Researchers describe secrets of 'magic' antidepressant

Aug 19, 2010
The bottom slide shows regeneration of synaptic connections in group receiving ketamine, compared to control group. Credit: Courtesy of Yale University

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, not only quickly improves depression-like behaviors but actually restores connections between damaged by .

"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.

Ketamine traditionally has been used as a general anesthetic for children, but a decade ago researchers at the Connecticut Mental Health Center found that, in lower doses, the drug seemed to give patients relief from depression, Duman said. In these initial clinical studies, which have been replicated at the National Institute of Mental Health, almost 70 percent of patients who are resistant to treatment with all other forms of antidepressants were found to improve within hours after receiving ketamine. However, its clinical use has been limited because it has to be delivered intravenously under medical supervision and in some cases can cause short-term . It has also been used as a recreational drug, known as "Special K" or sometimes just "K."

So Duman, colleague George Aghajanian and the Yale team set out to map the molecular action of the drug in the of rats that could lead to potential targets for a safer and more easily used drugs. The team discovered that ketamine acts on a pathway that rapidly forms new between neurons—a process called "synaptogenesis."

"The pathway is the story. Understanding the mechanism underlying the antidepressant effect of ketamine will allow us to attack the problem at a variety of possible sites within that pathway," Aghajanian said.

The team identified a critical point in the pathway, the enzyme mTOR, which controls protein synthesis required for new synaptic connections. There are already promising leads on ways to sustain the initial rapid effect of ketamine by intervening at specific downstream targets.

An estimated 40 percent of people suffering depression do not respond to medication. And many others only respond after many months or years of trying different treatments. The authors note that ketamine also has been tested as a means to rapidly treat people with suicidal thoughts, a benefit usually not seen until weeks of treatment with traditional .

Explore further: Scientists identify critical new protein complex involved in learning and memory

Related Stories

Researchers explore the antidepressant effects of ketamine

Feb 21, 2008

Drug treatments for depression can take many weeks for the beneficial effects to emerge. The excruciating and disabling nature of depression highlights the urgency of developing treatments that act more rapidly. Ketamine, ...

Ketamine reduces suicidality in depressed patients

Sep 10, 2009

Drug treatment options for depression can take weeks for the beneficial effects to emerge, which is clearly inadequate for those at immediate risk of suicide. However, intravenous (IV) ketamine, a drug previously used as ...

Faster-acting antidepressants closer to becoming a reality

Jul 24, 2007

A new study has revealed more about how the medication ketamine, when used experimentally for depression, relieves symptoms of the disorder in hours instead of the weeks or months it takes for current antidepressants to work. ...

Study shows how 'horse tranquiliser' stops depression

May 02, 2008

Researchers have shown exactly how the anaesthetic ketamine helps depression with images that show the orbitofrontal cortex – the part of the brain that is overactive in depression – being ‘switched off’.

First ever large-scale study of ketamine users published

Nov 16, 2009

The first ever large-scale, longitudinal study of ketamine users has been published online today in the journal Addiction. With Ketamine (K, Special K) use increasing faster than any other drug in the UK (British Crime ...

Recommended for you

How the body fights against viruses

14 hours ago

Scientists of the Max F. Perutz Laboratories of the University of Vienna and the Medical University of Vienna, together with colleagues of the ETH Zurich, have now shown how double stranded RNA, such as viral ...

Fast way to measure DNA repair

20 hours ago

Our DNA is under constant attack from many sources, including environmental pollutants, ultraviolet light, and radiation. Fortunately, cells have several major DNA repair systems that can fix this damage, ...

Protein expression gets the heart pumping

22 hours ago

Most people think the development of the heart only happens in the womb, however the days and weeks following birth are full of cellular changes that play a role in the structure and function of the heart. ...

User comments : 11

Adjust slider to filter visible comments by rank

Display comments: newest first

yyz
4 / 5 (3) Aug 19, 2010
Ketamine acts on the NMDA and AMPA receptors involved with the neurotransmitter glutamate. This may explain its rapid effects compared to existing antidepressants that interact with serotonin and norepinephrine receptors. Also, ketamine is racemic, and its stereoisomers exhibit different effects on the body. It seems there may be many uses of ketamine at sub-anesthetic doses.

http://en.wikiped...sant_use
bottomlesssoul
3.7 / 5 (3) Aug 19, 2010
I have suffered with depression my whole life. When I finally tried drugs to my surprise the effect was remarkable. The side effects however are barely tolerable so I can only treat severe episodes and only until I can't tolerate the side effects any longer.

