Exploring Predictors of Ketamine Response in Adolescent Treatment-Resistant Depression

J Child Adolesc Psychopharmacol. 2024 Mar;34(2):73-79. doi: 10.1089/cap.2023.0047. Epub 2024 Jan 3.


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.

Keywords: adolescent; clinical trial; ketamine; major depression; predictors.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antidepressive Agents / therapeutic use
  • Child
  • Depression / drug therapy
  • Humans
  • Ketamine* / therapeutic use
  • Midazolam / therapeutic use
  • Selective Serotonin Reuptake Inhibitors


  • Ketamine
  • Midazolam
  • Antidepressive Agents
  • Selective Serotonin Reuptake Inhibitors

Associated data

  • ClinicalTrials.gov/NCT02579928