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HEALTH AND STRESS
The Newsletter of
The American Institute of Stress
May
2007
MORE ON FAKE DRUGS FOR
FAKE DISEASES & FDA FRAUD
KEYWORDS: Havidol, DSACDAD, indolebant, MoDeD, Oblomov, Sanatogen, Kräftigungsmittel, Zelnorm, restless
legs syndrome, Requip, ADHD, Mirapex, compulsive gambling, Permax, PEARLS study, Dostinex, valvular disease
As emphasized in a previous Newsletter, pharmaceutical companies have been very successful
in converting healthy people into patients by fabricating new diseases and exaggerating the
seriousness of trivial complaints. This has been achieved largely through TV ads that can be
so skillful at persuading viewers that there is cause for alarm, that even spoofs created by
amateurs have been stunningly successful. An Australian artist, Justine Cooper, created a
marketing campaign for a non-existent drug called Havidol (as in Have it All) for Dysphoric
Social Attention Consumption Deficit Anxiety Disorder (DSACDAD), which she also invented.
Her mock television, print and billboard advertisement displays during a multi-media exhibit
at a posh Manhattan gallery were so convincing, that few realized they were fake.
However, Havidol really took off on the Internet. In the first few days after the web site
went up 3 months ago, www.havidol.com had 5,000 hits. It now has had close to 500,000
visitors. PHARMED, the drug's fictitious manufacturer, claims that more than 50% of people
over the age of 18 may have various degrees of DSACDAD and that Havidol (slogan: "when
more is not enough") is the "first and only" treatment. Havidol even has a generic name
(avafynetime HCL) but is currently only available in a gold 20-mg. tablet or suppository.
Patients don't have to stop drinking or taking sedatives, since, as indicated in the following
Safety Information, if you do, Havidol is not for you.
"IMPORTANT SAFETY INFORMATION Problems can be avoided if you take HAVIDOL
only when you are able to immediately benefit from its effects. To fully benefit from
HAVIDOL patients are encouraged to engage in activities requiring exceptional mental,
motor, and consumptive coordination. HAVIDOL is not for you if you have abruptly stopped
using alcohol or sedatives. Havidol should be taken indefinitely. Side effects may include
mood changes, muscle strain, extraordinary thinking, dermal gloss, impulsivity induced
consumption, excessive salivation, hair growth,
markedly delayed sexual climax, inter-species
ALSO INCLUDED IN THIS ISSUE
communication, taste perversion, terminal smile,
• A Follow-Up On The Epidemic Of New
and oral inflammation. Very rarely users may
Diagnoses That Are Also Deceptions
experience a need to change physicians. Talk to
your doctor about HAVIDOL."
May 2007
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Page 2
So how can you find out if you have Dysphoric Social Attention Consumption Deficit Anxiety
Disorder (DSACDAD) and how serious your problem might be? Simply by taking the free
"Zing Self Assessment Quiz" and answering "Not often, Sometimes, Often or All the time" to
the following fifteen questions:
1. Multitasking makes me feel powerful
2. I feel empty after a full day of shopping
3. I am impatient if I feel I am not my best
4. I don't feel as young as I used to be
5. I constantly feel I need to improve myself
6. I care more about others than myself
7. What used to make me happy no longer does
8. I enjoy new things more than used ones
9. I measure my happiness by my achievements and possessions
10.Life seems better when I have more than others
11.I enjoy my life more when someone else is watching
12.I don't like feeling like a wallflower
13.People look at me with envy
14.I stress for success
15.I like to feel special
The test is then automatically scored and the results are reported as follows'
Z I N G S E L F A S S E S S M E N T R E S U LT S
"If your score falls between 40-60 you should see your doctor immediately.
If your score is between 30-40 you may be on the brink of succumbing to
DSACDAD. Be aware of this possibility and be prepared by discussing your
options with your doctor.
If your score falls between 15-30 take a moment to check in with yourself.
Determine if you are answering as truthfully as possible. It's okay to need help.
And thankfully help is available."
