Molecular Psychiatry
October 3, 2018
M. Fava, M. Freeman, M. Flynn et al.
438 citations
Intravenous ketamine at 0.5 mg/kg and 1.0 mg/kg produces rapid antidepressant effects in adults with treatment-resistant depression, with most improvement seen one day after a single 40-minute infusion. Lower doses (0.1 mg/kg and 0.2 mg/kg) did not show consistent benefit. The study compared four ketamine doses against an active placebo (midazolam) in 99 outpatients across six U.S. sites. Higher doses caused more dissociative symptoms and temporary blood pressure increases, but infusions were generally well tolerated. The findings indicate a range of effective subanesthetic doses, with no clear advantage for doses below 0.5 mg/kg.
Journal of Affective Disorders
February 18, 2014
D. Luckenbaugh, M. Niciu, D. Ionescu et al.
282 citations
In treatment-resistant inpatients with major depressive or bipolar disorder, the dissociative side effects of a single ketamine infusion predicted a more robust and sustained antidepressant response. Greater dissociation measured 40 minutes after infusion correlated with greater improvement in depression scores at 230 minutes and 7 days later. In contrast, psychotomimetic symptoms, manic symptoms, and changes in blood pressure or pulse were not significantly linked to antidepressant efficacy. The findings suggest that dissociation, rather than other side effects, may be a marker or mediator of ketamine's antidepressant action, though further prospective research is needed.
Journal of Affective Disorders
January 1, 2019
D. Ionescu, Kate H Bentley, M. Eikermann et al.
179 citations
Repeated doses of ketamine did not reduce depression or suicidal ideation more than placebo in outpatients with severe, treatment-resistant depression and chronic suicidal thoughts. Twenty-six medicated adults received six infusions of ketamine or saline over three weeks. Neither depression severity nor suicidal ideation differed between groups during the infusion phase. At three months, two patients in each group had remitted from depression. The authors suggest that the standard 0.5 mg/kg dose may be insufficient for this severely ill outpatient population.
European Neuropsychopharmacology
June 2, 2021
A. Feeney, R. Hock, Marlene P. Freeman et al.
33 citations
A single intravenous infusion of ketamine may reduce suicidal ideation in patients with treatment-resistant depression for up to 30 days, but early effects diminish rapidly. In a double-blind randomized trial, 40 patients received ketamine and 16 received midazolam placebo; all had clinically significant suicidal ideation at baseline. By day 30, the ketamine group had a lower mean suicide score (2.03) than the placebo group (3.00). However, among those whose suicidal ideation initially resolved by day 3, there was no significant difference between groups in later scores. Recurrence of suicidal ideation was common in both groups. The findings suggest a possible role for ketamine as an adjunct to standard treatments.