A record number of comments (over 300) were generated at pharmalot.com over an article written about the gunman from
Northern Illinois University, 27-year-old Stephen Kazmierczak, going on a shooting spree and the initial speculation that he may have been withdrawing from an SSRI (he was, Prozac).
During my residency days Selective Serotonin Reuptake Inhibitors (SSRIs) like fluoxetine (Prozac, Sarafem), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and sertraline (Zoloft), were pushed as being better than older drugs like imipramine, since they specifically acted on the serotonin transporter, and therefore didn’t have many of the side effects that were said to result from non-specific effects on many neurochemical systems, including dry mouth. Contrary to popular belief, however, the newer generations of antidepressants don’t work any better than the old ones, with the possible exception of the dual reuptake inhibitors.
The primary improvement of SSRIs over tricyclics is a questionable decrease in side effects, and the fact that you can’t kill yourself by taking an overdose of them. However, drop out rates are not a lot worse with the old drugs and the new drugs, suggesting that new side effects are just as bad as the old ones. In general the sexual dysfunction and jitteriness that come with the SSRIs can be just as bad as the sedation and dry mouth that come with the old ones. The conquering of the market by the SSRIs was mainly a triumph of marketing skills.
The SSRI medications have not been shown to work better than the older tricyclics. In fact, they actually have less efficacy than is commonly believed (DUAG 1990). The Danish Study Group found that the older tricyclic medication clomipramine worked better for severe depression than paroxetine, although it had more side effects. A review from 15 years ago showed that fluoxetine had only modest efficacy over placebo, with over 80% of the improvement accounted for by a placebo effect (Kirsch et al 2002). A more recent meta analysis from data submitted to the FDA also showed that 80% of the improvement with antidepressants come from the placebo response. When the data of all studies performed on venlafaxine (Effexor), fluoxetine (Prozac), and nefazodone (Serzone), was lumped together, there was only about a 2-point improvement on a 62 item scale (the 21 item Hamilton Depression Scale) above and beyond the placebo response. The response to this was that the effects of antidepressants are modest, even if real, and that it is not ethical to give placebo.
It was also pointed out that the efficacy of SSRIs is greater than other areas of medicine, like the use of statins. Others have argued that SSRIs may not be much better than placebo, but that the relapse rate is much higher on placebo. However, studies following patients who were treated with antidepressants did not show that they did better over the long haul, in fact they may have done worse, even accounting for baseline differences in symptom severity (Moncrieff and Kirsch 2005). There are no studies showing that in the long run people treated with antidepressants are better off. It might be questioned whether a 2 point increase on a 62 item scale that may not be sustainable is a clinically meaningful improvement.
Worry over the efficacy of SSRIs prompted a re-examination of the efficacy of antidepressants in general, and a look at how placebos may work just as well. A meta-analysis showed that there was a highly variable response to placebos, up to 50%, and that the placebo response rate in studies of depression seemed to be growing over the years. In addition, studies in private research firms seemed to be having higher placebo response rates than in universities, suggesting differences in populations, assessments, or inducements for participation.
A more troubling problem is the potential for suicidality associated with SSRIs. The FDA recently added a warning that SSRI antidepressants may increase the risk of suicidal thoughts or suicide. A recent meta-analysis of adults taking SSRIs showed no increase in suicidal thoughts or attempts, while there was a 57% increase in non fatal self harm with SSRIs that was of borderline statistical significance. Another meta-analysis did show a greater than two-fold increase in fatal and non-fatal suicide attempts in patients on SSRI versus placebo, and on SSRI compared to other non-medication treatments. The risk was 5.6 per 1000 patient years (the number of years people take the drug times the number of patients). In other words, if 100 people each took an SSRI for 10 years, about five of them would make a suicide attempt that they wouldn’t have done if they weren’t on suicide.
There was no difference, however, between SSRIs and the older tricyclic antidepressants, suggesting that all antidepressant medications may carry an increased risk of suicide. Questions about suicidal thinking with antidepressants have been around for years, and occurred with the tricyclics. Some doctors, including my father (who is a retired psychiatrist) offer the explanation that the increase in energy that antidepressants experience often gives the suicidal patient enough stamina to go through with the act.
Another disturbing trend that came from this analysis was the change in suicidal thoughts over time. There are 24.5 million visits for depression in the US per year, a 70% increase from 15 years ago. Sixty nine percent of these visits result in a prescription for an antidepressant. The analysis showed that the risk of suicidal thinking and suicide itself has been gradually increasing over the years. It is unclear if this is fueled by an increase in prescribing, primarily by primary care physicians, or other causes.
