Baseline Cognition Is Not Associated With Depression Outcomes in Vortioxetine for Major Depressive Disorder: Findings From Placebo-Controlled Trials

J Clin Psychiatry. 2024 Sep 4;85(4):24m15295. doi: 10.4088/JCP.24m15295.

Abstract

Objective: Major depressive disorder (MDD) is a common psychiatric disorder for which pharmacologic standard-of-care treatments have limited efficacy, particularly among individuals with cognitive dysfunction. Cognitive dysfunction is observed in approximately 25%-50% of those with MDD, wherein response to standard-of-care medications is reduced. Vortioxetine is an approved antidepressant that has shown evidence of procognitive effects in patients. It is not known if it has greater clinical efficacy in MDD patients with cognitive dysfunction, a more difficult to treat population, than other antidepressants.

Methods: This study was a reanalysis of 1,812 subjects with MDD across 4 placebo controlled trials. Baseline cognition was measured by the Digit Symbol Substitution Test (DSST), the primary measure used to demonstrate vortioxetine's procognitive effects in clinical studies. Analyses examined whether baseline cognitive function was associated with differences in treatment outcomes.

Results: Baseline DSST did not predict placebo-adjusted treatment effects of vortioxetine on depressive symptoms (pooled Cohen d = -0.02, 95% CI = -0.12 to 0.07). Analyses of additional cognitive measures similarly did not predict placebo-adjusted treatment effects on depression (all 95% CI contained zero). Finally, analyses of trials with selective serotonin reuptake inhibitors (SSRIs)/serotonin and norepinephrine reuptake inhibitors (SNRIs) as active comparators also revealed no prediction of SSRI/SNRI adjusted treatment effects of vortioxetine on depression.

Conclusions: These findings, taken together, suggest that cognitive function does not moderate depression outcomes in vortioxetine, with results comparable to other antidepressants.

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Cognition / drug effects
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / etiology
  • Depressive Disorder, Major* / drug therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Treatment Outcome
  • Vortioxetine* / pharmacology
  • Vortioxetine* / therapeutic use

Substances

  • Vortioxetine
  • Antidepressive Agents
  • Selective Serotonin Reuptake Inhibitors