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Assessment of Anti-Fatigue Effects of Ketamine in Double-Blind, Placebo-Controlled, Cross

Ketamine for Bipolar disorder with resistant fatigue / chronic fatigue syndrome

  1. Scrofula
    Study Author(s):
    Leorey N. Saligan, Ph.D., R.N.a, David A. Luckenbaugh, M.A.b, Elizabeth E. Slonena, B.S.b, Rodrigo Machado-Vieira, M.D., Ph.D.b, and Carlos A. Zarate Jr., M.D.b
    Journal Name:
    Journal of Affective Disorders, April, 192, 115-110
    Publication Date:
    April 2016
    Background—Fatigue is a multidimensional condition that is difficult to treat with standard monoaminergic antidepressants. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist produces rapid and robust improvements in depressive symptoms in treatment-resistant depression. However, there is a dearth of literature examining the anti-fatigue effects of ketamine. We hypothesize that ketamine will rapidly improve fatigue symptoms in treatment-resistant depressed patients.
    Methods—This is an exploratory analysis of data obtained from two double-blind, randomized, placebo-controlled, crossover trials. A total of 36 participants with treatment-resistant bipolar I or II disorder in a depressive episode (maintained on therapeutic levels of lithium or valproate) received a single infusion of ketamine hydrochloride intravenously (0.5mg/kg over 40 minutes) or placebo. A post-hoc analysis compared fatigue scores on ketamine vs. placebo at 10 time points from baseline through 14 days post-treatment using the National Institute of Health-Brief Fatigue Inventory.
    Results—A linear mixed model showed that ketamine significantly lowered fatigue scores compared to placebo from 40 minutes post-treatment to Day 14 with the exception of Day 7. The largest difference in anti-fatigue effects between placebo and ketamine was at day 2 (d=.58, p < .05). The effect remained significant after controlling for changes in non-fatigue depressive symptoms.