Re: Statin Adverse Effects FAQ: MEMORY LOSS, AMNESIA

From: Bill (xxx_at_yy.zz)
Date: 01/10/05 

Date: Mon, 10 Jan 2005 00:56:14 GMT

"Sharon Hope" <shope@anet.net> wrote in message
news:UKSdnU-OZ45eUXzcRVn-vg@comcast.com...
> Statin Adverse Effects FAQ: MEMORY LOSS & STATINS, AMNESIA & STATINS
>
>
>
>
>
> To my physician,
>
>
>
> I believe that my symptoms may be due to the adverse effects a_ssociated
> with cholesterol-lowering statin drugs. I need your help to understand the
> cause of my symptoms, treatment options, and the prognosis for my recovery.
>
>
>
> Please review the references below, published medical studies that show
> similar problems a_ssociated with statin drugs. These are made available
> via the National Institutes of Health (NIH,
> http://www.ncbi.nlm.nih.gov/Entrez/) library of biomedical journal citations
> and other major repositories of medical research.
>
>
>
> Also, I am respectfully requesting that you file an adverse effects report
> with the FDA (http://www.fda.gov/medwatch/how.htm), and that you please send
> a copy of the report to the to the NIH-funded Statin Study, attention: Dr.
> Beatrice Golomb, Principal Investigator.
> Statin Study website: http://medicine.ucsd.edu/statin/
> Statin Study contact info: http://medicine.ucsd.edu/statin/contactinfo.html
> UCSD STATIN STUDY E-MAIL ADDRESS: statinstudy@ucsd.edu
> MAILING ADDRESS: UCSD Statin Study 9500 Gilman Dr. La Jolla, CA 92093-0995
> PHONE NUMBER: (858) 558-4950
>
>
>
> Thank you
>
>
>
>
>
>
>
> MEMORY LOSS & STATINS, AMNESIA & STATINS
>
> References (updated as of January 7, 2005):
>
>
>
> Randomized trial of the effects of simvastatin on cognitive functioning in
> hypercholesterolemic adults.Am J Med. 2004 Dec 1;117(11):823-9. Muldoon MF,
> Ryan CM, Sereika SM, Flory JD, Manuck SB.Center for Clinical Pharmacology,
> University of Pittsburgh, Pennsylvania 15260, USA. mfm10@pitt.edu"This study
> provides partial support for minor decrements in cognitive functioning with
> statins. Whether such effects have any long-term sequelae or occur with
> other cholesterol-lowering interventions is not known." This is the second
> of two studies by Muldoon, both showing measurable cognitive decline in
> statin groups after only 6 months, using Neuropsychological (NP) testing.
> Further, this study identifies the subset of NP tests that are "statin
> sensitive" in detecting the cognitive deficits.
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15589485
>
>
>
> Effects of lovastatin on cognitive function and psychological well-being.
>
> Muldoon MF, Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, Manuck
> SB.
> After 6 months, 100% of the patients on placeboes showed a measurable
> increase in cognitive function, while the statin patients showed a
> measurable decrease in cognitive function in some areas.
> Am J Med. 2000 May;108(7):538-46.
> PMID: 10806282 [PubMed - indexed for MEDLINE]
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10806282&dopt=Abstract
>
>
>
>
>
> Cognitive impairment a_ssociated with atorvastatin and simvastatin.King DS,
> Wilburn AJ, Wofford MR, Harrell TK, Lindley BJ, Jones DW.Department of
> Medicine, University of Mississippi Medical Center, Jackson, Mississippi
> 39216, USA. dking@pharmacy.umsmed.eduPharmacotherapy. 2003
> Dec;23(12):1663-7. "we report two women who experienced significant
> cognitive impairment temporally related to statin therapy. One woman took
> atorvastatin, and the other first took atorvastatin, then was rechallenged
> with simvastatin. Clinicians should be aware of cognitive impairment and
> dementia as potential adverse effects a_ssociated with statin therapy."
> PMID: 14695047
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14695047
>
>
>
> "DRUGS THAT MAKE YOU FORGET"
> Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the
> FDA)
> Volume 17, Number 3, August 1998, section 3, page 3
> Simvastatn is listed under "DRUGS THAT MAKE YOU FORGET"
> Recognizing the 14 reports of Amnesia under that drug, .8% of the total
> adverse effects for that drug.
> www.health.gov.au/tga/docs/pdf/aadrbltn/aadr9808.pdf
>
>
>
>
>
> Statin-a_ssociated memory loss: analysis of 60 case reports and review of
> the literature.
> Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM.
> Drug Information Service, Duke University Medical Center, Durham, North
> Carolina 27710, USA. Pharmacotherapy. 2003 Jul;23(7):871-80.
>
> This study searched the MedWatch drug surveillance system of the Food and
> Drug Administration (FDA) from November 1997-February 2002 for reports of
> statin-a_ssociated memory loss. They also reviewed the published literature.
> References from the study are good for follow-up research.
>
> Abstract:
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12885101&dopt=Abstract
>
> Full Study Text free on Medscape:
>
> http://www.medscape.com/viewarticle/458867
>
>
>
>
>
> The Role of Lipid-Lowering Drugs in Cognitive Function: A Meta-Analysis of
> Observational Studies
>
> from Pharmacotherapy
> Posted 06/30/2003
>
> Mahyar Etminan, Pharm.D., Sudeep Gill, M.D., FRCPC, Ali Samii, M.D., FRCPC
>
> Although this study does bring the cognitive issues to light, it is a very
> poor study. The authors left out the pivotal study by Dr. Muldoon, that
> showed 100% of statin users had a measurable loss of cognitive ability
> after 6 months, while 100% of the placebo group improved their scores.
>
> Abstract:
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12820814&dopt=Abstract
>
> Full Study Text free on Medscape:
>
> http://www.medscape.com/viewarticle/456866
>
>

