An assessment of the anti-fatigue effects of ketamine from a double-blind, placebo-controlled, crossover study in bipolar disorder

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 (0.5mg/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. 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.

Anti‐fatigue activity of sea cucumber peptides prepared from Stichopus japonicus in an endurance swimming rat model

“…Fatigue is a state of sharply decreased ability to complete bodily daily activities and work-related tasks, and is often accompanied by feelings of drowsiness and tiredness. 35,36 Generally, endurance capacity is the commonly used convenient and objective indicator applied to assess fatigue, 37 which is reflected by the swimming time of rats in this research. In this study the anti-fatigue effect of SCP was measured by an exhaustive swimming test, which is a commonly used experimental exercise model for evaluating anti-fatigue effect.…”

Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion

“…With the exception of anhedonia (Lally et al, 2014), fatigue (Saligan et al, 2016), and suicidal ideation (DiazGranados et al, 2010b; Reinstatler and Youssef, 2015), the literature looking at specific depressive symptom improvement after ketamine has been limited. In MDD patients who remit with citalopram, residual depressive symptoms, most commonly sleep and appetite disturbance, persist (Nierenberg et al, 2010).…”

Ketamine: translating mechanistic discoveries into the next generation of glutamate modulators for mood disorders

“…Notably, ketamine has also been found to rapidly and robustly improve key dimensions such as anhedonia, fatigue, and suicidal thoughts in individuals with treatment-resistant major depressive disorder or bipolar depression. 4–7 …”