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Michael J. Fox Foundation Grant Will Fund First Clinical Trial of Ketamine to Treat Depression in People With Parkinson’s Disease

November 16, 2021

Two Yale Department of Psychiatry researchers have been awarded a $2 million grant from the Michael J. Fox Foundation for Parkinson’s Research to conduct the first clinical trial of ketamine to treat depression in people with Parkinson’s disease.

Sophie E. Holmes, PhD, assistant professor of psychiatry and neurology, and Gerard Sanacora, MD, PhD, George D. and Esther S. Gross Professor of Psychiatry, are the co-principal investigators of the study. Sule Tinaz, Sina Nikayin, and David Matuskey are also involved in this pioneering work, which is part of a new Yale research program bridging the Psychiatry and Neurology Departments. The program is headed by Holmes.

Yale Department of Psychiatry researchers were first to discover that treatment-resistant depression patients experienced near immediate relief from symptoms when they took small amounts of the anesthetic ketamine. Their continued work in clinical trials led to the recent FDA approval of ketamine as a rapid-acting antidepressant.

“This is the first investigation of ketamine as an antidepressant in a neurological disorder," said John H. Krystal, MD, chair of the Yale Department of Psychiatry, who pioneered the discovery of ketamine as an antidepressant. "Results of this seminal trial could pave the way for a new generation of treatments for psychiatric symptoms in neurology.”

“Depression is recognized as one of the most common complications of Parkinson’s disease, yet our ability to effectively provide treatment for the debilitating depressive symptoms associated with the disease remains extremely limited,” Sanacora said.

Depression is recognized as one of the most common complications of Parkinson’s disease, yet our ability to effectively provide treatment for the debilitating depressive symptoms associated with the disease remains extremely limited.

Gerard Sanacora, MD, PhD, George D. and Esther S. Gross Professor of Psychiatry

Holmes and Sanacora will compare the efficacy of ketamine (six infusions administered intravenously over three weeks) to placebo in 50 individuals with Parkinson’s disease and depression. Using cutting-edge brain imaging they will also study the mechanistic effects of ketamine on synaptic connections and functional networks in the brain.

“We need to do better at treating depression in Parkinson’s disease,” Holmes said. “The findings of this research could change the way that it’s treated, leading to the discovery of fast-acting and effective treatments that in turn improve the quality of life for the many individuals with PD that suffer from depression.”

David Hafler, MD, chair of Neurology, stated, “There is clear comorbidity between neurological and psychiatric disorders. This trial and Dr. Holmes’ research program will drive cross-departmental collaboration, which will be crucial in the understanding and treatment of psychiatric symptoms in neurological disease.”

Submitted by Christopher Gardner on November 16, 2021