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Marina Picciotto, Ph.D.

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Advances in How to Think About and Treat Depression

Posted: 12/10/10 08:10 AM ET

Did you know that there are almost twice as many suicides each year in the United States as there are murders? I was surprised to find out that in 2007, the most recent year on which the CDC provides data, there were almost 35,000 suicides in the Unites States and more than 18,000 murders. These statistics are important because many people still write off psychiatric illness as less important than diseases of the rest of the body, like heart disease and cancer, with the false assumption that psychiatric disease is not fatal. As you can see from these CDC stats, this is just not true. We spend a lot of effort and a lot of money trying to reduce the murder rate, so we should be spending even more trying to treat the central cause of suicide: major depressive disorder.

The good news for depression is that we do have medications that work for some patients. Unfortunately, these medicines do not work for everyone. In fact, STAR*D, a large study funded by the National Institutes for Mental Health, found that less than half of patients got completely well after a single antidepressant was taken, and although more patients got well once they were switched to another medicine, the proportion of those who got better decreased each time a person had to switch to another medication. Since most of the medicines used for depression target similar mechanisms, there is still urgent need for new medications.

Luckily, there have been real advances in what we know about depression and how to treat it. Some of this new research was highlighted at the recent Annual Meeting of the Society for Neuroscience.

One exciting avenue of research has been the identification of interactions between the immune system and depression. Sickness behavior has some common features with depression; for example, both result in fatigue and loss of interest in usually fun activities, and some people become depressed due to an immune response to illness or stress. Scientists have found that blocking the immune system's chemical interleukin-6 (IL-6) can increase motivation for a pleasurable activity in mice that have been sick.

Humans with depression can show increased levels of IL-6. But also people who are not depressed, but are treated for other illnesses with medicines that increase immune function, and therefore levels of chemicals like IL-6, often become depressed. This provides a new way to think about treating depression through actions on both the body and the brain. While studies of agents related to interleukin-6 function are still at the pre-clinical stage, clinical trials are still actively investigating the link between circulating cytokines and depression, particularly in cancer patients.

A number of other studies have found new molecules that are required for antidepressants to work. Both p11 and cdk5 could be new targets for development of medications to treat depression. Depressed patients have lower levels of p11 and this protein seems to be critical for the ability of animals to respond to antidepressants. Animals without cdk5 look like animals treated with an antidepressant, so blocking this protein may be a new way to treat depression.

This year there has also been excitement about speeding up the action of antidepressants. Normally, a patient has to take an antidepressant medicine for several weeks before they start to recover. A medicine called ketamine is exceptional in that people given ketamine are less depressed almost immediately. New research shows that the reason for this response is that ketamine changes communication between nerve cells by activating mTOR that helps make new connections between nerve cells. Ketamine is currently in Phase I clinical trials for rapid treatment of major depression.

Another new approach to depression has been to use drugs that block the action of acetylcholine in the brain. Most antidepressants used today increase the action of serotonin or norepinephrine in the brain. Adding a blocker of acetylcholine can decrease the symptoms of depression in patients who don't respond to existing antidepressants.

Some of these new avenues for treating depression are already close to the clinic and others still need more research before they can be used in humans. A new way to identify medicines that might make it into the clinic is to use fish to screen rapidly through chemicals that act like existing antidepressants. When placed in stressful situations, zebrafish (with a mutation in a receptor important in stress management) displayed depression-like behavior, which was reversed when the fish were given Prozac. This finding not only shows that stress can lead to depression even in fish, it provides a new model to test antidepressants.

It is clear that there is a need for new ways to help patients with depression. Basic research into the causes of depression and the mechanisms of antidepressant effects has provided new targets for developing treatments for depression, but this is just the beginning. Research into the causes and treatments of depressive illness provides hope that patients will not have to suffer with this disease, and perhaps we can hope for the day that death from depression in the United States is no longer more likely than death by murder.

 
Did you know that there are almost twice as many suicides each year in the United States as there are murders? I was surprised to find out that in 2007, the most recent year on which the CDC provides ...
Did you know that there are almost twice as many suicides each year in the United States as there are murders? I was surprised to find out that in 2007, the most recent year on which the CDC provides ...
 
 
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HUFFPOST SUPER USER
dancinggrandma
Therapist, writer, dancer
12:02 PM on 12/13/2010
As a therapist who's treated hundreds of people with major depression over thirty years, I remain appalled that drugs are being pushed to treat depression with hardly a word about the only real "cure" for the vast majority of sufferers: talk therapy. Anti-depressants are meant to be the training wheels to the bike (talking through & resolving painful issues). They're for stabilizing the process of grieving losses, getting objective help to identify the psychological roots of depression, and containing the anxiety inherent in making explicit that which has remained implicit for a lifetime. I see it as downright unethical for doctors to prescribe these medications WITHOUT insisting that their patients enter therapy. Only therapy can resolve and release the material which created the depression in the first place. There are always exceptions in which biology, illness, or other physical causes underly depression, but most cases are deeply-rooted in emotional pain carried for a lifetime. Drugs are an "assist", but not the answer to depression
02:44 PM on 12/14/2010
I understand that antidepressants may be over-prescribed in our country. However, I can't agree with you that drugs are only ever an 'assist'. I see that you did state that there are exceptions, but seeing as I am one of those exceptions, I don't think you stress that enough.