I've told you 2 or 3 times that the above statement is false. The study did
not show that that 100% of statin users had a measurable loss of cognitive
ability.

Bill

>
> Simvastatin-A_ssociated Memory Loss
> Amanda Orsi, Pharm.D., Olga Sherman, Pharm.D., and Zegga Woldesela_ssie,
> Pharm.D.,
> Abstract: The statins are widely used to treat dyslipidemias. They are
> generally a_ssociated with mild adverse effects, but rarely, more serious
> reactions may occur. A 51-year-old man experienced delayed-onset,
> progressive memory loss while receiving simvastatin for
> hypercholesterolemia. His therapy was switched to pravastatin, and memory
> loss resolved gradually over the next month, with no recurrence of the
> adverse effect.
> from Pharmacotherapy
> Posted 06/01/2001
> Page 1 of 3:
> http://www.medscape.com/viewarticle/409738?WebLogicSession=PXke2H8h99pyNVSCajAh5clptzOAHJSZuNBobSwWmi9veWjdJ2A3%7C-1468812056489609316/184161392/6/7001/7001/7002/7002/7001/-1
> full printable version: http://www.medscape.com/viewarticle/409738_print
>
> ADR of the Month
> September 2001 Vol. 6 No. 9
> EDITORS
> Michelle W. McCarthy, Pharm.D.
> Anne E. Hendrick, Pharm.D.
>
> University of Virginia Health System
> Department of Pharmacy Services
> Drug Information Center
> PO Box 800674
> Charlottesville, VA 22908-0674
> http://hsc.virginia.edu/pharmacy-services/Newsletters/ADR%20of%20the%20Month/ADRMonth%209-01htm.html
>
>
>
>
> Do HMG-CoA reductase inhibitors impair memory?
> The Tablet, a general member benefit published by the British Columbia
> Pharmacy A_ssociation, September 2001, Volume 10 no 8.
> Excerpt:
> Do HMG-CoA reductase inhibitors impair memory? After taking simvastatin for
> a year, a 51-year-old patient developed short term memory loss, to the
> extent of being unable to complete his sentences because he would forget
> what he was going to say. The drug was discontinued, replaced by
> pravastatin, and within one month his memory returned.14 In a separate case,
> a 67-year-old woman developed impaired short-term memory, altered mood,
> social impairment, cognitive impairment and dementia after one year of
> atorvastatin therapy. When atorvastatin was discontinued, her memory, mood
> and cognition improved completely.15 Memory impairment in a patient
> receiving atorvastatin has been reported to the BC Regional ADR Centre.
> REFERENCES:
> 14. Orsi A, Sherman O, Woldesela_ssie Z. Simvastatin-a_ssociated memory
> loss.
> 15. King DS, Jones DW, Wofford MR et al. First report of cognitive
> impairment in an elderly patient: case report. Pharmacotherapy 2001 Mar; 21:
> 371.
>
> http://www.bcpharmacy.ca/publications/thetablet/pdf_version/BCPhA_Tablet-Sep2001.pdf
> See page 11 of 16:
>
>
>
> AMNESIA & STATINS
>
>
> Lipitor, Thief of Memory
>
> Dr. Duane Graveline, retired family MD, USAF Flight Surgeon, researcher in
> space medicine and US Astronaut, who suffered adverse effects from Lipitor.
> The book is available through Amazon.com. Dr. Graveline maintains several
> websites and is working on a second book about statin drug side effects:
> www.spacedoc.net (you can start here and read about his life and his books)
> http://www.spacedoc.net/lipitor_thief_of_memory.html
> http://www.spacedoc.net/lipitor.htm
> http://www.spacedoc.net/statin_dialogues.htm
>
> Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the
> FDA)
> Volume 17, Number 3, August 1998, section 3, page 3
> Simvastatn is listed under "DRUGS THAT MAKE YOU FORGET"
> Recognizing the 14 reports of Amnesia under that drug, .8% of the total
> adverse effects for that drug.
> www.health.gov.au/tga/docs/pdf/aadrbltn/aadr9808.pdf
>
>
>
>
>
> ===========
>
> Please see also:
>
>
>
> Mechanistic and epidemiologic considerations in the evaluation of adverse
> birth outcomes following gestational exposure to statins.Am J Med Genet.
> 2004 Dec 15;131A(3):287-98. Edison RJ, Muenke M.Medical Genetics Branch,
> National Human Genome Research Institute, National Institutes of Health,
> Department of Health and Human Services, Bethesda,Maryland 20892-3717,
> USA."The cholesterol-lowering "statin" drugs are contraindicated in
> pregnancy, but few data exist on their safety in human gestation. We
> reviewed case reports for patterns suggesting drug-related effects on
> prenatal development and considered a variety of mechanisms by which such
> effects, if confirmed, might occur. This uncontrolled case series included
> all FDA reports of statin exposures during gestation, as well as others from
> the literature and from manufacturers. Exposures and outcomes were reviewed
> and were tabulated by individual drug. Age-specific rates of exposure to
> each drug among women of child-bearing age were estimated. Of 214
> ascertained pregnancy exposures, 70 evaluable reports remained after
> excluding uninformative cases. Among 31 adverse outcomes were 22 cases with
> structural defects, 4 cases of intrauterine growth restriction, and 5 cases
> of fetal demise. There were two principal categories of recurrent structural
> defects: cerivastatin and lovastatin were a_ssociated with four reports of
> severe midline CNS defects; simvastatin, lovastatin, and atorvastatin were
> all a_ssociated with reports of limb deficiencies, including two similar
> complex lower limb defects reported following simvastatin exposure. There
> were also two cases of VACTERL a_ssociation among the limb deficiency cases.
> All adverse outcomes were reported following exposure to cerivastatin,
> simvastatin, lovastatin, or atorvastatin, which are lipophilic and
> equilibrate between maternal and embryonic compartments. None were reported
