Background: 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.
Objectives: 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.
Design: This is a secondary analysis of a previously published multicenter observational study.
Methods: 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).
Results: 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.
Conclusion: 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.
Keywords: abuse liability; antidepressant effect; ketamine abuse; major depressive disorder; psychopharmacology; real-world clinical data; suicidal ideation; treatment response.
An observational study assessing changes in esketamine liking and cravings through a 4-week treatment course of patients with treatment resistant depression Depression is a serious mental illness that can be difficult to treat in some patients. Intranasal esketamine is a newer agent that can be added to an antidepressant to enhance the response. Esketamine is a drug derived from ketamine, which is a medication that has been used for many years in anesthesia and pain medicine, It is also a drug that can be abused or misused. One concern about medical use of esketamine is whether patients would “like” its psychological effects, or begin to crave it. This would be concerning as it may lead to misuse, over use, or seeking black market ketamine. To our knowledge, this is the first study that evaluates level of drug liking and craving along with improvement in mood in real world patients treated with esketamine. Twenty nine patients completed drug liking/craving and mood questionnaires through their course of esketamine treatments. Results are reassuring because most patients rated a neutral “liking” and minimal or no “craving” for esketamine, even after repeated treatments. While clinicians still must be cautious in use of esketamine, this study suggests that the medication is not likely to be abused or misused by patients taking it for depression.
© The Author(s), 2025.