Quantcast
free-downloads CSEVideos


Neurontin and Lyrica are a Death Sentence for New Brain Synapses : Shocking Study

Discussion in 'Neurology' started by Egyptian Doctor, Aug 19, 2018.

  1. Egyptian Doctor

    Egyptian Doctor Moderator Verified Doctor

    Joined:
    Mar 21, 2011
    Messages:
    9,678
    Likes Received:
    3,301
    Trophy Points:
    16,075
    Gender:
    Male
    Practicing medicine in:
    Egypt

    Neurontin and its newer more potent version, Lyrica, are widely used for off-label indications that are an outright flagrant danger to the public. These blockbuster drugs were approved for use even though the FDA had no idea what they actually did in the brain. A shocking new study shows that they block the formation of new brain synapses1, drastically reducing the potential for rejuvenating brain plasticity – meaning that these drugs will cause brain decline faster than any substance known to mankind.

    The problem of these drugs is compounded by their flagrant illegal marketing. Neurontin was approved by the FDA for epilepsy back in 1994. The drug underwent massive illegal off-label promotion that cost Warner-Lambert 430 million dollars (the very first big fine for off-label promotion). The drug is now owned by Pfizer. Pfizer also owns Lyrica, a super-potent version of Neurontin. It has been approved by the FDA for various types of pain and fibromyalgia. Lyrica is one of four drugs which a subsidiary of Pfizer illegally marketed, resulting in a $2.3 billion settlement against Pfizer.

    Even though the marketing of these drugs has been heavily fined, they continue to rack up billions in sales from the off-label uses. Doctors use them for all manner of nerve issues because they are good at suppressing symptoms. However, such uses can no longer be justified because the actual mechanism of the drugs is finally understood and they are creating a significant long-term reduction in nerve health.

    What is the suitable medical specialty for your personality, try our: Free Medical Specialty Quiz

    The researchers in the above study try to downplay the serious nature of the drugs by saying “adult neurons don’t form many new synapses.” That is simply not true. The new science is showing that brain health during aging relies on the formation of new synapses. Even these researchers managed to question the common use of these medications in pregnant women. How is a fetus supposed to make new nerve cells when the mother is taking a drug that blocks them?

    These are the kind of situations the FDA should be all over. As usual, the FDA is sitting around pondering a suicide warning for Lyrica while its off-label uses include bi-polar disorder and migraine headaches. The FDA is likely to twiddle its thumbs for the next decade on the brain damage issue. Consumer beware.

    Referenced Studies

    The Gabapentin Receptor α2δ-1 is the Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis: by Çagla Eroglu, Nicola J. Allen, Michael W. Susman, Nancy A. O’Rourke, Chan Young Park, Engin Özkan, Chandrani Chakraborty, Sara B. Mulinyawe, Douglas S. Annis, Andrew D. Huberman, Eric M. Green, Jack Lawler, Ricardo Dolmetsch, K. Christopher Garcia, Stephen
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791798/

    [​IMG]

    Source
     

    Add Reply

  2. dr.omarislam

    dr.omarislam Golden Member

    Joined:
    Apr 30, 2017
    Messages:
    2,043
    Likes Received:
    34
    Trophy Points:
    4,075
    Gender:
    Male
    Practicing medicine in:
    Egypt
    thanks for sharing
     

  3. zawminchit

    zawminchit Young Member

    Joined:
    Nov 8, 2013
    Messages:
    3
    Likes Received:
    0
    Trophy Points:
    10
    Gender:
    Male
    Practicing medicine in:
    Myanmar
    This is my personal response to the post "Neurontin and Lyrica are a Death Sentence for New Brain Synapses : Shocking Study" which has been shared and shocked by healthcare professionals nowadays on social media.


    If you have read the contents of that post, please proceed to see the original article on which the above scandal is based. The scientific article name is "Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis" which was written by Dr. Ben A. Barres, MD, PhD, Professor and Chair of Neurobiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. The article was published in a journal called "Cell" on 16th Oct 2009.(Volume 139, Issue 2, p380–392). It can be retrieved freely from this link. https://www.cell.com/cell/pdf/S0092-8674(09)01185-4.pdf


    Some sort of confusion may arise on reading that neurobiology article. So may I suggest you to see official medical news from Stanford website which compiled and explained the scientific finding of the above article as "Study pinpoints key mechanism in brain development, raising questions about use of antiseizure drug" in https://tinyurl.com/nlhighlight (shorten url). That news clearly highlighted the essence of the article in comprehensive way as

    - Gabapentin halts the formation of new synapses, possibly explaining its therapeutic value in mitigating epileptic seizures and chronic pain

    - Gabapentin does not dissolve pre-existing synapses, but only prevents formation of new ones. That greatly diminishes gabapentin’s potential danger to adults.