I can't survive without the antidepressants. I proved that to myself by trying to go off of them and causing myself and my family great pain in the process. And yes, I have done talk therapy and it's been incredibly helpful, but it's useless without being on the drugs for the long haul. Some of us just aren't wired right for whatever reason. I really don't care WHAT the reason is at this point. I think I've suffered enough. The drugs keep me from going over the edge, and I am grateful that I have them.
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HUFFPOST SUPER USER
Kringle
Resurrection of the Gifting Spirit
12:36 PM on 12/12/2010
Why is HuffPost using images of Prozac?

Cannabis is a FAR-more effective medicine than Prozac or any of the other anti-depressants the quacks have ever prescribed for me in my lifetime.

FAR safer too!
09:15 AM on 12/13/2010
You know, I always see people commenting on the wonders of pot on these threads. You do realize that the effects of pot are not going to be the same for every person who uses it, right? Just like every other drug available to us humans today.

I tried pot years ago and it was horrible. I had more side effects from that than I do from my anti-depressants I take for severe anxiety/depression. It caused a massive panic attack that I still cringe at many years later.

And just because something is 'natural' does not automatically mean it's 'safe'. There are countless 'natural' plants out there that will kill you quite quickly if you ingest them, no help needed from the 'quacks' you seem to hate so much.
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Heartless Riot
I... What?
11:14 AM on 12/12/2010
I am fairly certian that if you give any one ketamine they will immediately be happier, but biopsych tends to relay too much on the biology surrounding depression and not enough on treatments other than medication. We need to stop looking at things this way. Why should a person who is depressed because of life events or stress be given medication and sent on their merry way when most often it is lack of social support that is causing the depression in the first place? Additionally, some one with chronic depression shouldn't simply be given medication and sent on their way; especially since we know that there are such failure rates with medications.
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03:31 AM on 12/12/2010
Let's have a show of hands:
How many reading this article have dealt with depression?
12:10 AM on 12/12/2010
If you read what I said and thought about it you would recognize that I sed some of us do not believe in God, however regardless, remedy for happiness comes from GOD not mankind. You cannot by happiness with all the money in the world. If you cant see the light at the end of the tunnel, then you have not given God much thought
Hay Phishfan, God dos not need us we need him, God gave man brains so that they can create medical balance, a lumbergene cannot run on gas only it also must have a battery to spark and charge
I believe in all efforts any one puts forth for cur never the less I get my real charge when I am humbled by GOD’s Grace and filled with his hopeful light Clearwater Hop is a good thing Happy Holiday all
06:41 PM on 12/12/2010
What in the world is Clearwater Hop; is it a new dance by Creedence Clearwater Revival?
I hope you don't believe that Ἰησοῦς was born anywhere near the Winter Solstice which caused the incident which resulted in the events which resulted in Hanukkah. Sinterklaas day was DECember 6th. I guess he changed from horses to reindeer when he moved from Spain to the North Pole.
07:59 PM on 12/11/2010
Gives me hope.
12:18 AM on 12/12/2010
Hop is a sign of healing hopeless people don’t want cur. I love your name Clear water is hardly ever found
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03:18 AM on 12/12/2010
In hopelessness there's neither wanting nor not wanting a cure.
07:51 PM on 12/11/2010
Only real life testimonies of satisfactory outcomes to defeat depression disorder can be accounted for now that all the PhD’s and Modern Madison has failed to charm there way in to a human mind for a quick fix or cure of this killer disorder.

Depression is the result of total denial of expectance of “GOD.†The light, serenity, solitude, contentment, humbleness, and happiness are found in him and no money in the world can by this freedom
The soul and the spirit without the light, guard, and blessings of GOD will also eventually dye a slow painful lonely death.
Medical experts have fallen helpless to finding the cure for Depression. If the recepy for cure is blended with the power of all creations "GOD" that is, we would have perfected the concoction for cure of Depression.
God is not the believe of all so DO NOT try to fake your believe in GOD for cur, this remedy dos not permit hypocrisy a reverse reaction will eventually intensify the disorder and will cause suicide. The cure is not available for all; for healing and cure is not man maid it is God maid. A cure permitted by God to heal a conscientious mind that believes and appreciates the giving of GOD.
The mind in so many words my friends can play the deadliest tricks on you unless guarded by an ante-evil. To disregard the importance of the source of life produces a lifeless human labeled “Depressedâ€
10:22 PM on 12/11/2010
Believing in God doesn't increase the serotonin levels in the brain. Of course you're anti science and anti intellectual. You don't believe in climate change either, right? You know it is ok to think for yourself.
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03:20 AM on 12/12/2010
I find your certainty irritating.
02:35 PM on 12/11/2010
I was extremely depressed. I was also anti-medication and very skeptical.

It was the best thing I ever did was getting on an antidepressant along with talking to a therapist. The most important part, I feel.