The site has a store for various gifts, including a T- Shirt with a logo and a white ultrasuede
jacket with avafynetyme HCl's chemical composition hand silk screened in metallic gold.
There is also a 24ct gold plated stainless steel Havidol tablet resting on an ultrasuede pillow
with a similar metallic gold hand silk screen, as shown below next to a photo of a typical
DSACDAD sufferer.
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The owner of the gallery where Havidol made its debut indicated that it did not attract just the
"artsy" crowd but that doctors and medical students had been asking for more information.
As he told one reporter, "The thing that amazes me is that it has been folded into real Web
sites for panic and anxiety disorder. It's been folded into a Web site for depression and into
hundreds of art blogs."
However, Havidol and DSACDAD are not the only new manufactured maladies with phony
pharmaceuticals that people have fallen for. The April 1, 2006 issue of the respected British
Medical Journal featured an article entitled "Scientists find new disease: motivational
deficiency disorder." It began as follows:
Extreme laziness may have a medical basis, say a group of high profile Australian
scientists, describing a new condition called motivational deficiency disorder
(MoDeD). The condition is claimed to affect up to one in five Australians and is
characterised by overwhelming and debilitating apathy. Neuroscientists at the
University of Newcastle in Australia say that in severe cases motivational
deficiency disorder can be fatal, because the condition reduces the
motivation to breathe.
Neurologist Leth Argos is part of the team that has identified the disorder, which
can be diagnosed using a combination of positron emission tomography and low
scores on a motivation rating scale, previously validated in elite athletes. "This
disorder is poorly understood," Professor Argos told the BMJ.
"It is
underdiagnosed and undertreated."
Professor Argos is an adviser to a small Australian biotechnology company,
Healthtec, which is currently concluding phase II trials of indolebant, a
cannabinoid CB1 receptor antagonist. Although still unpublished, the preliminary
results from the company's phase II studies are promising, according to Professor
Argos: "Indolebant is effective and well tolerated. One young man who could not
leave his sofa is now working as an investment adviser in Sydney."
Professor David Henry, a clinical
pharmacologist at the University of
Newcastle and long time critic of
pharmaceutical
marketing
strategies, says that although he
appreciates that some people with
severe
motivational
deficiency
disorder may need treatment, he is
concerned that the prevalence
estimates of one in five are inflated
and that ordinary laziness is being
medicalised. "Indolebant may bring
some relief to those with a
debilitating form of MoDeD, but
common laziness is not a disease.
People have an absolute right to
just sit there." (BMJ 2006;332:745)
People with motivational deficiency
disorder are more than couch
potatoes; they lack a desire to
feel or do just about anything.
The article went on to state that a study of the economic impacts of motivational deficiency
disorder could be costing the Australian economy the equivalent of $1.7 billion U.S./year in
lost productivity and that Professor Henry was organizing a conference at Newcastle
University to discuss what he referred to as "disease mongering." The conference was held
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two weeks later and the audience learned that the enthusiasm with which news outlets had
uncritically reported the mock motivational deficit disorder and the drug indolebant had
surprised their creators. As Dr. Henry noted, "We said 20 per cent of the population have it,
and about half of these people need treatment. And we just sent that message out, and we
took it through an authoritative source, in this case the British Medical Journal, and people
really believed it, and journalists believed it, even though we put in a lot of clues that it was
an April 1st joke." . . . nevertheless, when I Googled the name of the drug this morning,
(April 11) and this drug doesn't exist, there were over 15,000 sites." The media coverage
showed, "that it is relatively easy to get out the concept of a disease that doesn’t exist and a
treatment that doesn’t exist". The reason is, "that people are looking for solutions that we all
have characteristics of and are not very happy about. I have lots of them. But once they're
turn into disorders rather than characteristics, then you can sell products."
