Abuse liability for esketamine in a cohort of patients undergoing an acute treatment course to manage treatment-resistant depression: a secondary analysis of an observational study in real-world clinical practicee.
Gilmar Gutierrez, Gustavo Vazquez, Nisha Ravindran, Raymond W. Lam, Peter Giacobbe, Karthikeyan Ganapathy, Annette Kowara, André Do, Anusha Baskaran, Sean Michael Nestor, Jennifer Swainson
Therapeutic advances in drug safety 2025 DOI: 10.1177/20420986251347360 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Secondary analysis of a multicenter observational study Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Patients with treatment-resistant depression within major depressive disorder (MDD-TRD) receiving an acute course of intranasal esketamine |
| Duration | Eight dosing sessions |
| Topics | Depression Esketamine Ketamine |
| Keywords | Abuse liability Antidepressant effect Ketamine abuse Real-world clinical data Suicidal ideation Treatment response Severe depression Low abuse potential Neutral liking No cravings No heightened risk Psychopharmacology research study Assessed Promising results |
| Citations | 5 |
| Key findings | An acute course of intranasal esketamine treatment was not associated with high levels of drug liking or cravings, and these did not increase over eight treatments. |
Abstract
Intranasal (IN) esketamine has become an effective and well-tolerated therapeutic option for the management of treatment-resistant depression within major depressive disorder (MDD-TRD). Despite these promising benefits, given the prevalence of ketamine abuse, concerns remain over the addiction liability that may be associated with esketamine treatment. The objective of this study is to assess the real-world abuse liability of this substance by tracking changes in likeability and cravings through an acute treatment course. This is a secondary analysis of a previously published multicenter observational study. Likeability and craving for esketamine were assessed using the Likeability and Cravings Questionnaire (LCQ) in MDD-TRD patients receiving an acute course of IN esketamine treatment (eight dosing sessions). The data were analyzed using descriptive statistics, multivariate analysis of variance (MANOVA), and pre-post effect size (Cohen's d). Twenty-three patients (52.2% female, 43.5 ± 11.9 years old) were assessed. Most patients reported a neutral liking and no cravings for esketamine after their first dosing session. These metrics did not increase significantly by treatment endpoint. MANOVA showed that neither age, sex, baseline depression scores, the presence of side effects, or the study site had a statistically significant impact on LCQ scores either alone or in combination. These results agree with the available literature, showing that an acute course of IN esketamine treatment was not associated with high levels of drug liking or cravings, and this did not increase through the course of eight treatments. Though larger studies are needed, esketamine does not appear to be associated with significant abuse liability when used in an acute course of treatment for patients with MDD-TRD. These are important results for this patient population and for clinical practice.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 7
- Case report of S-ketamine as treatment option for suicidal ideation and treatment-resistant depression in adolescents with early-onset psychosis Neuropsychiatrie August 25, 2026
- Treating addiction with an addictive drug: the ketamine paradox revisited Frontiers in Psychiatry July 9, 2026
- Evaluating the abuse liability of ketamine in the treatment of mood disorders: A systematic review. Journal of Psychopharmacology June 24, 2026
- Ketamine and esketamine for the prevention of postpartum depression: A systematic review and network meta-analysis, with an integrated evidence synthesis. Psychiatry Research May 12, 2026
- Mental health professionals' perspective on the use of esketamine in treatment-resistant depression and their motivation to adopt it: a Saudi cross-sectional study. Frontiers in Psychiatry 2026
and 2 more in the library
Cites 35
- 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
- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism American Journal of Psychiatry August 29, 2018
- Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. American Journal of Psychiatry March 29, 2019
- Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression The Journal of Clinical Psychiatry April 20, 2020
and 30 more in the library