Single-dose Ketamine Treatment to Improve Depression in Mild Cognitive Impairment

This open-label trial (n=15) will assess the safety and tolerability of a single sub-anesthetic (35mg/70kg) intravenous (IV) ketamine treatment in individuals aged 50-90 with mild cognitive impairment and depression (MCI-D).

It aims to determine whether treatment with a single dose of ketamine may improve mood or cognition in individuals with MCI-D. The study also explores the influence of Alzheimer’s disease biomarker status on the effectiveness of ketamine treatment and examines brain connectivity changes after ketamine treatment. The study involves screening, a baseline visit, a single infusion of IV ketamine, and follow-up visits over approximately one month.

Primary outcome measures include the number and severity of symptom events assessed by the Patient Rated Inventory of Side Effects (PRISE), and secondary outcome measures include depressive symptoms assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) and cognition assessed with the NIH Toolbox Cognition Battery.

The study is conducted by the Icahn School of Medicine at Mount Sinai, with Rachel Fremont as the principal investigator. Recruitment is ongoing in New York, New York, United States, and the study started on October 18, 2023, with an estimated completion date in December 2025.

Trial Details

Ketamine is a NMDA-receptor antagonist that promotes synapse formation and has been shown to rapidly improve symptoms in depression. Even a single dose of ketamine has been shown to improve depression and cognition with short-term memory, inhibitory control, cognitive flexibility, and processing speed showing improvements within days of treatment. The mechanism behind ketamine's rapid action is not clear but some groups have speculated it may be related to enhanced neuroplasticity, particularly in the frontal areas and the hippocampus. If this mechanism is accurate, ketamine may be especially effective in treating mild cognitive impairment and depression (MCI-D) where changes in the hippocampus and frontal areas have been implicated. Although few studies have been published on the effects of ketamine in older adults, some small pilot studies suggest that ketamine treatment might be effective in improving depression in older adults and relatively safe. There are no studies looking at the effects of ketamine treatment in patients with MCI-D. The research team hypothesize that IV ketamine treatment will be well-tolerated and will improve depression and cognition in patients with MCI-D. The study team will explore the effects of brain imaging abnormalities and amyloid biomarker status on the responsiveness to ketamine. The study team will conduct an open-label pilot study designed to gather data to support an application for a larger NIH-funded study.

Trial Number NCT06069843

Data attribution

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