I realize that the below article is not necessarily from a reliable source but I just wanted input on this theory. Namely that the increase in BDNF caused by SSRIs is really actually caused by an increase in pro-inflammatory signals in the brain. So SSRIs trigger this pro-inflammatory assault on the brain and then the brain responds by increasing BDNF. The author notes that this is why SSRIs do not seem to work as well when combined with Anti-Inflammatory medications like Ibuprofen and Aspirin.
All relevant sited after the article....
Why Antidepressants Cause Brain Damage, Breast Cancer, and Early Mortality
Wednesday, October 10, 2012
Byron Richards, CCN
When you see a headline like this in the news, “Anti-inflammatory Drugs Reduce the Effectiveness of SSRI Antidepressants,” what does it make you think? The impression is that if you are taking an SSRI then you shouldn’t take any pain pills if you want the antidepressants to work, which is the clear message of the press release1 that accompanied the study. This means that SSRI antidepressants must be “working” by some type of inflammatory method.
It is now common knowledge that low-grade excess inflammation is behind virtually every disease of aging. The obvious contradictions don’t add up to health. Pulling strings further, as I explain in this article, leads to an understanding as to why antidepressants are associated with an increased risk of breast cancer, brain damage over time, and a significantly increased risk of early mortality. This is information the pill pushers at Big Pharma would prefer you never understood.
The study showed that the use of anti-inflammatory pain medications, such as ibuprofen, aspirin and naproxen, reduced the “effectiveness” of the most widely used type of antidepressants. A combination of an animal study and a large scale human data evaluation led researchers to conclude that the typical response rate to SSRIs of 54 percent dropped to 40 percent.
“The mechanism underlying these effects is not yet clear. Nevertheless, our results may have profound implications for patients, given the very high treatment resistance rates for depressed individuals taking SSRIs,” notes Dr. Jennifer Warner-Schmidt. “Many elderly individuals suffering from depression also have arthritic or related diseases and as a consequence are taking both antidepressant and anti-inflammatory medications. Our results suggest that physicians should carefully balance the advantages and disadvantages of continuing anti-inflammatory therapy in patients being treated with antidepressant medications.”
It appears that Dr. Warner-Schmidt is trying to say that if you want to help your brain pain you may need to live with your physical pain – a testament to the ineptitude of Western Medicine’s drug-based therapies. The real story is what isn’t being said or explained; as almost nobody would take an SSRI antidepressant for any length of time if he or she understood what was actually just discovered.
These researchers noted that SSRIs provoked a release of pro-inflammatory signals in the brain, TNFa and IFNy, which were blocked by the anti-inflammatory drugs. TNFa (tumor necrosis factor alpha) is an inflammatory cytokine produced by immune cells and by glial cells in the brain in response to a problem. For example, overweight people make far too much TNFa in their inflamed white adipose tissue, which can travel up to the brain, cross the blood brain barrier, and induce brain-inflammation resulting in the cognitive decline and depression that is so closely linked to obesity. IFNy (interferon gamma) is a potent activator of an immune-related response, typically to viral infection or a tumor. It specifically boosts the production of highly inflammatory nitric oxide (iNOS). This compound is essential for an immune system battle and is highly inflammatory to healthy nerve cells and to the cardiovascular system.
So how on earth could taking these brain-inflammatory SSRI antidepressant drugs help a person feel better mentally?
The BDNF Response to Health and Trauma
BDNF (brain-derived neurotrophic factor) is one of the most potent healing compounds in your brain. Adequate BDNF is needed for brain plasticity, cognitive intelligence, optimal learning, positive mood, etc. In other words BDNF is your brain rejuvenation compound. BDNF can prevent and treat Alzheimer’s disease. BDNF is even active outside your brain wherein it helps your muscles burn fat! A lack of BDNF sets the stage foraddictive behavior2, including compulsive overeating3. Those with the lowest levels of BDNF have the worst depression4.
