KET-MCI: A Pilot Safety and Tolerability Study of Single Infusion Intravenous Ketamine for Older Adults with Depression and Mild Cognitive Impairment

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.