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.

Intranasal esketamine, used for treatment-resistant depression, does not appear to carry significant abuse liability during an acute course of treatment. In a secondary analysis of a multicenter observational study, 23 patients with major depressive disorder reported neutral liking and no cravings for esketamine after their first dosing session, and these measures did not increase over eight sessions. Neither age, sex, baseline depression severity, side effects, nor study site influenced liking or cravings. The findings align with existing literature suggesting that acute esketamine treatment is not associated with high drug liking or cravings, though larger studies are needed.

Study at a glance

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.