Of the new antidepressants, vortioxetine looks the best

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  • A meta-analysis of specific doses of 3 antidepressants introduced in the past decade suggests that 10 mg/d vortioxetine (Trintellix) offers the best balance of efficacy and side effects.
  • More studies are needed to identify optimal doses of levomilnacipran (Fetzima) and vilazodone (Viibryd).

Why this matters

  • Previous studies have not yet shown how efficacy of vortioxetine changes with dose.
  • Meta-analyses of vilazodone and levomilnacipran pooled results of different doses, which may have masked dose effects.

Study design

  • Meta-analysis identified 22 randomized controlled studies for vortioxetine, levomilnacipran, and vilazodone.
  • Efficacy and tolerability were calculated using Montgomery-Asberg Depression Rating (MADRS) and risk ratio (RR; discontinuations for adverse events), respectively.
  • Funding: National Natural Science Foundation of China; Xi'an Jiaotong University.

Key results

  • The weighted mean difference (WMD, mean change in MADRS score from baseline) for all 3 drugs compared with placebo:

—Vortioxetine (5/10/15/20 mg/d): −2.38/−3.12/−3.10/−4.86

      —Levomilnacipran (40/80/120 mg/d): −3.26/−3.45/−4.90

      —Vilazodone (20/40 mg/d): −2.50/−3.58

  • The tolerability of vortioxetine  at 5/10/15/20 mg/d was (RR) 1.14/1.42/1.78/1.80, respectively; that of levomilnacipran and vilazodone ranged from (RR) 3.91 to 7.40 and 2.09 to 2.79, respectively.
  • Based on the benefit/risk, 10 mg/d vortioxetine (WMD, −3.12/RR, 1.42) was deemed optimal.


  •  Lacks long-term efficacy and safety data.

Coauthored with Chitra Ravi, MPharm