A 10-month, open-label evaluation of desvenlafaxine in outpatients with major depressive disorder

Abstract

Background: The primary objective was to evaluate the long-term safety of desvenlafaxine (administered as desvenlafaxine succinate) during open-label treatment in adult outpatients with a primary DSM-IV diagnosis of major depressive disorder (MDD).

Method: Depressed adult outpatients (≥ 18 years) who had completed 8-week, double-blind therapy (desvenlafaxine, venlafaxine extended release, or placebo) in a phase 3 study of desvenlafaxine for MDD received up to 10 months of open-label treatment with flexible-dose desvenlafaxine (200 to 400 mg/d). Safety assessments included physical examination, measurement of weight and vital signs, laboratory determinations, and 12-lead electrocardiogram recordings. Adverse events (AEs) and discontinuations due to AEs were monitored throughout the trial. The primary efficacy outcome was mean change from baseline on 17-item Hamilton Depression Rating Scale (HDRS-17) total score. The trial was conducted from August 2003 to March 2006.

Results: The safety population included 1,395 patients who took at least 1 dose of open-label desvenlafaxine. Treatment-emergent AEs were reported by 1,238 of 1,395 patients (89%) during the open-label, on-therapy period. Treatment-emergent AEs reported by 10% or more patients were headache, nausea, hyperhidrosis, dizziness, dry mouth, insomnia, upper respiratory infection, nasopharyngitis, and fatigue. Adverse events were the primary reason for study discontinuation in 296 of 1,395 patients (21%). Ten patients (< 1%) had serious AEs that were considered possibly, probably, or definitely related to the study drug during the on-therapy period. No deaths occurred during the study.

Conclusions: Desvenlafaxine can be safely administered for up to 12 months. No new safety findings were observed in this study.

Trial registration: clinicaltrials.gov Identifier: NCT01309542.

Figures

Figure 1

Patient Flowchart aCompleters were defined as patients who had at least 297 days of exposure to the study drug and who also completed the evaluations scheduled for study day 300; some patients, although completing the visit schedule, were not considered to be completers because their final evaluation occurred before day 297. Abbreviation: HDRS-17 = 17-item Hamilton Depression Rating Scale.

Figure 2

Percentage of Patients Reporting Nausea During the Acute Phase + Extension Study and During the Extension Study Only

Figure 3

HDRS-17 Total Score Mean Change From Baseline (LOCF, ITT population) aExtension study day 0 = week 8 from the acute-phase studies. Abbreviations: HDRS-17 = 17-item Hamilton Depression Rating Scale, ITT = intent to treat, LOCF = last observation carried forward.

Figure 4

HDRS-17 Remission Rates (LOCF, ITT) aExtension baseline = week 8 from the acute-phase studies. Abbreviations: HDRS-17 = 17-item Hamilton Depression Rating Scale, ITT = intent to treat, LOCF = last observation carried forward.