You can activate BDNF with aerobic exercise, even consistent moderate aerobics. Aerobics in older adults has been shown to stop brain shrinkage5 and boost BDNF while preventing depression. Many nutrients6 facilitate the production and release of BDNF (DHA, pantethine7, acetyl-l-carnitine8, zinc9, blueberries10, curcumin11, niacin12, DHEA13, and likely many others). Nutrients work very well to maintain BDNF levels in the face of high levels of stress14, as any of the prior study links will explain. To properly activate BDNF also requires proper function of thyroid hormone15, which is problematic in many people with depression.
BDNF production in your brain occurs within glial cells (astrocytes). It is very important to understand that BDNF production can be activated by multiple signals coming into the glial cells, not just one type of input. In other words, we have glial cell activation in response to healthy behaviors like exercise and good nutrition. This is part of the ongoing process of keeping your brain rejuvenated and in tip-top working condition. In animal experiments following stroke, voluntary exercise16 helps produce high levels of BDNF and nerve regeneration whereas forced exercise does not.
BDNF is also activated during times of brain injury, to repair the injury17. Nerve cells do not split and divide like other cells in your body. Rather, nerve cells must either fix themselves or have a strategy to develop new nerve growth; both processes require BDNF. Thus, one way to stimulate BDNF is to injure nerve cells.
It is this latter strategy that SSRI antidepressants utilize – in a manner never intended by Mother Nature. The details of this rather bizarre method of operation are explained in a detailed review article18. In brief, one way SSRIs are supposed to work is by enhancing the flow of serotonin, an effect that would be felt immediately upon taking them. However, it is well recognized that an additional mechanism is in play, as for many it takes several weeks or longer before their mood seems to improve. This latter effect is due to the SSRI medication progressively accumulating in glial cells, inducing a highly inflammatory toxic response, and triggering the release of BDNF. Now you can understand why taking anti-inflammatory drugs would interfere with SSRI function.
Understand that such a strategy to boost BDNF production is highly problematic. It can just as readily result in suicide or worsened depression. A person who is depressed is lacking BDNF. This means their credit cards for BDNF have been maxed out trying to cope with the stress in their life. In essence, SSRI antidepressants are like getting a new BDNF credit card from a loan shark. The interest rates are astronomically high, i.e., the loan is given in the form of excitotoxic brain cell injury. Talk about robbing Peter to pay Paul. This is a very short term remedy, at best.
According to the review article above, the method of BDNF activation by SSRI antidepressants utilizes a specific gene signaling pathway called TrkB (Tropomyosin-associated kinase). The overexpression of this particular gene signal is known to cause breast cancer19. It is not that BDNF causes breast cancer. Indeed, just about every nutrient listed above that boosts BDNF production naturally also protects against breast cancer. This is the difference between nutrition and drugs. Nutrients and exercise act in harmony with the brain to bolster its natural function, while nourishing and protecting other areas of the body. In this case SSRIs manipulate an injury recovery strategy to boost BDNF by actually poisoning brain cells. This strategy was never intended to be used on an ongoing basis. It is quite clear that the TNFa activation of BDNF20 can have deleterious effects on the nervous systems and may not help BDNF production at all. The science provides a direct link to cancer, especially breast cancer.
Breast Cancer and SSRI Use
Human data regarding SSRI use and breast cancer is highly controversial. The reason is due to Big Pharma-funded “scientists for hire” who crank out studies that say there is no risk. And this is only one aspect of the blatant and fraudulent misrepresentation of SSRI risks and benefits.
This issue came front and center in an April 2011 open access article published in Plos One21 that reviewed 61 studies regarding breast and ovarian cancer and antidepressant use. The overall data showed an 11 percent increased risk for breast and ovarian cancer associated with all types of antidepressants. The association between the SSRI type of antidepressants and cancer was stronger than for any other type of antidepressant. All SSRI studies but one showed an increased risk of female cancer. Additionally, this April 2011 study also evaluated the financial ties of study authors to the companies that make antidepressants. Shockingly, none of the 15 researchers with financial ties to the industry found any risk for breast/ovarian cancer in the studies they conducted, whereas 43 percent of the researchers without industry ties found clear evidence of cancer risk. The authors called for more research to determine the exact nature of this risk, since 10 percent - 15 percent of women are on these drugs. Don’t expect the FDA to do anything meaningful any time soon.
