Research uncovers how antidepressants actually work

Feb 18, 2010

(PhysOrg.com) -- Australian researchers at UQ's Queensland Brain Institute have uncovered how antidepressants stimulate the brain to improve a person's mood.

They have discovered the class of drugs that increase levels of a neurotransmitter known as ‘norepinephrine' triggers neurogenesis - the growth of new neurons - in a region called the .

“If you block hippocampus neurogenesis, no longer work,” lead researcher Dr Dhanisha Jhaveri said.

“That suggests antidepressants must up-regulate neurogenesis in order for them to actually have any affect on behaviour.”

However, the neuroscientists also found not all antidepressants worked in the same way.

Dr Jhaveri said surprisingly, the class of antidepressants that increase levels of the called serotonin - Prozac is a common example - fails to stimulate neurogenesis.

is basically binding directly onto the precursors which then initiate a signal which leads to the production of more neurons,” she said.

“Serotonin just doesn't do that. Prozac doesn't work by regulating the precursor activity - it may work outside that region, but it isn't regulating the hippocampus directly. More research is needed to find out what actually does.”

Using rodent models the research, published today in the , established that selectively blocking the re-uptake of norepinephrine directly activated hippocampal stem cells thereby discovering a much larger pool of dormant precursors in the hippocampus than previously thought to exist.

The researchers also improved their understanding of the mechanisms by which norepinephrine activated the precursors in the hippocampus and found the expression of beta3 adrenergic receptors is critical in mediating the effect.

Fellow researcher and team leader Professor Perry Bartlett said armed with this information, the team would be able to explore improved treatments for depression as well as dementia.

“Since dementia, especially in the ageing population, appears to be related to a decrease in neurogenesis this discovery opens up exciting new ways to stimulate the production of new to alleviate the devastating effects of dementia in our society,” Professor Bartlett said.

Dr Jhaveri said the findings would also allow researchers to develop specific and more effective antidepressants.

“Depression is such a complex disorder, so we are going to test different behavioural outcomes to see whether the compounds that increase norepinephrine levels or stimulate beta3 adrenergic receptors work only for certain aspects of depression. We just don't know yet but it may, for example, improve learning and memory, or reduce anxiety,” Dr Jhaveri said.

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More information: Journal of Neuroscience -- www.jneurosci.org/

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Nemo
3 / 5 (2) Feb 18, 2010
I thought it was established that anti-depressants actually don't work, or are just marginally better than placebos and only then in the most serious cases.

Myself I suffered for years and drugs were no help, then I discovered that I was sensitive to caffeine ( among other drugs) and I've been largely symptom free ever since.
NeilFarbstein
3 / 5 (2) Feb 18, 2010
what stimulates beta 3 adrenergic recetors? Adrenaline? Depressive have problems feeling excitement but if they are excited a lot they will grow new neurons. What can prime the pump?
NeilFarbstein
4 / 5 (3) Feb 18, 2010
I thought it was established that anti-depressants actually don't work, or are just marginally better than placebos and only then in the most serious cases.

Myself I suffered for years and drugs were no help, then I discovered that I was sensitive to caffeine ( among other drugs) and I've been largely symptom free ever since.


...take your protein pills and put your helmet on...
otto1923
3 / 5 (2) Feb 18, 2010
I thought it was established that anti-depressants actually don't work, or are just marginally better than placebos and only then in the most serious cases.
That was last week- I didn't check, but I wondered if the patents on some of the latest drugs like effexor were soon to expire or if there is a new class about ready for market. And, according to the article this week, the placebo effect is more powerful than they thought. As I read the above article I was thinking that perhaps more neurons don't necessarily make you happier.
otto1923
3 / 5 (1) Feb 18, 2010
what stimulates beta 3 adrenergic recetors? Adrenaline? Depressive have problems feeling excitement but if they are excited a lot they will grow new neurons. What can prime the pump?
Womens. No seriously, we're made to reproduce and if we're not doing it, something's got to give. It's not sex but the results of it that are supposed to make us happy, fulfilled. Perhaps they should investigate the chemical changes in people who have recently conceived and produce drugs to simulate that.
zielwolf
2 / 5 (1) Feb 19, 2010
what stimulates beta 3 adrenergic recetors? Adrenaline? Depressive have problems feeling excitement but if they are excited a lot they will grow new neurons. What can prime the pump?