After 3 months I feel incredible and finally have control. If any of you are reading this and are depressed, go get help. I waited way too long but the important thing is I got help. Don't wait...it's so worth it.
09:31 AM on 12/11/2010
Yet another article on treating depression which completely ignores non-medication treatments!
I know that pharmaceutical companies pay a lot of money for research on their products, but it is troubling that leading academics like Dr. Picciotto would seem to be blinded to non-medication treatment.
Pills are not the answer to everything.
10:24 PM on 12/11/2010
They definitely aren't. I agree with you completely. Until I started taking what I'm taking. It's very subtle but it's unbelievable how it does what it does.
10:41 PM on 12/11/2010
you took the words right out of my fingers. thank you. I'm glad I'm not the only who immediately noticed that
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froidytoidy
Underwhelmed Independent
01:28 AM on 12/11/2010
Thanks for the informative article. I would hope that before prescribing antidepressants, doctors will first check TSH and vitamin D levels in all patients. High TSH can mimic the worst of depressions and it is relatively easy to correct. Actually, it should be protocol.
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maveet
Needed: DemFems 4 Congress
04:12 AM on 12/11/2010
TSH levels are highly over-rated. But what you're probably relating to is people who are hypothyroid, and therefore depressed. Check out the wonderful thyroid information at http://www.drlowe.com

I've been treated with thyroid since adolescence. After 7 years ME/CFS, I found the underlying reason and how I might see some recovery in Dr. Lowe's research and protocols.
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teresa1960
11:24 PM on 12/11/2010
Bingo. Depression is often a "symptom" of a hormonal imbalance. Dr. Lowe is great and also check out Dr. Ken Holtorf who also addresses hormones and an ex CFS patient himself. I have Fibromyalgia, and I use 5-HTP when I feel depressed, it really helps and no side effects.
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maveet
Needed: DemFems 4 Congress
06:20 AM on 12/11/2010
I have posted several other responses on this thread re vitamins, minerals, amino acids, thyroid. I lay in bed thinking about this and realized that all of it, my whole history as emotional rollercoaster, can be traced back to low thyroid. It is likely that when I finally have the appropriate T3 in my system that I won't need my long list of vitamins and amino acids.

There are epidemic numbers of people suffering immune disorders as well as depression. This in a society that wants people to wear smiley faces. Stress and pollutants of all sorts are interacting with our genetics, and a lot of us are falling over. There are some who believe this is not accidental. In the 1970's synthyroid became THE thyroid replacement, TSH the standard for testing low thyroid. Millions of people are mis-treated and under-treated because MD's dare not deviate from this protocol. Untold numbers of people are therefore depressed, and suffering with scores of complaints that will never be resolved, for the lack of T3. Truly, I do not exaggerate. Had I known this information 30 years ago my life would have been very different.
Namaste
12:46 AM on 12/11/2010
Any non-chemical based solutions on the horizon??? Neuroplasticity theory seems promising.
11:53 PM on 12/10/2010
I suffered for over 15 years with severe (and undiagnosed) Chronic Fatigue Syndrome, which presents with many of the same symptoms as depression. Tried several different SSRI-class drugs without effect, Provigil, and various dietary changes and supplements.

The only thing that has had a noticeable and consistent effect on my mood and energy has been Concerta (time-release version of Ritalin). I now stay awake and energized throughout the day and no longer have trouble sleeping. Works about 85-90% of the time for me; an absolute blessing after years of debilitating fatigue.
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maveet
Needed: DemFems 4 Congress
04:14 AM on 12/11/2010
Hi okakura. I also have ME/CFS, recently discovered http://www.drlowe.com/ You might have an underlying thyroid issue. cheers.
01:28 PM on 12/11/2010
Maveet: I appreciate the link. No underlying thyroid issues in my case, however - one of the first things tests ruled out.
09:22 AM on 12/11/2010
It's an ampetamine-like stimulant, thus would make perfect sense, this is what some kids with A.D.H.D. and A.D.D are treated with!
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Bettysdad
The arc of human history is to the left.
11:40 PM on 12/10/2010
Recent study shows that every adult man that's diagnosed with depression should have his testosterone level checked.
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Ken Kinstle
Helping People Experience Wellness
11:25 PM on 12/10/2010
I have had issues with mood swings, bouts with depression, fatigue and a basic lack of energy now for what seems like over ten years. I am sure that many others have the same battles as I have experienced. I do think I have found an answer which has worked for my wife and myself.

http://ezinearticles.com/?Could-a-Little-Vitamin-B-12-Really-Make-That-Much-Difference?&id=3408193
09:22 AM on 12/11/2010
See a doctor dude!
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thebearschick
11:24 PM on 12/10/2010
The problem is, basically ALL the commercials for antidepressants have warnings for increased risk of suicide. I believe that SSRIs and other anti-depressants are needed and necessary in severe cases of depression, but doctors today are very liberal and hand them out like candy. As someone who didn't really have depression and was given prozac for "anxiety", I did not have good results. I was bouncing off the walls and couldn't sleep. I don't think medications are bad per se, but they are bad when they are overprescribed.