Depression and Anxiety
December 30, 2018
Naji C. Salloum, Maurizio Fava, Marlene P. Freeman et al.
49 citations
In a double-blind trial, 99 people with treatment-resistant depression received either a single intravenous dose of ketamine (0.1, 0.2, 0.5, or 1.0 mg/kg) or midazolam (0.045 mg/kg). Among them, 45 had high baseline anxiety and 54 did not. No significant difference in depression improvement was found between the ketamine and midazolam groups for either anxious or nonanxious participants at 1 or 3 days after infusion. The results suggest that ketamine may work similarly for both anxious and nonanxious treatment-resistant depression, unlike some traditional antidepressants.
Journal of Clinical Psychopharmacology
April 25, 2020
Marlene P. Freeman, Rebecca S. Hock, George I. Papakostas et al.
45 citations
Higher body mass index (BMI) and obesity are linked to a stronger acute antidepressant effect from a single intravenous dose of ketamine in patients with treatment-resistant depression. In a randomized, double-blind, placebo-controlled trial, patients with obesity showed a significantly greater reduction in depression symptoms 24 hours after ketamine infusion compared to those with normal BMI. Overweight patients also showed a trend toward greater improvement. Similar but weaker effects were observed at 72 hours. The findings suggest that obesity may enhance the rapid antidepressant response to ketamine, which could have clinical relevance for the many patients with both major depressive disorder and obesity.
JAMA
May 24, 2019
Ole Köhler‐forsberg, Cristina Cusin, Andrew A. Nierenberg
18 citations
Recent evidence shows that several nonpharmacological and drug therapies can benefit people with major depressive disorder. Effective options include exercise, a Mediterranean diet with structured dietary support, ketamine and esketamine, anti-inflammatory drugs, brexanolone, and psilocybin.
The Journal of Clinical Psychiatry
November 14, 2022
Anna Feeney, Bettina B. Hoeppner, Marlene P. Freeman et al.
9 citations
Among people with treatment-resistant depression, those taking oral benzodiazepines alongside a single intravenous infusion of ketamine showed less improvement in depression scores 24 hours later if they were on higher benzodiazepine doses. The same pattern was not seen in those who received a midazolam placebo. By day 3 after the infusion, benzodiazepine use no longer affected depression scores. The findings suggest that higher doses of benzodiazepines may temporarily weaken ketamine's rapid antidepressant effect.
Journal of affective disorders
August 1, 2026
Ching-Hua Julie Lee, Yunzhe Qian, Weiqun Yu et al.
Compared with injectable ketamine, esketamine was linked to higher risks of suicidal ideation (24% increase), generalized anxiety disorder (55% increase), insomnia (25% increase), and cardiac arrest (57% increase). Compared with oral antidepressants in treatment-resistant depression, esketamine was associated with lower risks of suicidal ideation (11% decrease), suicide attempt (29% decrease), and generalized anxiety disorder (18% decrease), but a higher risk of cardiac arrest (109% increase). Injectable ketamine showed a more favorable safety and effectiveness profile than esketamine. Head-to-head clinical trials are needed to validate these findings.
J Affect Disord
May 14, 2026
Joshua Curtiss, Laya Dasari, Julianne Origlio et al.
Patients with treatment-resistant depression whose symptoms are loosely connected before ketamine therapy are more likely to respond than those with tightly linked symptoms. Among 447 patients receiving intravenous ketamine or intranasal eskatamine, non-responders had denser pre-treatment symptom networks (global strength 4.03) compared with responders (global strength 1.06). After treatment, responders' network strength increased, while non-responders' decreased. Sparse baseline symptom networks may indicate greater capacity for reorganization, making pre-treatment network density a potential marker of ketamine response.