This was vividly illustrated in a video interview with the neurologist, Professor Leth Argos, of
Hypnos Torpor Medical School, who described the disease. "In its mild form, persons can't
get off the beach," but in more severe cases, they are "unmotivated to breath, and die." He
was exuberant about the success of the early clinical trials and told how a patient's wife, in
tears of joy, telephoned him: "After using indolebant her husband had mowed the lawn,
repaired the gutter, and paid an electricity bill-all in one week." Dr. Argos defended his
financial links to the mythical manufacturer HealthTech by explaining that he was convinced
that the company was solely interested in improving the health of patients. The video also
featured Roy Moynihan, who wrote the BMJ spoof, as a typical MoDeD sufferer. He
complained that at first, he simply had difficulty getting off the beach or taking care
of his garden but eventually he lost his job and that, "All my life people have called
me lazy.
But now I know I was sick."
Be sure to click on
www.youtube.com/watch?v=RoppJOtRLe4 to see just how realistic and convincing this
presentation is. Professor Henry, explained that, "when it comes to health, people suspend
the skepticism they use in other areas of their life" and become much more gullible.
The three-day conference also featured discussions of relevant topics that illustrated this.
Professor David Healy, from Cardiff University’s Department of Psychological Medicine, told
the audience that "it is easy to sell the good kind of message about pills, but it is awfully hard
to say there may be risks with them". He disputed the claims of drug industry funded
patients' groups that "people who use 'mood stabiliser' drugs are better off than those who
don't." As noted in prior Newsletters, Dr. Healy was one of the first physicians to call
attention to the suicidal effects of Prozac and other SSRI antidepressants, especially in
children.
Other examples of disease mongering included discussions on female sexual
dysfunction, selling bipolar disorder, restless legs syndrome, drugs looking for a disease and
how regulatory authorities and pharmaceutical manufacturers conspire to deceive the public.
See www.diseasemongering.org for more information on this groundbreaking event as well as
http://collections.plos.org/plosmedicine/diseasemongering-2006.php for papers subsequently
published in PLoS Medicine, a superb peer reviewed publication.
The British Medical Journal posted a number of e-mail replies to the April 1 article on their
Rapid Response column that revealed their readers were not as naïve or as easily duped as
the media (www.bmj.com/cgi/eletters/332/7544/745-a#130892) such as:
This is an excellent April Fool's Day article. However, as a constant sufferer from
MoDeD it took me a full 24 hours to type these few words.
This is an excellent joke! I have a friend who describes his religion as "apathist"
(creed: "We can't be bothered to work out if we are atheists or agnostics.") But,
I do just worry that someone might take this seriously, after all many human
traits have become medicalised as "illnesses" in the past twenty years, and in
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some cases the drugs to treat these conditions got invented before the illnesses
were patented: we are now in the land of Victor Borge's old joke "My father
invented a drug for which there was no illness, but unfortunately, my
mother died of the side effects."
As a sufferer of MoDeD, I felt compelled to write about your article. Then I
decided, why bother? But I finally roused myself to take issue with the estimates
of the economic costs of the disorder. This ignores the fact that MoDeD sufferers
are responsible for an estimated 35% of consumption of snack foods, 40% of
viewing of all reality TV shows, and 45% of all purchases of popular music. In
addition, MoDeD sufferers produce 35% fewer green-house gasses due to their
tendencies to stay at home. A more comprehensive analysis of the full economic
impact of MoDeD should be done, preferably by someone other than me.
We actually identified this disease several years ago, but couldn't be bothered
following it up.
The publication date was of course April 1st.
have re-discovered Oblomov.
It sounds as though the authors
I had no clue as to what "Oblomov" was but a little research revealed that Oblomov,
published in 1858, is the best known book by the Russian writer Ivan Goncharov, whom I
had also never heard of.
Oblomov, the central character, was a young, generous
nobleman who was incapable of making important decisions or undertaking any significant
actions. Throughout the novel he rarely leaves his room and actually failed to leave his
bed for the first 150 pages. The book was considered a satire of Russian nobility whose
social and economic functions were increasingly being criticized in mid-nineteenth century
Russia. The novel was so popular that Oblomov subsequently became a Russian word
(o) to describe someone with personality traits of sloth or inertia similar to the
novel's main character.