    - This insight, however, may lead physicians to reconsider the circumstances in which the drug should be prescribed to pregnant women.

    - Alpha2delta-1’s key role in synapse formation carries important implications for understanding the cause of pain and of epilepsy and developing improved medications for these conditions.




    My finding and opinion after reading original article and this scandal topics are

    - Research only included gabapentin not pregabalin.

    - The scandal was started by a Nutritionist in public website with low credibility.

    - On the start of this topics, the name of the reference article is mentioned in offensive way (not as original) and main author name & web link is removed.

    - As for safety of the drugs, every medication has its own risks and benefits. Please see the scientific evidences before prescribing to your patients.

    - Lastly, this spreading topic is in top 10 medical scandals of year 2009 and has been spreading till now.




    Cheers,
     

  4. zawminchit

    zawminchit Young Member

    Joined:
    Nov 8, 2013
    Messages:
    3
    Likes Received:
    0
    Trophy Points:
    10
    Gender:
    Male
    Practicing medicine in:
    Myanmar
    Science On The Internet – Friend or Foe – Review of an Article for the MS Community
    https://lifescienceforensics.com/20...oe-review-of-an-article-for-the-ms-community/

    Posted by lifesciforensics on January 27, 2018
    Today an interesting article was brought to my attention, but not entirely. By this I mean it was an OpEd piece that reviewed it on a blog/website, with the title, “Neurontin and Lyrica are Highly Toxic to New Brain Synapses” that was referencing a totally separate article in a highly respected peer-reviewed journal called Cell.

    The conversation was with MS patients, real ones, reaching out to each other in the exceptional on-line communities that pop-up to support each other, and where they are able to ask real people about their own experiences. One person asked about others’ experiences with pregabalin (Lyrica) and gabapentin (Neurontin and others). Another smart gentleman posted a link to this OpEd piece, which references another article, “Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis” (Eroglu et al., 2009).

    First, I went and read the source paper for this study. Trust me, it is a hard read, go for it if you are inclined but it is not intended for the layperson. I would caution against making judgments against single source papers but I will give you my “science brain” unbiased view from the snooty point of view as a science critic:

    1. Some anti-epileptics and the like got in trouble for off-label uses. But they don’t mean for what MS patients are using it for: neuropathic pain, they mean it as adjuvant therapy for psychiatric diseases like bipolar disorder. Now, there’s nothing wrong with off-label use, but there are in fact multiple trials that look at it for this use (Postherpetic Neuralgia), not just epileptic disorders.
    2. They only use rats and mice (in vivo), some (limited) in vitro (my preferred – cell lines in a test tube) testing. Not humans. Because guess what, it’s the best we have and it turns out people get all bent out of shape about experimenting on real live humans. Always remember though, you are not a rat, nor is your brain, and these are only to say “ok it sucked for the mousies, let’s put a safety factor on it and infer that it’s gonna happen this way in humans”. There’s no other way, and neurotoxicity studies are notoriously hard and have a TON of variables you just can’t control for, which means, you can never be certain your results are because of the stuff you just fed them, or other totally unrelated reasons (called confounders), and they are a Bench (thanks The Good Place – best show ever!) to account for – note this study does not go into detail about confounders – red flag. Believe me, I wish there was more. Studies I have been involved in have had to use zebra fish and surf clams and it sucks, but it’s all we’ve got. So just remember though, while it’s the best we have, people are not mice.
    3. Re: #2, this study does give me enough pause to say that in the future I would advocate to my patients to discontinue use while pregnant and nursing, while their fetuses and neonates are undergoing neurogenesis (making a brain) and early synaptogenesis (making synapses that are making memories). It is already NOT recommended for use in children 3 years or under. I would really, really go with that.
    4. Synaptogenesis is reduced, not eliminated. In other words, neurons still are being made, just not a lot. It appears that this reduction is what is causing clinically valuable outcomes, like controlling pain and zaps and twitches. And not all the mice responded, actually, only half of them did. “Only 50% of the mice responded strongly to GBP (gabapentin) injections. It is possible that a critical threshold concentration of GBP in the cerebrospinal fluid is required to be effective in blocking synapse formation, which is only achieved in half of the mice”. This means, in English: (a) it’s probably very likely dose dependent, and they never figured out what that dose was, and (b) there is something else going on here, and again, they don’t know what that is.
    5. “Since GBP strongly blocks TSP-induced synapse formation within its therapeutic concentration, it is possible that inhibition of excitatory synapse formation is an important mode of its therapeutic action in epilepsy and pain. Reactive astrocytosis is prominent both in epileptic lesions and in the spinal cord after peripheral nerve injury that leads to neuropathic pain”. This is saying, gabapentin-reducing synapse formation = A GOOD THING, because it’s reducing pain. But not at the expense of turning you into a zombie.
    6. Synaptogenesis in general follows long-term potentiation (which means an increase in strength of nerve impulses along pathways that have been used previously, either short-term or long-term). This happens in the hippocampus, and it’s how long-term memories are formed. This has nothing to do with motor issues, which is what MSers are dealing with. This is most active when we are kids, but in grown-ups, if we had the same level of synaptogenesis, it would actually be bad, because it would interfere with already pre-existing circuits. This is actually a big deal with kids with Autism Spectrum Disorder. They don’t undergo enough “synaptic pruning” and so we can see that they just have these big jumbles of neurons and that their hippocampuses are bigger than normal (Onore, Careaga, & Ashwood, 2012; Sara B. Johnson, Ph.D. & , Robert W. Blum, M.D., Ph.Db, and Jay N. Giedd, 2010; Sullivan, 2015). So what I get out of this is, hey, interesting future research for early-identified children with ASD as a potential therapy. But not a humongous potential problem for grown-ups taking gabapentin. What it also says to me is, if you are having memory issues, going on a drug holiday to see if gabapentin is contributing to them is not a terrible idea to see if it makes a difference, but again, is unlikely to be the whole issue.
    7. OVERALL:
    • Chronic pain and epilepsy are both characterized as involving an excess of synaptic connections. Synaptogenesis isn’t stopped completely, but reduced to a level that offers benefit to patients in this category.
    • The point of the study was to see HOW gabapentin worked, aka it’s mechanism.
    • “Wellness Resources” did a bang-up job with their marketing by saying it effectively causes brain death to get people to pay attention to it! Kudos to that, friends. Because “Neurontin and Lyrica are Highly Toxic to New Brain Synapses” is a way more catchy title than the study’s title of “Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis”.
    • A well-done paper. Except for the statistics, which were relatively glossed over, and I would want to see the raw data and crunch it myself. Publish on Science Direct with the raw data attached and let researchers critique it for real and we’ll talk.
    • You can’t make an assessment based on one non-peer reviewed OpEd piece.
    References:

    Eroglu, C., Allen, N. J., Susman, M. W., O’Rourke, N. A., Park, C. Y., Ozkan, E., … Barres, B. A. (2009). Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell, 139(2), 380–92. http://doi.org/10.1016/j.cell.2009.09.025

    Onore, C., Careaga, M., & Ashwood, P. (2012). Brain , Behavior , and Immunity The role of immune dysfunction in the pathophysiology of autism. Brain Behavior and Immunity, 26(3), 383–392. http://doi.org/10.1016/j.bbi.2011.08.007

    Sara B. Johnson, Ph.D., M. P. H., & , Robert W. Blum, M.D., Ph.Db, and Jay N. Giedd, M. D. (2010). NIH Public Access – Adolescent Maturity and the Brain: The Promise and Pitfalls of Neuroscience Research in Adolescent Health Policy. Journal of Adolescent Health, 45(3), 216–221. http://doi.org/10.1016/j.jadohealth.2009.05.016.Adolescent

    Sullivan, D. L. (2015). Temporality of Risk Factors and the Gender Differential Related to Autism Spectrum Disorder Diagnosis. Walden University. Retrieved from http://scholarworks.waldenu.edu/cgi/viewcontent.cgi?article=1274&context=dissertations
     

    Last edited: Aug 30, 2019
  5. zawminchit

    zawminchit Young Member

    Joined:
    Nov 8, 2013
    Messages:
    3
    Likes Received:
    0
    Trophy Points:
    10
    Gender:
    Male
    Practicing medicine in:
    Myanmar
    https://anesthesiology.duke.edu/?p=538


    By Duke Medicine News and Communications

    A Duke University Medical Center researcher who spent years looking for the signals that prompt the brain to form new connections between neurons has found one that may explain precisely how a well-known drug for epilepsy and pain actually works.

    The finding may also point to new therapies for brain injury and neuropathic pain.

    The role of neurons in the brain and nervous system is well known, but astrocytes, a different type of brain cell, still are largely a mystery.