The latest group of antidepressants has dual reuptake inhibition for serotonin and norepinephrine (SNRIs), and includes venlafaxine (Effexor) and duloxetine (Cymbalta). In general, effexor and duloxetine have shown better treatment response for depression than SSRIs and tricyclics. One study looked at data from a number of randomized, placebo controlled trials of Effexor, tricyclic antidepressants and SSRIs for the treatment of depression. Treatment response was defined as a 50% reduction in symptoms of depression. Forty-four studies with 4033 patients were included. Overall, venlafaxine had a success rate of 74% that was statistically significantly better than SSRIs, which only had a 61% success rate, and tricyclics, which only had a 58% success rate. The difference in the efficacy of tricyclics and SSRIs was not statistically significant. However, it is worth noting that a larger number of patients dropped out of treatment while on tricyclics because of side effects. Other studies have shown better responses for venlafaxine and duloxetine than tricyclics and SSRIs. Venlafaxine has been associated with a dose dependent increase in blood pressure. Venlafaxine seems to carry the greatest risk of suicidality amongst all of the antidepressants, with a three fold increased risk of attempted or completed suicides.
DUAG (1990): Danish University Antidepressant Group: Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. Journal of Affective Disorders 18:289-299.
Kirsch I, Moore TJ, Scoboria A, Nicholls SS (2002): The Emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration., Prevention & Treatment, Vol 2005.
Moncrieff J, Kirsch I (2005): Efficacy of antidepressants in adults. British Medical Journal 331:155-159.
Additional citations for the studies reviewed in this post are here.
February 17, 2008.
Do Statins Make You Stupid??
If you have been reading this blog you might have come to the conclusion as I have that only stupid women
take statins to prevent heart attacks or death
and that only stupid men think that it will save their lives if they don't have a prior history of heart disease. But now
there is increasing attention to the fact that statins may also make you... well... stupid.
Some statins cross the blood-brain barrier (see below) and therefore potentially can affect brain function. They reduce
cholesterol concentrations and cholesterol is an essential component of cell membranes, including neurons in the brain.
There are a large number of individuals
reporting memory problems in reply to articles this week in the
WSJ, in which a doctor was quoted as saying "Lipitor makes women stupid," followed by an article in the
NY Times . In 2003 an
article cited 60 reported cases of memory impairment, most commonly with Zocor, less
with Lipitor and only one case with Pravachol. Since Zocor is the most lipophilic (meaning most likely to get into the
brain) and Pravachol is not lipophilic, this pattern is consistent with a relationship between statins and memory problems.
Half had the onset of memory problems within two months of starting statins.
Most (56%) patients improved when they went off the drug, and there
were four patients who had memory problems return when they went back on the drug.
Muldoon and colleagues writing in 2000 reported on 209
healthy adults treated with Mevacor (lovastatin) or placebo for cholesterol reduction. Mevacor treated patients
had significant reductions in attention and psychomotor speed compared to placebo treated patients.
These problems are the inevitable result of a push to give statins to people with normal cholesterol concentrations.
This is in my opinion a cause for concern. For one thing, we are introducing medications with potentially dangerous
side effects to people who do not have a disease. Secondly, cholesterol is a normal part of the body and is required
for a number of processes, like the construction of cell membranes. Very low cholesterol concentrations have been
linked to depression and suicide.
Statins also may increase the risk for depression. Cholesterol is the essential building block of neurotransmitters
and hormones, changes in which have been associated with the development of depression. This may explain why many
patients feel so much worse when their cholesterol is lowered. Statins increase the risk of a return of depression
in patients previously treated for depression; if you take a statin after being treated with an antidepressant,
your risk of having the depression come back is 61% compared to 40% if you didn’t take a statin (Steffens et al 2003).
Steffens DC, McQuoid DR, Krishnan KRR (2003): Cholesterol-lowering medication and relapse of depression. Psychopharmacology Bulletin 37:92-98.
A doctor developed such severe problems with memory that he wrote a book about his experiences called Lipitor Thief of Memory
As usual the medical establishment is rushing to say that there is no association between statins and memory problems. The medical
consultant to abcnews.com said he had to set the record straight and say that the "benefits outweigh the risks".
A doctor who said "Statins make women stupid" was said to have made "inflammatory" comments. "Inflammatory" to who? Pfizer's business plan?
February 11, 2008.
Effects of Yoga on Health
Americans are increasingly looking for alternatives to prescription medications to promote
health and prevent disease. I previously
wrote about the effects of Mindfulness Based Stress Reduction (MBSR)
on promoting mental health and reducing anxiety. What about other alternative approaches?
Yoga is a discipline derived from India combining mental and physical exercises that is increasingly
catching on in the U.S. Not really knowing how to describe it I looked up the handy
online dictionary for a definition of the word.
Yoga (noun); the word yoga derives from the Sanskrit, literally, yoking, from yunakti ("he yokes").
1. a Hindu theistic philosophy teaching the suppression of all activity of body, mind, and will in order that the self may realize its distinction from them and attain liberation
2: a system of exercises for attaining bodily or mental control and well-being
Assuming that people were practicing yoga to promote their physical and/or mental health as well as sense of well being,
I followed my tradition of relentless questioning, and asked, is there any evidence that this stuff actually works?
