A multicenter, randomized, double-blind, duloxetine-controlled, non-inferiority trial of desvenlafaxine succinate extended-release in patients with major depressive disorder

J Affect Disord. 2023 May 15:329:72-80. doi: 10.1016/j.jad.2023.02.067. Epub 2023 Feb 20.

Abstract

Background: Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses. This study evaluated the non-inferiority of desvenlafaxine extended-release (XL) to duloxetine in patients with major depressive disorder (MDD).

Methods: In this study, 420 adult patients with moderate-to-severe MDD were enrolled and randomly assigned (1:1) to receive 50 mg (once daily [QD]) of desvenlafaxine XL (n = 212) or 60 mg QD of duloxetine (n = 208). The primary endpoint was evaluated using a non-inferiority comparison based on the change from baseline to 8 weeks in the 17-item Hamilton Depression Rating Scale (HAMD17) total score. Secondary endpoints and safety were evaluated.

Results: Least-squares mean change in HAM-D17 total score from baseline to 8 weeks was -15.3 (95% confidence interval [CI]: -17.73, -12.89) in the desvenlafaxine XL group and - 15.9 (95% CI, -18.44, -13.39) in the duloxetine group. The least-squares mean difference was 0.6 (95% CI: -0.48, 1.69), and the upper boundary of 95% CI was less than the non-inferiority margin (2.2). No significant between-treatment differences were found in most secondary efficacy endpoints. The incidence of the most common treatment-emergent adverse events (TEAEs) was lower for desvenlafaxine XL than for duloxetine for nausea (27.2% versus 48.8%) and dizziness (18.0% versus 28.8%).

Limitations: A short-term non-inferiority study without a placebo arm.

Conclusions: This study demonstrated that desvenlafaxine XL 50 mg QD was non-inferior to duloxetine 60 mg QD in efficacy in patients with MDD. Desvenlafaxine had a lower incidence of TEAEs than duloxetine did.

Keywords: 17-item Hamilton Depression Rating Scale; Desvenlafaxine; Duloxetine; Major depressive disorder; Non-inferiority.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / adverse effects
  • Depressive Disorder, Major* / chemically induced
  • Depressive Disorder, Major* / drug therapy
  • Desvenlafaxine Succinate / adverse effects
  • Double-Blind Method
  • Duloxetine Hydrochloride / adverse effects
  • Humans
  • Treatment Outcome

Substances

  • Duloxetine Hydrochloride
  • Desvenlafaxine Succinate
  • Antidepressive Agents