BRAIN ATTACK

©1999 ROMESH SENEWIRATNE

In an effort to analyse and understand the medical
advertising industry, I have deliberately avoided informing
the pharmaceutical industry about my postal or personal
address for several years. When I resumed general practice
earlier this year, however, they discovered my postal address
and since then I have received more and more drug
promotional mail. Some of this is personalised, but none of it
is personal. I have refused to work for the pharmaceutical
industry for as long as I have been a family physician. I do not
believe that one can serve the pharmaceutical industry and
the health interests of the public at the same time. I also do
not think that medical education and research should serve
pharmaceutical interests rather than the health and
wellbeing of the world’s population, so I was disturbed by the
brain attack I received in the mail today.

Today’s mail contained the following items:
1. A plastic envelope containing a copy of the “Australian Doctor” subtitled “The
Independent Weekly Newspaper for Australian GPs”, with several glossy
coloured enclosures, and a front cover sheet addressed to “DR RB
SENEWIRATNE, PO BOX 2268, CAULFIELD JUNCTION, VIC 3161”.
2. A copy of the “MIMS ISSUE NO.5 1999”, wrapped in a glossy envelope that
doubled as an ad for “New PriTor” from “Glaxo Wellcome”, with a cover note
addressed to “Dr R B Senewiratne, Melbourne Wholistic Medicine, 257 Tucker

Road, ORMOND” where I worked doing general practice sessions for most of
this year.
3. An offer from Parke-Davis “Neurology Care” to send me some “Parke Davis
Epilepsy Education” regarding epileptic patients’ fitness to drive with a
fold-out glossy enclosure titled “epilepsy, driving and safety”.
4. An offer from Schering to send me “excellent resources on treatment and
management along with practical education and support services”, should I
have a particular interest in Multiple Sclerosis (MS) and specifically if I am “one
general practitioner out of every twenty managing a Betaferon patient”.
5. A separate plastic envelope containing the “MIMS Supplement No.3 1999
Annual” introducing “Celebrex” for arthritis treatment and Micardis/Pritor, a
“new angiotensin II receptor antagonist for mild to moderate hypertension”,
enclosed with a A5 sized booklet described as a “MIMS Product Review”
introducing “Clopidogrel: Plavix” credited to “Dr Greg Conner, Vascular
Physician, Darlinghurst, NSW; Professor Geoffrey Donnan, Department of
Neurology, Austin Hospital, Heidelberg, Victoria; and “Dr Andrew Taylor, Heart
Centre, Alfred Hospital, Prahran Victoria”.

The last of these five items contained an A5 sized glossy
covering letter which reads as follows:
“Dear Doctor,

We are pleased to announce an important advance for your
patients at risk of myocardial infarction (MI) and ischaemic
stroke and vascular death: New PLAVIX®.

“PLAVIX® is indicated for the prevention of vascular ischaemia
associated with atherothrombotic events (myocardial
infarction, stroke, vascular death) in patients with a history of
symptomatic atherosclerotic disease.

“This new ADP receptor antagonist provides a targeted
mechanism of action specifically designed to prevent thrombus
formation that causes MI and ischaemic stroke.

“In fact, in the landmark CAPRIE trial of 19,185 patients,
PLAVIX® provided an 8.7% relative risk reduction (p=0.043) of
vascular ischaemic events, over and above the 25% risk
reduction of vascular ischaemic events accepted to be
provided by aspirin.

“Based on the CAPRIE trial and Antiplatelet Trialists’
Collaboration meta-analysis, aspirin can be expected to
prevent 19 ischaemic events for every 1000 patients treated
per year. In contrast, PLAVIX® can be expected to prevent 24
ischaemic events for every 1000 patients treated per year, a
26% difference.

“In addition, PLAVIX offers your patients with
atherothrombosis a favourable safety profile with improved
gastrointestinal safety and gastric tolerability (significantly
lower incidence of gastric bleeding and GI ulcers than aspirin),
(p<0.05). With one 75 mg tablet, once daily dosage, PLAVIX® is
convenient and easy to use.

“Please note that PLAVIX® is contraindicated in the following
conditions: hypersensitivity to the active substance or any
component of the medicinal product, severe liver impairment,
active pathological bleeding such as peptic ulcer or intracranial
haemorrhage, and breast feeding.

“With its proven efficacy and favourable safety profile,
PLAVIX® should be a valuable addition to your
armamentarium.

“Your Sanofi representative will be contacting you soon with
more important information about PLAVIX®. In the meantime,
if you desire immediate information, please call 1800 188
206.”

It is 7.15 p.m. on Monday 22.11.99, and I called the number
listed above, to find out more about “plavix” and the company
that heralds this new miracle drug. I listened to a repeating
recorded message from “the customer service section of
Sanofi Synthelabo” which explained in a robotised, young,
female voice that my call is important to them and to leave my
name and number, so that the call could be answered during
office hours. The problem is, no opportunity was provided to
leave a message, and after three repetitions of the same
message, I was given an engaged tone. I suppose I will have to
find out about the drug from the “MIMS product review” and
read the writing attributed to two specialist doctors and a
professor of neurology.

