Baseline Working Memory Predicted Response to Low-Dose Ketamine Infusion in Patients with Treatment-Resistant Depression

Abstract

Introduction Pretreatment neurocognitive function may predict the treatment response to low-dose ketamine infusion in patients with treatment-resistant depression (TRD). However, the association between working memory function at baseline and the antidepressant efficacy of ketamine infusion remains unclear. Methods A total of 71 patients with TRD were randomized to one of three treatment groups: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HDRS) at baseline and after treatment. Cognitive function was evaluated using working memory and go-no-go tasks at baseline. Results A generalized linear model with adjustments for demographic characteristics, treatment groups, and total HDRS scores at baseline revealed only a significant effect of working memory function (correct responses and omissions) on the changes in depressive symptoms measured by HDRS at baseline (F=12.862, p<0.05). Correlation analysis further showed a negative relationship (r=0.519, p=0.027) between pretreatment working memory function and changes in HDRS scores in the 0.5 mg/kg ketamine group. Discussion An inverse relationship between pretreatment working memory function and treatment response to ketamine infusion may confirm that low-dose ketamine infusion is beneficial and should be reserved for patients with TRD.

Factors Associated with Antidepressant Effects of Ketamine: A Reanalysis of Double-Blind Randomized Placebo-Controlled Trial of Intravenous Ketamine for Treatment-Resistant Depression

“…Moreover, higher body mass index was correlated with a greater reduction in the 17-item Hamilton Depression Rating Scale (HAM-D-17) total score at 1 d and 230 min after ketamine infusion in patients with MDD and BD [10]. Other studies have reported the association of following factors with better response to ketamine treatment: lower number of treatment failures and lower baseline severity of illness [11], younger age and no history of neuromodulation treatment [12], lower baseline intelligence quotient [13], lower pretreatment working memory function [14], lower adiponectin [15], higher brain-derived neurotrophic factor (BDNF) after ketamine administration [16], single nucleotide polymorphism (SNP) in the Val/Val BDNF allele at rs6265 [17], and smaller left hippocampal volume [18]. However, these studies had several limitations, such as the study design heterogeneity (e. g., a combination of open-label and randomized placebo-controlled trials, including both MDD and BD).…”

Baseline cognitive function predicts full remission of suicidal symptoms among patients with treatment-resistant depression and strong suicidal ideation after low-dose ketamine infusion

“…Working memory and go/no-go tasks were performed prior to infusion (Chen et al, 2022;Zimmermann, 1997). In the go/no-go task, participants were asked to respond as quickly as possible after the × symbol appeared.…”

Association of Neurofilament Light Chain With the Antidepressant Effects of Low-Dose Ketamine Infusion Among Patients With Treatment-Resistant Depression

“…They also identified an inverse correlation between cognitive function and NFL concentration among patients with major depressive disorder; a higher NFL concentration was associated with poorer cognitive function ( Bavato et al, 2021 ). Our previous study suggested an association between baseline cognitive function and response to treatment with ketamine infusion ( Chen et al, 2022a ). This inspired us to further elucidate the role of baseline NFL concentrations in the antidepressant effects of low-dose ketamine.…”