Alcohol works pretty well as a stimulant medicine, but there's a big downside as well of course...
ghinckley68
4 / 5 (2) Feb 19, 2010
I take 20mg of celxia(Cilatopram HBR) a day and I can tell you it does make a very big difference in my life. It allows me to function like a human and be happy. Placebo effect are not, the change is noticeable by me and my friends and family. Also there are physical withdrawal symptoms if i stop taking them.
For me at least they seem to work.
Most of the research that Serotonin Re-uptake Inhibitors don't work came out right after all the patents expired and generics became available. So one has to question
1. Who paid for these studies
2. Are they truly unbiased
3. Why for 20 years where these the wonder drugs that worked wonders in case study after case study
JoeySimpson
3 / 5 (1) Feb 19, 2010
Neuroplasticty. Evolution baby. Diet, environment, exercise, community, the better the input, the better the output. Yeah, use this information for better drugs guys, that's it. What about proven effects of fish oils, optimal diet, exercise and community on the brain? I rely on the power of nature to help me fix my brain thank you very much.
rsmith
1.2 / 5 (5) Feb 19, 2010
Depression is the result of the suppression of traumatic childhood and history. No one will admit how widespread poor child-rearing practices are because it requires them to re-engage their own histories, which is emotionally difficult to cope with when done with genuine curiosity...

Depression is not a disease to be treated with drugs; it's the scar tissue of a brain which did not properly develop due to childhood trauma (verbal abuse, physical abuse / corporal punishment, withdrawal of affection, infliction of religion, or sexual abuse, etc.)
HappiEverAfter
3 / 5 (1) Feb 20, 2010
Lexapro is a permanent life long cure for any depression if you can survive the treatment. I was given Lexapro by a PCP. He also decided it was a good idea to start kissing me and grabbing me in his office. The Lexapro did such a good job getting me up and doing things, lots of things, but I believe it also may have made me nervous and delusional because it raised my blood pressure from it’s usual 120/80 to 145/110. I could drink twelve shots of straight liquor and still be walking around for hours. This was the busiest year of my life. I managed to get 2 DUI’s 4 drunk in publics and an involuntary commit for suicide. I saw lots of doctors & counselors and got lots more drugs all year. I finally got off the Lexapro while in jail for DUI and have never been depressed again, things could be a lot worse. Nothing ever gets me down now! 100% permanent cure!
dsl5000
3 / 5 (1) Feb 20, 2010
Maybe that's another reason why there are so many depressed people in America lol...caffeine is one of the most used drugs now-a-days. Ah so drink coffee and you'll be happier :) but once you stop i suppose things'll start to flop :O
Neophile
5 / 5 (2) Feb 21, 2010
"Depression is the result of the suppression of traumatic childhood and history"

Bullshit! I NO serious issues in my childhood. No abuse, great family, lot's of love, no religion, no corporal punishment, nothing remotely traumatic. I've suffered serious depression as far back as I can recall and the only thing that has made a bit of difference are SSRIs.

Neophile
Feb 21, 2010
This comment has been removed by a moderator.
otto1923
3 / 5 (1) Feb 21, 2010
Depression is the result of damage, defect, and deterioriation from any number of causes throughout our prenatal and postnatal lives. Our brains are too fragile and resource-hungry. They start to go long before the rest of us does.

Antidepressants have little effect on mild depression which they are most often prescribed for. But they do cause strange and unpleasant, and severe, withdrawal symptoms- jolts, sensory distortion, odd thoughts and emotions. Worthless with painful withdrawal- that makes them the equivalent of tobacco, yes? They also make you look older, adding sags and wrinkles, like tobacco.
drjsmithson
1.5 / 5 (2) Feb 22, 2010
The Title of YOUR ARTICLE is so misleading as to be actionable legally if anything else depends on it. This does NOT show how antidepressants "work" (you still think they do? In what "illnesses"? This does not prove the catecholamine hypothesis of depression or the notion that anti-depressants "work" in any fashion any more than the rubbish data on CSF serotonin in completed suicides.
yyz
4.3 / 5 (3) Feb 22, 2010
I see that most responders here mention the use of a specific antidepressant used to alleviate their depression. Current research has shown that neurotransmitters norepinephrine, serotonin, dopamine and possibly GABA, acetylcholine and others may play a part in mood regulation as well as physiologic factors, and may have a different mode of action in different individuals. I think the science of mood regulation is just in its infancy.
yyz
3 / 5 (1) Feb 23, 2010
otto1923 says:

"Perhaps they should investigate the chemical changes in people who have recently conceived and produce drugs to simulate that."

They have. They're called endorphins and dopamine. These modulate the 'feel good' moments we humans sometimes experience.
yyz
3 / 5 (1) Feb 23, 2010
Almost forgot anandamide: http://en.wikiped...andamide
barakn
3 / 5 (1) Feb 25, 2010
How about oxytocin?