Studies comparing yoga to exercise such as swimming show that yoga reduces anger, depression, and fatigue to an equal degree
as swimming (and better than doing nothing) and in some cases yoga is better than swimming.
Controlled studies have shown that yoga is equally efficacious as exercise and better than doing nothing for reducing fatigue and promoting energy in patients with multiple sclerosis. Yoga has proven beneficial in promoting health in patients with asthma, diabetes,
breast cancer and epilepsy.
Yoga has also been shown to be useful in the treatment of major depression, with one study
showing a response rate of 67% in patients in yoga compared to 73% for patients treated for a month with an antidepressant drug. Other
studies showed yoga to be effective for reducing anxiety, although studies in this area were not
well controlled.
There is increasing evidence that interventions promoting mind-body relationships are a good alternative to prescription medications. So limber up and get those moves going!
February 8, 2008.
Dr. Jarvik Update: He Can't Prescribe or Row
I've always wondered why anyone would buy Lipitor from a doctor that made an artificial heart that usually
killed people within one year. But give credit to John Mack for outing that Dr. Jarvik didn't have prescribing priviledges,
and now we discover that he wasn't actually rowing the boat in his Lipitor commercials on TV.
We don't know much about Dr. Jarvik's medical history, but as I previously posted
("Zetia, Schmetia" and "A Tale of Two Deceptions"), if he doesn't have risk factors for heart disease or a history
of heart disease it is unlikely that he is deriving much benefit from his Lipitor, at least in terms of his health.
Let's Stop the Numbers Chasing Game
Editorial Note: American healthcare has gone nuts with the numbers chasing game. As I
posted previously on the numbers game related to aggressively getting LDL cholesterol levels down to very low levels, aggressive lowering of LDL
cholesterol is associated with an increased risk of cancer. And chasing the bone mineral density numbers is an equally useless game.
Now we have evidence that getting blood sugars down to very low levels can cause more harm than good. It is time to stop chasing numbers and only
use prescription medications when there is proven benefits that outweighs the risk of harm (i.e. treat/prevent the disease, not the numbers).
February 7, 2008.
Bisphosphonate Drugs for Osteoporosis Cause Bone Pain
Health care consumers are increasingly up in arms about side effects from drugs that were either
not emphasized or ignored when they received their prescription medications. Lately there
has been increasing heat related to bone, joint and muscle pain side effects with bisphosphonates (Fosamax, Actonel, Boniva), which has led to an FDA
warning on the issue. As I wrote previously ("Ladies, Don't Fall Into the BMD Rat Maze") these drugs are of limited benefit,
and chasing after a bone mineral density number won't necessarily prevent osteoporotic fracture. In addition,
these drugs can cause osteonecrosis of the jaw, or bone death, which is very difficult to treat.
February 6, 2008.
Intensive Blood Glucose Lowering with Medications Increases Death Rate in Type 2 Diabetics
Today the NHLBI announced that the Action to Control Cardiovascular Risk in Diabetes (ACCORD)
study would be stopped because of an increased risk of death in patients on intensive glucose lowering treatment regimens. 10,251 patients with
Type 2 diabetes were being treated with a range of medications for glucose control and were divided into intensive versus standard glucose
lowering groups. There were 257 deaths in the group receiving intensive treatment to lower HbA1C (a marker of elevated blood glucose levels) to below 6%
compared to 203 deaths in the standard treatment group (HbA1C 7-7.9%). Deaths included sudden death and cardiovascular causes. Reactions
from medical experts included "surprise" and "shock", and yet this should not have come as any surprise since the fact that glitazone medications used for
diabetes, including Avandia (rosiglitazone) and Actos (pioglitazone) carry a cardiovascular risk was previously known. For example, last year an article in the New England Journal of Medicine showed that Avandia (rosiglitazone) increased heart attack risk by 43%. These drugs also cause fluid retention which increases the risk of heart failur. For instance, in the A Diabetes Outcome Progression Trial (ADOPT) 4360 patients with poorly controlled Type-2 diabetes were randomly assigned to four years of treatment with rosiglitazone, metformin, or glyburide. Rosiglitazone caused more heart failure than glyburide, and was associated with more weight gain (+4.8 kg—convert to pounds, v -2.9 kg for metformin) and fluid build up or edema (probable cause of the heart failure). 22 rosiglitazone patients developed heart failure, compared to 19 with metformin and 9 with glyburide.
