A single dose of intranasal ketamine (50 mg) produced rapid antidepressant effects compared to placebo in unmedicated inpatients with major depression and current suicidal ideation, but did not significantly reduce suicidal thoughts. Patients with comorbid alcohol use disorder showed a statistical trend toward greater improvement in suicidality, though the primary outcome was not met. The treatment was well tolerated. The antidepressant benefit was largely unaffected by the presence of alcohol use disorder or the type of mood disorder (unipolar or bipolar). Among those receiving ketamine, improvement in depression correlated with reduced suicidal ideation only in patients without alcohol use disorder.
Fatigue, a multidimensional condition that often overlaps with depression, responds only modestly to standard antidepressants and mood stabilizers but has shown positive response to intravenous ketamine, which is limited by cost and access. This study evaluated a single 50 mg dose of intranasal ketamine in 28 individuals with major depressive disorder or bipolar depression, about 60% of whom also had alcohol use disorder. The group by time interaction for the NIH-Brief Fatigue Inventory score was significant, favoring intranasal ketamine over placebo at 4, 24, and 48 hours post-treatment. Intranasal ketamine was well-tolerated with minimal adverse effects. The findings suggest intranasal ketamine induces rapid anti-fatigue effects and may serve as an alternative rapid-acting option for fatigue across different medical conditions.