Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan;39(1):49-65.
doi: 10.1177/02698811241303597. Epub 2024 Dec 17.

Is there a risk of addiction to ketamine during the treatment of depression? A systematic review of available literature

Gianmarco Ingrosso  1   2 , Anthony J Cleare  1 , Mario F Juruena  1
Affiliations

Is there a risk of addiction to ketamine during the treatment of depression? A systematic review of available literature

Gianmarco Ingrosso et al. J Psychopharmacol. 2025 Jan.

Abstract

Background: Ketamine has demonstrated both rapid and sustained efficacy in treating depression, especially in treatment-resistant cases. However, concerns regarding the addictive potential of ketamine during long-term depression treatment persist among clinicians.

Aim: This review aimed to summarise the evidence on addiction phenomena associated with ketamine treatment of depression.

Methods: A comprehensive search was conducted in MEDLINE, Embase, PsycInfo and Global Health databases, with additional relevant studies identified through reference lists. Sixteen studies were included, comprising six randomised controlled trials, three single-arm open-label studies, one retrospective study, three case series and three case reports, for a total of 2174 patients.

Results: The studies employed various routes of administration, including intravenous, intramuscular, intranasal, oral and sublingual. Ketamine was administered in the racemic form, except for the studies that utilised intranasal esketamine. Among the included population, four patients were reported to exhibit clear signs of tolerance to the antidepressant effect of ketamine or dependence on the drug, while the majority did not. Cases of addiction phenomena reported in studies that did not meet the inclusion criteria are also discussed.

Conclusions: Despite the heterogeneity in study designs and outcome assessment methods, the review underscores the relative safety of ketamine treatment for adult patients with depression, emphasising the importance of medically supervised administration, vigilant monitoring and judicious dosing. Future long-term studies employing quantitative scales to assess dependence phenomena could contribute to strengthening the evidence for the safe and effective use of ketamine in the treatment of depression.

Keywords: Addiction; dependence; depression; esketamine; ketamine.

PubMed Disclaimer

Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. MFJ has within the last year received honoraria for speaking from Lundbeck, Janssen, Takeda, Bial, Artmed, and EMS, and honoraria for consulting from Janssen and Neurocentrx. MFJ receives copyrights from Nature/Springer Books, Cambridge Press and Elsevier Press and has a patent about the indication and use of Oral Ketamine. AJC has received honoraria for speaking from Janssen, Otsuka, Viatris, COMPASS Pathways and Medscape and honoraria for consulting from Janssen, Otsuka and COMPASS Pathways. GI has no conflicts of interest to declare.

Publication types

MeSH terms