Another response that required some research was the following:
Moynihan's article is the apotheosis of arrogance in purporting to have
discovered a new disease - Motivational deficiency disorder.
Not only the
syndrome but treatment strategies for its management are far from new. The
earliest "modern" intervention I can trace (within the standard diurnal envelope and apologies for the German) is of the use of Sanatogen by the Imperial
Kreigsmarine during the First World War. For much of the war the capital ships
of the German Navy were confined to bases on the North Sea coast, only going
to sea twice - once at the Battle of Jutland (1916) and finally to surrender to the
British Fleet.
Enforced confinement in limited space with long periods of inactivity coupled with
the need to move to a battle footing at short notice created major physiopsychological problems, which were said to exercise the minds of senior naval
personnel including Tirpitz, Scheer and Von Hipper. In consultation with the
extensive German chemical industry the idea of amino acid supplementation to
improve energy levels among the sailors was tried - not dissimilar to the use of L
tryptophan in depressive disorder, promoted in the 1980's in the U.K.
Sanatogen, a white powder largely consisting of casein but with other protein
products to be mixed with milk was widely promoted. A proprietary medicine - it
was widely advertised for the use of German sailors as a "nerve tonic" SANATOGEN FUR ALLES KRAFTSGUNSMITTEL!
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Perhaps Professor Leth Argos (Latinesque for lethargy) and colleagues should
have done a somewhat more historically based literature search. I suspect they
just couldn't be bothered.
I was suspicious that this might be a spoof but some more research revealed that there was
indeed such a tonic that was widely advertised 90 years ago that could be purchased as a
dietary supplement or in a wine, as illustrated below:
Kräftigungsmittel!
Kräftigungsmittel apparently means "strengthening center" in German. I also learned that the
same Sanatogen wine is currently "Britain's most popular Tonic Wine". Bayer Healthcare still
sells the Sanatogen protein supplement as well as a new line of Sanatogen® vitamin and
mineral supplements for different age groups in the U.K.
A Follow-Up On The Epidemic Of New Diagnoses That Are Also Deceptions
Phony diseases such as the two fake diagnoses described above are much easier to detect
than others manufactured by pharmaceutical companies and approved by the FDA. As noted
in recent Newsletters, exaggerating the seriousness of trivial complaints has become
increasingly common in an effort to create new diseases to increase sales of drugs previously
approved for other conditions. Many feel that collections of complaints, previously referred to
as syndromes, that have now been converted into diseases due to political and public
pressures, have also contributed to "What’s Making Us Sick Is an Epidemic of
Diagnoses". That was the title of an article by Dartmouth and Veterans Administration
researchers that appeared in the New York Times earlier this year. It went on to state, "For
most Americans, the biggest health threat is not avian flu, West Nile or mad cow disease. It's
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our health-care system. More and more of us are being drawn into the system not because of
an epidemic of disease, but because of an epidemic of diagnoses." They describe the
"medicalization of everyday life, "wherein "everyday experiences like insomnia, sadness,
twitchy legs and impaired sex drive now become diagnoses like sleep disorder,
depression, restless leg syndrome and sexual dysfunction. Perhaps most worrisome is
the medicalization of childhood. If children cough after exercising, they have asthma; if they
have trouble reading, they are dyslexic; if they are unhappy, they are depressed; and if they
alternate between unhappiness and liveliness, they have bipolar disorder. While these
diagnoses may benefit a few with severe symptoms, one has to wonder about the effect on
the many whose symptoms are mild, intermittent or transient."
They also addressed the increasing tendency to lower the diagnostic criteria for defining
different diseases. "Thresholds for diagnosing diabetes, hypertension, osteoporosis and
obesity have all fallen in the last few years. The criterion for normal cholesterol has dropped
multiple times. With these changes, disease can now be diagnosed in more than half
the population." Their suggestion was that, "Perhaps someone should start monitoring a
new health metric: the proportion of the population not requiring medical care. And the
National Institutes of Health could propose a new goal for medical researchers: reduce
the need for medical services, not increase it."
