Q&A 303.3
Do statins cause amnesia?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
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Date prepared: March 2014
Background
In November 2009, The Medicines and Healthcare Regulatory Agency published a Drug Safety Update (2) which outlined changes to the product literature for the group of drugs known as the statins (HMG Co-A Reductase Inhibitors: simvastatin, atorvastatin, pravastatin, fluvastatin and rosuvastatin). The changes were to reflect updated information of adverse effects of the statins, including listing memory loss as an adverse effect (2). The Food and Drug Administration (FDA) in the US now also warns about memory loss potentially caused by statins (1).
This effect is believed to be due to the fact that cholesterol synthesis is essential for neuronal function. As lipids account for about 50% of the dry matter in the central nervous system, cholesterol is an essential component of myelin sheaths and synapses. This would suggest a possible mechanism for memory loss (3).
Answer
Atorvastatin
Amnesia is listed as an uncommon adverse effect on the summary of product characteristics (SPC) for atorvastatin (4). In one case report, a 68 year old female suffered memory loss which resolved upon stopping atorvastatin. Subsequent re-challenge led to a return of symptoms which abated again when the atorvastatin was stopped (5). In a further case report a 65 year old male on atorvastatin 10 mg/day for one year showed altered neuronal activity when taking atorvastatin. These symptoms appeared to reverse upon discontinuation of atorvastatin (6).
Pravastatin
There are no case reports of pravastatin causing memory loss in the literature. Indeed, there is one case report of a 51 year old male who suffered memory loss on simvastatin which resolved when replaced with pravastatin. It has been suggested that this may be due to the fact that pravastatin is less lipophillic than simvastatin (7), although the SPC for pravastatin does mention memory loss as a class effect for statins (8).
Simvastatin
In clinical trials the occurrence of memory loss in the simvastatin treatment group was similar to that in the placebo group (9) (10) (11). There were 333 reports worldwide of memory loss obtained from the manufacturer by the MHRA in which seven patients suffered positive re-challenge and three recorded a positive de-challenge. 85 of the reports described resolution of symptoms on stopping simvastatin and 25 reports indicating persistence of symptoms. The MHRA state that a causal relationship can not be ruled out (12).
Fluvastatin
There are 40 medically confirmed post marketing cases of memory loss reported for fluvastatin, of which 14 were serious and 26 were non serious. 14 of the reports also had other possible explanations (11). Other explanations were that statins tend to be prescribed to older people, so there could be other co morbidities such as dementia, Alzheimer’s disease and other forms of memory loss that are more prevalent in an ageing population.
Rosuvastatin
Health Canada received four reports of memory loss associated with rosuvastatin, 2 of which had positive de-challenge (13). In data provided to the MHRA by the manufacturer, the incidence rate was 3-0 per 1,000 patient years for rosuvastatin. There were no reports of memory loss in the placebo group (11) and 41 post marketing case reports of memory loss that have been medically verified. Time of onset is known in 16 of these reports and ranges from 2-210 days (11). Just over half of the cases (56%) occurred within the first month of starting treatment. Among this group there where 10 reports of positive de-challenge (11). Memory loss is listed as a very rare adverse event in the SPC for Crestor ® (rosuvastatin)(14).
Statins as a class
A systematic review looking at how statins affected cognitive function, included 57 studies in total (19 randomised controlled trials, 26 cohort studies, 6 case control studies and 6 cross sectional studies).
The authors concluded that based on moderate strength evidence, statins posed no increased risk of dementia. They also concluded that statins were not associated with Alzheimer’s Disease, though this is based on low strength evidence only. Moderate strength evidence suggested no worsening of cognitive function in the absence of dementia, though the available data included in the study is limited. (16)
Summary
There is limited supporting evidence of statins causing amnesia. Statins are widely prescribed- from January 2011 to December 2011 there were 41,133,943 prescriptions for simvastatin (15). Considering the relatively small number of case reports, it is likely that the incidence of memory loss associated with statin therapy is low.
The fact that statins are also often prescribed to older people may also be a limiting factor as this population are more susceptible to memory loss as a normal sign of aging or due to the presence of co-morbidities.
