Skip to comments.Why antidepressants don't work for so many
Posted on 10/23/2009 10:20:20 AM PDT by Pharmboy
Northwestern research finds drugs aim at wrong target
CHICAGO --- More than half the people who take antidepressants for depression never get relief.
Why? Because the cause of depression has been oversimplified and drugs designed to treat it aim at the wrong target, according to new research from the Northwestern University Feinberg School of Medicine. The medications are like arrows shot at the outer rings of a bull's eye instead of the center.
A study from the laboratory of long-time depression researcher Eva Redei, presented at the Neuroscience 2009 conference in Chicago this week, appears to topple two strongly held beliefs about depression. One is that stressful life events are a major cause of depression. The other is that an imbalance in neurotransmitters in the brain triggers depressive symptoms.
Both findings are significant because these beliefs were the basis for developing drugs currently used to treat depression.
Redei, the David Lawrence Stein Professor of Psychiatry at Northwestern's Feinberg School, found powerful molecular evidence that quashes the long-held dogma that stress is generally a major cause of depression. Her new research reveals that there is almost no overlap between stress-related genes and depression-related genes.
"This is a huge study and statistically powerful," Redei said. "This research opens up new routes to develop new antidepressants that may be more effective. There hasn't been an antidepressant based on a novel concept in 20 years."
Her findings are based on extensive studies with a model of severely depressed rats that mirror many behavioral and physiological abnormalities found in patients with major depression. The rats, after decades of development, are believed to be the most depressed in the world.
Little Overlap Between Stress and Depression Genes
Redei used microarray technology to isolate and identify the specific genes related to depression in these animals. She examined the genes in the brain regions -- the hippocampus and amygdala -- commonly associated with depression in rats and humans.
Then she took four genetically different strains of rats and exposed them to chronic stress for two weeks. Afterwards, she identified the genes that had consistently increased or decreased in response to the stress in all four strains in the same brain regions.
Redei now had one set of depression-related genes that came out of an animal model of depression and one set of stress-related genes that came our of her chronic stress study.
Next she compared the two sets of genes to see if there were any similarities. "If the 'stress causes depression theory' was correct, there should have been a significant overlap between these two sets of genes," she said. "There weren't."
Out of a total of over 30,000 genes on the microarray, she discovered approximately 254 genes related to stress and 1275 genes related to depression, with an overlap of only five genes between the two.
"This overlap is insignificant, a very small percentage," Redei said. "This finding is clear evidence that at least in an animal model, chronic stress does not cause the same molecular changes as depression does."
Antidepressants Treat Stress Not Depression
Most animal models that are used by scientists to test antidepressants are based on the hypothesis that stress causes depression. "They stress the animals and look at their behavior," she said. "Then they manipulate the animals' behavior with drugs and say, 'OK, these are going to be good anti-depressants.' But they are not treating depression; they are treating stress."
That is one key reason why current antidepressants aren't doing a great job, Redei noted. She is now looking at the genes that differ in the depressed rat to narrow down targets for drug development.
She said another reason current antidepressants are often ineffective is that they aim to boost neurotransmitters based on the popular molecular explanation of depression, which is that it's the result of decreased levels of the neurotransmitters serotonin, norepinephrine and dopamine. But that's wrong, Redei said.
Drugs Aim at Wrong Molecular Target
In the second part of the study, Redei found strong indications that depression actually begins further up in the chain of events in the brain. The biochemical events that ultimately result in depression actually start in the development and functioning of neurons.
"The medications have been focusing on the effect, not the cause," she said. "That's why it takes so long for them to work and why they aren't effective for so many people."
Her animal model of depression did not show dramatic differences in the levels of genes controlling neurotransmitters functions. "If depression was related to neurotransmitter activity, we would have seen that," she said.
Similarities Between Human and Rodent Brains
Her findings in depressed rats, she said, are very likely applicable to humans.
"The similarities between these regions of the human and rodent brain are remarkable," Redei explained. "The hippocampus and amygdala are part of the so-called ancient lizard brain that controls survival and are the same in even primitive organisms."
Contributors to the study from Redei's lab include Brian Andrus, Kristen Dennis and Daniel Schaffer, research assistants, and Pradeep Shukla, a postdoctoral fellow. Jelena Radulovic, M.D., Dunbar Scholar and associate professor in psychiatry and behavioral sciences at the Feinberg School, also contributed as did Peter Vedell, a postdoctoral associate in professor Gary Churchill's group at The Jackson Lab, Bar Harbor.
Mental health genes ping
What was the question again?
Rats are rats but so are Democrats.
One of the best things for depression is exercise. Not a solution but better than taking lots of pills.
Depression can be caused by endocrine disorders.
