Is 100mg of Zoloft (sertraline) less effective than 20mg of Trintellix (vortioxetine)?

Comparing Antidepressant Potency: Sertraline 100mg vs Vortioxetine 20mg

No, 100mg of sertraline (Zoloft) is not less powerful than 20mg of vortioxetine (Trintellix)—both demonstrate comparable efficacy for major depressive disorder, with vortioxetine showing superior tolerability. 1

Direct Efficacy Comparison

The most relevant head-to-head comparison data comes from an indirect analysis of pivotal trials that calculated Number Needed to Treat (NNT) for response versus placebo:

• Sertraline NNT: 6 (95% CI 4-13) 1
• Vortioxetine NNT: 9 (95% CI 7-11) 1

Lower NNT values indicate greater efficacy, meaning sertraline actually demonstrates slightly better efficacy on this metric. However, both fall within overlapping confidence intervals, indicating statistically equivalent antidepressant efficacy between the two medications. 1

Tolerability Profile Differences

The critical distinction emerges in tolerability, where vortioxetine demonstrates clear advantages:

• Sertraline NNH (discontinuation due to adverse events): 7 (95% CI 5-12) 1
• Vortioxetine NNH: 43 (95% CI 28-91) 1

Higher NNH values indicate better tolerability. The Likelihood to be Helped or Harmed (LHH) ratio—which contrasts efficacy against tolerability—reveals:

• Sertraline LHH: 1.2 1
• Vortioxetine LHH: 5.1 1

Vortioxetine is 5.1 times more likely to produce response than cause discontinuation due to adverse events, compared to only 1.2 times for sertraline. 1 This represents a substantial tolerability advantage for vortioxetine despite equivalent antidepressant efficacy.

Sertraline Dosing Considerations

The 100mg sertraline dose represents a standard therapeutic dose:

• The starting dose of 50mg/day is typically the optimal therapeutic dose for most patients 2
• Mean plasma concentrations at 100mg daily are approximately 19±18 ng/mL, within the therapeutic range of 10-50 ng/mL 3
• Dose escalation from 50mg to 150mg in non-responders at 3 weeks showed no significant additional benefit, with 40% overall remission rates regardless of dose 4

Common sertraline side effects include sweating, tremors, nervousness, insomnia or somnolence, dizziness, gastrointestinal disturbances, and sexual dysfunction. 3

Clinical Bottom Line

Both medications demonstrate comparable antidepressant efficacy for major depressive disorder. The choice between them should prioritize tolerability profiles rather than perceived "power" differences. Vortioxetine's superior tolerability profile (5.1 vs 1.2 LHH ratio) makes it less likely to cause treatment discontinuation while achieving similar response rates. 1