Another angle is that women with breast cancer are often put on SSRI medications because they are depressed about their health. According to a February 2010 open access article published in the British Medical Journal22, the SSRI antidepressants block the effectiveness of Tamoxifen causing up to a 91 percent increased risk of death from breast cancer in a 2.5 year period of follow-up.
The Disturbing Picture of the Cruel SSRI Scam
The SSRI literature cover-up extends far beyond attempting to hide or negate the link to breast cancer. The fraudulent scam goes to the heart of the matter- whether the drugs even work very well at all.
In 2008 the New England Journal of Medicine exposed the extent of the antidepressant deception. The great majority of negative SSRI studies were never published. A whistleblower who had worked at the FDA and was familiar with the data forced the data to public view. It showed 37 studies the FDA considered positive were published, whereas only three negative studies were published. Of the 33 studies the FDA considered negative or questionable, 22 were not published, and 11were published with spin to look positive when they were not. This made antidepressant studies appear 96 percent positive in the literature, when in fact the studies were only 51percent positive. In fact, as Newsweek magazine explained in January 2010, that “benefit” was hardly any different than the placebo.
On the other hand, rather extreme side effect data from taking SSRI antidepressants continues to pour in. In November 2008, it was shown that anyone over the age of 50 taking SSRIs on a continual basis had double therisk for fractures, as excessive serotonin production directly blocks new bone formation. In March 2009 it was reported in a large study of women that antidepressant use, independent of other variables, was linked to a statistically increased risk of sudden cardiac death. In December 2009 researchers reported that in 136,000 postmenopausal women taking SSRIs there was a 45 percent increased risk of stroke of any kind, a 32 percent increased risk of mortality23 from any cause, a 212 percent increased risk of a hemorrhagic stroke, and a 210 percent increased risk that the stroke damage would be so severe it would cause death. As mentioned at the beginning of this article, the increased rate of inflammation in the brain, especially activating highly inflammatory iNOS in response to INFy, is a clear mechanism that could cause these dangerous strokes in the brain.
The issue of cardiovascular, breast cancer, and mortality adverse effects from SSRIs is far from settled. The industry will do everything in its power to pay scientists to publish studies that state or imply there are no problems. The battle will go on for years, with massive litigation expenses hanging over the heads of Big Pharma. The FDA, as always, is missing in action. However, to the person taking an SSRI to feel better, it is clear that the drugs work by inflammatory mechanisms that are not healthy over the long haul and possibly not even in the short term. SSRIs are a credit card at best; one day you will need to pay up.
While I am well aware of people who feel symptomatic improvement from taking antidepressants, this information serves as a wake-up call. Hopefully it will help such people find alternative solutions such as exercise, weight loss, a better diet, and dietary supplements that can help boost BDNF, improve stress management skills, and get nondrug psychotherapy as needed. Getting off SSRI medications requires that you work with your doctor with the long term goal to be off medications because you don’t need them. I have first hand knowledge of many people who have been injured by SSRI medications, including suicide. The fact that the SSRI medications, while helpful to some, are clinically proven to be no better than a placebo, represents one of the great con jobs of all time on the unsuspecting American public. Maybe Congress should investigate this issue instead of wasting time and taxpayer money on Barry Bonds and Roger Clemens.
[color=#336699 !important]Referenced Studies:[/color][color=#242424]
- ^ Effectiveness of SSRI Antidepressants Reduced by Anti-inflammatory Drugs Proceedings of the National Academy of Sciences Jennifer L. Warner-Schmidt, Kimberly E. Vanover, Emily Y. Chen, John J. Marshall, and Paul Greengard.