    Duke scientist Cagla Eroglu, PhD, has discovered a receptor that receives messages from astrocytes so that the brain can form excitatory synapses, the cell-to-cell connections that can become overactive in conditions such as epilepsy.

    Working with a team of scientists from other institutions, Eroglu found this receptor is also blocked by the anti-convulsant drug gabapentin (Neurontin™).

    The study appears online in the latest issue of Cell.

    “The study links astrocytes and their role in synapse formation to diseases, so if the normal process goes wrong, this may explain why people get epilepsy, why epilepsy gets worse, or why they have neuropathic pain,” said Eroglu, assistant professor in the Duke Department of Cell Biology.

    “It’s a fine balance, because synapse formation has to occur during development for neurons to transmit brain signals, but if this happens in an uncontrolled manner in the adult brain, it could lead to these debilitating conditions.”

    Eroglu spent years looking for this neuronal receptor, which prompts synapse formation.

    “The key clue came when we chopped thrombospondin, a protein that comes from astrocytes and triggers establishment of synapses, into small fragments and put it onto neurons. We found that a specific portion of thrombospondin, the EGF-like domain, was equally effective as the whole protein. This gave me the clue that was necessary to identify its neuronal receptor. However it took me a while to do so.”

    On advice she heard from a lecture by another scientist, Nobel laureate Linda Buck — “Spend more time thinking about your experiments and your results before designing new experiments” — Eroglu took a short break from her bench-work, went home, and reasoned her way through several possibilities, finally settling on the idea that a receptor for the molecule gabapentin might be a key to regulating the formation of synapses.

    Excited, she returned to the lab and verified the interaction between proteins. “When I discovered that gabapentin completely blocked synapse formation between isolated neurons, I could not sleep for days until I replicated the results.”

    The research also points to the need for further research on gabapentin’s actions, Eroglu said. The drug gabapentin strongly blocks the receptor, reducing synapse formation in rodents.

    “The question is whether gabapentin might be linked with or interfere with cognitive ability, especially in the developing fetus of a woman taking the drug to control epilepsy,” Ergolu said. “But of course this needs to be balanced with the mother’s need to prevent her from having seizures.”

    “Likewise, while it is rare that a young child is given gabapentin for seizures, I think scientists need to study whether this possibly could be linked with side effects of this drug in children such as hyperactivity, irritability and maybe even cognitive problems,” she said.

    Gabapentin may also be a boon for certain conditions that haven’t yet been studied, she said. For example, in soldiers who have severe head wounds, many go on to develop epilepsy in the months after their injuries.

    “Maybe their injuries trigger the development of excess excitatory synaptic connections, and blocking or modulating this preemptively with gabapentin could help to prevent in this situation.”

    She said that understanding how the receptor works could also help patients who have neuropathic pain because of advanced diabetes or an injury.

    “Neuropathic pain is not perceived by patients in the same way as other types of pain,” Eroglu said.

    “Regular anti-analgesic drugs do not successfully ease this type of pain. Based on our findings it is possible that aberrant new synaptic connections that occur after injury contribute to neuropathic pain, and gabapentin might work by breaking this cycle of synapse formation.”

    The research was supported by grants from the National Institute of Drug Addiction, the National Heart, Lung and Blood Institute, the National Institutes of Health, the Human Frontiers Scientific Program long-term fellowships, and the Helen Hay Whitney postdoctoral fellowship.

    The senior author of the work is Dr. Eroglu’s mentor Ben A. Barres, of the Department of Neurobiology at Stanford University School of Medicine in Stanford, Calif. Other authors include Nicola J. Allen, Michael W. Susman, Chan Young Park, Chandrani Chakraborty, Sara B. Mulinyawe, Andrew D. Huberman, Eric M. Green, and Ricardo Dolmetsch, of the Stanford Department of Neurobiology; Jack Lawler, of the Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School in Boston; Nancy A. O’Rourke, Engin Özkan, K. Christopher Garcia, and Stephen J. Smith, all of the Department of Molecular and Cellular Physiology at Stanford (Özkan and Garcia are also in the Stanford Department of Structural Biology and Howard Hughes Medical Institute); Z. David Luo, of the Department of Anesthesiology & Perioperative Care, University of California, Irvine; Arnon Rosenthal, of MazoRx Inc., Redwood City, Calif.; and Deane F. Mosher and Douglas S. Annis of the Department of Medicine, Medical Sciences Center, University of Wisconsin, Madison.
     

Share This Page

<