August 19, 2010
Ketamine Mechanism Against Depression
Yale researchers find ketamine's rapid action against depression comes as a result of ketamine's stimulation of synaptogenesis (formation of connections between neurons).
Yale researchers have discovered how a novel anti-depressant can take effect in hours, rather than the weeks or months usually required for most drugs currently on the market. The findings, described in the August 20 issue of the journal Science, should speed development of a safe and easy-to-administer form of the anti-depressant ketamine, which has already proven remarkably effective in treating severely depressed patients.
The Yale scientists found that, in rats, ketamine not only quickly improves depression-like behaviors but actually restores connections between brain cells damaged by chronic stress.
"It's like a magic drug—one dose can work rapidly and last for seven to 10 days," said Ronald Duman, professor of psychiatry and pharmacology at Yale and senior author of the study.
This reminds me of another recent study where ketamine caused amazingly rapid relief from bipolar disorder.
A single intravenous dose of the anesthetic agent ketamine appears to reduce symptoms of depression within 40 minutes among those with bipolar disorder who have not responded to other treatments, according to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
"Bipolar disorder is one of the most severe psychiatric disorders and ranks in the top 10 causes of medical disability worldwide," the authors write as background information in the article. About 4 percent of Americans will develop bipolar disorder in their lifetimes, and depressive symptoms dominate for most of the course of the illness. Several treatments for bipolar depression are currently approved, but some patients do not respond to these therapies despite adequate trials. In addition, existing treatments are associated with a lag of onset; most patients do not respond within the first week of therapy, resulting in considerable illness and increased suicide risk.
Also see my previous post Ketamine Lifts Depression Rapidly and Scopolamine Lifts Depression In A Few Days.
Perhaps memory destruction lifts depression, he says with tongue in cheek.
This may be a superficial analysis, but could generation of neurons be lifting depression in the same way that playing with a novel puzzle or toy can relieve boredom? That is, could new connections be changing the thought process -- resulting in an occupied period of reorganization, neuron training, and new thoughts -- while leaving the main thrust of emotion and mood mostly unchanged?
Even if this were an accurate portrayal, then I wouldn't doubt that, like any mind-altering effects, the effect could still be leveraged to get out of a depression. But it would be interesting to see exactly what relation this specific effect has with the ways we use our neurons in the absence of pharmacological enhancements.
Also interesting to note that ketamine suppresses inflammation - even life-threatening systemic inflammation.
Ketamine also reduces TNF-alpha levels, as does the drug, Enbrel, which rapidly reverses Alzheimer's symptoms in some patients.
To not anon or anonymous...
Yes. I learned to recognize my depressive process and to refocus thought and action. I allowed myself the introspection and learning thru the introduction of street grade marijuana, in the 70's. I've often stated that 'what I did for myself no doctor or psychiatrist could have done for me'.
Depressive behaviors in lab rats may be a useful marker for identifying drugs with potential for human therapeutic use but there is a long slog in between the two.
Ketamine is a dissociative anesthetic, so their is a serious question whether the observed effect is merely a supression of some specific symptoms, or if it represent something more substantial. Simply put, the rats are in no position to tell us whether their failure to exhibit the behavior represents any improvement in their mood state. Consider that if you give most any critter enough ketamine you can supress just about any behavior.
And even if the effect is not simply dissociation leading to supression given ketamine's long history of abuse, and the profound mood disturbances that are associated with chronic abuse, I'll remain skeptical but hopeful. Maybe this research will lead to better understanding of the proceses and/or receptors involved and perhaps guide the development of some chemical analogs that posess the desired benefits without ketamine's known disadvantages.
Wolf-dog- "these" drugs? Just because they are both psychiatric medicines, though separated by many decades? You're serious? Or have you got some other issue about psychiatric medicines in general?
"It's like a magic drug," said Ronald Duman.
Have actually used IV ketamine in conjunction with standard anesthetics during Electroconvulsive therapy in patients who were pathologically depressed and who were not responding to usual theraputics or ECT. We had some patients that responded. I am not surprised that the researchers are finding more data to support the role of ketamine in depression. It is also a great drug to be used peri-operatively to reduce pain scores and morphine amounts. ( the nmda receptor seems to have a modulatory effect on the mu/kappa,etc receptors involved with pain/narcotics). I am a huge fan of this medication, and I look forward to more studies! ( and by the way, by their very definition as anesthetics and amnestics they interfere with memory. This is not news)
Wolf-dog. My apologies. I didn't read closely and jumped to conclusions.
Ketamine is an NMDA receptor agonist, and has a similar mechanism of action to Dextromethorphan (DXM), which is the active ingredient in most cough syrups.
As you may know, both ketamine and DXM are used recreationally.
I know from personal experience and experimentation in my youth, that most drugs leave you with some kind of hangover. You feel tired, or slow, or headachy, or used-up, moody, etc.
DXM is the only exception to this I can think of. The day after using DXM, you feel great. Colors look brighter, and you feel positive, emotionally balanced, & even 'wise'. It makes sense that this would be useful for treating depression.
A word of warning to anyone thinking of drinking a bottle of cough syrup:
1) Cough syrups often have other active ingredients. Ironically, an overdose of acetaminophen or pseudoephedrine is much more dangerous than the drug that gets you high.
2) DXM causes 'drunk-like' clumsiness, and bizarre thought patterns. Don't take more than you are physically & psychologically capable of handling.
I am a Bipolar II alcoholic and was trying to stop drinking when I switched to "cold medicine." On my own I ingorantly took huge doses (up to 300 mg a day) of DXM (no acetaminophen) for two weeks. At my monthly appointment my psychiatrist warned me of seratonin syndrome and convinced me to stop. My intention only had been to stop drinking, but the DXM knocked me out of a five-year anxious depression. I believe I have mild hypomania now, but my psychiatrist is closely monitoring me and adjusting my Geodon to stabilize me. 13 years ago postpatum depression had kick started my eventual bipolar disorder; now this is the best I have felt since then.
*I recognize that what I did was dangerous and would not recommend abusing DXM as I did.
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