Patricia Andrews, MD, Associate Professor of Psychiatry and Behavioral Sciences and Director of the Division of Geriatric Psychiatry, has received grant funding from the Alzheimer’s Association to evaluate the safety and tolerability of intravenous (IV) ketamine for depression in people with mild cognitive impairment (MCI) or mild Alzheimer’s dementia.
Though common in those with Alzheimer’s-related conditions, depression also increases the risk of cognitive decline.
“A fast, safe and effective treatment of depression may reduce the likelihood of such progression and improve quality of life and function,” Andrews said. “Severe depression often interferes with patients’ capacity to discuss treatment options, which can limit use of newer treatments that alter and delay disease progression. Rapid improvement of depressive symptoms with ketamine could represent treatment that allows them to be able to receive these therapies faster.”
Though current treatment for depression in Alzheimer’s disease-related disorders is with medications called selective serotonin reuptake inhibitors and norepinephrine reuptake inhibitors, Andrews said their efficacy is limited.
“Ketamine may be potentially appropriate for this population because it produces a rapid antidepressant effect with improvement of depressive symptoms reported two hours post-infusion that continues for several days in younger adults with depression,” she said.
“In adults over the age of 60 years, a recent pilot study demonstrated that repeated intravenous ketamine was safe and effective, resulting in improvement of depression and executive function. Another pilot study published earlier this year demonstrated that one infusion of ketamine was safe and improved depression in patients with MCI. Both studies were open label, therefore did not compare ketamine with placebo. These findings provide preliminary evidence but do not establish efficacy.”
Potential risks include increased blood pressure and confusion, though both resolve after the infusion.
If the KeTADiD study — “Ketamine for Treatment of Alzheimer’s Disease related Depression” — points to ketamine as being safe for this population, Andrews plans to design a large, multisite, randomized controlled trial that would evaluate not only whether ketamine improves depression, but also the durability of benefit and its longer-term effects on cognition, functioning, quality of life and safety.
“This would provide the evidence needed to determine whether ketamine could be incorporated more broadly into clinical care for older adults with MCI or mild Alzheimer’s dementia,” she said.
Outside of the study, Andrews added that older adults who are struggling with depression, memory, or other cognitive concerns can be evaluated in the Vanderbilt Memory and Aging Clinic, where the team has expertise in both cognitive disorders and mental health in older adults.
“We can provide an individualized evaluation and, when appropriate, connect patients with research opportunities,” she said. “As part of the Center for Cognitive Medicine, we are currently enrolling participants in several other Alzheimer’s disease research studies as well.”
Andrews’ study will include men and women over 60 who have major depressive disorder and either MCI or mild dementia, “with evidence of Alzheimer’s disease pathology based on biomarkers,” she said. The study will last 10-14 weeks, including five in-person visits, eight phone calls and four monitored IV infusions of either ketamine or placebo twice a week for two weeks.
Enrollment is slated to begin in December, but those interested in participating can be placed on a registry to be notified when the study is open. Contact Beverly Burchfield at beverly.burchfield@vumc.org, 615-875-3722 or Kiara Baker at kiara.baker@vumc.org, 615-327-7117.