> following exposure to pravastatin, which is minimally present in the embryo.
> Statins reaching the embryo may down-regulate biosynthesis of cholesterol as
> well as many important metabolic intermediates, and may have secondary
> effects on sterol-dependent morphogens such as Sonic Hedgehog. The reported
> cases display patterns consistent with dysfunction of cholesterol
> biosynthesis and Sonic Hedgehog activity. Controlled studies are needed to
> investigate the teratogenicity of individual drugs in this cla_ss."PMID:
> 15546153 [PubMed - in process]
>
>
> Statins and risk of polyneuropathy, A case-control study
> D. Gaist, MD, PhD; U. Jeppesen, MD, PhD; M. Andersen, MD, PhD; L.A. García
> Rodríguez, MD, MSc;
> J. Hallas, MD, PhD; and S.H. Sindrup, MD, PhD
> http://213.4.18.135/87.pdf full text
>
> Preclinical safety evaluation of cerivastatin, a novel HMG-CoA reductase
> inhibitor.
> von Keutz E, Schluter G.
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9737641&dopt=Abstract
> Institute of Toxicology, PH-Product Development, Bayer AG, Wuppertal,
> Germany
> Am J Cardiol. 1998 Aug 27;82(4B):11J-17J.
> PMID: 9737641
> "In dogs, the species most sensitive to statins, cerivastatin caused
> erosions and hemorrhages in the gastrointestinal tract, bleeding in the
> brain stem with fibroid degeneration of vessel walls in the choroid plexus,
> and lens opacity."
>
> Subchronic toxicity of atorvastatin, a hydroxymethylglutaryl-coenzyme A
> reductase inhibitor, in beagle dogs.
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8864188&dopt=Abstract
> Walsh KM, Alba_ssam MA, Clarke DE.
> Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann
> Arbor, Michigan 48105, USA.
> "The toxicity of atorvastatin (AT), an inhibitor of
> hydroxymethylglutaryl-coenzyme A reductase (HMG), was evaluated in beagle
> dogs. hemorrhage in gallbladder and brain, demyelination of optic nerve, and
> skeletal muscle necrosis"
>
> Finally, on memory loss and statins: Sworn testimony from the Baycol trial
> in Corpus Christi, Texas. From the transcript of the AM Session on 03-05-03,
> in the case Hollis Haltom Vs. Bayer Corporation. Testifying under oath,., in
> response to the plaintiff's attorney's question, "What is your current
> position at Bayer?", LAWRENCE POSNER, M.D of BAYER stated: "I'm the --
> currently I'm the head of worldwide regulatory affairs for our prescription
> drug business, which means I have responsibility in somewhere between 60 and
> 100 countries where we sell products for registrations, compliance, things
> of that nature." Excerpts from the trial transcript follow, with the Q
> indicating counsel's Question, and the A indicating Dr. Posner's Answer:
> Q. So there are some concerns addressed here back in 1995 about testing up
> to .8. And do you know what the nature of the concern was?
> A. Yes. It was related to a side effect that occurred in the brain.
> Q. Of what kind of animal?
> A. It occurred in the brain of dogs.
> Q. Okay. So there was a side effect that occurred in dogs, and then there
> was a concern about whether you wanted to go forward and test at this higher
> dose level in human beings, given what you had learned about the dogs,
> right?
> A. That's correct.
> Q. Okay. Now, did you just say, well, let's forget about these concerns and
> we'll go ahead and put .8 on the market anyway, or did you do some further
> analysis that was not mentioned the other day?
> A. Yes. The authors of this had -- they had two concerns. One concern was
> the toxicity that they found in the brain of dogs. But the other was that
> they had no way to identify this and who might be at risk before it
> happened. So there was no way to detect that someone was at risk for this
> side effect.
> [skip some testimony on other topics]
> Q. Do you remember in one kind of animal there had been some studies done
> that there could be a particular kind of problem with one kind of animal?
> A. Oh, yeah. Yes, from the -- that's correct, from the toxicology studies.
> Q. Okay. And were you able to demonstrate to your own satisfaction, to
> SmithKline's satisfaction, to the FDA's satisfaction, that that particular
> problem that showed up with that kind of animal is not something that
> happens in human beings?
> A. Yes. We did it -- we did it by explaining the toxicology data. We also
> explained it on the basis of kinetic data. That actually at the higher
> levels of drug, what happens is a certain amount of drug is bound to
> proteins in the body that circulate; and therefore, is not -- cannot cause
> side effects. And actually, a much smaller proportion of the drug is free.
> And that what you corrected for that, you actually found out that the
> margins of safety were in fact greater than you would predict just from the
> animal data.
> Q. And as you move forward then and got approval and sold Baycol from 1997
> through 2001, did that problem that had shown up with that one kind of
> animal ever become a problem with human beings?
> A. It was actually shown with other statins as well. It wasn't unique to
> cerivastatin. It was a problem -- it was identified early on with lovastatin
> and some of the others. In fact, for none of the statins did it ever predict
> for any clinical problem or toxicity.
> Q. So these animals would have that same problem regardless of which
> statin -- or at least with other statins?
> A. Certainly with lovastatin it was true.
> Q. But when it came time to human beings, that just wasn't something that
> happened to human beings?
> A. And I think today no one pays much attention to it.
>
>
>
>
>
>
>
>