¨ Memory loss can be associated with many medical complaints.
¨ As the process of memory involves lipids this is a potential mechanism for this adverse effect.
¨ The more lipophillic statins appear to have the greatest potential to cause memory loss although data is limited.
¨ The balance of benefits from statin therapy still outweigh the risk of adverse effects associated with these drugs.
Limitations
The information included in this Q&A was correct at the time of writing. Prescribing figures are from England only.
Quality Assurance
Prepared by
Vincent J Cassidy, Regional Drug and Therapeutic Centre, Newcastle upon Tyne
Date Prepared
10th March 2014
Checked by
Hayley Johnson, Regional Drug & Therapeutics Centre, Newcastle upon Tyne
Date of check
29th July 2014
Search strategy
Embase (2012 -current)[Atorvastatin or Pravastatin or Simvastatin or Fluvastatin or Rosuvastatin] + [amnesia or memory loss]
Medline (2012-current) [Hydroxymethylglutaryl-COA reductase inhibitors] + [memory disorder
MHRA - Personal communication 9th February 2010
In house databases
Prescription Pricing Authority
References
(1) FDA consumer update via http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm293330.htm
(2) MHRA Drug Safety Update 2009 ; 3(4); 11 http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON062553
(3) Tuccori M, Lapi F Testi A, et al. Statin-associated Psychiatric adverse events. Drug Safety 2008; 31(12): 1115-1125
(4) Summary of Product Characteristics-Lipitor (atorvastatin). Pfizer Ltd. Accessed via http://www.emc.medicines.org.uk/medicine/1424/SPC/Lipitor+10mg%2c+20mg%2c+40mg%2c+80mg+Tablets/ on 10th March 2014. [Date of revision of text 15/01/2014]
(5) King DS, Wilburn AJ, Wofford MR, et al. Cognitive impairment associated with atorvastatin and simvastatin. Pharmacotherapy 2003; 23(12): 1663-1667
(6) Parker BA, Polk DM, Rabdiya V, et al Changes in memory function and neuronal activation associated with atorvastatin therapy Pharmacotherapy 2010 vol 30 236-240
(7) Wagstaff LR, Mitton MW, Arvik BM, et al. Statin associated memory loss: Analysis of 60 case reports and review of the literature. Pharmacotherapy 2003; 23(7): 871 – 880
(8) Summary of Product Characteristics- Lipostat (pravastatin). Bristol Meyers Squibb Pharmaceuticals Ltd. Accessed via http://www.emc.medicines.org.uk/medicine/1424/SPC/Lipitor+10mg%2c+20mg%2c+40mg%2c+80mg+Tablets/ on 10th March 2014. [Date of revision of text 17/05/2013]
(9) Pedersen TR, Berg K, Cook TJ, et al. Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian simvastatin survival study. Archives of internal medicine 1996; 156: 2085 – 2092
(10) De Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs delayed conservative simvastatin strategy in patients with acute coronary syndromes: Phase Z of the A to Z trial. JAMA 2004; 292(11): 1307-7316
(11) MRC/BHF Heart protection study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo controlled trial. The Lancet 2002; 360: 7 – 22
(12) MHRA public assessment report statins: updates to product safety information November 2009 http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON062558
(13) Health Canada. Canadian Adverse reaction newsletter. 2005; 15(4): 2. http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/carn-bcei_v15n4-eng.pdf
(14) Summary of Product Characteristics- Crestor (rosuvastatin) Astra Zenica UL limited accessed via http://www.medicines.org.uk/EMC/medicine/11976/SPC/Crestor+5mg%2c+10mg%2c+20mg+and+40mg+film-coated+tablets/ accessed 10th March 2014 (last updated 04/02/14)
(15) Personal communication with the Prescription Pricing Authority 16th March 2012.
(16) Richardson K, Schoen M, French B, et al Statins and cognitive function Annals of Internal Medicine 2013; 159(10) 688-698
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Available through NICE Evidence Search at www.evidence.nhs.uk