In the PROspective pioglitAzone Clinical Trial in macroVascular Events (PROactive) Study, 5238 patients with Type-2 diabetes and evidence of vascular disease were randomly assigned to treatment with pioglitazone or placebo to be taken with their typical treatment regimen. There was no signficant difference in the primary outcome of any vascular event; 281 patients on pioglitazone developed heart failure compared to 198 on placebo, a 42% increase which was highly statistically significant. Most people don't know that glitazones cause weight gain and actually
create new fat cells, making you more "fatty'. So in other words, they are promoting the thing that causes Type 2 diabetes in most people (i.e. weight gain),
and causing the thing that we are trying to prevent by treating diabetes (i.e. heart attacks and heart failure). Not a very good deal.
January 29, 2008.
Increased Influenza Resistance to Tamiflu
It was reported today that there has been an increase in influenza resistance to the drug Tamiflu (oseltamivir).
Although previously less that 1% of influenza viruses were resistant to Tamiflu, now as many as 13% of influenza viruses are resistant. As quote in The Star of Canada
"The European Centre for Disease Control has reported that laboratory analysis of 148 H1N1 flu viruses so far this season turned up 19 viruses with a mutation on the neuraminidase protein – the N in a flu virus's name – at position 274." All of these resistant strains were in the human influenza virus. The experts were quoted as saying that they were "surprised" that the virus could mutate to a form that is transmissable to humans and still be viable.
I hate to say that I told you so, but in a previous post "Bird Flu Drugs are for Bird Brains" , I pointed out that if bird flu mutated to have human to human transmition, that bird flu drugs probably wouldn't work anymore. But of course
that didn't stop the promotional machine from scaring the living daylights out of people and pumping up sales for Tamiflu, for which Don Rumsfeld made a million dollars. All I got for posting my freebee comments on the Huffington Post was a comment that I was a "snark". Had to look that one up. Means "snidely derisive". Oh and someone said "we really don't know what will happen if it mutates." Hmmph. OK enough snarkness for now.
January 17, 2008.
Delays and Suppression of Clinical Trial Study Results: A Tale of Two Deceptions
This has been an interesting week for medical news. First there was the announcement that the cholesterol lowering drug Vytorin (which combines Zetia (ezetimibe) with the statin Zocor (simvastatin)) does not prevent the development of atherosclerotic plaque better than Zocor alone. If anything Vytorin is worse for plaque than Zocor alone. And in spite of the fact that Vytorin reduces cholesterol to lower levels than Zocor, it isn’t better at preventing heart attacks and strokes. It didn't take long for a statement from the American Heart Association
to come sliding through the fax machine at the Emory Department of Cardiology stating that lowering cholesterol is good and that patients should not stop taking their medicines.
The obvious conflict of interest that AHA gets a million dollars a year from Merck and Schering-Plough was quickly pointed out... but denied all around. Now we have
daily full page ads in the NYT invoking us not to stop taking our Vytorin (I sing the ads in my head to the tune of the song by Journey "Don't stop believing, hang on to that feeling").
Scientists have known for years that LDL cholesterol reduction isn’t the only game in town when it comes to preventing heart attacks. Statins probably prevent heart attacks in other ways besides lowering cholesterol, and decreasing your cholesterol level doesn’t necessarily prevent a heart attack. But the cholesterol numbers game is great for marketing, especially when you can sell a drug like Vytorin to patients who didn’t get their cholesterol down with a statin alone. And when Vytorin costs over two dollars a pill and simvastatin costs less than a dollar. But what is most disturbing about this morality play is that the manufacturers, Merck and Schering-Plough, delayed publicizing the study results for almost two years. That was worth a couple of billion dollars of sales that they wouldn’t have gotten if doctors and patients knew how useless Vytorin was compared to the much cheaper generic statins.
This week in The New York Times, an article raised this issue and asked, is lowering cholesterol really the key to heart attack prevention? The article was written as if no one had ever considered the question before. And yet it was only last year Pfizer’s new drug, Torcetrapib, which lowers “bad” LDL cholesterol and raises “good” HDL cholesterol, was shown to actually increase the risk of fatal heart attacks. For years scientists in the cardiology field have known that cholesterol lowering is not the only mechanism by which statin drugs work to prevent heart attacks. They act on inflammatory pathways and by other means that are not fully understood. Why has this news been slow to disseminate to the public? Since half of Americans over age 35 have an LDL cholesterol that is in the elevated range, and since these drugs definitely lower LDL cholesterol, it is easier to sell them on that basis. In fact, Zetia got approved solely on the basis of its ability to get LDL levels down. The FDA didn’t require the manufacturer to prove that it did what we want it to do, that is prevent heart attacks.
And before we get too excited about generic simvastatin, consider how many people with multiple risk factors need to be treated for five years to save one from a heart attack. About 250. That means a risk of heart attack reduction of about 0.2%. And with the risk of muscle pain that doesn't go away right away ("That Statin is Killing My Tennis Game"). Put that stuff in your own damn drinking water.
