Vortioxetine vs SSRI: Without Industry Funding

A head-to-head of two antidepressants

STUDY: Mishra S et al, Journal of Family Medicine and Primary Care 2026

STUDY TYPE: Randomized, open-label trial

FUNDING: Independent

Background

Vortioxetine looked superior to other antidepressants for cognitive symptoms of depression, but what about mood? Here is a head-to-head study against escitalopram in primary care depression.

Earlier Results

Eight trials compared vortioxetine to SNRIs, where it was equal to venlafaxine but slightly less effective than duloxetine for depressive outcomes. However, a sensitivity analysis raised concerns that only two of these studies used comparable dosing, and vortioxetine demonstrated better tolerability and cognitive profile than duloxetine.

One large trial in older adults compared vortioxetine to SSRIs. There, the two were equal in depression, cognition, and tolerability.

The New Study

• 100 adults with major depressive disorder at an Indian tertiary care center.
• Randomized to escitalopram (10 mg/day) or vortioxetine (10 mg/day) for 4 weeks.
• Open-label, with symptoms tracked using the Depression scale (HAM-D) at baseline, week 2, and week 4.

Results

Both drugs eased depression, but escitalopram pulled ahead by week four. Scores started nearly identical (17.2 vs 17.1) and stayed similar at week two. By week four, patients on escitalopram averaged a HAM-D score of 14.2 versus 16.3 for vortioxetine, a barely statistically significant difference (P = 0.04).

Cognitive outcomes, where vortioxetine is often thought to have an edge, weren’t measured in this trial.

Side Effects

Both drugs were well tolerated, with minimal side effects reported.

Limitations

Not blinded, excluded patients with anxiety or other psychiatric comorbidities.

Practice Implications

1. Vortioxetine may have a slight cognitive advantage, but it is not detectable in all trials. In other trials, it improved digit symbol substitution — available as a computerized test through THINC-it — but not other tests. It may also have fewer sexual side effects.
2. This new trial reminds us that vortioxetine is not more effective than traditional antidepressants.
3. Tip: When switching from an SSRI/SNRI to vortioxetine, taper the first med while adding the new one, as vortioxetine will not treat serotonin withdrawal symptoms.

—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report

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