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Association of intravenous ketamine with change in depressive symptoms in a large integrated health care system.

Li Kevin J, Slama Natalie E, Chen Ingrid, Lee Catherine, Ridout Samuel, Hamilton Steven P, Iturralde Esti

Psychiatry Research 2025 DOI: 10.1016/j.psychres.2024.116273 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Retrospective cohort study Peer reviewed
Sample size 570
Population Adults with treatment resistant depression receiving care in a large integrated health care delivery system
Interventions Racemic ketamine intravenous treatment standard medication management
Dose 0.5 mg/kg
Duration 3-week intervention
Topics Depression Ketamine Esketamine
Keywords Bipolar disorder Treatment resistant depression Ketamine therapy Mental health treatment Clinical research
Key findings Intravenous ketamine treatment was significantly associated with depression response (PHQ-9 reduction >50%) compared to medication management, with an adjusted risk ratio of 1.72.

Abstract

Racemic ketamine intravenous treatments (KIT) are widely used in community clinics for treatment resistant depression (TRD), but we lack studies on symptom improvement during standardized delivery to clinically complex patients with TRD. We aimed to assess depression symptom change for patients receiving standardized KIT for TRD in a large integrated health care delivery system relative to similar patients receiving standard medication management. In this retrospective cohort study (n = 570), depression symptom change measured by the 9-item Patient Health Questionnaire (PHQ-9) was examined in 143 adults with TRD receiving 0.5mg/kg 40-minute KIT infusion twice weekly for 3 weeks from 01/01/2018 to 12/31/2022 and 427 contemporaneous patients with medication management (MM) matched on variables including sex, race, age, and baseline depression symptom score. We excluded patients with major neurocognitive disorder, schizophrenia, or pregnancy. The KIT group was more likely to achieve depression response (PHQ-9 reduction >50 %) compared to MM (adjusted risk ratio [aRR]= 1.72, 95 % CI = 1.17 - 2.53; P = 0.006). The KIT group (8 % vs 5 %) was more likely to achieve depression remission (i.e. PHQ-9 < 5); however, the adjusted risk with KIT vs MM was not statistically significant. Baseline depression symptoms were associated with higher depression symptoms at follow up, as were co-occurring anxiety and personality disorders. KIT was significantly associated with depression response and symptom improvement compared to MM. Clinicians should consider comorbid personality disorder, anxiety disorders, and baseline depression severity as potential predictors of KIT and other treatment response in TRD.

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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