Here is another example game of the numbers game run amuck: bone mineral density (BMD) testing ("Ladies, Don't Fall Into the BMD Rat Maze"). BMD testing is used to screen for osteoporosis, and drugs like Fosamax can certainly drive up BMD. The FDA approves drugs for osteoporosis based on their ability to increase bone mineral density (BMD), not based on their ability to do what we want, which is prevent fractures. Since half of women in their 70s meet criteria for osteoporosis, focusing on screening and treatment of BMD spurs drug sales. However, the increase in BMD as a result of most of these drugs is not necessarily in the part of the bone that matters. For example, one of the drugs the FDA approved, Miacalcin (calcitonin), has no positive effect on fractures.
The point is that the focus on the cholesterol and BMD number adds to the confusion of healthcare consumers and presents a distorted view of the safety and efficacy of medications. Marketing gone wild has led to a situation where half of Americans take prescription medications, and at 100,000 per year the number of deaths from prescription dwarfs those from street drugs.
Often the distortions associated with how well a drug works results from the fact that the clinical trial study data is never published. For example, analysis of data from studies of 12 antidepressant medications showed that data from 37 of 38 clinical trials that were viewed as having positive results by the FDA were published in medical journals. Out of 36 trials viewed by the FDA as negative, 22 were not published, and 11 were published in a way that made their outcome look positive (even though the FDA didn’t think it was). This means that if you look at the medical literature, you would think that 94% of the studies show that antidepressants work, when in fact only 51% were positive.
Some will argue that it is difficult to get studies published with negative results, or that people don’t get as excited about them. The implication is that negative studies are not as important as positive studies, but that simply isn’t true. We need all of the data related to drugs, not a selective sampling that presents a biases picture. And the fact is that you can always find a journal to publish negative results from large, important studies such as those reported on here. Holding back a negative study results creates a biased view of the efficacy of a drug, so that doctors, and thus the public, don’t have a good idea about how well it really works. Spinning the numbers, whether it’s the cholesterol or BMD numbers game, is not in the interest of healthcare consumers.
January 16, 2008.
ZETIA, SCHMETIA
Recently some unsettling news has come from the FDA about the risks of the cholesterol lowering medication Vytorin (a combination of Zetia (Ezetimibe) and the statin drug Zocor (simvastatin)). Data from the Enhance trial that was not previously revealed by the manufacturer, Merck/Schering-Plough, showed that the combination drug did not reduce atherosclerotic plaque any better than the generic statin drug, simvastatin, when given alone. In fact, if anything Vytorin seemed to make atherosclerotic plaque worse, although it had a greater effect on lowering cholesterol. Vytorin has also been associated with an alarming increase in risk of liver damage. In addition, the Zetia that is in Vytorin has never been shown to reduce the risk of heart attacks or strokes. And Vytorin, at $2.84 a pop, as well as Zetia ($2.63) costs a heck-of-a-lot more than simvastatin, which is less than a dollar per pill.
Doctors use cholesterol lowering drugs to get cholesterol down to normal levels. However just because a drug lowers cholesterol levels doesn’t mean it will do what patients care about most, that is save your life, or even reduce the risk of heart attacks and strokes.
The most commonly prescribed drugs to lower cholesterol, the statins, include Lipitor, Zocor, Crestor, Mevacor, and Pravachol. Statins lower LDL cholesterol by blocking an enzyme that churns out LDL cholesterol in the liver, called HMG CoEnzymeA reductase. Thirteen million prescriptions are written for statins every year. Ezetimibe (Zetia) is a drug that blocks absorption of LDL cholesterol by the small intestine, thus lowering LDL cholesterol levels in the blood. Zetia acts on cells lining the small intestine to interfere with their uptake of cholesterol.
If we followed the recommendations of the experts, cholesterol lowering drugs would be given to every American with an LDL of greater than 130 mg/dL over age 45. Since half of Americans over age 35 have an LDL greater than 130 that would mean that almost half of all Americans or 100 million people should, theoretically, be taking statins. Since a year of statins costs up to $3000, that would cost $300 billion a year. Comparing national guidelines for who should take a statin across different countries, the guidelines which called for the most liberal use of statins (you guessed it, the U.S.) which called for 25% of the population to be on statins, saved no more lives than the guidelines for one of the most restrictive countries, New Zealand, which would treat 13% of the population.
For healthy males without a history of heart disease and without risk factors for heart disease (smoking, hypertension, family history of heart disease, familial hypercholesterolemia, hypertension, obesity and diabetes), there isn’t any evidence that cholesterol lowering drugs are helpful in terms of preventing heart attacks and strokes. For men with risk factors, the majority of the studies show that they may prevent heart attacks but don’t decrease your risk of dying. Cholesterol lowering does not prevent heart attacks in women without heart disease or in men without heart disease who are over the age of 70.
And taking a statin won’t prevent you from having a heart attack or dying if you have heart disease. It only slightly lowers your risk, by about 0.2% per year.
