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.
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.
Journal of Clinical Psychiatry
May 30, 2022
D. Iosifescu, A. Jones, C. O'gorman et al.
In a six-week phase 3 trial, the combination drug dextromethorphan-bupropion (AXS-05) reduced depressive symptoms more than placebo in adults with major depressive disorder. Those taking the drug showed an average 15.9-point drop on the Montgomery-Asberg Depression Rating Scale versus a 12.0-point drop with placebo, a statistically significant difference. Benefits appeared as early as one week. At six weeks, 39.5% of the drug group achieved remission compared to 17.3% of the placebo group, and 54.0% had a clinical response versus 34.0%. Common side effects included dizziness, nausea, and headache. The drug was not linked to weight gain or sexual dysfunction.
American Journal of Psychiatry
May 18, 2022
H. Tabuteau, A. Jones, Ashley Anderson et al.
In a randomized trial, the combination drug dextromethorphan-bupropion (AXS-05) improved depressive symptoms more than bupropion alone in adults with moderate-to-severe major depressive disorder. Over six weeks, the average reduction in depression scores was 13.7 points with the combination versus 8.8 points with bupropion. By week six, 46.5% of those taking the combination achieved remission, compared to 16.2% taking bupropion. The combination was generally well tolerated, with common side effects including dizziness, nausea, and dry mouth, and was not linked to weight gain or sexual dysfunction.