Yesterday I attended psychiatry grand rounds, where Andy Miller presented his latest research. Andy has been a pioneer in the field of psychoneuroimmunology and an exponent for the view that major depression reflects systemic inflammation. (I have published a review of this literature recently in Frontiers in Psychology which is available for download).
Andy discussed his data suggesting that treatment refractory depression (that is, depression that doesn’t respond to an SSRI) are more likely to show elevations in inflammatory markers. Andy then discussed his findings on the brain function of those with elevated markers of systemic inflammation. He spent a lot of time on the dopaminergic areas of the brain.
Andy’s brain imaging suggests that individuals with systemic inflammation look a lot like Parkinson’s patients. As most everyone knows, Parkinson’s disease occurs when big centers for dopamine in the brain die. Andy had additional data that less dopamine is released in response to drugs like amphetamines (a big trigger for dopamine release) in those individuals exhibiting systemic inflammation.
Moreover, when given the opportunity for reward, in those with systemic inflammation, there is less activity in brain reward areas, which also is about less dopamine release. So Andy’s data makes a strong case that those individuals with depression who are unresponsive to SSRIs exhibit systemic inflammation, which somehow suppresses the dopamine system in the brain.
Then I remembered the drug adds I saw on TV the night before. “If your depression is still with you despite taking your antidepressant as prescribed, ask your doctor about Seroquel.” Of course, Seroquel is a drug which sits on the receptor for dopamine and blocks access. Whatever else Seroquel might do, it is definitely a damper on dopamine.
Seroquel is being marketed aggressively for treatment resistant depression. In fact, when I went in for my yearly physical, I was checked in electronically. I responded to the questions regarding changes in insurance, and then came the advertisement for Seroquel. “If your depression is still with you despite taking your antidepressant as prescribed, ask your doctor about Seroquel.”
I queried my physician about his awareness of this marketing. He indicated that his practice was given the check in devices for free and he did not know about the advertisement. I guess the marketing is everywhere.
I wonder how many psychiatrists believe that Seroquel is the next step for treatment resistant depression. How many psychiatrists know about Andy Miller’s data? How many internists, who may be the biggest prescribers of drugs to treat depression, are aware of just how confused the field of psychiatry is?
Jill,
The *non-professionals* have been even more confused than the “profession.”
However, it seems as though the non-professionals are quickly getting ahead of the learning curve – moving toward more *sane* approaches* to overall health and well-being.
Hopefully, the professionals will begin join in the movement.
Duane
And I do appreciate your knowledge and insight into nutrition and integrative (sane) approaches!
Duane
Yes, I’ve also seen similar ads about adding Abify to depression.
This cartoon one is so cute.
http://www.youtube.com/watch?v=tGymr78FtbU&feature=endscreen
The funniest part is when the doctor draws down a paper and on the paper is another version of him who explains about the side-effects! Haha, why won’t they do that in office.
They left out the shrinkage of the cortex by 14% which was documented by Ho, Andreasen and colleagues. Another interesting side effect.
Those elevations in inflammatory markers seen in the “treatment refractory” (if they exist) may be the result of repeated insult by serial medications.
Has anyone considered not meddling in brain chemistry of these people for a while to see if such markers decrease?
or it could be that being miserble makes you more susecptible to being ill?That might raise inflamatory markers in some people who have a diagnosis of depression. Certainly stress hormones go up when you’re in a mood. Who knows what the relationship is? Or how valid the research is?
I also read one recent study which said that SSRI increased cytokines (inflammatory markers) such as TNF-α in frontal lobes but not in general body. Another study says that anti-inflammatives decreased the effect of SSRI. What’s to make of that?
The study on aspirin decreasing the impact of SSRIs was by Greengard (a nobelaureate) and colleagues. They had an explanation regarding interference with a specific mechanism. There are other literatures demonstrating that anti-inflammatories from the health food store (omega-3s, turmeric, folate, N-acetylcysteine) work on depression. I reviewed the literature in the Frontiers article which suggests that SSRIs, while initially being anti-inflammatory, in the long term, go in the opposite direction.
With the expansion in use of neuroleptics among people reporting or being diagnosed with depression…and bipolar…and ADHD…autism…and, of course, schizophrenia…it is hardly a wonder that Smoller, etc. identified what they claim to be similar epigenetic traits among individuals with these diagnoses.
Neuroleptics will damage the brain regardless of what diagnosis a person has.
Awful about the ads on the electronic check in device…and that doctors don’t seem to know better.
The recent article by Smoller et al that you are referring to has nothing to do with epigenetics. Thus use of neuroleptics cannot explain their findings.
There is a problem when people who don’t understand the science use it to support and refute their preconceived idea as it is convenient.