The only study to show that statins reduce risk of death in patients without heart disease showed that although after 15 years men taking Pravachol had fewer deaths (106 versus 135 on placebo), there was a 51% increase in prostate cancer. Other studies have shown a slight increase in the risk of cancer, especially with the use of high dose statins to bring cholesterol down to very low levels. Statins can also cause liver damage, depression, memory problems, and joint pain. They can also cause damage to the muscle tissue which results in muscle pain. In rare cases this can lead to a breakdown of the muscle tissue which results in kidney failure. Zetia can headache, dizziness, diarrhea, muscle and joint pain, and more rarely jaundice, gall stones or inflammation of the pancreas.
Bottom line? The drugs you are taking to prevent heart disease may not be as useful as you think, and in some cases may be doing more harm than good. Let the buyer beware.
Remember that commercial where the graceful but aging woman is talking about
how she got shorter? And that if you had the same problem you should 'talk to your doctor'.
Well I don't recommend talking to your doctor for any reason unless you are really sick (and
not just think that you are sick or might have undetected disease). Why? Well first of all
most doctors are boring (yours truly included). Second of all, in spite of common beliefs
to the contrary amongst both doctors and their patients, there is no evidence that going to the
doctor if you aren't sick is good for your health. In fact, both the American Medical Association
(ever heard of them?) and the Canadian Medical Association recommend against the annual physical checkup for healthy people.
Now I can understand why doctors wouldn't mind charging people for the priviledge of sitting in their
waiting rooms for three hours, but why would you pay a hundred dollars to have someone poke needles
in your arm and fingers up your butt when it doesn't do you any good (stop that).
But what about my bone mineral density (BMD) test, you protest? What if I have hidden
osteoporosis and my leg snaps off while I am pirouhetting across the skating rink? Well
have no fear, my dears, your limbs won't snap off as soon as you think.
You see the most disabling of fractures occurs in the elderly, in the hipbone, specifically
the femoral neck, which is associated with considerable loss of mobility.
More commonly, fractures occur in the vertebral body (bones in your spine), which usually
are not associated with pain; they may cause a bowing of the back, and shortness.
Bone density, or how thick your bones are, is currently tested using a bone mineral density test (BMD).
Normal values for these tests are based on how far off the patient’s results are from those of
the average healthy young woman, using something called t scores.
I believe the logic of this measure is deeply flawed -- to judge older women by applying standards for young
women doesn’t make any sense. That’s like having a 70 year old run a 100 yard dash against a
20 year old, and then if he loses, saying that the older man has a disease. Bone density normally declines
with age, and therefore there is no reason to think that this is necessarily a cause for concern.
For example, if you are a woman who gets BMD testing and follows the WHO criteria, there is a 50%
chance you will be diagnosed with osteoporosis at the age of 72 (t score less than -2.5), and a good chance
your doctor will recommend medication treatment. Your risk of having osteopenia (t score less than -1.0),
for which your doctor may recommend medication to “prevent” osteoporosis, is 50% by age 52. In other words,
according to the guidelines, half of postmenopausal women
should be taking medication for osteoporosis. However, recommendations for
so many women to take bone medications don’t make any sense.
Osteoporosis is commonly treated with bisphosphonates like Fosamax.
Bone turnover is regulated by cells called osteoblasts and osteoclasts. While the osteoblasts are building
up bone in area, the osteoclasts are breaking down bone in another. This leads to a balance in normal bone. What the
bisphosphonates drugs do is turn off the osteoclasts, so that bone isn’t broken down, thereby slowing the loss of bone
density with aging. But they also turn off the osteoblasts, so that if there is a fracture, it won’t heal.
All of the studies have shown that bisphosphonates increase BMD and reduce the risk of
vertebral fracture in women with osteoporosis (t score of less than -2.5). But what is the significance of a vertebral
fracture? Vertebral fracture is merely defined as a reduction of the height of the vertebra by 20% on radiological tests
like MRI. To have a vertebral fracture defined in this way, you don’t have to have pain, change in posture, or anything at all
that would make you aware of any problem. In fact, most of the time the only person who knows you have a vertebral fracture
is your radiologist.
What about fractures that matter? Most of the studies, including the the
Alendronate Phase III Osteoporosis Treatment Study, the
Fracture Intervention Trial (FIT), The
FOSamax International Trial (FOSIT), and the
Vertebral Efficacy with Risedronate Therapy (VERT) study
collectively performed in thousands of women with osteoporosis based on BMD, did not show a reduction in hip fractures,
the kind of fracture most clearly associated with lasting disability. In terms of fractures in other parts of the body, referred to
collectively as nonvertebral fractures (in places like the clavicle or the wrist) the findings are more mixed, with differing findings
depending on whether there is a prior history of fractures and other factors.
