Editorial Note: This is a third post on Statins. The first two were Birth of a Statinista and The Legacy Effects of Statins. This one deals with one of the more complex problems these drugs can cause – cognitive failure. Many people might ask why post a story like this here and court media attention – this is a scientific issue to be dealt with in journals. This case has already appeared in BMJ – see below – but with no effect.
In 2001, a 57-year-old man presented to hospital with end-stage renal failure secondary to kidney disease. He was started on dialysis for his renal failure. At this point he was on medication for blood pressure and was begun on 40 mg of simvastatin – Zocor. He was still working.
Over time he got physically worse and got more distressed. His primary care doctor prescribed an antidepressant, dosulepin, but later changing this to sertraline – Zoloft. His Zocor was changed to 10 mg rosuvastatin – Crestor. Prior to the change to Crestor, his cholesterol level had tracked at a healthy 4.5 mmol/L but had jumped to 6.3 mmol/L (lower than mine). On Crestor his cholesterol level dropped to 3.0 mmol/L.
This was February 2005. At this point the medical notes contain no mention of confusion. In February, two bizarre episodes happened. In one, he made 40 cups of tea but could later give no reason for this other than he must have been dreaming of having guests to the house. In the other, during home dialysis he had cut the lines into the dialysis machine with a pair of scissors. He vaguely remembered freeing himself from the lines and retiring to bed.
The renal physicians apparently knew what was going on – this incident and concerns that he might be drinking more water than advised led them to think he was trying to commit suicide. They referred him to me. He didn’t seem remotely depressed and denied any thoughts of self-harm. But he described feeling that there were further episodes happening for which he had no recall. There was no evidence that he was psychotic or delirious.
In September, the man’s wife reported that he was having episodes when he was uncertain where he was or what he was supposed to be doing. He complained of feeling disorganized at these times.
He was later obliged to retire against his wishes on ill-health grounds. This made him very unhappy but when I interviewed him he did not appear to depressed or psychotic.
When trying to work out what was going on, we considered the possibilities of transient ischaemic attacks (mini-strokes) or some metabolic disturbance as possible triggers for these episodes. But physical examination was normal. There was no evidence of neurological abnormality. An electroencephalogram was normal. Routine blood tests were normal. Cognitive function testing showed no abnormality.
In November 2005, after his retirement, the patient was again referred to the liaison service complaining of flashbacks from his military experience after watching a war film. At this point, he complained that he was lacking direction and losing time – for example, when doing a crossword. But he presented as a man who took pride in his appearance and he was open and co-operative. There was no evidence of psychosis. He appeared to be adjusting to retirement. He scored within the normal range on the hospital anxiety and depression (HAD) scale. He acknowledged that some of his problems were due to retirement and loss of roles.
In January 2006, he had a further blow – he was being withdrawn from the kidney transplant list owing to the appearance of blood in his faeces. He was unhappy at this. Although his HAD depression score rose to 15, I stopped his sertraline in the hope that this would eliminate his rectal bleeding and re-open the possibility of a transplant.
In May he came back to my attention when he reported that he was completely unable to remember anything for a full day after his previous dialysis session. This worried him.
At this point the coin dropped for me. I raised the possibility of a statin-induced global amnesia. I gave him a series of vignettes from Duane Graveline’s Lipitor: The Thief of Memory to read. He reported a few days later that he could identify with these so much that he had already discontinued his statin. When reviewed 3 weeks later, he reported no further amnestic bouts and was euthymic.
We considered the possibility of a depressive disorder or anxiety disorder but rejected these as explanations for his amnestic episodes. We considered and screened for all other common conditions and ruled these out.
This man’s problems started on Crestor (rosuvastatin) and cleared when this was stopped. Over the following 9 months, he was under considerable physical and mental stress. His physical condition worsened. After transplant was conclusively ruled out, he was very dispirited. He died 9 months after the events above. But despite the difficulties of his situation, there was no further evidence of amnesia, strange behaviours or of depression.
When published this was a first report of transient global amnesia linked to Crestor – rosuvastatin. It is likely to be a general problem linked to statin intake. There are reports of transient global amnesia linked to Zocor simvastatin and Pravachol pravastatin. While this man’s difficulties emerged when Zocor was switched to Crestor, this switch effectively increased the dose of statin and hence the problem may have been a dose-related problem general to all statins rather than a specific problem linked to Crestor. The problem resolved with discontinuation of statin treatment.
Transient global amnesia was first described in the late 1950s. Episodes of global amnesia that are transient have since been described linked to epilepsy and migraine. Brain tumours, trauma or infections have been linked to a global amnesia that may be transient initially but these usually progress to a permanent amnesia. In addition to these disorders, a differential diagnosis must take hysteria, and the likelihood of a concomitant depressive disorder, into account.
