KET-MCI: A Pilot Safety and Tolerability Study of Single Infusion Intravenous Ketamine for Older Adults with Depression and Mild Cognitive Impairment
Rachel Fremont, Amelia Karim, Tanya Peguero Estevez, Catherine Mcdonough, Arianna Labarbiera, Adriana Feder, Georges Naasan, Andrew D. Delgado, Dennis S. Charney, James W. Murrough
American Journal of Geriatric Psychiatry February 24, 2026 DOI: 10.1016/j.jagp.2026.02.005 via OpenAlex
Summary
AI-generated from the abstractIn an open-label clinical trial, a single intravenous infusion of ketamine (0.5 mg/kg) was safe and well tolerated in 13 patients with mild cognitive impairment and major depressive disorder. No serious adverse events occurred. Depression severity, measured by the Montgomery-Asberg Depression Rating Scale, dropped from a mean of 27.4 before treatment to 5.7 at 24 hours after the infusion—a large-magnitude improvement. For 8 of the 13 patients, this improvement persisted for up to one month, with a mean score of 12.1 and at least a 50% reduction. These findings suggest ketamine may be effective for depression in this population, but larger randomized controlled trials are needed to confirm efficacy and assess cognitive effects.
Study at a glance
| Characteristics | Open-label clinical trial Randomized Peer reviewed |
|---|---|
| Sample size | 13 |
| Population | Patients with mild cognitive impairment and Major Depressive Disorder (MCI-D) and moderate to severe depression |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Single infusion, with follow-up at 24 hours and up to 1 month |
| Topics | Ketamine |
| Keywords | Tolerability Cognitive impairment Depression economics Cognition |
| Citations | 1 |
| Key finding | A single ketamine infusion was safe and well tolerated in patients with MCI-D and was associated with large-magnitude improvements in depression severity at 24 hours, with persistent benefit in 8 of 13 patients up to one month. |
Abstract
OBJECTIVE: This open-label clinical trial primarily examined the safety and tolerability of ketamine treatment in patients with mild cognitive impairment and Major Depressive Disorder (MCI-D). Preliminary efficacy was also explored. METHODS: The trial was conducted between November 2023 and March 2025. Patients with MCI-D and moderate to severe symptom levels of depression received a single intravenous ketamine infusion (0.5 mg/kg). Safety and tolerability were evaluated. Antidepressant efficacy was also explored by evaluating change in the Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to 24 hours after the infusion. RESULTS: Thirteen eligible patients received treatment and completed study procedures. No serious adverse events were reported and all participants tolerated study procedures. The treatment was associated with large-magnitude improvement in depression symptom severity from baseline (mean MADRS = 27.4[SD = 6.4]) to 24 hours after the infusion (mean MADRS = 5.7[SD = 4.7]) in all patients with improvements in MADRS persisting for 8 individuals up to 1 month after treatment (mean MADRS = 12.1[SD = 6.9], ≥50% improvement). CONCLUSIONS: Findings from this open-label clinical trial support the safety and tolerability of ketamine treatment is in individuals with MCI-D. Ketamine may also be effective for improving depression in this population. Large-scale randomized controlled trials are needed to determine the efficacy and potential cognitive effects of this promising treatment in this patient population.