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Experimental Antidepressant Aims to Use Ketamine as a Model

by Brenda Evans, published
Photo: Harvard University Drug and Alcohol Peer Advisors

experimental antidepressant

The National Institute of Health is working with an experimental antidepressant called AZD6765, using the properties of ketamine as a model.

Clinical trials run by The National Institute of Health (NIH) have shown that the experimental drug relieves symptoms of depression within minutes.

Previous studies done at Yale have shown that the club drug, ketamine, is a quick response antidepressant that acts through the brain's glutamate chemical messenger system. Glutamate is the primary excitatory neurotransmitter in the central nervous system.

According to an NIH press release, existing antidepressants work through the brain’s serotonin system whereas AZD6765 works by blocking the glutamate from binding to a protein on the surface of neurons, called the NMDA receptor. It is a less powerful blocker of the NMDA receptor than ketamine, which may be a reason why it has less adverse side effects.

Depression is a prevalent mental health issue in the United States today. According to Centers for Disease Control, one in every ten adults report suffering from depression and a 2011 report states that 11 percent of Americans age 12 or older take antidepressant medication such as SSRIs.

While depression can effect anyone and causes range from chemical to environmental, the American Psychiatric Association states that woman are two times more likely to suffer from depression than men. It is one of the most wide ranging mental disorders, but it is also among the most treatable.

While many patients respond well to currently available antidepressants, according to the American Psychiatric Association full benefits of the medication may not be realized for two to three months and the dosage often needs to be altered to get the optimal response.

The original link between ketamine and relief of depression was made at the Connecticut Mental Health Center in New Haven by John Krystal, chair of the department of psychiatry at Yale and Dennis Charney, dean of Mt. Sinai School of Medicine.

Ronald Duman, co-author of the Yale review that suggests that ketamine helps regenerate synaptic connections between brain cells damaged by stress and depression, followed Krystal and Charney's studies.

“The rapid therapeutic response of ketamine in treatment-resistant patients is the biggest breakthrough in depression research in a half century,” said Duman.

Ketamine is a schedule three non-narcotic. It is legally used as an anesthetic for both humans and animals. Also referred to as "special K," ketamine is considered by the  Drug Enforcement Administration as a dissociative anesthetic that has some hallucinogenic effects.

Although Ketamine is a more effective antidepressant, to reduce the likelihood of experiencing the adverse side effects, researchers have looked to ASD6765.

According to the release, about 32 percent of the 22 treatment-resistant patients given ASD6765 showed a response within 80 minutes that lasted for about half an hour with some residual antidepressant effects lasting two days.

"Our findings serve as a proof of concept that we can tap into an important component of the glutamate pathway to develop a new generation of safe, rapid-acting practical treatments for depression," said Carlos Zarate, M.D., of the NIH’s National Institute of Mental Health.

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