- ^ Adequate BDNF Helps Stop Addiction Brain Res. McGinty JF, Whitfield TW Jr, Berglind WJ.
- ^ BDNF and Obesity New England Journal of Medicine Joan C. Han, M.D., Qing-Rong Liu, Ph.D., MaryPat Jones, M.S., Rebecca L. Levinn, B.A., Carolyn M. Menzie, B.S., Kyra S. Jefferson-George, Diane C. Adler-Wailes, M.S., Ethan L. Sanford, B.A., Felicitas L. Lacbawan, M.D., George R. Uhl, M.D., Ph.D., Owen M.
- ^ Low BDNF in Schizophrenia and Depression Molecular Psychiatry F Angelucci, S Brenè and A A Mathé.
- ^ Aerobic Exercise, Depression, and BDNF Neuroscientist. Erickson KI, Miller DL, Roecklein KA.
- ^ Brain Boosting Nutrition Nature Reviews Neuroscience Fernando Gómez-Pinilla
- ^ Pantethine Helps Your Brain Med Hypotheses. Tsai SJ.
- ^ ALC Helps Sustain BDNF Levels Under Stress Neurosci Lett. Bigini P, Larini S, Pasquali C, Muzio V, Mennini T.
- ^ Zinc and BDNF J Neural Transm. Sowa-Kućma M, Legutko B, Szewczyk B, Novak K, Znojek P, Poleszak E, Papp M, Pilc A, Nowak G.
- ^ Blueberries Boost BDNF Production Free Radic Biol Med. Williams CM, El Mohsen MA, Vauzour D, Rendeiro C, Butler LT, Ellis JA, Whiteman M, Spencer JP.
- ^ Curcumin Offsets Chonic Stress by Boosting BDNF Brain Research Ying Xua, Baoshan Kub, Li Cuic, Xuejun Lib, Philip A. Barisha, Thomas C. Fosterc and William O. Oglea.
- ^ Niacin Boosts BDNF Production Stroke. Cui X, Chopp M, Zacharek A, Roberts C, Buller B, Ion M, Chen J.
- ^ DHEA Boosts BDNF Production Neuroscience. Pinnock SB, Lazic SE, Wong HT, Wong IH, Herbert J.
- ^ Curcumin Boosts BDNF Production, Alleviates Depression Neurosci Lett. Huang Z, Zhong XM, Li ZY, Feng CR, Pan AJ, Mao QQ.
- ^ Thyroid Function, BDNF, and Brain Plasticity Mol Cell Neurosci. Shulga A, Blaesse A, Kysenius K, Huttunen HJ, Tanhuanpää K, Saarma M, Rivera C.
- ^ Voluntary Exercise is Best for Boosting BDNF PLoS One. Ke Z, Yip SP, Li L, Zheng XX, Tong KY.
- ^ BDNF, A Key to Repairing and Maintaining Your Brain Brain Willson ML, McElnea C, Mariani J, Lohof AM, Sherrard RM.
- ^ BDNF and SSRIs PLoS One. Scarlett B. Pinnock, Alastair M. Blake, Nicola J. Platt, and Joe Herbert
- ^ Inapproproate BDNF/TrkB Activation May Lead to Cancer PLoS One. Cameron HL, Foster WG.
- ^ Mechanism of NF-kappaB Activation Determines if BDNF Helps Brain Cells J Neurosci. Gutierrez H, O’Keeffe GW, Gavaldà N, Gallagher D, Davies AM.
- ^ Plos One
- ^ British Medical Journal
- ^ Are Antidepressants Killers? Arch Intern Med. Jordan W. Smoller; Matthew Allison; Barbara B. Cochrane; J. David Curb; Roy H. Perlis; Jennifer G. Robinson; Milagros C. Rosal; Nanette K. Wenger; Sylvia Wassertheil-Smoller
Edited by High_Probability, 23 March 2014 - 01:00 AM.