The
Hip Intervention Program (HIP) Study assessed the effects of three years of risedronate or placebo
in 9331 women over age 70 with dramatic losses of bone mineral density (t score less than -4), with -2.5 being regular osteoporosis) or t score less than -3 with a risk factor for hip fracture, like propensity to fall. Overall 2.8% of women on risedronate suffered hip fracture versus 3.9% on placebo, a difference of 1.1% that although statistically significant was not very impressive. In the only study of men to date, bishphosphonates did not prevent painful vertebral fractures or nonvertebral fractures, including fractures of the hip.
And what about treatment beyond three years? The implication of the educational campaigns about osteoporosis is that this is a disease for which you need to be treated for the rest of your life. But is there evidence of added benefit of long-term treatment, or perhaps harm? The studies I reviewed above showed that after five years there is no benefit.
In other words after five years they seem to stop working. How could this be?
Again, bisphosphonates act by inhibiting osteoclasts, the cells that act to break down bone. So although they increase BMD for a few years, in the long run they decrease bone turnover. Animals treated with bisphosphonates have a decrease in bone turnover. Women on alendronate were found to take up to two years to heal after a fracture, and had markedly suppressed bone formation on biopsy. In the long run bisphosphonates may decrease the ability of bones to resist fracture, making bones more brittle. They also are not metabolized, meaning that they bisphosphonates you are taking now will be in your bones for life, resulting in a long term reduction in bone turnover.
This decrease in bone turnover underlies the scariest potential side effect of bisphosphonates: osteonecrosis. Osteonecrosis is a degeneration of the bone in the jaw that may require surgery. Osteonecrosis was seen in “Fossy Jaw” or “Phossy Jaw”, which developed in workers in 19th Century match making factories exposed to phosphorus. The phosphorus would get into the bone of the jaw, much like the bisphosphonates do, and stop bone turnover, leading to death of the bone tissue. The outcome was so painful and disfiguring that it sometimes led people to kill themselves.
Although most of the cases of osteonecrosis of the jaw have been reported in patients with bone metastases or myeloma treated with intravenous bisphosphonates, there are now emerging cases in patients who took the medication only for the “prevention of osteoporosis.” This shows there are those out there for whom there is little potential benefit and unfortunately much to lose in taking bisphosphonates.
A total of 15 cases of osteonecrosis have been reported with oral alendronate, one with oral risedronate and one with ibandronate, taken for the treatment of osteoporosis or Paget’s Disease (a disease of that makes bones weak and fragile).
January 7, 2008.
TOP TEN MEDICAL BREAKTHROUGHS OF 2007? VEH!
I almost threw away my Time magazine in disgust after reading about the
“Top 10 Medical Breakthroughs of 2007”. These shills couldn’t stop gushing about the wonderful advances our medical science has made this year. Well since 7/10 were directly related to a product created by the Medical Industrial Complex, and two will probably lead to a new and improved “test” that will also be marketed as a product, most of the gushing is going to be in the form of profits for their manufacturers. (BTW the other breakthrough involved chopping on your penis; not sure how to interpret that one). Before you all get giddy with excitement about the wonderful progress that has been made this year in the field of medical treatments, read on and consider an alternative analysis of this year’s accomplishments.
#1 “Circumcision Reduces Risk of HIV”. Well that certainly makes me want to run out and get my genitalia chopped on. How about you? The risk reduction, however, is only 51%. Using a condom pretty much prevents HIV, and whatever change in sensation it is associated with is temporary. Well on the plus side since it looks like the next step is to push it on African males (since they are too primitive to understand how to use condoms?) maybe that’ll make us more culturally sensitive to their customs of genitally circumcising women.
#2 “Test for Metastatic Breast Cancer”. A new test allows doctors to find out if there are cancerous cells in the lymph nodes adjacent to the breast right away rather than having to wait two days. It prevents you from having to come back for a second surgery, but since these surgeries are usually done under local anesthesia, coming back isn’t that big of a deal. And the cancer won’t spread in two days. More hype than hope for this one.
#3 “Human Vaccine Against Bird Flu”. As I wrote in my blog “Bird Flu Drugs are for Bird Brains,”
what our bird brain “public health officials” aren’t telling you is that if the bird flu mutates to be transmissible to humans, the vaccine probably won’t work anymore. Remember the bubonic plague? Now that was a medical news story that the media could really sink their teeth into. Hmmm. Seems like they are running out of topics these days.
#4 “Help for Dieters: Alli”. Now this one was my favorite. Help for dieters? Geez. This is just a repackaging of the prescription diet pill Orlistat for over the counter use, a drug which blocks fat absorption and may lead to vitamin deficiency, embarrassing flatulence, or even more embarrassing public losses of bowel control. Here is Gastroenterology 101. The mouth is connected to the stomach and the bowels by means of a tube called the esophagus. What you put in your mouth ends up in your bowels. So if you want to absorb less fat in your bowels, put less in your mouth. BTW no diet pills have been shown to lead to lasting decreases in weight which persist after you stop taking them.