That type of depression, IMO, can only be cured with medicine specific to the endocrine disorder that causes it.
I believe most depression is caused by some sort of physical problem. It can be illness or an abnormality in the nervous system/brain or any kind of imbalance.
I don’t know if they can ever discover all the root causes, but treating the root cause is far better than just handing out anti depressant medication which often makes things worse.
‘Rats ARE rats.Let’s never forget that.
Describes the condition of Rats such as Pelosi and Reid after their health care, cap and trade and other initiatives end up in the dustbin.
What do depressed rats do? Or what do depressed rats NOT do? Who watches them?
‘Clinical depression’ is such a nasty and dark state of mind —— too many end up dying because of it. If this leads to additional efforts to help those afflicted then way to go.
Agree with your post 10.
hmmm......I’m detecting a pattern here...
Yesterday stories claiming that many long-advocated cancer screenings were not really necessary.
Today story is many drugs not really that effective.
I think the table is being set for Obamacare rationing. So when the Public Option managers begin saying no to patients, the template will already be out there that “you know, that stuff was found to be not all that effective anyhow”.
You seem to be right...maybe she was someone taped for the commercial but wound up on the cutting room floor.
Depression coupled with fatigue and extreme irritability are classic signs of a severe iron deficiency — but the miniscule amounts of iron in health food store capsules aren’t enough to reverse it; RED MEAT coupled with supplemental iron can reverse severe depression/fatigue/irritability in mere weeks.
But, not, of course, if the depression is due to other causes.
In our contemporary western society drugs are the answer.
What does a rat have do be depressed about? Being locked up in a cage perhaps? How does one tell? Are there shrinks for rats, is the wife a bitch? Is the taxman after you? Maybe that giant in the white labcoat has something to do with it.
I admit that I am quite often depressed but I think that encounters with smiling idiots has a lot to do with it.
I wonder how many of Obama’s inner circle is on anti-depressants? I’ve heard one of the side-effects is constantly licking the lips to moisten them. Wasn’t there a video recently showing one of his aides doing this while speaking to a group of high school kids?
The mind is so complex that it is indeed a bit arrogant to think that we know the biomolecular and/or neural pathways that cause it. Researchers and physicians who study this should be (and most are) very humble.
Possibly, but that’s often a sign of nervousness/anxiety as well.
I thought the same thing when they talked about the cancer screenings yesterday. How's the water, McFrog? It's getting a little too warm for me in this pot ; )
Guess what? Tamiflu may not work so well on H1N1 either. In the July outbreak at the Air Force Academy in which over 130 first year cadets fell ill with verified H1N1, the half who received Tamiflu fared no better than the ones who didn’t receive it.
Fortunately, since first year Academy cadets are usually 17 or 18 years old and in perfect health, none of them got very ill and all recovered quickly.
All of his little rat friends dying of cancer long before their time from getting 1000 times the normal dose of saccharine.
When I feel that “feeling”, I just decide not to be a participant. I can’t stop it from happening but I can choose to not help it. I find that being thankful helps take my mind off it.
Too many depressed people are self-centered. All they ever talk about is themselves and their problems. I don’t think that is an accident.
[i]I thought the same thing when they talked about the cancer screenings yesterday. How’s the water, McFrog? It’s getting a little too warm for me in this pot ; )[/i]
The MSM seems to be flooded with similar takes on other conditions, too — for instance, did you know that Dementia should be considered a terminal disease and that treating pneumonia in a patient with Dementia is futile?
I wonder how Big Pharma feels about all these recent articles?
If we do not treat so-called ‘untreatable’ illnesses, how will we ever discover any cures? Are we supposed to HALT all medical research? Should we simply program all humans to “Self-Destroy” at age 39????
Here's something that sounds silly, but I would hope people who get "down" try it (it will not work for major depression). Next time the blues or whatever come, force a smile on your face and hold it for a minute or so (don't do this in public--LOL!). You'll feel better in 10 minutes or so...
Well, the one thing that sucks about many antidepressants for men is the side effect of icantgetaboneritis. That tends to negate the benefits of antidep meds.
My understanding is that they more often cause a delay in time to orgasm (in fact, they are used to treat premature ejaculation). But, they can lead to problems in this area also...
I feel very sad and the only thing that gives me hope is I believe the Dallas Cowboys are going to the Super Bowl this yr. Should I be marched off to a padded room straightaway?
In a way, it’s like saying “Next time you get drunk, sober up”. I can feel the chemical release. It’s like a drug hitting my system. But it doesn’t mean that I need to live into it.
Funny. The opposite of Depression is not happiness. I can be happy and be depressed. I’m happy almost all the time. The opposite is panic. They cannot live together.
