Safety outcomes of ketamine for treatment-resistant depression in clinical settings and development of the ketamine side effect tool-revised (KSET-R).

Background: Ketamine and its derivates (e.g. esketamine) are increasingly used in clinical settings for treatment-resistant depression (TRD). Ketamine can give rise to acute, cumulative and longer-term side effects (SEs) across a treatment course. The Ketamine Side Effect Tool (KSET) examines adverse effects though its length has affected feasibility for use in clinical settings.

Objective: To estimate the frequency of ketamine SEs occurring in real-world settings using the KSET, additional validated scales and laboratory measures. Utilising this naturalistic data, to develop a shorter, more feasible and validated tool (KSET-Revised; KSET-R).

Methods: Retrospective patient and safety data from three outpatient services were collected which included KSET symptom questions, standardised scales and laboratory measures. We calculated frequency of SEs occurring intra-session, intersession and at follow-up. Revision of the KSET included removal of items based on a priori criteria. Construct and concurrent validity were examined by comparison of specific KSET items and the overall tolerability rating with standardised scales.

Results: Descriptive statistics including SE frequencies are reported and the KSET-R is detailed: a shorter tool with construct and concurrent validity for specific items, along with the overall tolerability rating.

Limitations: small sample size for follow-up data; predominantly subcutaneous racemic and intranasal esketamine analysed - other routes and formulations not examined; and subjective not objective cognition measured.

Conclusions: Naturalistic data gives an estimate of frequency of ketamine SEs within session, between sessions and at follow-up. The KSET-R has improved feasibility and clinical utility and is recommended for use in clinical practice where ketamine is prescribed.