Statin Adverse Effects FAQ: NERVE DAMAGE & 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

NERVE DAMAGE & STATINS

References (updated as of  January 7, 2005):

Statin-a_ssociated peripheral neuropathy: review of the literature.

Chong PH, Boskovich A, Stevkovic N, Bartt RE. Pharmacotherapy. 2004
Sep;24(9):1194-203. Review. PMID: 15460180 [PubMed - indexed for
MEDLINE]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15460180"Based
on epidemiologic studies as well as case reports, a risk of peripheral
neuropathy a_ssociated with statin use may exist; however, the risk appears
to be minimal. On the other hand, the benefits of statins are firmly
established. These findings should alert prescribers to a potential risk of
peripheral neuropathy in patients receiving any of the statins; that is,
statins should be considered the cause of peripheral neuropathy when other
etiologies have been excluded."  Disorder resembling Guillain-Barre syndrome
on initiation of statin therapy.Rajabally YA, Varakantam V, Abbott RJ.
Muscle Nerve. 2004 Nov;30(5):663-6. PMID: 15389662 [PubMed - indexed for
MEDLINE]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15389662"We
report a disorder resembling Guillain-Barre syndrome, occurring on
initiation of simvastatin, in a 58-year-old man, who had experienced a
similar but milder episode after starting pravastatin 6 months earlier. This
case suggests that acute polyradiculoneuropathy may represent a rare but
serious side-effect of statin treatment. It also raises the issue of the
pathophysiology of acute neuropathy on statin exposure, with a
hypersensitivity reaction resulting in an immune-mediated process being
possible instead of the hypothesized mitochondrial dysfunction in chronic
cases."  Simvastatin-induced mononeuropathy multiplex: case report.Scola RH,
Trentin AP, Germiniani FM, Piovesan EJ, Werneck LC. Arq Neuropsiquiatr. 2004
Jun;62(2B):540-2. Epub 2004 Jul 20. PMID: 15273860 [PubMed - in
process]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15273860"The
a_ssociation between the use of statins and neuromuscular disease is
currently being intensely discussed. We relate a 63 years old man with
possible case of statin-induced neuropathy in a patient with dislipidemia in
use of simvastatina at high doses. The electrophysiologic studies disclosed
findings compatible with mononeuropathy multiplex, suggested by clinical
prescutation of asymmetrical numbness and weakness. More common causes of
mononeuropathy multiplex were excluded and the patient improved after the
discontinuation of the drug."
Statins and risk of polyneuropathy, A case-control study
D. Gaist, MD, PhD; U. Jeppesen, MD, PhD; M. Andersen, MD, PhD; L.A. Garc?a
Rodr?guez, MD, MSc;
J. Hallas, MD, PhD; and S.H. Sindrup, MD, PhD
http://213.4.18.135/87.pdf full text

From the abstract: "The authors verified a diagnosis of idiopathic
polyneuropathy in 166 cases. The cases were cla_ssified as definite (35),
probable (54), or possible (77). The odds ratio linking idiopathic
polyneuropathy with statin use was 3.7 (95% CI 1.8 to 7.6) for all cases and
14.2 (5.3 to 38.0) for definite cases. The corresponding odds ratios in
current users were 4.6 (2.1 to 10.0) for all cases and 16.1 (5.7 to 45.4)
for definite cases. For patients treated with statins for 2 or more years
the odds ratio of definite idiopathic polyneuropathy was 26.4 (7.8 to 45.4).
CONCLUSIONS: Long-term exposure to statins may substantially increase the
risk of polyneuropathy."

Are users of lipid-lowering drugs at increased risk of peripheral
neuropathy?
David Gaist, Luis Alberto Garc?a Rodr?guez ? Consuelo Huerta ? Jesper Hallas
? S?ren H. Sindrup
http://213.4.18.135/75.pdf full text
http://213.4.18.135/76.2.pdf full text
http://213.4.18.135/87.pdf full text text

Pharmacodynamics: Statins and peripheral neuropathy
U. Jeppesen (2), D. Gaist (1)(2), T. Smith (1), S. H. Sindrup (1)(2)
(1) Department of Neurology, Odense University Hospital, DK-5000 Odense C,
Denmark Tel.: +45-6541-2474, Fax: +45-6541-3389
(2) Department of Clinical Pharmacology Odense University, Odense, Denmark
Received: 6 July 1998 / Accepted in revised form: 1 October 1998
Abstract Volume 54 Issue 11 (1999) pp 835-838
http://link.springer-ny.com/link/service/journals/00228/bibs/9054011/90540835.htm
"Within the past 3 years seven cases of reversible peripheral neuropathy
apparently caused by statins have been reported. Here we report seven
additional cases a_ssociated with long-term statin therapy, in which other
causes of neuropathy were thoroughly excluded. The neuropathy was in all
cases axonal and with affection of both thick and thin nerve fibers. The
symptoms of neuropathy persisted during an observation period lasting from
10 weeks to 1 year in four cases after statin treatment had been withdrawn.
We suggest that long-term statin treatment may be a_ssociated with chronic
peripheral neuropathy."

