999; 54(1-2):49–54.Google Scholar
Okuda, A, Suzuki, T, Kishi, T, et al.Duration of untreated illness and antidepressant fluvoxamine response in major depressive disorder. Psychiatry Clin Neurosci. 2010; 64(3):268–273.Google Scholar
Bukh, JD, Bock, C, Vinberg, M, Kessing, LV.The effect of prolonged duration of untreated depression on antidepressant treatment outcome. J Affect Disord. 2013; 145(1):42–48.Google Scholar
Ghio, L, Gotelli, S, Marcenaro, M, Amore, M, Natta, W.Duration of untreated illness and outcomes in unipolar depression: a systematic review and meta-analysis. J Affect Disord. 2014; 152-154:45–51.Google Scholar
Moylan, S, Maes, M, Wray, NR, Berk, M.The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications. Mol Psychiatry. 2013; 18(5):595–606.Google Scholar
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.Google Scholar
Soares, CN, Fayyad, RS, Guico-Pabia, CJ.Early improvement in depressive symptoms with desvenlafaxine 50 mg/d as a predictor of treatment success in patients with major depressive disorder. J Clin Psychopharmacol. 2014; 34(1):57–65.Google Scholar
DeMartinis, NA, Yeung, PP, Entsuah, R, Manley, AL.A double-blind, placebo-controlled study of the efficacy and safety of desvenlafaxine succinate in the treatment of major depressive disorder. J Clin Psychiatry. 2007; 68(5):677–688.Google Scholar
Liebowitz, MR, Manley, AL, Padmanabhan, SK, Ganguly, R, Tummala, R, Tourian, KA.Efficacy, safety, and tolerability of desvenlafaxine 50 mg/day and 100 mg/day in outpatients with major depressive disorder. Curr Med Res Opin. 2008; 24(7):1877–1890.Google Scholar
Boyer, P, Montgomery, S, Lepola, U, et al.Efficacy, safety, and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/day for major depressive disorder in a placebo-controlled trial. Int Clin Psychopharmacol. 2008; 23(5):243–253.Google Scholar
Tourian, KA, Padmanabhan, SK, Groark, J, Brisard, C, Farrington, D.Desvenlafaxine 50 and 100 mg/d in the treatment of major depressive disorder: an 8-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial and a post hoc pooled analysis of three studies. Clin Ther. 2009; 31 Pt 1:1405–1423.Google Scholar
Iwata, N, Tourian, KA, Hwang, E, Mele, L, Vialet, C, for the Study 3359 investigators. Efficacy and safety of desvenlafaxine 25 and 50 mg/day in a randomized, placebo-controlled study of depressed outpatients. J Psychiatr Pract. 2013; 19(1):5–14.Google Scholar
Clayton, AH, Kornstein, SG, Dunlop, BW, et al.Efficacy and safety of desvenlafaxine 50 mg/d in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder. J Clin Psychiatry. 2013; 74(10):1010–1017.Google Scholar
Dunlop, BW, Reddy, S, Yang, L, Lubaczewski, S, Focht, K, Guico-Pabia, CJ.Symptomatic and functional improvement in employed depressed patients: a double-blind clinical trial of desvenlafaxine versus placebo. J Clin Psychopharmacol. 2011; 31(5):569–576.Google Scholar
Soares, CN, Endicott, J, Boucher, M, Fayyad, RS, Guico-Pabia, CJ.Predictors of functional response and remission with desvenlafaxine 50 mg/d in patients with major depressive disorder. CNS Spectr. 2014; 19(6):519–527.Google Scholar
Lam, RW, Endicott, J, Hsu, MA, Fayyad, R, Guico-Pabia, C, Boucher, M.Predictors of functional improvement in employed adults with major depressive disorder treated with desvenlafaxine. Int Clin Psychopharmacol. 2014; 29(5):239–251.Google Scholar
Sheehan, DV.Sheehan Disability Scale. In: Rush, AJ, Pincus, HA, First, MB, eds. Handbook of Psychiatric Measures. Washington, DC: American Psychiatric Association; 2000:113–115.Google Scholar
Liebowitz, MR, Tourian, KA, Hwang, E, Mele, L, for the Study 3362 investigators. A double-blind, randomized, placebo-controlled study assessing the efficacy and tolerability of desvenlafaxine 10 and 50 mg/d in adult outpatients with major depressive disorder. BMC Psychiatry. 2013; 13(1):94.Google Scholar
Hamilton, M.A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23:56–62.Google Scholar
