Trintellix (Vortioxetine) Efficacy for Major Depressive Disorder
Trintellix is effective for treating major depressive disorder in adults, demonstrating statistically significant superiority over placebo across multiple doses (5-20 mg/day), with response rates 33-91% higher than placebo and remission rates 45-68% higher at therapeutic doses. 1
Evidence from FDA Registration Trials
The efficacy of Trintellix was established through six randomized, double-blind, placebo-controlled studies lasting 6-8 weeks, plus one maintenance study 1:
Response rates (≥50% improvement in depression scales) were significantly higher than placebo for:
Remission rates were significantly higher than placebo for:
Number needed to treat (NNT) for response versus placebo was 7-9, meaning approximately 7-9 patients need treatment for one additional patient to respond compared to placebo 2, 3
Comparative Efficacy with Other Antidepressants
Trintellix demonstrates similar efficacy to other second-generation antidepressants but does not appear superior 4:
Network meta-analyses found no significant differences in efficacy between vortioxetine and other second-generation antidepressants when used as switching strategies for treatment-resistant depression 4
Direct comparison studies showed vortioxetine response rates were lower than SNRI comparators at 5 mg (12% lower), 15 mg (22% lower), and 20 mg (18% lower) doses 2
The American College of Physicians guidelines state that existing evidence does not justify choosing any second-generation antidepressant over another based on greater efficacy, including vortioxetine 4
Efficacy in Special Populations
Elderly patients (aged 64-88 years) showed significant benefit with Trintellix 5 mg/day, with a placebo-subtracted difference of -3.3 points on the Hamilton Depression Scale 1
No differential responsiveness was found based on age, gender, or race in subgroup analyses 1
Clinical Positioning
Trintellix should be selected based on adverse effect profile, cost, and patient preferences rather than superior efficacy, as all second-generation antidepressants demonstrate comparable effectiveness 4:
Tolerability advantage: Trintellix has a favorable discontinuation profile with NNH of 36-43 for discontinuation due to adverse events, compared to 7-8 for some SNRIs 3, 5
Likelihood to be helped or harmed (LHH): Trintellix is 5.1 times more likely to produce response than cause discontinuation due to adverse events, higher than most comparators 5
Treatment Duration and Monitoring
Initial assessment: Monitor therapeutic response and adverse effects beginning within 1-2 weeks of initiation 4, 6
Adequate trial duration: Modify treatment if no adequate response within 6-8 weeks 4
Continuation therapy: Continue treatment for 4-9 months after satisfactory response for first episode; longer duration (years to lifelong) for patients with ≥2 episodes 4
Common Pitfalls
Nausea is the most common adverse event with vortioxetine, occurring in a dose-dependent manner with NNH of 6 versus placebo 3. This can lead to early discontinuation if patients are not counseled appropriately.
Two U.S. studies of the 5 mg dose failed to show effectiveness 1, suggesting that 10 mg/day is the appropriate starting dose for most patients, not 5 mg.
Sexual dysfunction concerns: Unlike some SSRIs, vortioxetine at standard doses does not significantly increase sexual dysfunction and may actually improve treatment-emergent sexual dysfunction from prior antidepressants 7