Safety and Tolerability of the Acute Ketamine Treatment in Treatment-Resistant Depression: Focus on Comorbidities Interplay with Dissociation and Psychomimetic Symptoms

There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety concerns arise regarding adverse drug reactions in specific subpopulations. The aim of this study was to investigate the safety of intravenous ketamine treatment in relation to dissociative and psychotic measures in TRD inpatients with Major Depressive Disorder (MDD) and Bipolar depression (BP) with comorbidities. In total, 49 inpatients with MDD or BP were treated with ketamine following the registered naturalistic observational protocol in a tertiary reference unit for mood disorders (NCT04226963). This dataset represents an intermittent analysis of an observational study performed for interim modeling of observational learning. The observations were applied to the inhomogeneous TRD population in a single site with no blinding and were limited to acute administration. The presence of epilepsy was significantly associated with an elevation in the BPRS over time (p = 0.008). Psychotic symptomatology with BPRS scores for comorbid conditions excluding epilepsy turned out to be insignificant (p = 0.198) regardless of the diagnosis. However, for a subgroup of patients with epilepsy (n = 6), a substantial fluctuation was seen across all administrations in the time course of the study. The study results contribute to the literature on the safety and tolerability profile of CNS adverse drug reactions in short-term treatment with intravenous ketamine as an add-on intervention to current standard-of-care psychotropic medication in TRD-MDD and TRD-BP inpatients with comorbidities. The careful consideration of comorbidities and concomitant medication is needed with ketamine administration along with close-clinical supervision at every visit.