Oh, I believe you...you may also feel the release with the dumb-sounding thing I suggested.
Well, your sadness may end if Romo gets his QB rating up 30 or so points.
Antidepressants such as Prozac which are serotonin reuptake inhibitors will not work if there is a deficiency of serotonin in the body. About 90% of the serotonin is produced in the enterochromaffin cells in the lining of the stomache and intestines. I can show that stress causes the erector spinae muscle to contract along the dorsal area of the spine to block afferent neuron reception. The spinal nerves cell body head is outside the spine in the dorsal root ganglia, thus the muscle contraction serves as a neural block by putting a compression hold on the vertebrae, disc(causing backache) and the afferent neuron. This leads to disk compression which in turn compresses the efferent spinal neuron (in the front of the spine) sending signals to the intestinal area. The result is that digestion does not process properly and the serotonin is not produced by the enterochromaffin cells, thus leading to depression. The associated back pain is in the central lumbar region.
Fasting as a spiritual practice also suppresses serotonin production. Since serotonin acts as a blocking neurotransmittor for emotions being transmitted across the synaptic cleft, the deficiency of serotonin causes emotions to rise to the surface and facilitates spiritual cleansing.
The countering effect is food consumption, especially carb’s which increases serotonin production, thus the cause of emotional or stress eating.
This is a simplification of the process but it is fairly easy to prove by stimulating the emotional traumatic memory and watching the muscle contraction response.
This same methodology is true relating to emotional trauma relating to betrayal issues. Except that the neural block appears to be anchored between the T2 and T3 vertebrae. This is the proverbial “knife in the back” feeling relating to the muscle contraction and the efferent neuron compressed and blocked innervates the upper central region of the heart and causes the related “heart ache” of the betrayal issue. What I am saying is not in the medical texts but is easily proven in a scientific setting. I have shown this many, many times in demonstrations...
Just my humble opinion, but I have found that it is relatively easy to resolve depression by removing the emotional intensity attached to the memory. I’ve done this many times with individuals in private and in front of groups during demonstrations. Generally, I can totally remove the trauma which causes PTSD in less than a minute (and it never returns). It’s easy to demonstrate and explain. I’ve done the same with emotional trauma relating to rape. This is not done with hypnosis or power of suggestion, but by physically altering the stored emotional memory.
Don’t forget the correlation between vitamin D (Cholecalciferol) deficiency and depression, too.
You should try living in Nashville; the Titans’ combined scores this year would make a major league pitcher jealous.
I am surprised, saddened, and ashamed on behalf of my FReeper FRiends country-wide that you didn’t receive kudos galore for your beautiful (if slightly obscure) comment! Thanks for a good chuckle!
I have had an interesting thing happen. After having been on and off SSRIs for years and, before that, tricyclics (with varying and inconsistent results), now that I have been taking 2,000-4,000 IU/day of D3 for several months I am almost free of symptoms (depression and anxiety). We'll see if the effect lasts. Depression is complex and multifactorial in causation so there will never be one cure-all for everyone. But I may have hit on mine by accident.
If you’re interested in doing a little reading; this site has some free academic articles. http://highwire.stanford.edu/. Just type in vitamin d deficiency (or any topic you’re interested in).
Even in the summer, 20 minutes of sun w/o sunscreen will give you enough natural D.
Your statement...”Depression is complex and multifactorial in causation so there will never be one cure-all for everyone.”
This is very true. Depression is a symptom and yes, there can be many causes. I have found that the actual causes are almost always psychological, based upon perception. Many times this is at the emotional subconscious level and when a person begins to access it, the anxiety and panic attacks serve to block the recovery of the emotional issue. Even the biochemistry of the body changes based upon perception of the environment.
Depression runs in my husbands family. He has a cousin who is completely off the rails now. This cousin lives in your area I hope you are not next door neighbors.
Clinical depressed ? No
Clinical stark raving insane ? Yes
True, and my guess is that the key is in the hippocampus (+ long term stress):
Such atrophy is centered in a brain region called the hippocampus. This structure plays a critical role in learning and memory, and the magnitude of the hippocampal volume loss (nearly 20% in some reports;) helps explain some well-documented cognitive deficits that accompany major depression. These were careful and well-controlled studies, in that the atrophy was demonstrable after controlling for total cerebral volume and could be dissociated from variables such as history of antidepressant treatment, electroconvulsive therapy, or alcohol use. Moreover, more prolonged depressions were associated with more severe atrophy.
A possible explanation:
Because synapses have the potential for rapid response, synapse loss probably underlies the rapid deterioration of mood that depressed patients sometimes experience, said Hajszan. Thus, it is possible to elevate mood rapidly by generating new hippocampal synapses, which is attainable by certain drugs we are testing.