The effect of intranasal (R,S)-ketamine on symptoms of fatigue in severe major depressive disorder or bipolar depression with and without comorbid alcohol use disorder: Results from a randomized, double-blind, placebo-controlled trial.
Rodrigo Machado‐Vieira, Gregory H Jones, Alan C. Courtes, Ana C Ruiz, Courtney M Vecera, Ioline D. Henter, Scott D Lane, Carlos A. Zarate, Jair C Soares
Journal of Affective Disorders December 15, 2024 DOI: 10.1016/j.jad.2024.08.183 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 28 |
| Population | Individuals with major depressive disorder or bipolar depression I/II currently experiencing a depressive episode with active suicidality, approximately 60% with comorbid alcohol use disorder |
| Dose | 50 mg |
| Duration | Single dose, assessments at 4, 24, and 48 hours post-treatment |
| Topics | Addiction Depression Ketamine Esketamine |
| Keywords | Bipolar Ketamine therapy Mental health treatments Fatigue management Depression medication Intranasal drug delivery |
| Key findings | Intranasal ketamine produced significantly greater reductions in fatigue scores compared to placebo over 48 hours in individuals with depression, with or without comorbid alcohol use disorder. |
Abstract
Fatigue is a multidimensional condition that may overlap with depression. Initial studies found that fatigue responds in only a limited way to standard monoaminergic antidepressants and mood stabilizers but does respond positively to intravenous (IV) racemic (R,S)-ketamine (ketamine). However, IV ketamine's use is limited by cost and access barriers. To date, no study has evaluated intranasal (IN) ketamine in individuals with fatigue. This study sought to evaluate the anti-fatigue effects of a single 50 mg dose of IN ketamine in individuals with major depressive disorder (MDD) or bipolar depression (BDep), both with and without comorbid alcohol use disorder (AUD). Twenty-eight individuals with primary diagnoses of MDD or BDep I/II currently experiencing a depressive episode with active suicidality were enrolled; approximately 60 % had comorbid AUD. Changes in the NIH-Brief Fatigue Inventory (NIH-BFI) were assessed at baseline and at 4, 24, and 48 h post-treatment. The group x time interaction for NIH-BFI score was significant (F = 3.44, p = 0.022), favoring IN ketamine over placebo. IN ketamine was well-tolerated with minimal adverse effects. Limitations include the limited sample size, short duration, and single, fixed dose. IN ketamine appears to induce rapid anti-fatigue effects in individuals with severe MDD and BDep both with and without comorbid AUD. This suggests that IN ketamine holds potential as an alternative, rapid-acting, anti-fatigue option for different medical conditions.