In many instances, this unwarranted rush to prescribe what are really off-label uses of
existing drugs has had disastrous results. As noted in a past Newsletter, Novartis's Zelnorm
was approved by the FDA in 2002 for the treatment of irritable bowel syndrome. The IBS
diagnosis requires a year's history of at least 12 weeks of pain or abdominal discomfort that is
relieved by defecation or is associated with a change in stool frequency or form. Symptoms
are relatively mild, intermittent and not disabling in well over 90% of patients who require no
treatment or get relief with over the counter medications. Others with similar gastrointestinal
complaints like "spastic colon", chronic constipation, abdominal cramps, and "mucous colitis"
are not infrequently treated for IBS and many patients take it for much longer than the
recommended 10-12 week limit. Zelnorm was only 5 to 10 percent better than placebo in
clinical trials and even this minimal benefit faded away after four weeks. It was specifically
approved for the short-term treatment of IBS only in women whose predominant
complaint was constipation. However, the promotional campaign with bloated bellies and
magic markers showing the "ABC's" of IBS (Abdominal Pain, Bloating, Constipation) was so
convincing to anyone with any of these symptoms that sales skyrocketed to $10 billion in less
than two years. Advertisements failed to emphasize that Zelnorm was contraindicated in
women with a history of frequent or severe diarrhea (which is what most IBS
patients suffer from) as well as children and had not been shown to be safe or effective in
men. This was obviously omitted in the "ABC'" advertisements. As a result, the FDA ordered
significant changes to be made in Zelnorm's warning label because of reports of ischemic
colitis that resulted in four deaths and required hospitalization in fourteen patients. There
were also 21 reports of diarrhea so severe that it caused low blood pressure and fainting and
16 had to be hospitalized. Since over 90% of adverse drug reactions are never reported,
these figures were undoubtedly low.
As a follow-up, Novartis was forced to withdraw Zelnorm from the market last month after
complaints that it was associated with an increased risk of heart attack, stroke and worsening
of anginal chest pain. A retrospective analysis of data from 29 clinical trials of Zelnorm
requested by the FDA confirmed a statistically significant increase in the incidence of
cardiovascular ischemic events such as heart attack, stroke and unstable angina in patients
who received the drug, compared to patients who took placebo. These serious complications
occurred in thirteen of 11,614 patients treated with Zelnorm compared to only one in 7031
patients who received a placebo. Despite the negative publicity and sterner label warnings
that were mandated, 2006 sales had rebounded to close to $500 million and analysts had
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forecast sales of more than $1 billion for this year. This is not the first time the FDA has been
overly hasty in approving an irritable bowel syndrome drug. GlaxoSmithKline's Lotronex was
approved in February 2000 but had to be withdrawn only nine months later because of
serious, life-threatening gastrointestinal side effects. In an amazing reversal, the agency
again approved Lotronex in 2002 as part of a drug company sponsored educational program
that would restrict its use only in women with IBS who suffered from severe and persistent
diarrhea that failed to respond to any other treatment. It seems very likely that the FDA will
also re approve Zelnorm with certain limitations despite the fact that they will be impossible
to enforce since they are based on whatever the patient claims.
As also reported in the same Newsletter, Restless Legs Syndrome (RLS), is another disorder
few people had ever heard of. It had originally been described in 1683 by Thomas Willis, an
English physician, who wrote, "Wherefore to some, when being in bed they betake themselves
to sleep, presently in the arms and legs, leaping and contractions of the tendons and so great
a restlessness and tossing of the members ensure, that the diseased are no more able to
sleep, than if they were in the place of the greatest torture!" The condition attracted very
little attention over the next 250 years until 1945, when Karl Ekborn, a Swedish neurologist,
described a disorder characterized by sensory symptoms and motor disturbances in the limbs,
mainly during rest. It was known as Restless Leg or Ekborn's Syndrome and was considered
to be relatively rare, except in patients with Parkinson's disease. As a result, not much was
heard about it until GlaxoSmithKline launched a huge publicity blitz in 2003 describing the
benefits of Requip. This is a drug that had been approved in 1997 for Parkinson's disease that
few doctors were aware of and had not been selling well until numerous advertisements
claimed "New survey reveals common yet under recognized disorder — restless legs
syndrome — is keeping Americans awake at night" and" This is the most common disorder
your doctor has never heard of", and that "many people can suffer in silence for years before
it is recognized". It also suggested that 10-12 million people were affected. People were
referred to the not-for-profit Restless Legs Foundation where they were encouraged to ask
their doctor whether restless legs might explain problems such as insomnia, feelings of
fatigue, depression and attention deficit disorder in children. However, patients were never
informed that the "nonprofit" Foundation was entirely funded and controlled by
GlaxoSmithKline, which provided an initial grant of close to $500,000.