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Publishing; 1994.Google Scholar
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Text Revision. 4th ed. Washington, DC: American Psychiatric Publishing; 2000.Google Scholar
Montgomery, SA, Asberg, M.A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979; 134:382–389.Google Scholar
Sheehan, DV, Harnett-Sheehan, K, Spann, ME, Thompson, HF, Prakash, A.Assessing remission in major depressive disorder and generalized anxiety disorder clinical trials with the discan metric of the Sheehan disability scale. Int Clin Psychopharmacol. 2011; 26(2):75–83.Google Scholar
Sheehan, KH, Sheehan, DV.Assessing treatment effects in clinical trials with the discan metric of the Sheehan Disability Scale. Int Clin Psychopharmacol. 2008; 23(2):70–83.Google Scholar
Gallop, RJ.Determination and interpretation of the OOP for ROC’s with PROC LOGISTIC. Proceedings of the NorthEast SAS Users Group. Baltimore, MD: NorthEast SAS Users Group; 2001:777–782.Google Scholar
Gorwood, P, Vaiva, G, Corruble, E, Llorca, PM, Bayle, FJ, Courtet, P.The ability of early changes in motivation to predict later antidepressant treatment response. Neuropsychiatr Dis Treat. 2015; 11:2875–2882.Google Scholar
Pristiq [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals, Inc, a subsidiary of Pfizer Inc; 2018.Google Scholar
Thase, ME, Kornstein, SG, Germain, JM, Jiang, Q, Guico-Pabia, C, Ninan, PT.An integrated analysis of the efficacy of desvenlafaxine compared with placebo in patients with major depressive disorder. CNS Spectrums. 2009; 14(3):144–154.Google Scholar
Quitkin, FM, McGrath, PJ, Stewart, JW, Taylor, BP, Klein, DF.Can the effects of antidepressants be observed in the first two weeks of treatment? Neuropsychopharmacology. 1996; 15(4):390–394.Google Scholar
Stewart, JW, Quitkin, FM, McGrath, PJ, et al.Use of pattern analysis to predict differential relapse of remitted patients with major depression during 1 year of treatment with fluoxetine or placebo. Arch Gen Psychiatry. 1998; 55(4):334–343.Google Scholar
Quitkin, FM, Taylor, BP, Kremer, C.Does mirtazapine have a more rapid onset than SSRIs? J Clin Psychiatry. 2001; 62(5):358–361.Google Scholar
Posternak, MA, Zimmerman, M.Is there a delay in the antidepressant effect? A meta-analysis. J Clin Psychiatry. 2005; 66(2):148–158.Google Scholar
Stassen, HH, Angst, J, Hell, D, Scharfetter, C, Szegedi, A.Is there a common resilience mechanism underlying antidepressant drug response? Evidence from 2848 patients. J Clin Psychiatry. 2007; 68(8):1195–1205.Google Scholar
Khan, A, Redding, N, Brown, WA.The persistence of the placebo response in antidepressant clinical trials. J Psychiatr Res. 2008; 42(10):791–796.Google Scholar
Tokuoka, H, Takahashi, H, Ozeki, A, et al.Trajectories of depression symptom improvement and associated predictor analysis: an analysis of duloxetine in double-blind placebo-controlled trials. J Affect Disord. 2016; 196:171–180.Google Scholar
Henssler, J, Kurschus, M, Franklin, J, Bschor, T, Baethge, C.Trajectories of acute antidepressant efficacy: how long to wait for response? A systematic review and meta-analysis of long-term, placebo-controlled acute treatment trials. J Clin Psychiatry. 2018; 79(3).Google Scholar
Henssler, J, Kurschus, M, Franklin, J, Bschor, T, Baethge, C.Long-term acute-phase treatment with antidepressants, 8 weeks and beyond: a systematic review and meta-analysis of randomized, placebo-controlled trials. J Clin Psychiatry. 2018; 79(1).Google Scholar
Kudlow, PA, McIntyre, RS, Lam, RW.Early switching strategies in antidepressant non-responders: current evidence and future research directions. CNS Drugs. 2014; 28(7):601–609.Google Scholar
Supplementary material: File

Soares et al. supplementary material

Soares et al. supplementary material 1

Download Soares et al. supplementary material(File)
File 23 KB