More recently, diagnostic criteria have been proposed for transient global amnesia. The attacks should be witnessed by an observer, should be accompanied by clear-cut anterograde amnesia, should not be accompanied by clouding of consciousness or other evidence of cognitive disturbances, should not demonstrate focal neurological abnormalities, should show no evidence of epilepsy or head injury, and should resolve within 24 hours.
Our patient had a series of episodes, a number of which were witnessed by an observer. He had anterograde amnesia. His episodes lasted less than 24 hours. There was no evidence of epilepsy or head injury. There was no clouding of consciousness on either side of the episodes, but it is not clear whether there might have been clouding of consciousness in the course of episodes.
Although not originally linked to drug treatment, transient global amnesia has been linked to treatment with benzodiazepines and clioquinol. The first cases linked to statin use were reported to regulators in the 1990s, with a first published report in 2001. There have been very few published cases, but in 2003 Wagstaffe described 60 cases reported to regulatory authorities. These cases presented equally in men and women, with a mean age of 62 years, although this may be an artefact of the populations to whom statins are prescribed.
The case reported here maps on to these cases. It was broken open when we were able to show Duane Graveline’s descriptions of the problem in his book Lipitor: Thief of Memory to our patient. This is by far the best account of the problem there is.
Amnesia with benzodiazepines is different to a statin-related amnesia in that all users of benzodiazepines have very clear and easily demonstrated anterograde amnesia but there are as yet no consistent cognitive abnormalities linked to statin intake.
At present it remains unclear whether all cases of transient global amnesia associated with statins resolve fully on discontinuation of treatment. The cardiovascular difficulties for which statins are prescribed could conceivably lead to cognitive difficulties that only come to attention following a more dramatic episode, and which might complicate any assessment as to whether the index problem had resolved. There are no published cases of amnestic difficulties on treatment that clear on dechallenge and reappear on rechallenge. However, in unpublished reports submitted to the regulators, rechallenge appears to reproduce the amnesia.
The mechanisms by which such an effect may be produced remains obscure. But in the interim, the take home message seems to be these drugs can produce profound amnesia.
The contrast between this account and a published case report can be seen here. The published version gives the academic references missing here.
The primary difference between this and a published version seems to be that the publication format for a journal imposes a rigid style that is plain unhelpful and redundant. The journal also charges money for access to an article and so any good that might come out of the sufferings of a man like this are hidden.
The idea that publication in a journal makes for scientific acceptability is rather twentieth century. Medicine might be in better shape if it sought an outlet in the New York Times or Daily Telegraph rather than in the New England Journal of Medicine. The Times and Telegraph are more concerned about the integrity of their primary sources than NEJM is. In the process, we might save our newspapers and our trees.
July 27, 2013
Statin Medication History.
1993 begin Mevacor (20 mg) For high cholesterol. 3 years then memory problem.
1996 changed to Prevacol (20 mg). 2 years then more memory problems.
1998 changed to Lipitor (40 mg). 10 years then more memory problems.
August 1, 2009 stopped Statin medication; against doctor’s order.
I asked the doctor if I could stop the medication abruptly, and he told me yes. That evening I got on the Internet to check about stopping the Statin medication abruptly, and found one doctor who said to taper off the medication as there were a few people who stopped abruptly and after about two weeks they had strokes. Seems something happened to the blood platelets that caused the stroke.
While on the computer I decided to look up the side-effects of Statin medication. That was scary as many of those noted were already a problem for me. Let me say here that I had no pain so really did not know I was having a physical problem. I had the memory problem, trouble walking, from wonderful penmanship to not being able to write my name clearly, plus other problems.
About 2003-04 when pheasant hunting I was having a problem walking the rice fields, and when duck hunting had a problem walking the pond to get to the duck blind.in 2008 I had to stop bird hunting, and deer hunting because of my balance.
In 2008 I also had to stop fishing as I could not get up, and down, the creek and river banks.
2009 I stopped playing golf because of my balance.
Thought the above problems were related to Old Age until I checked the Statin side-effects on the Internet.
I have gone to many doctors with different disciplines for help, but only one (Neurologist) believed Statin medication had anything to do with my problem; another Neurologist did not.
The only relief I get is through Acupuncture With Electrical Stimulation. It is no cure as I only get relief for a few days where I can walk without using my cane; but I carry in case I need it.
I expect I would have never thought of Acupuncture for my problem, but when looking for different doctors I found a Holistic doctor in the phone book and he had an MD after his name. I made an appointment and found he only did acupuncture. I had a treatment and walked out of his office better than I had walked for some time.
I do not know where I am going from here as I do not have any aches, or pains. When laying down, or sitting I feel like I can tackle any project, but when I stand I cannot do anything. My legs do not do what my brain tells them to do. Fortunately when sitting in the car I can drive comfortably without any problem with my legs.