Relevant Pages

  • Re: Statin Adverse Effects FAQ: MEMORY LOSS, AMNESIA
    ... > similar problems a_ssociated with statin drugs. ... I am respectfully requesting that you file an adverse effects report ... > adverse effects for that drug. ... > and cognition improved completely.15 Memory impairment in a patient ...
    (sci.med.cardiology)
  • Statin Adverse Effects FAQ: MEMORY LOSS, AMNESIA
    ... Statin Adverse Effects FAQ: MEMORY LOSS & STATINS, ... Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the ...
    (sci.med.cardiology)
  • Re: Cognitive problems with simvastatin?
    ... This cognitive damage from statin drugs is well documented. ... but also the muscle and nerve damage adverse effects. ... case of Lipitor memory loss and cognitive damage has been confirmed, ... Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the ...
    (sci.med.cardiology)
  • Statin Adverse Effects FAQ: MEMORY LOSS, AMNESIA
    ... Statin Adverse Effects FAQ: MEMORY LOSS & STATINS, ... Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the ...
    (sci.med)
  • Re: Statin Adverse Effects FAQ: MEMORY LOSS, AMNESIA
    ... Memory, and Memory Recall, the mean for the statin group was consistently ... I am respectfully requesting that you file an adverse effects ... >> adverse effects for that drug. ... >> mood and cognition improved completely.15 Memory impairment in a patient ...
    (sci.med)