Dissociative symptoms with intravenous ketamine in treatment-resistant depression exploratory observational study

Abstract

There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety and tolerability concerns arise regarding adverse drug reactions and specific subpopulations. This paper aims to investigate the relationship between dissociative and psychometric measures in course of intravenous ketamine treatment in TRD inpatients with major depressive disorder and bipolar disorder.This study result represents safety data in a population of 49 inpatients with major depressive disorder and bipolar disorder subjects receiving eight 0.5 mg/kg of ketamine intravenous infusions, with a duration of 40 min each, as an add-on treatment to standard-of-care pharmacotherapy, registered in the naturalistic observational protocol of the tertiary reference unit for mood disorders (NCT04226963). The safety psychometrics assessed dissociation and psychomimetic symptomatology with the Clinician-Administered Dissociative States Scale (CADSS) the Brief Psychiatric Rating Scale (BPRS).The significant differences in CADSS scores between measurements in course of the treatment were observed (P = .003). No significant differences between BPRS measurements were made after infusions. In each case, both BPRS and CADSS values dropped to the "absent" level within 1 hour from the infusion. Neither CADSS nor BPRS scores were associated with the treatment outcome.The study demonstrates a good safety profile of intravenous ketamine as an add-on intervention to current psychotropic medication in TRD. The abatement of dissociation was observed in time with no sequelae nor harm. The study provides no support for the association between dissociation and treatment outcome.This study may be underpowered due to the small sample size. The protocol was defined as a study on acute depressive symptomatology without blinding.

Pharmacological modelling of dissociation and psychosis: an evaluation of the Clinician Administered Dissociative States Scale and Psychotomimetic States Inventory during nitrous oxide (‘laughing gas’)-induced anomalous states

“…Morgan et al 2010 ), researchers have not generally used ketamine to specifically provoke dissociation, instead generally viewing dissociation as an off-target effect in clinical trials for depression (e.g. Niciu et al 2018 ; Włodarczyk et al 2021 ). However, there is some evidence that dissociation is an important predictor of antidepressant response to ketamine (Niciu et al 2018 ; Mathai et al 2020 ).…”

A transdiagnostic systematic review and meta-analysis of ketamine’s anxiolytic effects

“…of dissociation may lead to more improvement in depression symptoms(Correia-Melo et al, 2017;Luckenbaugh et al, 2014;Sos et al, 2013). Our analysis showed no significant relationship between the two at either time point, suggesting that ketamine'sWłodarczyk et al, 2021). Nevertheless, our analysis was done using a small number of data points and more work should be done to further investigate these conclusions.Several limitations of our study are of note.…”

Buddhist-like opposite diminishing and non-judging during ketamine infusion are associated with antidepressant response: an open-label personalized-dosing study

“…Specifically, the dose level and frequency for the ketamine infusion were adjusted individually in close consultation with the patient with the overall goal to maximize antidepressant benefits and tolerability of the infusion (personalized antidepressant dosing). Treatment started with an initial ketamine infusion (Ketamine Inresa) with a dose of 0.5 mg/kg body weight and a runtime of 40 min to evaluate the patient’s initial response to the treatment—this dosage is an internationally used standard that has been proven to be safe and has often shown antidepressant response ( Berman et al, 2000 ; Zarate et al, 2006 ; Murrough et al, 2013 ; Xu et al, 2016 ; Niciu et al, 2018 ; Włodarczyk et al, 2021 ). After these initial (up to three) infusions of 0.5 mg/kg, each patient’s individual response in terms of tolerability and change in depressive symptomatology determined the dose level and frequency of the subsequent infusions.…”

“…In each session, patients completed the BDI-II 3 before the ketamine infusion (as well as additional questionnaires that were not part of the present study). No later than 40–60 min after the end of the infusion, all mind-altering effects of the ketamine were expected to have subsided ( Włodarczyk et al, 2021 ). Within this post-infusion time window and after inspection by the experienced professional, the ASCI (Reissmann et al, under review) was administered, followed by the second administration of the BDI-II.…”