A_ssociation of HMG-CoA reductase inhibitors with neuropathy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2549960&dopt=Abstract
Ann Pharmacother. 2003 Feb;37(2):274-8.
Backes JM, Howard PA.
Department of Pharmacy Practice and Lipid, Atherosclerosis, Metabolic and
LDL-Apheresis Clinic, University of Kansas Medical Center, Kansas City, KS
66160-7231, USA. jbackes@kumc.edu
"Epidemiologic studies and case reports suggest an increased risk of
peripheral neuropathy with statin drugs. The majority of cases were at least
partially reversible with drug cessation." (emphasis added)

Selenoprotein synthesis and side-effects of statins.Moosmann B, Behl C.
Lancet. 2004 Mar 13;363(9412):892-4. Review. PMID: 15031036 [PubMed -
indexed for
MEDLINE]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15031036

"We noted that the pattern of side-effects a_ssociated with statins
resembles the pathology of selenium deficiency, and postulated that the
mechanism lay in a well established, but often overlooked, biochemical
pathway--the isopentenylation of selenocysteine-tRNA([Ser]Sec). A negative
effect of statins on selenoprotein synthesis does seem to explain many of
the enigmatic effects and side-effects of statins, in particular,
statin-induced myopathy."

Statin therapy and small fibre neuropathy: a serial electrophysiological
study.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2639733&dopt=Abstract
Lo YL, Leoh TH, Loh LM, Tan CE.
J Neurol Sci. 2003 Apr 15;208(1-2):105-8.
Department of Neurology, Singapore General Hospital, Outram Road, Singapore.
gnrlyl@sgh.com.sg
Describes 3 patients who developed neuropathy after ONE MONTH of statin
therapy. "One patient redeveloped small and large fibre neuropathy when the
similar drug was readministered."

Peripheral Neuropathy and Lipid-Lowering Therapy
Paul E. Ziajka, MD, PhD, and Tammy Wehmeier, RN, Orlando, Fla.
Abstract: We report a case of peripheral neuropathy induced and excerbated
by several commonly used HMG-CoA reductase inhibitors including lovastatin,
simvastatin, pravastatin, and atorvastatin, and the vitamin niacin. A review
of the literature shows similar cases with individual lipid-lowering drugs,
but this case shows the cross-reactivity of the neuropathic process to
different HMG-CoA reductase inhibitors, and is the first reported case of a
peripheral neuropathy exacerbated by the use of niacin.
http://www.sma.org/smj1998/julysmj98/ziajka.pdf

Peripheral neuropathy a_ssociated with simvastatin.
Phan T, McLeod JG, Pollard JD, Peiris O, Rohan A, Halpern JP.
J Neurol Neurosurg Psychiatry. 1995 May;58(5):625-8.
PMID: 7745415 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7
745415&dopt=Abstract

"Four patients are described who developed sensorimotor neuropathy while
being treated with simvastatin and had complete or partial resolution of
clinical abnormalities after withdrawal of treatment. In one case onset was
within days of commencing treatment, but in two cases symptoms did not
develop for two years. The electrophysiological and pathological features of
the neuropathy were those of axonal degeneration. Clinical evidence of
proximal and distal weakness and muscle fasciculations and persistent
abnormalities of sensory conduction after recovery suggest the possibility
of toxic damage to anterior horn cells and dorsal root ganglia. Thirty eight
other cases with symptoms suggestive of peripheral neuropathy have been
reported to the Australian Adverse Drug Reactions Advisory Committee, 22 of
whom recovered after cessation of treatment; in five cases there was
recurrence after re-exposure to the drug. Simvastatin should be considered
among the causes of peripheral neuropathy, and the drug should be withdrawn
if patients receiving it develop muscle weakness or sensory disturbances."

Lovastatin and peripheral neuropathy.
Ahmad S.
Am Heart J. 1995 Dec;130(6):1321. No abstract available.
PMID: 7484806 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7
484806&dopt=Abstract

Vestibular vertigo and lovastatin therapy.

Ahmad S.
South Med J. 1996 Feb;89(2):257-8. No abstract available.
PMID: 8578368 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=8578368

HMG-CoA reductase inhibitor therapy and peripheral neuropathy.

Jacobs MB.
Ann Intern Med. 1994 Jun 1;120(11):970. No abstract available.
PMID: 8172444 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8
172444&dopt=Abstract

Medication-induced peripheral neuropathy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2507417&dopt=Abstract
Curr Neurol Neurosci Rep. 2003 Jan;3(1):86-92. Review.
Weimer LH.
Neurological Institute of New York, 710 West 168th Street, Unit 55, New
York, NY 10032, USA. Lhw1@columbia.edu
PMID: 12507417 [PubMed - indexed for MEDLINE]
"Although most cases demonstrate acute or subacute onset after exposure,
recent experiences with statin drugs raise the possibility of occult toxic
causes of chronic idiopathic neuropathy."

Neuropathy due to drugs.

Le Quesne PM.

In: Dyck PJ, Thomas PK, Griffin JW, et al, eds. Peripheral neuropathy. 3rd
ed. Philadelphia: Saunders, 1993:1571-1581.
(Book, no link)