A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder

Abstract

This multinational, randomized, double-blind, flexible-dose study evaluated the short- and long-term antidepressant tolerability and efficacy of escitalopram and paroxetine. Tolerability was assessed by monitoring adverse events throughout the study, and discontinuation events during brief treatment interruption and tapered withdrawal. Discontinuation-emergent effects were evaluated in two separate double-blind periods. First, to mimic the consequences of non-compliance, patients were randomized to one of two treatment interruption periods (placebo-substitution for 3-5 days). Second, patients were randomized to a 1-2-week tapered withdrawal period randomly scheduled between weeks 28 and 31. The pre-specified primary efficacy endpoint was the mean change from baseline in total Montgomery-Asberg Depression Rating Scale (MADRS) score at week 8, using the principle of last observation carried forward. A total of 323 patients entered 8 weeks of double-blind treatment and received at least one flexible dose of escitalopram (10-20 mg/day) or paroxetine (20-40 mg/day). Patients who demonstrated evidence of a significant clinical improvement (Clinical Global Impression-Improvement of 1 or 2) at week 8 entered a 19-week, double-blind maintenance period during which they were treated with the same dose they received at week 8, followed by a 1-2-week tapered withdrawal period. A total of 89 patients (28%) withdrew during the study; significantly (P<0.01) more patients withdrew from the paroxetine group (34%) than from the escitalopram group (21%), and significantly (P<0.05) more paroxetine patients withdrew due to lack of efficacy. The mean MADRS total score improved for both treatment groups from baseline to week 8, with no statistical difference between groups. In severely depressed patients (baseline MADRS total score >or=30), escitalopram was superior (P<0.05) to paroxetine at week 27 (end of maintenance treatment). There was a high prevalence of sexual dysfunction at baseline: the mean Arizona Sexual Experience Scale (ASEX) score was approximately 20 points in both treatment groups. Mean total ASEX scores increased slightly above baseline values during the acute period and declined slightly below baseline values towards the end of the maintenance period. During taper and cessation of treatment, patients in the paroxetine group demonstrated significantly more discontinuation symptoms relative to escitalopram based on the Discontinuation Emergent Signs and Symptoms scores.

Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review

“…Baldwin et al [45] evaluated the difference between abrupt and tapered discontinuation when using paroxetine or escitalopram in patients with MDD. Discontinuation-emergent effects were assessed in two separate double-blind periods.…”

Sexual Dysfunction associated with Second-Generation Antidepressants in Patients with Major Depressive Disorder: Results from a Systematic Review with Network Meta-Analysis

“…Antidepressants were the most frequently dispensed prescription drugs in the United States (US) in 2011 accounting for $11 billion in sales and 264 million prescriptions filled [2]. Sexual dysfunction, which can involve any or all phases of the sexual response cycle (i.e., libido, arousal, orgasm and ejaculation), is associated with both the condition and the treatments used, can affect up to 50 percent of untreated depressed patients [3,4].…”

Selective Serotonin Reuptake Inhibitors, are They All Equal? A Pharmacoepidemiological Study

“…However, escitalopram was significantly more effective in 3 studies [18][19][20] while no significant difference was found in 2 studies [21,22]. Two of the 3 studies comparing escitalopram with paroxetine showed the superiority of escitalopram with respect to both safety and efficacy [3,23,24]. All other RCTs found no significant differences in safety or efficacy between SSRIs: escitalopram and fluoxetine [25,26]; citalopram and sertraline [27]; fluoxetine and sertraline [28]; fluoxetine, sertraline and paroxetine [29] and fluvoxamine, sertraline and paroxetine [30].…”

“…MDD is a serious psychiatric condition with a significant impact on public health. The medical burden of this pathology is tremendous: 70% of suicides are committed by depressed individuals, not treated nor diagnosed [3,4]. In this context, the efficacy and safety of medical treatments are essential.…”