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

O’brien O’Brien,Lijffijt Lijffijt,Swann Swann,Wells Wells,Mathew Mathew

doi:10.3390/ph12030133

Abstract

Childhood maltreatment is associated with a poor treatment response to conventional antidepressants and increased risk for treatment-resistant depression (TRD). The N-methyl-D-aspartate receptor (NDMAR) antagonist ketamine has been shown to rapidly improve symptoms of depression in patients with TRD. It is unknown if childhood maltreatment could influence ketamine’s treatment response. We examined the relationship between childhood maltreatment using the Childhood Trauma Questionnaire (CTQ) and treatment response using the Quick Inventory of Depressive Symptoms–Self Report (QIDS-SR) in TRD patients receiving intravenous ketamine at a community outpatient clinic. We evaluated treatment response after a single infusion (n = 115) and a course of repeated infusions (n = 63). Repeated measures general linear models and Bayes factor (BF) showed significant decreases in QIDS-SR after the first and second infusions, which plateaued after the third infusion. Clinically significant childhood sexual abuse, physical abuse, and cumulative clinically significant maltreatment on multiple domains (maltreatment load) were associated with better treatment response to a single and repeated infusions. After repeated infusions, higher load was also associated with a higher remission rate. In contrast to conventional antidepressants, ketamine could be more effective in TRD patients with more childhood trauma burden, perhaps due to ketamine’s proposed ability to block trauma-associated behavioral sensitization.

Highlights

12.2% of US residents 13 years and older have a lifetime history of recurring major depressive episodes associated with major depressive disorder (MDD) or bipolar disorder (BD) [1]
We examine the influence of childhood maltreatment on ketamine treatment response after single and repeated infusions in moderate to severely depressed adults receiving treatment at an outpatient ketamine clinic
Patients were included if they had moderate to severe levels of depression at pre-treatment baseline irrespective of psychiatric disorder

Summary

Introduction

12.2% of US residents 13 years and older have a lifetime history of recurring major depressive episodes associated with major depressive disorder (MDD) or bipolar disorder (BD) [1]. TRD is associated with a lower quality of life and increased mortality [3,4]. The N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is a promising treatment option for TRD [5]. Randomized controlled trials in patients with TRD have consistently shown favorable antidepressant responses to single and repeated subanesthetic doses of ketamine compared to saline or active placebo [6,7,8,9]. Ketamine’s antidepressant effect has been related to pre- and post-synaptic NMDAR blockade, enhancing prefrontal [10] and hippocampal [11] glutamate concentrations which activate the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), enhancing synaptic plasticity via AMPAR-induced elevation of brain derived neurotrophic factor (BDNF) [12] and activation of the mammalian target of rapamycin (mTOR) signaling pathway [13]. The antidepressant response is often rapid, with patients maintaining substantial gains for up to two weeks [14,15,16]

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Discussion

Conclusion