Glaxo began running its multimillion dollar blockbuster TV ads between September 2004 and
November of 2005 to raise awareness of RLS and also promoted the disorder to doctors in
medical journal articles and ads. Although many physicians had already been prescribing
Requip for treating restless leg symptoms, it was not approved for this indication until May
2005, when the FDA announced that "Restless Legs Syndrome is a condition that affects
about ten percent of the population" based on Glaxo data. The media, including the New York
Times, also repeatedly cited this 10% figure even though this came from one study that used
a single question to identify restless legs syndrome rather than the following four standard
criteria:
1. An urge to move the legs due to an unpleasant feeling in the legs.
2. Onset or worsening of symptoms when at rest or not moving around
frequently.
3. Partial or complete relief by movement (e.g., walking) for as long as the
movement continues.
4. Symptoms that occur primarily at night and that can interfere with sleep
or rest.
Few patients receiving Requip satisfied all these criteria and in many instances, avoiding
alcohol, smoking and caffeine and a little massage was all that was needed to get relief. In
addition, as Woloshin and Schwartz emphasized at the conference on disease mongering,
"The less stringent definition inflates the estimate because people with other causes of leg
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symptoms (e.g., leg cramps or diabetic neuropathy) are counted incorrectly as having the
syndrome. They noted that a June 2005 study of over 16,000 adults found that only
7% of respondents reported all four diagnostic criteria of any frequency, 5% said
they occurred on a weekly basis while 2.7% said they experienced the symptoms "at least 2
times per week and were reported as moderately or severely distressing." However, they
believe that even the 2.7% figure of those with restless leg symptoms is exaggerated due to
the sampling methodology, since there was a phenomenal 98% response rate to the study's
survey. As they explained, "Most likely, the authors meant that 98% of individuals who
agreed to participate completed the survey. But respondents agreeing to participate in a
restless legs study are more likely to have leg-related symptoms than nonrespondents." A
company-sponsored article subsequently reported that almost 24% of patients from
a rural primary care practice in Idaho had all the symptoms of RLS during a 1-year
period. The 1% incidence in Japan, where there are no RLS Glaxo ads, seems much more
realistic and accurate.
Others were also skeptical. A UK industry watchdog reprimanded GlaxoSmithKline last year
for promoting an unlicensed drug "to treat the disputed condition." Disputed, because many
doctors claimed the condition has been concocted or at least exaggerated to help sell drugs,
according to the UK's Sunday Times. It was unlicensed since Requip had not yet been
approved for restless legs in the UK. A similar story appeared in the Wall Street Journal
several months ago under the title, "How Glaxo Marketed a Malady to Sell a Drug." After
Requip was approved, the company sent specialists to discuss the condition with general
practitioners, and sponsored so many seminars and continuing education programs in fancy
resort locations that even some doctors accused Glaxo of disease mongering. Requip was
featured in a Super Bowl commercial and the overall multimillion dollar promotional blitz paid
off handsomely. Sales more than quadrupled following approval and reached close to $500
million in 2006.
