American Journal of Psychiatry
March 17, 2021
R. Mcintyre, J. Rosenblat, C. Nemeroff et al.
694 citations
Ketamine and esketamine are the first non-monoamine-based antidepressants with rapid-onset efficacy for adults with treatment-resistant depression, offering hope to those who do not recover fully with standard antidepressants. However, concerns remain about their safety, tolerability, and appropriate placement in treatment algorithms. An international group of mood disorder experts synthesizes evidence on efficacy, safety, and tolerability, and provides guidance for clinical implementation, including practice parameters at point of care. Areas of consensus and future research directions are discussed.
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.
JAMA psychiatry
October 19, 2022
T. Rhee, S. Shim, B. Forester et al.
139 citations
A systematic review and meta-analysis of six clinical trials involving 340 patients with major depressive episodes found that electroconvulsive therapy (ECT) was more effective than ketamine for reducing depression severity in the acute phase, with a standardized mean difference of -0.69 favoring ECT. No significant differences were observed between the two treatments for cognition, memory, or serious adverse events. Ketamine carried lower risks of headache and muscle pain, while ECT carried lower risks of blurred vision, vertigo, diplopia, and dissociative symptoms. The findings suggest ECT may be superior, but treatment decisions should be individualized.
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.