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Vortioxetine and desvenlafaxine produced comparable improvement in depressive symptoms over 8 weeks in adults with major depressive disorder who had only a partial response to prior SSRI monotherapy. The primary endpoint, change in Montgomery-Asberg Depression Rating Scale total score at week 8, showed a numeric difference of -0.47 points in favor of vortioxetine (95% CI, -1.61 to 0.67; P = .420). The study concluded that vortioxetine was non-inferior to desvenlafaxine for depressive symptom reduction.

More patients treated with vortioxetine achieved symptomatic and functional remission than patients treated with desvenlafaxine. At week 8, remission defined by CGI-S score less than or equal to 2 occurred in 32.5% of vortioxetine-treated patients versus 24.8% of desvenlafaxine-treated patients, with an odds ratio of 1.48 (95% CI, 1.03 to 2.15; P = .034).

By contrast, MADRS response, MADRS remission, and CGI-I response rates were reported as similar between the two groups.

Vortioxetine showed significantly greater improvement than desvenlafaxine in specific areas of functioning, particularly autonomy (daily functioning) and interpersonal relationships (social functioning), as measured by the Functioning Assessment Short Test. Both treatments improved functioning over 8 weeks, and FAST total score improvement was numerically greater with vortioxetine in the overall study population, but the statistically significant between-group differences were in the autonomy and interpersonal relationship domains (P = .009 and P = .045, respectively).

Among working patients, vortioxetine was associated with greater improvement in overall functioning and higher remission rates than desvenlafaxine. In the subgroup of 361 patients who were employed or self-employed at baseline, change in FAST total score at week 8 was -16.6 with vortioxetine versus -14.1 with desvenlafaxine, for a difference of -2.52 points (95% CI, -4.88 to -0.15; P = .037).

Working patients treated with vortioxetine also had higher rates of symptomatic and functional remission by CGI-S criteria: 36.2% (63/174) versus 25.1% (44/175), with an odds ratio of 1.72 (95% CI, 1.08 to 2.75; P = .023). Daily and social functioning also improved significantly more with vortioxetine in this subgroup.

Tolerability was broadly similar overall, but nausea was more common with vortioxetine. Treatment-emergent adverse events occurred in 46.1% of patients receiving vortioxetine and 39.6% receiving desvenlafaxine, and more than 98% of adverse events in both groups were mild or moderate.

• The most common adverse events in both groups were nausea, headache, and dizziness.
• Nausea occurred in 20.0% of vortioxetine-treated patients versus 9.2% of desvenlafaxine-treated patients.
• Adverse events leading to study withdrawal were uncommon: 1.9% with vortioxetine and 1.0% with desvenlafaxine.
• One serious adverse event was reported, severe vomiting in the desvenlafaxine group, and it was considered unrelated to treatment.

The VIVRE trial studied adults aged 18 to 65 years with major depressive disorder and only partial response to SSRI monotherapy. Eligible patients had taken escitalopram, sertraline, paroxetine, or citalopram at an approved dose for at least 6 weeks, had a current major depressive episode lasting at least 3 months but less than 12 months, and had a baseline MADRS total score of at least 24.

The randomized population included 603 patients. Mean baseline MADRS total score was 30.7, mean CGI-S score was 4.5, and mean FAST score was 41.5, indicating moderate-to-severe depression with severe functional impairment.

This was a phase IV, randomized, double-blind, active-controlled, parallel-group study conducted across 77 sites in 12 countries. After stopping prior SSRI therapy, eligible outpatients with major depressive disorder were randomized 1:1 to vortioxetine or desvenlafaxine for 8 weeks, followed by a 4-week safety follow-up.

Vortioxetine was started at 10 mg/day and increased to 20 mg/day after 1 week in almost all patients, with adjustment to 10 or 20 mg/day allowed until week 4. Desvenlafaxine was given at 50 mg/day throughout the study.

This study is clinically relevant because it tested a common real-world switch decision after incomplete SSRI benefit and found that vortioxetine matched desvenlafaxine on depressive symptom reduction while outperforming it on remission, daily functioning, social functioning, and treatment satisfaction. The authors concluded that these findings support earlier use of vortioxetine in the treatment algorithm for patients with major depressive disorder who have only partial response to SSRI monotherapy.

The main limitation was the short 8-week treatment duration, which the authors noted is relatively brief given that major depressive disorder usually requires long-term treatment. The authors also stated that allowing dose-adjustment requests in the desvenlafaxine group without actually increasing the dose may have introduced expectation bias that could have affected outcomes.