Glaxo's strategy was very clever. Although a doctor is free to use an approved drug for any
condition where it might provide benefits, manufacturers are forbidden to promote its off-label
use to physicians. For example, Warner Lambert promoted Neurontin for patients with pain,
ADHD (Attention Deficit Hyperactivity Disorder), restless leg syndrome, and bipolar disorder
even though it had been approved only as an adjunctive therapy for epilepsy. The company
was fined by the FDA and had to pay more than $430 million to resolve criminal charges and
civil liabilities. However, there is nothing to stop a company from educating the public about
a disorder for which they have a drug that is likely to gain approval for its treatment. It is
therefore no surprise that Glaxo has subsidized the "non profit" National Sleep Foundation to
provide information on sleep disorders. Its 2005 "Sleep in America Poll" also reported a 24%
incidence of RLS symptoms and it has funded several studies to show that Requip is helpful in
promoting restful sleep and reducing daytime drowsiness. Requip for attention deficit and
hyperactivity complaints will probably be next on the agenda since they reported the
incidence of these to also be high in restless leg syndrome. Hypertension and heart disease
might soon follow based on a press release just received titled "Restless Legs Linked To Heart
Disease". It refers to a study in the current (April) issue of Neurology that monitored 10
patients in a sleep laboratory showing a modest transient rise in blood pressure associated
with periodic leg movement. The authors suggest this could increase risk of heart disease
and stroke.
The FDA does not require Glaxo to warn that Requip frequently makes restless leg
symptoms worse and ads don't reveal that side effects in clinical studies occur over twice as
often with Requip than a placebo, including nausea (40% of subjects,) vomiting (11%),
sleepiness (12 %), dizziness (11 %) and fatigue (8 %). There are no studies on long-term
side effects. Nor is it very effective, despite the price tag of $170 for a three-month supply.
In one trial, while 73% of subjects saw some improvement, so did 57% of the
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placebo group. Requip and other drugs like Mirapex, that are used to treat Parkinson's
disease because they increase dopamine, have also been shown to cause compulsive
gambling. A recent report now indicates that they can also cause this in restless leg
patients without any prior history of such problems. One patient seen in the Mayo Clinic
Sleep Disorders Center had been taking Mirapex for well over two years and although her
symptoms improved somewhat, she soon developed an uncontrollable urge to gamble when
visiting a nearby casino. As the dosage was increased her gambling compulsion grew
stronger and she was switched over to Requip, following which her restless leg complaints
became much worse. Prior to her treatment for RLS, she had no history of gambling and
viewed gamblers as "unfortunate individuals.” Nevertheless, these drugs caused her to
lose over $140,000. Her desire to gamble completely disappeared when Requip was
stopped but the troublesome leg sensations began to return. These were successfully
treated with Neurontin, which is not a dopamine agonist, and she has had no further
gambling urges, leg complaints or side effects. Mayo Clinic physicians have reported over
two-dozen other patients with a similar scenario, one of whom also lost well over $100,000.
Such problems due to these drugs are likely far more frequent than appreciated since few
physicians or patients would recognize any connection between the two. Although Mirapex
is also approved to treat restless legs syndrome, Boehringer Ingelheim, its manufacturer, as
well as Glaxo, is being sued by patients who suffered this and other impulse disorder side
effects.
Additional drugs like Permax and Dostinex used to treat Parkinson's disease have also
profited from the restless legs bonanza but the results have been disastrous and deadly for
some patients. Lilly's dopamine booster Permax was approved for the adjunctive treatment
of Parkinson's disease in 1988 but never did well and was administered to less than 20,000
patients. However, it had been widely prescribed for restless leg complaints because
nothing else was available for well over a decade. Permax is derived from ergot, which is
known to cause valvular heart disease and following a 2002 report linking Permax to this
serious problem, the FDA ordered that this warning be added to the labeling information.
