The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis.
Tuuli M. Hietamies, L. Mcinnes, A. Klise, Matthew J Worley, Jimmy J Qian, Leanne M Williams, Boris D. Heifets, Steven P. Levine
Journal of Affective Disorders May 1, 2023 DOI: 10.1016/j.jad.2023.04.141 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective controlled analysis Peer reviewed |
|---|---|
| Sample size | 2,758 |
| Population | Patients treated with ketamine intravenous therapy at ten community clinics across the US, with comparison data from previously published real-world studies of ketamine-naive depressed patients or patients starting standard antidepressant therapy |
| Intervention | Ketamine intravenous therapy (KIT) |
| Duration | Induction followed by maintenance up to one year post-induction |
| Measures | Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS), Generalized Anxiety Disorder 7-item (GAD-7) |
| Topics | Anxiety Depression Esketamine Ketamine |
| Key points | Ketamine intravenous therapy produced large reductions in depression and anxiety symptoms after induction (Cohen's d = 0.9 and d = 1.14, respectively), and greater depression symptom reduction at eight weeks than two external comparison datasets (d = -1.03 and d = -0.62). Symptom increases during maintenance were minimal up to one year post-induction. |
Abstract
Introduction: Ketamine intravenous therapy (KIT) appears effective for treating depression in controlled trials testing a short series of infusions. A rapidly proliferating number of clinics offer KIT for depression and anxiety, using protocols without a strong evidence basis. Controlled comparison of mood and anxiety from real-world KIT clinics, and the stability of outcomes, is lacking.
Methods: We performed a retrospective controlled analysis on patients treated with KIT in ten community clinics across the US, between 08/2017-03/2020. Depression and anxiety symptoms were evaluated using the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS) and the Generalized Anxiety Disorder 7-item (GAD-7) scales, respectively. Comparison data sets from patients who did not undergo KIT were obtained from previously published real-world studies.
Results: Of 2758 patients treated, 714 and 836 met criteria for analysis of KIT induction and maintenance outcomes, respectively. Patients exhibited significant and concordant reduction in both anxiety and depression symptoms after induction (Cohen's d = 1.14 and d = 0.9, respectively). Compared to two external datasets of KIT-naive depressed patients or patients starting standard antidepressant therapy, KIT patients experienced a significantly greater reduction in depression symptoms at eight weeks (Cohen's d = -1.03 and d = -0.62 respectively). Furthermore, we identified a subpopulation of late-responders. During maintenance, up to a year post-induction, increases in symptoms were minimal.
Limitations: Due to the retrospective nature of the analyses, interpreting this dataset is limited by incomplete patient information and sample attrition.
Conclusions: KIT treatment elicited robust symptomatic relief that remained stable up to one year of follow-up.
Comparable studies
Other observational and cohort studies on ketamine for anxiety, most cited first.
Citations in the library
Cited by 23
- Therapeutic mechanisms of psychedelics and entactogens. Neuropsychopharmacology July 24, 2023
- Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions? American Journal of Psychiatry March 1, 2025
- Ketamine for Depression, but at What Cost? A Review of Ketamine’s Neurotoxic Effects From Preclinical and Human Studies American Journal of Psychiatry September 10, 2025
- Perspectives in treatment-resistant depression: esketamine and electroconvulsive therapy. Wiener klinische Wochenschrift March 1, 2025
- Prolonged ketamine therapy differentially rescues psychobehavioural deficits via modulation of nitro-oxidative stress and oxytocin receptors in the gut-brain-axis of chronically-stressed mice. Psychoneuroendocrinology December 1, 2023
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Cites 18
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
- Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. American Journal of Psychiatry March 29, 2019
- Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial Psychological Medicine August 12, 2015
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