The added value of the patient-specific psycho-active effects of intranasal S-ketamine on outcomes in patients suffering from therapy-resistant depression

Abstract

Abstract

Introduction: Therapy resistant depression (TRD) is a disease with a broad arsenal of treatments. However, treatment results remain unsatisfactory leaving TRD a hard-to-treat disease. Since 2019, the atypical psychedelic, intranasal (IN) esketamine, has been approved as a treatment for patients suffering from TRD. Yielding promising results, it is hypothesised that patient specific psychoactive effects (PAE) induced by the known side effects of esketamine, dissociation and hallucinations, might have an added effect on depressive symptoms.

Methods: Firstly, patient reports regarding the esketamine sessions of participants of the Intranasal Esketamine Data Collection (INESKAD-) study are analysed using the Ketamine Side Effects Tool (KSET) and 6-item Clinician Administered Dissociative Symptoms Scale (CADSS-6), comparing both questionnaires in their ability to capture patient specific PAE. Secondly, a model was created in an attempt to capture patient specific PAE, quantifying the data from the patient reports and comparing them to the MADRS-score documented in the framework of the INESKAD-study.

Results: The average total number of capture pieces of information of the KSET and the CADSS-6 are 3,8 and 3,73 (p=0,731) respectively. The average decrease in MADRS-scores is 11 points (p=0,274). In patient reports an average of 18,8%, 27,2%, 29,0% and 25,0% of text was divided into primary, secondary, tertiary and unknown effects of IN esketamine respectively.

Conclusion: The KSET and CADSS-6 are not to be compared due to their different purposes. Both questionnaires fail to capture the patient specific PAE adequately. Furthermore, there seem to be a correlation between the prevalence of tertiary effects of ketamine and a decrease in MADRS-scores.