Leorey N Saligan1, David A Luckenbaugh2, Elizabeth E Slonena3, Rodrigo Machado-Vieira4, Carlos A Zarate5. 1. National Institute of Nursing Research, Division of Intramural Research, National Institutes of Health, 31 Center Drive, MSC 2178, Bethesda, MD 209892, USA. Electronic address: saliganl@mail.nih.gov. 2. Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, 10 Center Drive, Rm 4N222, MSC 1381 Bethesda, MD 20892, USA. Electronic address: luckenbd@mail.nih.gov. 3. Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, 10 Center Drive, Rm 4N222, MSC 1381 Bethesda, MD 20892, USA. Electronic address: elizabeth.slonena@nih.gov. 4. Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, 10 Center Drive, Rm 4N222, MSC 1381 Bethesda, MD 20892, USA. Electronic address: rodrigo.machadovieira@nih.gov. 5. Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, 10 Center Drive, Rm 4N222, MSC 1381 Bethesda, MD 20892, USA. Electronic address: zaratec@mail.nih.gov.
Abstract
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 (0.5 mg/kg over 40 min) 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 min 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=0.58, p<0.05). The effect remained significant after controlling for changes in non-fatigue depressive symptoms. LIMITATION: The retrospective nature and a small sample size are study limitations. CONCLUSIONS:Ketamine rapidly improved fatigue relative to placebo in a group of individuals with treatment-resistant bipolar depression. NMDAR is a glutamate receptor; hence, glutamate may represent a valuable target to study the clinical efficacy of new anti-fatigue approaches in multiple disorders. Published by Elsevier B.V.
RCT Entities:
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 depressedpatients. 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 (0.5 mg/kg over 40 min) 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 min 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=0.58, p<0.05). The effect remained significant after controlling for changes in non-fatigue depressive symptoms. LIMITATION: The retrospective nature and a small sample size are study limitations. CONCLUSIONS:Ketamine rapidly improved fatigue relative to placebo in a group of individuals with treatment-resistant bipolar depression. NMDAR is a glutamate receptor; hence, glutamate may represent a valuable target to study the clinical efficacy of new anti-fatigue approaches in multiple disorders. Published by Elsevier B.V.
Entities:
Keywords:
Depression; Fatigue; Glutamate; Ketamine; New therapeutics
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