Permax was promoted for "restless legs syndrome" (for which it was not approved) in a
2004 Eli Lilly sponsored European-Australian advertisement masquerading as a scientific
study in the journal, Neurology entitled "Efficacy of pergolide in treatment of restless legs
syndrome". This was referred to as the PEARLS Study, PEARLS being an acronym for
Pergolide European Australian Restless Legs Syndrome. This seemed appropriate since
authors came from medical facilities in Finland, Italy, The Netherlands, Australia as well as
three different German Universities. However, it concealed the fact that three of the
authors listed, who probably wrote the paper, were Eli Lilly employees from Indianapolis
with no medical school affiliation and one was not a physician. (Neuroloy 2004;62:13911397) . As might be expected, the benefits of therapy were magnified and serious side
effects such as hallucinations, delusions, difficulty moving, chest pain, fast or pounding
heartbeat, swelling of the face, throat, tongue, lips, eyes, hands, feet or legs, large weight
gain in a very short time period, dizziness, weakness, and shortness of breath were
trivialized. Although the authors referred to the article reporting the valvular disease
complication they found no evidence of this because they conveniently did not perform or
report any cardiovascular evaluations. Nor did they comment on a 2002 report linking
Permax to serious side effects of pulmonary and retroperitoneal fibrosis. Another company
sponsored article found Permax to be effective in Tourrette's syndrome in 19 children but
failed to mention that two patients dropped out at the request of the investigators, and 3
withdrew due to increased ADHD.
Two articles published in the New England Journal of Medicine earlier this year reported that
Parkinson's patients taking Permax or Dostinex were at significant risk of developing heart
valve damage. One study found that one in four had moderate to severe heart valve
May 2007
The Newsletter of THE AMERICAN INSTITUTE OF STRESS
Page 11
problems. The second reported that patients taking these drugs were between five to seven
times more likely to have leaky heart valves than patients taking other drugs for
Parkinson's. Permax was ordered to carry the FDA's strongest "black-box" warning label
stating that ''Some patients have required valve replacement, and deaths have been
reported.''
Such warnings, bordered in bold black, appear at the top of prescribing
information to attract attention. However, few patients read them when they pick up their
medications and although all physicians also receive a letter with this information, such
warnings rarely have the desired impact. A Harvard study of almost a million ambulatory
care patients revealed that more than 40% received over 200 different drugs with black box
warnings about health hazards, contraindications such as pregnancy and the need to
conduct periodic liver function or other laboratory tests. Physician compliance with
these recommendations was highly variable, ranging from less than 50% to only
three in 1000.
Last month, within 48 hrs. of the Zelnorm ban, the FDA also asked the current Permax
manufacturer Valeant Pharmaceuticals, as well as companies making generic versions, to
stop shipping the drug because it was associated with moderate to severe heart valve
problems requiring surgery in almost one in four patients. A limited supply will remain
available in pharmacies since it is dangerous to stop the drug abruptly and it must be
tapered off. As the agency explained, "This delay will allow time for healthcare professionals
and patients to discuss appropriate treatment options and to change treatments." Not
surprisingly, the FDA will also be considering continuing access to the drug through an
Investigational New Drug Application (IND). Pfizer's Dostinex, which was also linked to
valve disease in the NEJM articles, is used to treat Parkinson's disease in Europe but is only
approved in the U. S. for the treatment of patients with increased blood levels of prolactin.
Since this usually requires a much lower dose, Dostinex has no black box labeling, although
a milder ''precaution" warning about valve problems was included last month in the general
text of the information provided for doctors and patients. Nevertheless, as previously
emphasized, physicians can prescribe Dostinex for Parkinson's, restless leg syndrome or any
disorder for which they feel it might be beneficial.
And that's just the tip of the iceberg of how diseases are invented to increase drug company
profits. Psychiatry is far and away the most fertile field as pharmaceutical companies hire
specialists to sit around brainstorming new disease ideas like Intermittent Explosive Disorder
(Road Rage) and compulsive shopping, or exaggerating the significance of dubious
diagnoses like ADD, ADHD and bipolar disorder. More to follow on how this psychobabble
has had particularly disastrous effects on children, why FDA really stands for Flawed or
Fraud Drug Administration, and what is being done to stop these abuses so stay tuned!
Copyright©2007 by The American Institute of Stress. All rights reserved.
Health and Stress
The Newsletter of
The Ame rican Institute of Stress
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Paul J. Rosch, M.D., F.A.C.P.
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