DRUG LIKING AND CRAVING OF INTRAVENOUS KETAMINE WHEN PRESCRIBED FOR THE TREATMENT OF MOOD DISORDERS IN A MONITORED SETTING: A DESCRIPTIVE ANALYSIS

Background

Ketamine has emerged as a promising treatment for mood disorders, particularly major depressive disorder (MDD) and bipolar depression (BD). However, its dissociative and psychoactive properties, along with weak mu opioid agonist activity, raise concerns regarding abuse liability, especially as ketamine use expands into routine clinical practice. While its antidepressant effects are well established, characterization of acute subjective effects such as drug liking and craving, is essential for understanding abuse liability and informing evidence-based dosing, monitoring, and risk mitigation strategies.

Methods

254 patients with a treatment-resistant mood disorder, including MDD or BD, received an acute course of intravenous ketamine (four infusions over two weeks) at an outpatient community clinic in Ontario, Canada (ClinicalTrials.gov: NCT04209296). Patients were grouped by dose received at infusion four (0.45–1.2 mg/kg): ≤0.50 mg/kg (n=51), 0.55– 0.70 mg/kg (n=24), 0.75–0.90 mg/kg (n=175), and ≥0.91 mg/kg (n=4). Drug liking and craving were assessed immediately after infusion four using the Drug Liking and Craving Questionnaire (DLCQ). Craving for non-therapeutic and higher/unprescribed use was assessed using Craving A and Craving B subscales respectively. All items were scored on a 0–100 scale. Descriptive statistics included median and interquartile range (IQR). All patients were assessed by a mental health care provider after the fourth infusion to proactively assess for signs of substance use disorders or use of ketamine outside of clinical care.

Results

In patients receiving ≤0.5 mg/kg, median drug liking was 55 (IQR 20.5), with median Craving A and Craving B scores of 0 (IQR 10.5) and 0 (IQR 11.0), respectively. Among those receiving 0.55–0.70 mg/kg, median drug liking was 50 (IQR 2.3), while median Craving A was 5 (IQR 15.8) and Craving B was 11.5 (IQR 42.5). For patients receiving 0.75–0.90 mg/kg, median drug liking was 60 (IQR 24.5), with median Craving A of 4 (IQR 28.0) and Craving B of 3 (IQR 44.5). In the ≥0.91 mg/kg group (n = 4), median drug liking was 50.5 (IQR 18.8), while both craving medians were 0 (IQR 5). On clinical assessment, no cases of treatment-emergent substance use disorders were identified in this sample. There were no known instances of patients using ketamine illicitly or other signs or symptoms of potential misuse or development of a treatment-emergent substance use disorder.

Conclusion

To our knowledge, this study represents the largest real-world clinical sample assessing drug liking and craving of an acute course of ketamine with a standardized scale. Ketamine generally produced moderate drug liking and low craving at the fourth infusion across clinically administered doses. On clinical assessment, no patients were found to develop a treatment-emergent substance use disorder and there were no known cases of illicit ketamine use in this sample. These findings provide valuable insight into patients’ acute subjective experiences and may inform future evaluations of ketamine’s abuse liability.

Learning Objective 1: Characterize acute drug liking and craving following an acute course of treatment of intravenous ketamine for treatment-resistant mood disorders using a standardized assessment tool.

Learning Objective 2: Evaluate indicators of ketamine abuse liability across clinically administered doses, including subjective craving and the presence of treatment-emergent misuse or substance use disorders.

References

Le TT, Cordero IP, Jawad MY, et al. The abuse liability of ketamine: a scoping review of preclinical and clinical studies. J Psychiatr Res. 2022;151:476– 496. Juneja K, Afroze S, Goti Z, et al. Beyond therapeutic potential: a systematic investigation of ketamine misuse in patients with depressive disorders. Discov Ment Health. 2024;4(1):23.