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Researchers Explain How Ketamine Improves Depression Within Minutes After The First Dose

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Researchers Explain How Ketamine Improves Depression Within Minutes After The First Dose

Numerous precedent studies have shown that the drug called ketamine, if taken in small doses, is very effective for patients suffering from chronic depression. The studies have shown that the effect of the drug is immediate in relieving patient’s symptoms. For the past 10 years, researchers tried to explain this discovery, which was firstly made at the Yale University, in the United States of America.

Current evidence shows that ketamine, which is a known pediatric anesthetic, aids the regeneration of the synapses found between the brain cells. These damaged synapses are the result of chronic depression and stress. Researchers from the Yale School of Medicine  reported their results in the journal Science, on the 5th of October.

The antidepressants that are currently used in treating chronic depression take a few months until visible results are shown. Furthermore, these therapies are completely ineffective for almost one third of the patients. Ketamine, however, targets a different type of neurotransmitter, thus being able to aid a larger number of patients. If researchers were able to understand the mechanisms through which ketamine aids the synaptic regeneration, a novel class of antidepressants could be synthesized.

Ketamine Drug

Ketamine Drug

“The rapid therapeutic response of ketamine in treatment-resistant patients is the biggest breakthrough in depression research in a half century”, said the co-authors of the study, Ronald Duman, Elizabeth Mears and House Jameson. The authors of the study are also professors at the Yale University. The authors added that because the drug has many usage limitations, the understanding of its working mechanism is crucial for further drug development. If administered in small doses, the effects of ketamine are only visible for 7 to 10 days. However, if used in large doses, a major side effect is psychosis.

In previous research, professor Duman and his team showed that ketamine triggers the release of glutamate, which is a neurotransmitter that stimulates the growth of damaged synapses. This triggered release happens over a series of steps. Also, the team showed that chronic stress and depression are responsible for damaging the synapses. A single small dose of ketamine can rapidly reverse this damage, said the authors.

The first study that showed that ketamine is linked to relieving depression symptoms was published by John Krystal and Dennis Charney. Krystal is the chairman of the psychiatry department from the Yale University, whilst Charney is the dean of the Mount Sinai School of Medicine. The results of their several clinical trials that suggested the effect of ketamine on chronic depression.

Researchers have managed to reproduce the effects of ketamine in newly developed drugs, however, the action of the new drugs is slower than that of ketamine. Researchers are currently trying to identify alternative ways to duplicate the effectiveness of ketamine.

The study abstract can be found here: Science Magazine

The time-line of ketamine being developed as a new rapid, effective antidepressant

The first evidence of that glutamate and NMDA (Nmethyl-Daspartate), both neurotransmitters, have an important role in the cortical functions originated in the 1980’s.

Ketamin was first used to explore the mechanisms of ordinary psychiatric disorders in the 1990’s by researchers from the Yale University. The psychiatric disorders studied included alcoholism and schizophrenia. Based on the results of the trials, it was suggested that ketamine is very effective against these disorders. Scientists observed the rapid effect and high effectiveness of ketamine in patients. The symptoms ameliorated within a few hours and lasted for more than a day.

In they year 2000, the first double-blinded clinical trial that assessed the effect of ketamine on patients suffering from chronic depression was conducted. The results were published in the journal Biological Psychiatry. Researchers reported that ketamine has a rapid antidepressant effect, thus suggesting that it could be used for treating depression.

In 2006 the results of the clinical trial that took place in 2000 were replicated by a team from the NIMH (National Institute of Mental Health). One of the co-authors of the study also took part in the first clinical trial from 2000.

Another research coming from Yale, in 2010, suggested that the rapid antidepressants of ketamine is linked to the fact that a small dose increases the function and numbers of new synapses. This is a process called synaptogenesis and is reported to be a much faster process than the process of forming new neurons.

A more recent study, published in 2011 in the journal Biological Psychiatry, revealed that the administration of  a small dose of ketamine can reverse the dendrites atrophy caused by chronic stress. The study was conducted on rodents.

Timeline References:

www.ncbi.nlm.nih.gov/pubmed/8122957

www.ncbi.nlm.nih.gov/pubmed/9554431

www.ncbi.nlm.nih.gov/pubmed/10686270

www.ncbi.nlm.nih.gov/pubmed/16894061

www.ncbi.nlm.nih.gov/pubmed/20724638

www.ncbi.nlm.nih.gov/pubmed/21292242