D-Cycloserine: A novel treatment for tinnitus?

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I read this update from 2014 the other day,

Novel tinnitus therapy helps patients cope with phantom noise

Patients with tinnitus hear phantom noise and are sometimes so bothered by the perceived ringing in their ears, they have difficulty concentrating. A new therapy does not lessen perception of the noise but appears to help patients cope better with it in their daily lives, according to new research.

A pilot study at Washington University School of Medicine in St. Louis showed that patients participating in computer-based cognitive training and taking a drug called d-cycloserine reported greater improvements in the ability to go about their daily lives than patients who did the same cognitive training but took a placebo. The researchers note that the study was small, involving 30 patients.

The study appears Oct. 30 in JAMA Otolaryngology-Head & Neck Surgery.

What is cycloserine? According to Wikipedia,

Cycloserine, sold under the brand name Seromycin, is an antibiotic used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active drug resistant tuberculosis. It is given by mouth.

Common side effects include allergic reactions, seizures, sleepiness, unsteadiness, and numbness. It is not recommended in people who have kidney failure, epilepsy, depression, or are alcoholics. It is unclear if use during pregnancy is safe for the baby. Cycloserine is similar in structure to the amino acid d-alanine and works by interfering with the formation of the bacteria’s cell wall.

Cycloserine was discovered in 1954 from a type of Streptomyces. It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system

Why would a tuberculosis antibiotic increase brain plasticity and ameliorate things like tinnitus and schizophrenia? Is it really a side effect of the drug or is there some sort of stealth infection going on here? According to the main study

D-Cycloserine is a medication that has shown mixed but encouraging results at augmenting learning therapies through increasing neuroplasticity. Evidence suggests that D-cycloserine at single oral doses of 50 to 250 mg acts as a partial agonist at the N-methyl-D-aspartate (NMDA) receptor in the brain, enhancing long-term potentiation and thus strengthening new synaptic connections that may occur during a treatment. D-Cycloserine has been studied in numerous trials as an adjuvant therapy in the treatment of panic disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, traumatic brain injury, schizophrenia, Alzheimer disease, substance.abuse disorders, and autistic spectrum disorders. However, the ability of D-cycloserine to enhance learning has been most robust and consistent in trials related to anxiety disorders. In particular, D-cycloserine has been found in both human and animal studies to enhance the learning of information that disconfirms fears, such as in exposure therapy for anxiety. Given its ability to augment these therapies, studies have found that D-cycloserine is able to accelerate symptom reduction, lessen the time burden of learning therapies, and allow therapies to be administered at previously subtherapeutic levels…

At the first visit, participants were randomly assigned to either the treatment group receiving the Brain Fitness Program and 250 mg D-cycloserine or to the control group receiving the Brain Fitness Program and an identical-appearing placebo. Participants were instructed to work on the Brain Fitness Program 1 hour per day, 2 days per week, for 5 consecutive weeks, while taking their assigned pills 1 hour prior to working on the training program.

The dose of d-cycloserine used in this study was of 250mg only twice per week. The following also sounds interesting:

D-cycloserine is an excitatory amino acid and partial agonist at the glycine binding site of the NMDA receptor in the central nervous system (CNS); binding to the central NMDA receptor may result in amelioration of neuropathic pain.

Interesting, a drug that acts as a partial agonist of NMDA glutamatergic receptors and as an antibiotic against Gram-negative bacteria.

There have been reports of psychosis, depression and other significant psychiatric side effects within the context of taking one pill once or twice per day as a treatment of tuberculosis or schizophrenia and in conjunction with other anti-psychotics in the case of schizophrenia and in conjunction with other antibiotics in the case of tuberculosis.

It is speculated that this is due to its interaction with the effects of other drugs (i.e. antipsychotics for schizophrenia) at the level of the NMDA receptor. Cycloserine might also compete with glycine at the glycine recognition site of the NMDA receptor.

It is hard to get a realistic view of the side effects of this drug as a treatment for tinnitus where the drug is given only twice per week. The under-reported side effects from cycloserine in tinnitus might be because it is hardly used as opposed to other widely prescribed antibiotics such as ciprofloxacin, whose prevalent use have lead to the discovery of debilitating side effects.  Then the dose is only one pill twice per week in tinnitus as opposed to twice per day every single day for tuberculosis.

It might be worth experimenting with it in cases of severe tinnitus affliction, just as long as it is done with the awareness of its potential side effects and with careful monitoring of symptoms.

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