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Exploring Predictors of Ketamine Response in Adolescent Treatment-Resistant Depression

Alice Lineham, Victor J. Avila‐quintero, Michael H. Bloch, Jennifer B. Dwyer

Journal of Child and Adolescent Psychopharmacology January 3, 2024 DOI: 10.1089/cap.2023.0047 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Population Adolescents with treatment-resistant depression
Interventions Ketamine Midazolam
Duration Single-dose, assessed at 1 and 7 days postinfusion
Topics Anxiety Depression Ketamine Esketamine
Keywords Depression economics Antidepressant Rating scale Randomized controlled trial Serotonin reuptake inhibitor Clinical trial Clinical psychology Cognition
Citations 15
Registration NCT02579928
Key findings Fewer prior medication trials, shorter current depressive episode, and current selective serotonin reuptake inhibitor use predicted greater depression symptom improvement with ketamine in adolescents.

Abstract

Objective:Ketamine has proved effective as a rapid-acting antidepressant agent, but treatment is not effective for everyone (approximately a quarter to a half of patients). Some adult studies have begun to investigate predictors of ketamine's antidepressant response, but no studies have examined this in adolescents with depression. Methods:We conducted a secondary data analysis of adolescents who participated in a randomized, single-dose, midazolam-controlled crossover trial of ketamine for adolescents with treatment-resistant depression. We examined the relationship between 19 exploratory demographic and clinical variables and depression symptom improvement (using the Montgomery-Åsberg Depression Rating Scale [MADRS]) at 1 and 7 days postinfusion. Results:Subjects who had fewer medication trials of both antidepressant medications and augmentation treatments were more likely to experience depression symptom improvement with ketamine. Subjects with shorter duration of their current depressive episode were more likely to experience depression symptom improvement with ketamine. Subjects currently being treated with selective serotonin reuptake inhibitor medications, and not being treated with serotonin–norepinephrine reuptake inhibitor medications, also experienced greater symptom improvement with ketamine. When receiving the midazolam control, less severe depressive symptoms, as measured by the Children's Depression Rating Scale (CDRS) (but not MADRS), and a comorbid attention-deficit/hyperactivity disorder diagnosis were associated with increased response. Conclusions:Findings should be viewed as preliminary and exploratory given the small sample size and multiple secondary analyses. Identifying meaningful predictors of ketamine response is important to inform future therapeutic use of this compound, however, considerably more research is warranted before such clinical guidance is established. The trial was registered in clinicaltrials.gov with the identifier NCT02579928.

Comparable studies

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

Study Year Design Participants
Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial Patients with mood and anxiety spectrum disorders who presented with clinically... 2015 Randomized controlled trial n = 24
Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence Detoxified inpatients with heroin dependence 2007 Randomized controlled trial n = 59
Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study Patients with treatment-resistant generalized anxiety and social anxiety disorders who... 2020 Double-blind, psychoactive-controlled ascending dose study n = 12
Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant Patients with treatment resistant depression 2020 Randomized controlled trial
Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression Subjects with treatment-resistant depression 2018 Randomized controlled trial n = 99

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