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Change in Negative Affective Bias following a Single Ketamine Treatment for Treatment-Resistant Depression

Anna J. Harvey, Stevan Nikolin, Nicholas Chand, William Flanney, Liyi Tan, Adriano Moffa, Colleen Loo, Donel Martin

Depression and Anxiety August 19, 2023 DOI: 10.1155/2023/3371272 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized double-blind controlled study with an active control Peer reviewed
Sample size 44
Population Participants with treatment-resistant major depressive disorder and healthy controls
Interventions racemic ketamine hydrochloride midazolam hydrochloride
Duration Single treatment, assessments one day after treatment
Topics Depression Esketamine Ketamine
Citations 4
Key points A single ketamine treatment significantly improved negative processing bias on the Scrambled Sentence Task, but this improvement was not significantly associated with symptom change.

Abstract

Ketamine has recently emerged as a highly effective new treatment for people with treatment-resistant depression with rapid antidepressant effects. However, these effects are often short lasting, and the potential cognitive mechanisms underlying the therapeutic effects, such as effects on emotional processing bias, remain poorly understood. In the present study, we explored potential changes in emotional and cognitive processing following a single treatment of subcutaneous ketamine in a randomised double-blind controlled study with an active control. Participants with treatment-resistant major depressive disorder (MDD) were recruited from a single site from the Ketamine for Adult Depression Study (KADS Trial) and were randomly assigned to receive racemic ketamine hydrochloride ( n = 10 ) or midazolam hydrochloride ( n = 11 ) in a 1 : 1 ratio. A healthy control sample ( n = 23 ) was recruited to attend a single experimental session without any treatment. All MDD participants completed mood ratings and cognitive assessments prior to and one day after a single randomised treatment. The results showed no significant differences in performance changes after treatment across the majority of emotion-related (i.e., Emotional Stroop Task, Affective Go/No-Go Task) and cognitive (Ruff 2 and 7 Selective Attention Test, Controlled Word Association Test) outcome measures. Participants who received ketamine showed a significant improvement in a negative processing bias test (i.e., The Scrambled Sentence Task; Cohen’s d = .67 , p = .016 ), which was not significantly associated with improvement in psychological symptoms ( r = − .662 , p = .074 ). The results from this exploratory study suggest that a single ketamine treatment may modulate negative affective bias. Limitations to this study included the small sample size and lack of follow-up. Future larger trials are required to confirm this finding.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

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