#5 “New Diabetes Genes”. Four new genes were discovered which brought to 10 the number of genes that have been associated with risk for the
development of diabetes. Time went on to croon “Eventually, these discoveries will aid experts in pinpointing those at greatest risk for developing type 2
diabetes.” Well let me tell you something, Mr. Medical Reporter Sir. I’ve got a lot better way to predict who is going to develop diabetes: Sit outside a
McDonald’s and see who is scarfing down super sized meals there every day, cuz people who eat fast food a couple of times a week or more double their risk
of diabetes. And that is a lot more significant than that gene they found.
#6 “No More Periods”. Thanks to a new pill (Lybrel), a birth control pill that gets rid of those messy things entirely. I guess this one comes up
#6 cuz it has so many competitors, like physical (rather than merely pharmaceutical) genital mutilation (#1). Why don’t they just take the reproductive organs out
of women at birth, and let the whole reproductive process take place in a more scientific environment? Like in Brave New World you could do it free of messy
secretions, or even physical contact. Do the ladies want to remove those menstrual messies for themselves or their beaus? Tip to the ladies
out there, variety is the spice of life. BTW most pills (except for the progesterone only ones) eliminate ovulation, which can interfere
with that sexual attractiveness thing. To wit, a recent study showed that strippers on the pill make less money.
#7 “Relief from Fibromyalgia: Lyrica”. What a wonderful ad for Pfizer. Reading our Time shill you would think that this is the one and only
cure for this debilitating disease that affects so many Americans. However the study
comparing Lyrica to a placebo for fibromyalgia found that about half of the women taking Lyrica dropped out of the study, usually because they had
side effects, a major problem with the drug, or it wasn’t working. In those who finished the study, there was a 10% or 20% reduction in pain symptoms.
Not better than other drugs tested for this disease. No big medical breakthrough here. They just happened to be the first to get FDA approval. Cha-ching. Thanks FDA.
#8 “Early Stage Test for Lung Cancer”. The new LC Detect system is a blood test that permits early detection of lung cancer.
I’m not doing jumping jacks over this test yet cuz they haven’t actually yet shown that it saves lives, and if they do show it saves lives the
effects won’t be that great. You see in many cases once the cancer has developed and spread to the blood stream it is too late anyway. I heard
about this great book called The Easy Way to Stop Smoking. I think we should do a clinical trial to compare it to the blood test. I predict that
it will be found to be cheaper and more effective than the blood test at saving lives.
#9 “New Source for Stem Cells” Amniotic Fluid Derived Stem Cells (AFS) are seen as “farther along” in development than embryonic
stem cells and can be conveniently collected from pregnant women. They are less susceptible to criticism from evangelicals and more likely to lead to research in the US which has been blocked by mutton-headed biblical literalists who want to base our scientific agenda on a document written several thousand years ago by febrile Jews living in the desert (Or so they say. Come to think about it, don’t remember any mention of stem cells in the holy book). Hey there, Sam Brownback and Mike Huckabee, if you are listening, I’ve got an idea. Why don’t you all lead a raid on in vitro fertility clinics and save some of those embryos that were gonna get flushed down the toilet (and which you have so astutely saved from the barbaric onslaught of medical researchers). You can put them in test tubes and raise them to mature humans who can repopulate the Republican Party. I think that is about the only hope you have for the future.
#10 “Benefits of Vitamin D” The article says that a “slew of studies in 2007” showed that Vitamin D not only promotes bone strength, but prevents
multiple sclerosis (MS), diabetes, and cancer. Well Vitamin D may affect a measurement of bone strength, but doesn’t prevent clinically significant bone fractures
(like hip fracture) related to osteoporosis. MS? This was based on the Nurses Health Study
where 187,563 women were followed for 20 years. They found a 33% reduction in MS in women taking supplements compared to those who didn’t.
However since only 173 women developed MS, that means that only about 10 or 15 women were “saved” from MS, in other words about 0.03% of women.
This is one of the medical breakthroughs of the year? Geez. And I don’t want to take a supplement for 20 years for such a questionable benefit, do you?
And since those women who took supplements also probably did other things that were good for their health, it isn’t clear if Vitamin D does anything at
all. Cancer? Based on a single study
where a total of 50 women got cancer; that means that about 5 women were saved from cancer with Vitamin D supplements
Even the experts say that this is a small study and the results are premature. Diabetes? Maybe if you have a Vitamin D deficiency, which is unlikely in the current environment. I am getting depressed going on with this…
Bottom line? Take a walk in the winter sun (Vitamin D), use a love glove, don’t worry about getting messy with your man, eat your fruits and vegetables and cook your own meals. And stop reading that medical miracle crap in the magazines.
