Abstract
Ketamine has rapid-acting antidepressant properties but also potentially concerning transient dissociative side effects (SEs). Recent studies noted a positive correlation between treatment response to ketamine and general dissociative SEs, as well as "floating", a depersonalization SE (a subtype of the dissociative SEs). This analysis sought to determine whether floating mediates treatment response to ketamine. Data were pooled from three double-blind, crossover, placebo-controlled ketamine clinical trials across which 82 participants with treatment-resistant depression (TRD) (44 with bipolar depression and 38 with major depressive disorder) received placebo and ketamine (0.5 mg/kg) infusions. SEs were actively solicited in a standardized fashion before and after ketamine infusion. The hypothesis that a post-infusion experience of floating would mediate antidepressant response to ketamine was assessed at 230 min post-infusion and at Day 1. Montgomery-Asberg Depression Rating Scale (MADRS) total score was the dependent variable in a linear mixed effects model. Ketamine significantly decreased MADRS scores (p < 0.0001), but no relationship was detected between floating and MADRS score at either 230 min or Day 1 post-infusion. The hypothesized mediation effect of floating was also not detected at either 230 min or Day 1 post-infusion. Taken together, the findings do not support the hypothesis that ketamine's antidepressant effects are mediated by the dissociative depersonalization subtype SE of floating.