The recent article by Smoller et al that you are referring to has nothing to do with epigenetics. Thus use of neuroleptics cannot explain their findings.
There is a problem when people who don’t understand the science use it to support and refute their preconceived idea as it is convenient.
I don’t know what to make of the association between these “inflammatory markers” and depression or other mental distress. It could be that inflammation causes depression; it could be that external stressors, and our responses to them, cause both inflammation and depression.
But I am pretty sure of one thing: We need to be VERY skeptical of the concept of “treatment resistant depression” as a separate and more serious condition — especially when “TRD” is defined as a failure to respond to SSRI’s. For many years people who do not obtain relief from SSRI’s have been told they have this unusual and much more serious condition called “TRD.” It’s been used to induce compliance with ever more punishing chemical regimens, or ECT, assumed to be needed to counteract this terrible disease of “TRD.” It’s demoralizing, disempowering — and most importantly, there’s no basis for it.
In fact “failure to respond” to SSRI’s is extremely common; as Irving Kirsch pointed out, in a typical trial 50% feel better on SSRI’s — and 40% feel better on placebo. This supports the conclusion that as few as 10% may be having a genuine meaningful positive response to SSRI’s. And here’s one thing the doctors all know, but very few will admit: people who feel much better after a month on SSRI’s are far more likely to suffer from anxiety than depression.
There are some efforts underway to test TNF-Alpha blockers — incredibly expensive and toxic drugs like Enbrel — based on this theory of “inflammatory TRD.” Let’s be careful about accepting the existence of a disease defined by failure to respond to some company’s pet drug. When I failed to lose weight on the South Beach Diet, I didn’t say OMG, I have South Beach Resistant Obesity! I just decided South Beach wasn’t the miracle it was cracked up to be, and lost a bit of weight some other way. Ain’t exactly skinny yet, but still trying (g).
Oh, they try to find TNF-α blocker for treatment resistant depression? Now others say that SSRI work by increasing TNF-α, etc, in the brain. If this is true, I hope they at least don’t try to treat TRD by giving both SSRI and Enbrel.
It’s a bit confusing, some people say that inflammation in the body causes depression and some say that increasing these inflammation markers in the brain is the mechanism by with SSRI works.
http://thoughtbroadcast.com/2011/04/25/the-painful-truth-of-antidepressants/
And then TNF-α is related to BDNF. Oh well, I just started to study this inflammation thing a while ago and don’t understand much of its mechanisms, but it’s interesting to learn about its mechanisms.
In fact, the rest of the lecture by Andy Miller was on the use of an antibody to TNF-alpha to treat depression/fatigue in cancer patients who have been treated with chemo. Miller had done a genome wide scan of cancer patients who received the chemo and found that the chemo-treatment had left epigenetic changes on genes involved in immune system function such that these patients were more likely to be in a chronic state of inflammation. Those with the epigenetic changes were experiencing more fatigue/depression. Someone from the audience, asked whether the antibody to TNF might impair the capacity to fight the cancer. (In fact, Miller has raised the same question in his own published articles.) Miller responded that TNF is called Tumor Necrosis Factor alpha for a reason but reflected that there is not enough information to know yet how the antibody will impact the cancer. I wondered whether this little tid-bit of information is part of the informed consent form.
Johanna,
You make some great points about the fraud perpetrated in pushing the SO CALLED antidepressants that are anything but that especially when given for horrible, traumatic environments and situations. As Dr. Frank Ochbert, Trauma expert, wisely states, “Prozac won’t change the truth.”
There has been an explosion of exposure that these bogus SSRI drugs are basically no better than placebo for the most part while drug companies hid this fact and the lethal/deadly effects of these toxic drugs. This certainly exposes how deceitful and self serving psychiatry is when it adopted the Mitch Daniel BIG PHARMA ad ploy of “always blame the victim and their so called “mental illness” for any bad side effects that are most often the only effects. The gaul of this profession using the bogus TRD for their useless, deadly drugs, another nasty blaming the victim ploy to hide their own uselessness, fraud and dishonesty.
I love your “OMG,I have South Beach Resistant Obesity!” Hilarious and right on the mark! Oh, I forgot…you also must have a conscience that you would be honest about the situation unlike the BIG PHARMA/PSYCHIATRY cartel.
Correction: Dr. Frank Ochberg, Trauma Expert
As a matter of fact Enbrel, Humira and other TNF-A blockers carry a warning that they may cause lymphomas, especially in kids. There’s some basis to fear they promote tumor growth in general. And they definitely increase your risk of tuberculosis and other fungal and bacterial infections you would not pick up if your immune system was not being suppressed.
So these are not drugs to play around with. Of course, since they’re so lucrative, drug cos are trying to promote them for ever less drastic conditions.
Yes, I agree, psychiatry does support tumour growth.