Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis

Abstract

Objective. Antidepressants are frequently associated with treatment-emergent sexual dysfunction (TESD). Vortioxetine, which was approved for patients with major depressive disorder (MDD), has a receptor profile that suggests limited impact on sexual functioning.Methods. Arizona Sexual Experiences Scale (ASEX) patient-level data were pooled from 7 short-term vortioxetine trials (6 in MDD, 1 in generalized anxiety disorder) and analyzed for incidence of TESD at any post-baseline visit in patients without sexual dysfunction at baseline (defined as ASEX total score ≥19; individual ASEX item score ≥5; or a score ≥4 on any 3 ASEX items). The primary objective was to confirm the non-inferiority of vortioxetine 5-20 mg/day to placebo on the incidence of TESD. Comparisons were based on the common risk difference (95% confidence interval). Additional analyses compared vortioxetine to duloxetine and duloxetine to placebo. A sensitivity analysis, defined as TESD at 2 consecutive post-baseline visits, was conducted.Results. TESD incidence, relative to placebo, generally increased with vortioxetine dose with vortioxetine 5 mg non-inferior to placebo. Vortioxetine 10, 15, and 20 mg did not meet the non-inferiority criterion, but no dose had a significantly higher risk of developing TESD versus placebo. Changes in ASEX individual item scores supported the similarity of vortioxetine doses to placebo. Significantly higher TESD risk occurred with duloxetine 60 mg/day versus placebo and versus vortioxetine 5 or 10 mg. The sensitivity analysis was generally consistent with the primary analysis. Rates of spontaneously reported sexual adverse events were low.Conclusions. Vortioxetine was associated with rates of TESD that were not significantly different from placebo in short-term clinical trials.

Sexual Function Across Aging

“…Consideration may be given to use of bupropion or buspirone as adjunctive agents for antidepressantinduced sexual dysfunction or as primary pharmacotherapy for anxiety or depression, if appropriate, to help minimize or avoid development of sexual dysfunction. Vortioxetine [34] and vilazodone [35,36] are newer antidepressants that appear to have a lower incidence of sexual dysfunction associated with use and should be considered in treating patients with depression and anxiety who have experienced sexual dysfunction with other antidepressant medications.…”

Paroxetine, but not Vortioxetine, Impairs Sexual Functioning Compared With Placebo in Healthy Adults: A Randomized, Controlled Trial

“…19 The reported prevalence of sexual dysfunction in several shortand long-term studies in MDD patients treated with vortioxetine indicates that the incidence of TESD was generally similar to that with placebo at 5 and 10 mg and higher than with placebo at 20 mg. 20e27 Similarly, a post hoc pooled analysis that included a non-inferiority margin from the vortioxetine studies demonstrated that low doses of vortioxetine (5 mg) have minor effects on sexual function that are at the placebo level; although a dosedependent increase in the risk of TESD was observed with higher doses (10e20 mg), it was not significantly different from placebo. 28,29 The study presented here aimed to replicate the superior effect of vortioxetine compared with an SSRI on TESD and was conducted in healthy men and women to mitigate the confounding effect of MDD or other medical conditions on sexual functioning. Therefore, this study evaluated the effects on sexual functioning of vortioxetine (10 and 20 mg) compared with paroxetine, an SSRI known to cause sexual dysfunction, and placebo after 5 weeks of treatment in healthy volunteers.…”

“…The doses of vortioxetine were selected because they are within the Food and Drug Administration (FDA)-approved efficacious dose range. 28,29…”

Methodological differences as an explanation for the divergent results of studies on sexual dysfunction related to the use of vortioxetine

“…Interestingly, the difference between the use of spontaneous reports versus a validated questionnaire has already been investigated in patients using vortioxetine by Jacobsen et al (2015b). In a pooled analysis of six MDD studies and one GAD study, all of which were also included in the review of Baldwin et al, TESD was reported spontaneously in 2.2% of vortioxetine-treated patients.…”

“…Although the incidence of TESD increased with vortioxetine dose there was no statistically significant higher risk of developing TESD versus placebo. Higher TESD risk was reported for duloxetine 60 mg/ day versus placebo and versus vortioxetine 5 or 10 mg while no significant difference was determined between duloxetine 60 mg/day versus vortioxetine 15 or 20 mg.When comparing the papers of Baldwin et al (2016) and Jacobsen et al (2015b) that partially describe the same original studies, it again becomes clear that TESD is reported far more frequently when using a validated questionnaire versus spontaneous reports. Only reporting spontaneously mentioned sexual side effects may be less helpful for clinicians who together with their patients choose between different antidepressants based on side effect profiles reported in the literature.…”