A randomized, double-blind study comparing the efficacy and safety of trazodone once-a-day and venlafaxine extended-release for the treatment of patients with major depressive disorder

Abstract

This double-blind, randomized study evaluated the efficacy and safety of trazodone OAD (once-a-day) in comparison with venlafaxine XR (extended-release) in 324 patients (166 trazodone and 158 venlafaxine) with major depressive disorder (MDD). The primary efficacy endpoint was the mean change from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) at week 8. Both treatments were effective in reducing the HAM-D-17 total score at week 8 vs. baseline (intent-to-treat: trazodone –12.9, venlafaxine –14.7; per protocol: trazodone –15.4, venlafaxine –16.4). Patients in the venlafaxine group achieved better results after 8 weeks, whereas the trazodone group achieved a statistically significant reduction in HAM-D-17 following only 7 days of treatment. The most frequent adverse events (AEs) were dizziness and somnolence in the trazodone group, and nausea and headache in the venlafaxine group. Most AEs were mild-to-moderate in severity. This study confirmed that both venlafaxine XR and trazodone OAD may represent a valid treatment option for patients with MDD.

Early response to trazodone once-a-day in major depressive disorder: review of the clinical data and putative mechanism for faster onset of action

“…44,45 Analysis of variance (ANOVA) was used in cases where the statistical assumptions of ANCOVA were not met. 44 Two-sided 95% confidence intervals (CIs) were calculated for the differences in mean score change from baseline for trazodone OAD vs placebo, as well as trazodone OAD vs venlafaxine XR, for the same HAM-D17 outcomes analyzed by ANCOVA or ANOVA. 44 For trazodone OAD vs venlafaxine XR, the noninferiority was accepted if the upper limit of the 95% CIs for the difference between treatments did not surpass the threshold of 3, which represented the maximum difference associated with no clinical relevance.…”

“…48,49 Therefore, we also reviewed the efficacy of trazodone OAD in improving In the placebo-controlled study, conducted by Sheehan et al, 45 trazodone OAD showed a trend for early improvement at Day 7 in the HAM-D anxiety/somatization factor compared to placebo; however, this difference was statistically significant only at Day 21 for both the ITT [95% CI, À1.0; À0.1] and the PP [95% CI, À1.3; À0.2] populations (P < .05) (Figure 2A and Supplementary Figure S3A). In the active-comparator study by Fagiolini et al, 44 both trazodone OAD and venlafaxine showed similar improvements in the anxiety/somatization factor at Day 7, and the difference between the groups was statistically significant in the favor of venlafaxine XR at Days 35 [95% CI, 0.1; 1.0] and 56 [95% CI, 0.3; 1.3] for the ITT population and only at Day 56 [95% CI, 0.0; 1.0] for the PP population (P < .05) (Figure 2B and Supplementary Figure S3B).…”

Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure‐Activity Relationships

“…A phase‐III study of aripiprazole was terminated due to the risk of late neuroleptic malignant syndrome in treated patients (NCT00276978) [124] and no new safety signals were observed [125] . Trazodone, a serotonin modulator, [126] completed the phase‐II and III trial in which the efficiency of its prolonged‐release tablets was determined in depressive patients (NCT01524497) [127–128] . A phase‐III study of another drug olanzapine was also terminated (NCT00273624) as augmentation therapy in treatment‐resistance depression.…”

Trazodone: a multifunctional antidepressant. Evaluation of its properties and real-world use

“…The availability of different formulations (Table III) ensures the efficacy of trazodone in a wide range of 22 . The relatively short elimination half-life (6h) reduces the risk of morning drowsiness 30 . The prolonged-release (P.R.)…”

“…The extended-release (COAD) formulation provides an even more gradual and continuous absorption of the drug into the bloodstream. It allows a simplified once-a-day prescription schedule, thus enhancing adherence, improving tolerability, and avoiding see-sawing blood concentration patterns 30 .…”