Even as statins were being unleashed on the public as the answer to cholesterol and prescribed to millions, a growing list of side-effects was emerg-ing-ranging from muscle weakness to erectile dysfunction. And now, it appears that Lipitor (atorvastatin), the most successful drug of all time-with 2006 sales of $12.9 billion in the US alone-can cause cognitive impair-ment, and sudden and complete memory loss.
This new evidence surfaced when two doctors-aerospace scientist and flight surgeon Duane Graveline, and Jay S. Cohen, associate professor in preventive medicine and psychiatry at the University of California-decided to dig into the drugs, following Grave-line's own problems with atorvastatin.
When Graveline was first given atorvastatin, he suffered a six-hour bout of global amnesia. A year later when he tried the drug again, he had a 12-hour period during which the memory of his entire adult life disappeared. At the time, he could not even recognize his wife.
Graveline's family doctor contacted Pfizer, which makes atorvastatin, to ask for information on any memory impairment associated with the drug.
The document sent by Pfizer, containing the pre-release clinical data on the drug, showed that, of 2502 volunteers who'd otherwise tolerated the drug well, 11 cases of severe cognitive disturbance were reported-or 4.5 cases for every 1000 patients using the drug. This trans-lates to 4500 cases of severe cognitive impairment for every million patients using the drug.
Pfizer defined cognitive impair-ment as memory loss; impaired, worsening or general lapses of mem-ory; general forgetfulness; and short-term memory loss. They also included cases of difficulty concentrating; abnormal, slow or difficulty thinking; slowed or decreased mental activity; impaired intellect or judgment; and even irrational thinking.
As 36 milion Americans now take statins, an estimated 162,000 people in the US alone could be severely mentally impaired by these drugs.
Graveline and Cohen recently conducted a search on MedWatch, the US Food and Drug Association (FDA) database of reported drug side-effects, for reports on cases of severe cognitive impairment and other cognitive events associated with Lipitor (Townsend Letter, June 2009; 64-70; www.townsendletter.com/June2009/June2009. htm). The doctors limited their search only to those cases where some form of serious amnesia was reported, and did not look for forgetfulness or confusion.
Their search yielded 662 such reports, 399 of which were cases of amnesia, and 236 were memory impairment. Also, the number of reports increased in frequency over time, so that the largest number had been most recently filed.
When the doctors looked for reasons behind the steady increase in frequency, they found that the average dosage of atorvastatin between 1997 and 2001 was 15 mg whereas, by 2006, the average dosage had risen
to 22 g/day.
MedWatch estimates that it receives only 2.5-5 per cent of all adverse events from drugs, which means that the true figure of reported memory problems from statins could be closer to 66,000 cases or more.
Thus far, the medical community has never examined this side-effect other than through individual case studies. In one instance, a 67-year-old woman, who'd tolerated atorvastatin at 10 mg/day without side-effects, suddenly began to experience short-term memory loss when her dose was increased to 20 mg/day (Pharmacother-apy, 2001; 21: 371).
In another instance, a 68-year-old woman taking a cocktail of drugs for hypertension and menopause was prescribed atorvastin at a lower dose of 10 mg/day and, nine months later, reported noticeable memory impair-ment and general cognitive decline (Pharmacotherapy, 2003; 23: 1663-7). She was taken off the drug twice, but
given it again once her symptoms had resolved. However, her memory problems returned. After being taken off the drug yet again, she was given simvastatin, another statin, but her memory problems again returned until she was taken off all statins for good.
The numbers of those affected that are bandied about may represent only a tiny proportion of the true numbers affected, say Graveline and Cohen, as research suggests that these drugs can cause a subtle cognitive impair-ment in virtually all patients that goes largely unnoticed.
Cholesterol on the brain
It is well known that the brain needs cholesterol to process memory and recall but, as our usual LDL cholesterol is too big to pass through the blood-brain barrier, researchers have discovered that the glial cells of the brain, which perform certain housekeeping tasks, also handle the cholesterol system in the brain. Graveline and Cohen theorize that the effect of statin drugs in inhibiting cholesterol synthesis probably also extends to these glial cells as well. In addition, statins affect the attachment of sugars to neuropeptides, which are vital to the relay of emotion. As emotion is central to memory, it may also play a part in the process.
Still other researchers are discovering that statins also inhibit and cause mutations in parts of the mitrochondria, the 'power-packs' of cells. Indeed, many researchers now suspect that a number of neurodegenerative disorders are due to such mutated or altered mitochondria.
Vol. 20 04 July 2009