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Disentangling the association of depression on the anti-fatigue effects of ketamine.

Leorey N Saligan, Cristan A Farmer, Elizabeth D. Ballard, Bashkim Kadriu, Carlos A. Zarate

Journal of Affective Disorders February 1, 2019 DOI: 10.1016/j.jad.2018.10.089 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Secondary analysis of a double-blind, randomized, placebo-controlled, crossover trial Peer reviewed
Sample size 39
Population Patients with treatment-resistant major depressive disorder
Intervention Ketamine hydrochloride
Dose 0.5 mg/kg over 40 minutes
Duration Single infusion; outcomes assessed at Day 1 post-infusion
Measures National Institutes of Health-Brief Fatigue Inventory (NIH-BFI), Montgomery-Åsberg Depression Rating Scale (MADRS)
Topics Depression Esketamine Ketamine
Key findings Ketamine improved fatigue relative to placebo at Day 1 post-infusion, but the anti-fatigue effect disappeared when MADRS total depression scores were controlled for. The authors report the effect was mostly accounted for by changes in amotivation and depressed mood, and conclude that in this sample ketamine had no unique effect on fatigue outside its general antidepressant effects.

Abstract

Fatigue and depression are closely associated. The purpose of this secondary analysis was to understand the relationships between depression and improvements in specific depression domains on the anti-fatigue effects of ketamine, which we previously reported. This secondary analysis re-evaluated data collected longitudinally from 39 patients with treatment-resistant Major Depressive Disorder (MDD) enrolled in a double-blind, randomized, placebo-controlled, crossover trial using a single intravenous infusion of ketamine hydrochloride (0.5 mg/kg over 40 minutes) or placebo. A mediation model assessed the effect of depression on the anti-fatigue effects of a single dose of intravenous ketamine versus placebo at Day 1 post-infusion. Fatigue was measured using the National Institutes of Health-Brief Fatigue Inventory (NIH-BFI), and depression was assessed by the Montgomery-Ǻsberg Depression Rating Scale (MADRS). Compared to placebo, ketamine significantly improved fatigue (p = .0003) as measured by the NIH-BFI, but the anti-fatigue effects of ketamine disappeared (p = .47) when controlling for depression as measured by MADRS total score. In this study sample, the anti-fatigue effects of ketamine were mostly accounted for by the changes in amotivation and depressed mood scores. In this study, ketamine did not have a unique effect on fatigue outside of its general antidepressant effects in patients with treatment-resistant depression. Specifically, the anti-fatigue effects of ketamine observed in this study seem to be explained by the effects of ketamine on two symptom domains of depression: amotivation and depressed mood. The study findings suggest that the anti-fatigue effects of ketamine should be assessed by fatigue-specific measures other than the NIH-BFI or future studies should enroll fatigued patients without depression.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

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