Investigation of the NMDA Antagonist Ketamine as a Treatment for Tinnitus
Abstract
Veterans of military operations are regularly exposed to the hazardous noise levels that lead to hearing loss and tinnitus. Tinnitus is known to adversely affect quality of life and can be associated with anxiety, depression, and an impaired ability to think clearly. To date, there are limited treatments for tinnitus. While behavioral treatments are helpful for some, many of those who suffer with tinnitus remain untreatable. Ketamine is a Food and Drug Administration (FDA)-approved medication, used at higher doses as a general anesthetic, and at lower doses it has been found to be effective for neuropsychiatric syndromes including chronic pain, depression, and obsessive compulsive disorder. Ketamine acts at neurotransmitter systems including glutamate and GABA, which are major chemicals that the brain uses to transmit information and that are implicated in how the brain encodes and propagates tinnitus. Tinnitus often follows the loss of high frequency sounds in the ear. As the brain searches for this missing auditory input, it fills in phantom sound, or tinnitus. Research with ketamine indicates that it has the ability to reset connections in the brain and can change the gain in the auditory system to remodel the networks that encode tinnitus. Thus, the first aim of this research is to investigate whether ketamine is effective as a treatment for the symptoms of tinnitus. In humans, previous imaging research in tinnitus has shown that there is a decrease in GABA signaling in the auditory cortex, which processes hearing. At our institution, we have done imaging studies showing that ketamine increases GABA levels in the brain in major depression and obsessive-compulsive disorder, which have also been associated with reduced brain GABA levels. Thus, another goal of this research is to use imaging to investigate whether ketamine can restore GABA levels in patients with tinnitus. Subjects with tinnitus will be recruited through clinical services of the Department of Otolaryngology at the Columbia University Medical Center. Of the 40 subjects, 20 will report comorbid depressive symptoms, since depression is frequently associated with tinnitus. In this protocol, we propose to use imaging to investigate ketamine-induced changes in brain chemistry and tinnitus symptom severity. Research participants with chronic tinnitus will undergo two scanning sessions, one with low-dose ketamine (0.5 mg/kg), and another with placebo. This dose has been shown to reduce symptoms of anxiety and depression within minutes and to last 7-10 days. The doses of ketamine and placebo will be administered while magnetic resonance spectroscopy (MRS) scans are obtained, as performed previously by our group. Audiometry and tinnitus assessments will be performed using standard measures. Our hypothesis is that active ketamine will reduce the severity and loudness of tinnitus compared to placebo and that ketamine will increase GABA signaling in the auditory cortex.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810221
Entities
People
- Diana Martinez
Organizations
- Research Foundation For Mental Hygiene
- United States Army