Can Dissociative Side Effect of “Floating” Predict Response to Ketamine in MDD?

Among individuals with treatment-resistant depression (TRD), the dissociative side effect of “floating” is not related to an antidepressant response to ketamine and thus cannot be utilized as a predictor of treatment response. Results of the study were published in the Journal of Psychiatric Research.

The investigators sought to evaluate the association between treatment response and a floating sensation in individuals with either major depressive disorder (MDD) or bipolar depression (BD) who received treatment with a single intravenous (IV) subanesthetic dose of ketamine 0.5 mg/kg. They theorized that the experience of floating prior to and following an infusion of ketamine would positively correlate with treatment response at approximately 4 hours, as well as on day 1 postinfusion. Additionally, they hypothesized that the postketamine experience of floating would mediate the antidepressant response to the agent, with a more pronounced sensation of floating linked to an increased response to ketamine.

The current analysis (ClinicalTrials.gov identifier: NCT00088699) assessed pooled data from 3 double-blind, crossover, placebo-controlled ketamine clinical trials conducted among inpatients at the National Institutes of Mental Health, National Institutes of Health Clinical Research Center in Bethesda, Maryland.

Data were included from a total of 82 participants with TRD, 38 of whom had MDD and 44 of whom had BD. The patients were between 18 and 65 years of age. All of the participants received placebo and ketamine 0.5 mg/kg infusions over 40 minutes, and were pooled for retrospective analysis. Drug response was measured via use of the Montgomery-Åsberg Depression Rating Scale (MADRS).

Results of the study demonstrated that floating was among the 10 most common side effects reported post-ketamine infusion, being present in 60% of the participants. The sensation of floating typically peaked at 40 minutes postinfusion and was rarely reported postplacebo and/or at baseline—that is, at 60 minutes prior to the infusion.

At 230 minutes postinfusion, ketamine-induced floating was not significantly associated with treatment response (P =.48) nor did it mediate the impact of ketamine on MADRS scores (P =.39). At 230 minutes postinfusion, however, ketamine significantly reduced MADRS scores compared with placebo (P <.001), with the same pattern of results observed on day 1 as well.

Limitations of the study included its post-hoc design and a qualitative/subjective measure was being examined with a quantitative approach. Furthermore, differences between diagnostic groups could not be evaluated because diagnosis and study were confounding factors and because the data were treated as meta-analytic in nature.

The investigators concluded that based on the findings from this study, identification of clinical markers or predictors of treatment response could help to minimize the need to expose patients to the risks associated with ketamine use, especially with repeated dosing, and remains a potentially productive area of research.

Disclosure: Carlos A Zarate Jr is listed as a co-inventor on several patents. All other authors have no conflict of interest to disclose, financial or otherwise.

Reference

Acevedo-Diaz EE, Cavanaugh GW, Greenstein D, et al. Can ‘floating’ predict treatment response to ketamine? Data from three randomized trials of individuals with treatment-resistant depression. J Psychiatr Res. Published online July 30, 2020. doi: 10.1016/j.jpsychires.2020.06.012