Relapse Prevention Study Of Desvenlafaxine Succinate Sustained Release In Outpatients With Major Depressive Disorder

The primary purpose of this study is to compare the long-term efficacy and safety of desvenlafaxine succinate sustained release versus placebo in adults with Major Depressive Disorder, using a randomized withdrawal design. Randomized withdrawal means that after receiving desvenlafaxine succinate sustained release for a predetermined period of time, subjects will be selected by chance to either continue receiving the study drug or to be withdrawn from the study drug and receive placebo for the remainder of their participation in the trial. Subjects will not know to which group they have been assigned.

The study consists of an up to 14-day screening period followed by an 8-week open-label period in which subjects will knowingly receive 50 mg/day of desvenlafaxine succinate sustained release. Subjects who do not respond to treatment, demonstrating no significant change in their depressive symptoms, will be withdrawn from participation at the end of this period. Responding subjects will receive an additional 3 months of open-label desvenlafaxine succinate sustained release at the same dose. Subjects with stable response to treatment at the conclusion of this 3 month period will be randomized to either desvenlafaxine succinate sustained release at 50 mg/day or placebo in a blinded manner for an additional 6 months or until symptoms of depression return. Following discontinuation at any point after enrollment in the study, subjects will receive two weeks of follow-up monitoring, including one week of blinded taper with 25 mg/day of desvenlafaxine succinate sustained release treatment for any subjects who have been taking desvenlafaxine succinate sustained release prior to discontinuation. Subjects assigned to placebo will receive a blinded placebo taper. Following taper, subjects will be evaluated for one additional week to monitor safety.

• Drug: Desvenlafaxine succinate sustained release 50 mg
  50 mg tablet, once daily. 5 months open-label duration for all enrolled subjects; additional 6 months double-blind duration for randomized subjects assigned to this arm.
  Other Name: Pristiq
• Drug: Desvenlafaxine succinate sustained release 25 mg
  25 mg tablet for taper, once daily for 1 week
  Other Name: Pristiq
• Drug: Placebo
  Matching placebo tablet, once daily. 6 months double-blind duration for randomized subjects assigned to placebo.

• Experimental: Desvenlafaxine succinate sustained release 50 mg
  Interventions:

  • Drug: Desvenlafaxine succinate sustained release 50 mg
  • Drug: Desvenlafaxine succinate sustained release 25 mg
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Boyer P, Vialet C, Hwang E, Tourian KA. Efficacy of Desvenlafaxine 50 mg/d Versus Placebo in the Long-Term Treatment of Major Depressive Disorder: A Randomized, Double-Blind Trial. Prim Care Companion CNS Disord. 2015 Aug 27;17(4). doi: 10.4088/PCC.14m01711. eCollection 2015.
• McIntyre RS, Fayyad RS, Guico-Pabia CJ, Boucher M. A Post Hoc Analysis of the Effect of Weight on Efficacy in Depressed Patients Treated With Desvenlafaxine 50 mg/d and 100 mg/d. Prim Care Companion CNS Disord. 2015 Jun 4;17(3). doi: 10.4088/PCC.14m01741. eCollection 2015.
• McIntyre RS, Fayyad RS, Guico-Pabia CJ, Boucher M. An Analysis of Relapse Rates and Predictors of Relapse in 2 Randomized, Placebo-Controlled Trials of Desvenlafaxine for Major Depressive Disorder. Prim Care Companion CNS Disord. 2015 Feb 26;17(1). doi: 10.4088/PCC.14m01681. eCollection 2015.
• Thase ME, Fayyad R, Cheng RF, Guico-Pabia CJ, Sporn J, Boucher M, Tourian KA. Effects of desvenlafaxine on blood pressure in patients treated for major depressive disorder: a pooled analysis. Curr Med Res Opin. 2015 Apr;31(4):809-20. doi: 10.1185/03007995.2015.1020365. Epub 2015 Mar 26.
• Rosenthal JZ, Boyer P, Vialet C, Hwang E, Tourian KA. Efficacy and safety of desvenlafaxine 50 mg/d for prevention of relapse in major depressive disorder:a randomized controlled trial. J Clin Psychiatry. 2013 Feb;74(2):158-66. doi: 10.4088/JCP.12m07974.

Inclusion Criteria:

• Adult, outpatient with primary diagnosis of Major Depressive Disorder (depressive symptoms for at least 30 days prior to screening)
• Hamilton Psychiatric Rating Scale for Depression (HAM-D 17) total score of >= 20
• Clinical Global Impressions Scale-Severity (CGI-S) score of >= 4.

Exclusion Criteria:

• Significant risk of suicide as assessed by clinician judgment, HAM-D17 and Columbia Suicide-Severity Rating Scale scores.
• Past treatment with desvenlafaxine succinate sustained release.
• Other eligibility criteria also apply.