Can Vortioxetine Ameliorate SSRI-Induced Sexual Dysfunction in Well-Treated MDD?

Switching to vortioxetine appears to be a safe and effective alternative for patients experiencing sexual dysfunction during antidepressant therapy with a selective serotonin reuptake inhibitor.

Vortioxetine is an effective and safe switch therapy for treating selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction in adults with well-treated major depressive disorder (MDD) and produces greater improvements compared with escitalopram, according to a study published in CNS Spectrums. Additionally, study results suggest that improvements in sexual function with both escitalopram or vortioxetine may be influenced by age, sex, prior SSRI usage, and history of major depressive episodes (MDEs).

This phase 3b, 8-week, randomized, double-blind, head-to-head study ( identifier: NCT01364649) examined tolerability and treatment-emergent sexual dysfunction in adult participants with well-treated MDD (stable depressive symptoms with Clinical Global Impressions-Severity score [CGI-S] ≤3) following a therapy switch from citalopram, paroxetine, or sertraline to flexible doses of escitalopram or vortioxetine (10 mg and 20 mg). Sexual function was assessed using the Changes in Sexual Functioning Questionnaire-14 (CSFQ-14); antidepressant efficacy was assessed by the CGI-S/Improvement and Montgomery–Åsberg Depression Rating Scale scores; and tolerability was assessed by adverse events (AEs).

Of the 447 participants randomly assigned, 348 (77.9%) completed the study. Fifty-six (24.9%) participants who had switched to vortioxetine and 43 (19.4%) who had switched to escitalopram prematurely discontinued the study due to a treatment-emergent AE; this occurred in more vortioxetine participants (n=20; 8.9%) than escitalopram participants (n=14; 6.3%). Clinically meaningful improvements in sexual functioning (increase of 2 or more points on the CSFQ-14) were observed as early as week 2. While these improvements continued to increase for participants taking vortioxetine, participants taking escitalopram appeared to plateau.

Improvements were also evaluated across participant subgroups. For women, improvements in sexual function were greater with vortioxetine compared with escitalopram, regardless of age, but the improvements were statistically significant in women 45 years and older (mean difference, 2.9; P =.045).

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Improvements were similar between escitalopram and vortioxetine among participants with 1 year or less of prior SSRI therapy, but among those with less than 1 year, the improvements seen with vortioxetine were significantly greater than those seen with escitalopram, with a 4.4-point difference, (95% CI, 1.83-6.96; P =.001).

In participants with no prior MDEs, improvements were similar between groups, and although improvement with escitalopram was numerically better among participants with 3 or more MDEs, this was not statistically significant. Participants with 1 to 3 prior MDEs showed significantly greater improvements with vortioxetine with a difference of 3.5 (P =.001) vs escitalopram (95% CI, 1.38-5.69; P =.001).

By week 8, no significant differences were seen between participants treated with vortioxetine and escitalopram, respectively, in the percentage of MDD remittance, regardless of whether they switched from citalopram (81.2% vs 76.2%; P =.394), paroxetine (65.6% vs 69.0%; P =.877), or sertraline (80.6% vs 82.6%; P =.435), suggesting that both therapies at the study-administered dosage levels were adequate to sustain remission.

Both escitalopram and vortioxetine were generally well tolerated, with serious AEs occurring in 1 escitalopram participant and 3 vortioxetine participants. Prior treatment with SSRIs did not appear to influence treatment-emergent AEs in overall incidence or severity, except for nausea. Rates of nausea seen in prior SSRI treatment groups were low among participants switched to escitalopram (3.3%-6.1%) and were higher for participants switched to vortioxetine (20%-29.2%).

Study investigators conclude, “These analyses support the findings that switching SSRI antidepressant therapy to vortioxetine in well-treated adult MDD patients experiencing treatment-emergent sexual dysfunction can improve sexual dysfunction regardless of prior SSRI (citalopram, sertraline, and paroxetine,) while maintaining antidepressant efficacy and tolerability.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Jacobsen PL, Nomikos GG, Zhong W, Cutler AJ, Affinito J, Clayton A. Clinical implications of directly switching antidepressants in well-treated depressed patients with treatment-emergent sexual dysfunction: a comparison between vortioxetine and escitalopramCNS Spectr. 2020;25(1):50-63