Vortioxetine for major depressive disorder: An indirect comparison with duloxetine, escitalopram, levomilnacipran, sertraline, venlafaxine, and vilazodone, using number needed to treat, number needed to harm, and likelihood to be helped or harmed

- Vortioxetine is a relatively new agent for the treatment of major depressive disorder.
- Clinically intuitive effect sizes can be used to make indirect comparisons.
- Vortioxetine demonstrates similar efficacy (response) to other agents.
- Tolerability, as measured by discontinuation because of an adverse event, differs.
- Vortioxetine is ~5 times more likely to be help (response) than harm (discontinue).

BackgroundVortioxetine is approved for the treatment of major depressive disorder and differs from other antidepressants in terms of its pharmacodynamic profile. Given the limited number of head-to-head studies comparing vortioxetine with other antidepressants, indirect comparisons using effect sizes observed in other trials can be helpful to discern potential differences in clinical outcomes.MethodsData sources were the clinical trial reports for the pivotal short-term double-blind trials for vortioxetine and from publicly available sources for the pivotal short-term double-blind trials for two commonly used generic serotonin specific reuptake inhibitor antidepressants (sertraline, escitalopram), two commonly used generic serotonin-norepinephrine reuptake inhibitor antidepressants (venlafaxine, duloxetine), and two recently introduced branded antidepressants (vilazodone, levomilnacipran). Response was the efficacy outcome of interest, defined as a≥50% reduction from baseline on the Montgomery-Asberg Depression Rating Scale or Hamilton Depression Rating Scale. The tolerability outcome of interest was discontinuation because of an adverse event. Number needed to treat (NNT) and number needed to harm (NNH) for these outcomes vs. placebo were calculated, as well as likelihood to be helped or harmed (LHH) to contrast efficacy vs. tolerability.ResultsThe analysis included 8 studies for duloxetine, 3 studies for escitalopram, 5 studies for levomilnacipran, 1 study for sertraline, 4 studies for venlafaxine, 2 studies for vilazodone, and 11 studies for vortioxetine. NNTs for response vs. placebo were 6 (95% CI 5-8), 7 (5-11), 10 (8-16), 6 (4-13), 6 (5-9), 8 (6-16), and 9 (7-11), respectively. NNHs for discontinuation because of an adverse event vs. placebo were 25 (17-51), 31 (19-92), 19 (14-27), 7 (5-12), 8 (7-11), 27 (15-104), and 43 (28-91), respectively. LHH values contrasting response vs. discontinuation because of an adverse event were 4.3, 4.6, 1.8, 1.2, 1.4, 3.3, and 5.1 respectively. Limitations: Subjects were all participants in carefully designed and executed clinical trials and may not necessarily reflect patients in clinical settings who may have complex psychiatric and non-psychiatric comorbidities. The measured outcomes come from different studies and thus comparisons are indirect.ConclusionsVortioxetine demonstrates similar efficacy to that observed for duloxetine, escitalopram, levomilnacipran, sertraline, venlafaxine, and vilazodone, however overall tolerability as measured by discontinuation because of an adverse event differs. Vortioxetine is 5.1 times more likely to be associated with response than discontinuation because of an adverse event when compared to placebo.