I had Trans. Global Amnesia on only 1 occasion. Lost my memory for approximately 48 hours. I had been stressed because of my husband’s and my sister’s ill health. However, I had been prescribed statins because of high cholesterol and angina. I had also been prescribed amatriptylene for depression. I did not feel “right”. It’s the closest description for my situation. The amnesia occurred while having a telephone conversation with my sister. My husband phoned our doctor who told him to take me to hospital. I had a CT scan. I have no memory of this but I know my family were distraught. I recovered and returned to work.
Since this occasion I have felt as if there is something missing. Not myself. I asked my doctor for testing for Alzhiemers. She didn’t think it necessary which comforted me. However the memory issues kept recurring until I finally managed to get a referral for formal testing. Tests were inconclusive but I has referred for CT scan. I had an meeting with the doctor and was expecting to be told I was fine. It appears I am not. There are “changes”. The doctor was wonderful and explained there is no cure but drugs are available to “slow the progress”. I have been referred for another more in depth examination. As yet, no appointment. I am completely floored. I need to know what is happening to me. I have stopped the statins. I did not tell my GP. I have not seen her. I know she will have been informed of the results of scan but she has not contacted me to discuss. Have no idea how I or my family will cope. So sad.
I had been taking statins for 10 years in my late 40’s to late 50’s. I was having trouble concentrating and my memory was really deficient. I had one short amnesia episode that lasted less than 30 seconds. When exiting my usual supermarket I didn’t have a clue where I was. It never even crossed my mind that it could have been the statins I was taking. I blamed it all on getting older. Until, while having a casual conversation with a friend, he told me that he was taken off statins because they were affecting his cognitive functions. I discontinued the statins to test his theory without asking permission from my physician. Lo and behold, within 2 weeks my memory and concentration improved by at least 80% to levels when I was in my 30’s. I discussed it with my doctor on my subsequent visit and he said that it could not be the statins because he had never heard or read anything like that before! That was in 2011 and I was on 10 mg Crestor once per day. He looked it up on his computer and saw that it occurred less than 1% of the time so he brushed it off as insignificant but he didn’t insist that I continue taking them, he offered to lower the dose instead and I conceded to try but even the lower dose affected me. He finally changed my prescription to Fenofibrate, which also affected me. Last time I saw him I told him in no uncertain terms that I will no longer take anything to lower my cholesterol and that I would rather live with the risk of dying younger (if in fact that risk is even real) than lose my mental faculties which to me are imperative in my daily life being a business woman with a lot of responsibilities. My cholesterol levels are normal, but because I have type 2 diabetes they want them to be lower than normal as a preventive measure. The brain needs cholesterol to function and there is no way I will ever again allow anyone to attempt to lower my cholesterol to minimal levels.
one of the odd things about this is that lots of doctors would feel the same way about taking statins themselves – they just don’t seem to apply the same rules to those they give them to
The worst thing about it all is that while I was on statins with reduced cognitive functions, not only was I trying to look after my business that I was running from home, I was also home caring for my mom who had Alzheimer’s. I had to think for myself, my mom and my business. I thought I was losing it, but never ever suspected the statins. What a relief to relive normally again and take charge of my life and my mom’s, not to mention the business, when I stopped taking them. I get very angry when I think about what I went through because of low cholesterol levels. I reported the whole thing to Health Canada (I am from Canada) and I was told to encourage anyone who has lived similar experiences to file a report with them. Not that I believe that much will be done about it, you can label me a cynic, but at least it will be on record from as many people as possible.
If you can get anyone you know to file a report with RxISK we will try and make something happen
Yet again a story of medical ignorance, arrogance and incompetence. The strange thing is that doctors are brainwashed by the pharmaceutical companies to expect certain results, and therefore are incapable of really listening to the patients’ reactions, insisting that they have nothing to do with the drug.
If you never have had certain symptoms, and they suddenly appear shortly after you start taking a new drug surely it is not rocket science that the two things are correlated!
I was prescribed an anti acid drug, which shortly after I started taking it made me feel dizzy and gave me a fainting feeling. I had never experienced these symptoms before in my life. The next day the whole packet landed in the bin, and those strange symptoms have never returned.
I then went to the Internet and researched more holistic means for this problem. God knows what the prescription would have done to my brain!
I had a severe loss of short term memory and general thinking issues with words at my recommended dosage of 20mg of Creator. The experience with Lipitor was the same.
To prove it was the drugs, I went off and back on the drugs 3 times. Each time short term memory was confounded on the drug. Memory clear worth a couple of days after stopping it. Creator was even dose related. Cutting to 10mg eased the effects, but was still observable. I could see the effect in people eyes as well as observe myself.
The memory impact was slow to build up which is why most people miss it and don’t connect the drugs to it.
I also see the effect in my wife, but she continues to use it.
For me it is a quality of life issue. I am accepting a shorter life that I can remember and be active in.