I have to wait until I spend weeks weeping until I take the drugs. And I have to stop the drugs as soon as I recover just enough emotional regulation so I can go two days in a row day without weeping.

This usually lasts about 3 months until I have to start the cycle again.

I consider myself lucky (when I'm not on a down cycle) because I have good friends who have no such luck at all.
sender
5 / 5 (2) Aug 19, 2010
I hope Gacyclidine or GK-11 is the next candidate for such studies as being closely related to ketamine and has a lower neurotoxicity profile as well as higher neuroprotective property.
Roj
1 / 5 (1) Aug 20, 2010
Low gamma-aminobutyric (GABA) levels associated with depression are clinically improved with Yoga in 12-weeks, a potent therapy.
http://www.physor...979.html

Fish oil also reduces psychosis after 12-weeks
http://www.physor...561.html
StarDust21
1 / 5 (1) Aug 20, 2010
I heard similar stuff about MDMA(ecstasy)
Ravenrant
2.3 / 5 (3) Aug 20, 2010
Amazing, now suicidal tendencies can be brought to the surface quickly.

I think that the real problem with anti-depressants is that they are prescribed for depression that is caused by real things. If a teen is depressed because of acne, an anti-depressant will do NOTHING. People who are depressed because of real problems do not need an anti-depressant, they need the problem fixed.
Modernmystic
2.7 / 5 (3) Aug 20, 2010
Amazing, now suicidal tendencies can be brought to the surface quickly.

I think that the real problem with anti-depressants is that they are prescribed for depression that is caused by real things. If a teen is depressed because of acne, an anti-depressant will do NOTHING. People who are depressed because of real problems do not need an anti-depressant, they need the problem fixed.


Are you KIDDING? Our brains are complex chemical computers. It's well established science that you can make someone giggle like a school girl five minutes after you tell them their whole family has been killed in a car accident.

If you meant to say that these drugs are not long term solutions to problems then I'd have to agree with certain qualifiers, but these drugs absolutely do SOMETHING to the human brain.
shavera
4 / 5 (2) Aug 20, 2010
People who are depressed because of real problems do not need an anti-depressant, they need the problem fixed.

@Ravenrant, depression is itself a 'real problem.' Specifically, this article etc. refers to 'clinical depression,' a chemical imbalance that can cause, among other things, an emotionally depressive state. For instance, people with MS have higher rates of depression than people with other life-long diseases specifically because the brain neurons are being destroyed and thus leading to depression.
cmn
4.5 / 5 (2) Aug 21, 2010
I'm wondering how safe it is to give severely depressed and/or suicidal patients Ketamine (to be administered on their own)? The potential for abuse could be quite dangerous, unlike SSRIs or SNRIs, as Ketamine can produce PCP-like dissociative effects.
yyz
not rated yet Aug 21, 2010
@cmn,

Several studies of ketamine as an antidepressant(see my link above) noted that the drug was administered in an inpatient setting (and all used IV ketamine) and was titrated to sub-hallucinogenic doses. Usually it was given with a benzodiazepine as an adjunct to prevent these type of side effects. I don't really see this type of treatment being suitable for outpatient therapy. However, gacyclidine and other related compounds with potentially lessened hallucinogenic effects are being explored as possible future antidepressants (thanks for the tip, sender).

(Btw, ketamine was initially developed by Parke-Davis as a safer anesthetic alternative to PCP and was first used by battlefield medics in Vietnam.)
Lon_Nn
not rated yet Aug 23, 2010
Several studies suggesting that EPA and DHA contained in omega-3 oil (fish oil) might just be key to helping with depression. Then again there have also been studies showing not much improvement at all, but an improvement was shown.

Id say keep the diet under control, and exercise regularly. Many people do not consume enough omega-3. US diet is around 30:1 omega-6:omega-3 and the UK around 20:1.

Try hitting a 1:1 ratio. Google omegabrite.

More news stories

Volitional control from optical signals

(Medical Xpress)—In their quest to build better BMIs, or brain-machine-interfaces, researchers have recently begun to look closer at the sub-threshold activity of neurons. The reason for this trend is that ...

Neuroimaging: Live from inside the cell

A novel imaging technique provides insights into the role of redox signaling and reactive oxygen species in living neurons, in real time. Scientists of the Technische Universität München and the Ludwig-Maximilians-Universität ...

Mantis shrimp stronger than airplanes

(Phys.org) —Inspired by the fist-like club of a mantis shrimp, a team of researchers led by University of California, Riverside, in collaboration with University of Southern California and Purdue University, ...