TOPLINE:

A single intravenous ketamine infusion was safe and well-tolerated in older adults with mild cognitive impairment (MCI) and depression (MCI-D), with no serious adverse events (AEs) reported, a small open-label pilot study showed. Depression symptom severity scores also decreased substantially from baseline to 24 hours post-infusion, with improvements persisting in more than half of the participants up to 1 month after treatment.

METHODOLOGY:

• In an exploratory, open-label pilot study conducted from 2023 to 2025, 13 participants aged 50-90 years (mean age, 72 years; 54% men) with MCI and moderate-to-severe symptoms of major depressive disorder received a single intravenous ketamine infusion at 0.5 mg/kg over 40 minutes.
• The primary outcome was safety and tolerability through AE reports from infusion day until 1-month follow-up. Secondary outcomes included changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to 24 hours, 48 hours, 72 hours, 1 week, and 1 month post-infusion. Response was defined as a 50% or greater reduction in MADRS score and remission as a MADRS score < 10.
• Pre-post cognitive assessment was conducted using the National Institutes of Health cognition toolbox (NIH Toolbox-Cog). Exploratory analyses included the use of the Mini-Mental Status Exam (MMSE) to measure gross cognitive functioning.
• Participants were continuously monitored for physiologic and psychological responses during infusion.

TAKEAWAY:

• All participants completed the follow-up with no serious AEs, deaths, or hospitalizations. Twelve participants reported dissociative symptoms on the Clinician-Administered Dissociative States Scale, and four participants had transient blood pressure elevations that resolved spontaneously before discharge.
• The response rate was 100% and the remission rate was 85% at 24 hours post-infusion; 77% and 69%, respectively, at 1 week; and 69% and 54% at 1 month.
• MADRS scores decreased from a mean of 27.4 at baseline to 5.7 at 24 hours (within no-depression range), 7.8 at 1 week (mild depression), and 12.15 at 1 month (mild depression).
• No increases in suicidality were observed on the Beck Scale for Suicidal Ideation or Columbia Suicide Severity Rating Scale at any time point. MMSE scores showed no notable changes.

IN PRACTICE:

The investigators noted that there have been no previous “formal studies” that have assessed ketamine’s possible benefits for MCI-D, adding that their findings support the treatment’s safety and tolerability in this patient group.

“Ketamine may also be effective for improving depression in this population,” the investigators wrote.

“Large-scale randomized controlled trials are needed to determine the efficacy and potential cognitive effects of this promising treatment in this patient population,” they added.

SOURCE:

This study was led by Rachel Fremont, MD, PhD, Depression and Anxiety Discovery Center, Icahn School of Medicine, Mount Sinai, New York City. It was published online on February 24 in The American Journal of Geriatric Psychiatry.

LIMITATIONS:

The study was limited by a small sample size, an open-label design, the absence of randomization and a blinded placebo control, and lack of formal power analysis. As a single-site study that largely excluded adults aged 85 years or older, the findings were not generalizable to broader populations. Additionally, incomplete data for NIH Toolbox-Cog, with poor completion rates likely due to participant burden, fatigue, and cognitive impairment, limited the ability to comprehensively assess cognitive outcomes beyond gross measures such as MMSE.

DISCLOSURES:

This study was funded by the Icahn School of Medicine, the Ehrenkranz Center for Human Resilience, and Great Hill. Several investigators reported having financial or other ties with various entities, including pharmaceutical companies, which are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.