Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression

Introduction

Anxious depression—major depressive disorder (MDD) accompanied by high levels of anxiety—is a common clinical subtype present in roughly half of people with MDD and appears particularly prevalent and difficult to treat in treatment-resistant depression (TRD). Previous antidepressant trials, including large multisite studies, have reported lower remission and response rates in anxious versus nonanxious depression and greater suicidal ideation and side-effect burden in the anxious subgroup. Ketamine, an N-methyl-D-aspartate receptor antagonist with glutamatergic effects, has demonstrated rapid antidepressant activity in TRD in multiple controlled trials, but evidence specifically addressing its efficacy in anxious depression has been limited to a few post hoc analyses with mixed signals. Salloum and colleagues therefore used data from a multisite, randomized, double-blind, active placebo-controlled trial of single-dose intravenous ketamine (four dose levels) versus midazolam to examine whether high baseline anxiety moderated ketamine's acute antidepressant effects. The authors hypothesised, based on prior post hoc reports, that subjects with anxious depression would show greater response to ketamine than those without high anxiety at baseline. The present paper reports secondary analyses testing that hypothesis, focusing on early outcome time points up to 72 hours postinfusion.