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 (N-methyl-D-aspartate), 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

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    14 COMMENTS

    1. “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.” I don’t understand. What’s wrong with just using ketamine? Why do they need to understand how it works before developing drugs with similar effectiveness? They don’t know how any of the other antidepressants work that are on the market. And, with all of the clinical trials and if ketamine is a known child anesthetic, it must be quite safe.

      Why isn’t ketamine a very common treatment for this group of patients who cannot be helped by anything else? Perhaps in the future they will discover more/better treatments, but until then why not use the ketamine? I didn’t see any reasons cited in the article for why it isn’t being used already for this purpose…

    2. Ketamine is not considered a suitable antidepressant on its own righ due to the abuse potential. It has been used frequently as a recreational drug and had addictive potential. Thus, they are searching for a new substance with similar antidepressant effects but less abuse potential.

      • Thanks for clarifying, Christopher Steffen! Still, in acute cases of clinical depression, such as would be treated by ECT in combination with other medication(s), it sounds to me like ketamine, administered in an inpatient or doctor’s office setting, would be a better, less invasive and risky choice than ECT (which I don’t think has ever been FDA-approved for treatment of depression). Also, many other commonly used drugs for depression also are used as recreational drugs and have a high abuse potential, such as ritalin and Provigil. If administered judiciously directly by a doctor/nurse in a clinic (assuming you don’t need to take it daily), it sounds fairly safe to me. Which brings up another point: what is the dosing schedule? Does one treatment permanently cure the test mice or do they need follow-up doses? I look forward to reading more about about this potential treatment in future articles!

        • Just let me leave it here, quote from Thomas Szasz considering all drugs:
          “It isn’t just heroin and marijuana that are illegal — EVERY drug in America that’s any good is illegal, because if you have to go to a doctor to get a prescription to get a drug, ladies and gentlemen, it’s illegal. The medical people have forgotten this because we all get drugs like people in Russia (then the Soviet Union) have to get permission to emigrate.”

    3. Genius and Someone–I just have to laugh and agree. In addition to knives, almost any over-the-counter drug, if taken in large enough quantities, can kill a person. Nobody used the word “gun” either, but you can see where that line of thought leads.

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