The Impact of Childhood Maltreatment on Intravenous Ketamine Outcomes for Adult Patients with Treatment-Resistant Depression

Introduction

Major depressive disorder and bipolar depression affect a substantial proportion of the population and an estimated 35% of people with depression meet criteria for treatment-resistant depression (TRD), commonly defined as less than 50% improvement after at least two different antidepressant trials. TRD is associated with worse quality of life and higher mortality, so identifying predictors of response to alternative interventions is clinically important. Intravenous ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, produces rapid antidepressant effects in TRD, possibly via glutamate-mediated activation of AMPA receptors, increased brain-derived neurotrophic factor and mTOR signalling, but it is unknown whether childhood maltreatment influences ketamine response. Previous research has associated childhood maltreatment with poorer outcomes on conventional antidepressants, and there is emerging evidence for NMDAR antagonists in trauma-related disorders such as PTSD, but no clear data on how early-life maltreatment affects ketamine efficacy in TRD. O'brien and colleagues set out to examine whether self-reported childhood maltreatment, measured with the Childhood Trauma Questionnaire (CTQ), predicts antidepressant response to IV ketamine in a naturalistic outpatient sample. They tested two related hypotheses: first, that a history of childhood maltreatment would predict an unfavourable response to an acute single infusion and to a course of repeated infusions; and second, that greater maltreatment burden (a higher number of clinically significant maltreatment domains, termed maltreatment load) would be associated with poorer ketamine effectiveness.