The article begins:
“The term atherothrombosis refers to the two
interrelated phases of development of occlusive cardiovascular
disease, namely the development of atherosclerotic plaque
followed by the development of a platelet rich thrombus at the
site of plaque fissure or rupture”.

This sentence is followed by a small “1”, referring to the first of
42 references listed at the back of the article. This article is
listed as “Fuster V, Badimon L, Badimon JJ, Chesebro JH. The
pathogenesis of coronary artery disease and the acute
coronary syndromes. N Eng J Med. 1992; 326: 242-50, 310-18.

I don’t subscribe to the “New England Journal of Medicine”
and would not trust this article to support the idea that
“platelet rich thrombus at the site of plaque fissure or rupture”
is necessarily the “second stage of development of occlusive
cardiovascular disease”. Nevertheless, I read on:
“Thus the modern management of preventative
cardiovascular medicine is aimed at the control of processes
contributing to the premature development of atherosclerotic
plaque such as hypertension, diabetes mellitus and
dyslipidaemia with medications such as antihypertensive
agents, oral hypoglycaemic agents, insulin and lipid lowering
agents, as well as control of the thrombotic process by the use
of antiplatelet agents.”

This statement is hopelessly reductionist, and ironically
regressive, given the reference to “the modern management
of preventative cardiovascular medicine. What about stress
management, diet, anger management, exercise and rest?
What about psychocardiology and holistic approaches to
people rather than statistical analyses from “antiplatelet
collaborators”?

The article continues:
“The central role of the platelet in the atherosclerotic
process has provided the rationale for the use of antiplatelet
agents in many clinical trials of vascular event reduction.”

This sentence is followed by a little “2”, referring to the second
reference, which is described at the back of the article as
“Antiplatelet Trialists’ Collaboration. Collaborative overview of
randomized trials of antiplatelet therapy. 1: Prevention of
death, myocardial infarction, and stroke by prolonged
antiplatelet therapy in various categories of patients. Br Med J.
1994; 308: 80-106.”

This trial is described in the following way:
“The Antiplatelet Trialists’ Collaboration is a
meta-analysis of 142 randomised clinical trials of more than
73,000 patients who were considered to be at high risk for the
development of ischaemic cardiovascular events, and it
showed clear benefit for the use of antiplatelet agents in the
prevention of the commonly used combined endpoint of

myocardial infarction, ischaemic stroke or cardiovascular
death, with a calculated relative odds reduction in favour of
the use of antiplatelet agents of 27%. This relative risk
reduction was fairly consistent whatever the patients’
manifestation of cardiovascular disease.”

One of the problems with “randomised trials” comparing a
new drug with an older “benchmark” drug becomes evident
when “tolerability and safety” are discussed in the article:
“The safety profile of clopidogrel was well established
in the Clopidogrel versus Aspirin in Patients at Risk of
Ischaemic Events (CAPRIE) trial. Patients taking clopidogrel had
less indigestion, nausea and vomiting (clopidogrel 15.0% vs
aspirin 17.59%), less liver function test abnormalities
(clopidogrel 2.97% vs aspirin 3.15%), less intracranial
haemorrhage, and less gastrointestinal haemorrhage
(clopidrogel 0.52% vs aspirin 0.93%) and equal rates of any
bleeding disorder (9.3% in both groups). There was a slight
excess of rash (clopidrogel 6.0% vs aspirin 4.6%) and diarrhoea
(clopidrogel 4.5% vs aspirin 3.4%) in the clopidogrel group.”

This adverse effect discussion raises some concerns barely
hinted at in the Plavix promotional ad which refers only to
Plavix having “significantly lower” likelihood of causing
bleeding and gastrointestinal ulcers than aspirin. The whole of
the CAPRIE trial was based on the assumption that aspirin
causes as 25% improvement in risk from stroke, myocardial
infarction and coronary death. If it caused a total improvement
in life expectancy of 25% this would no doubt be mentioned,

but it doesn’t. Likewise one could mistakenly get the
impression that Plavix (clopidogrel) provides a 26% reduction
in these events, but that would be misreading the small print.

The risks being discussed are “relative risk improvements”
based on the assumption of a 25% reduction in risk from
aspirin. Thus only 24 ischaemic events can be expected to be
avoided per 1000 people treated with Plavix versus 19 per
1000 events with aspirin. But at what cost?

The actual and relative costs of Plavix are not mentioned in any
of the literature about the new drug sent to doctors, not even
the “MIMS Issue No 5” which has this to say about the new
drug from Sanofi-Synthelabo:

“PLAVIX CLOPIDOGREL
Sanofi-Synthelabo [CMI]
Use: Platelet aggregation
thromboembolic disorders.
Contra: Severe hepatic
pregnancy, lactation

inhibitor.

impairment;

Prophylaxis
active

of

bleeding;

Prec: Patients at risk of bleeding incl elective surgery,
intraocular lesions, GI lesions; hepatic impairment; acute
cardiovascular, cerebrovascular or peripheral vascular event.
Interact: Aspirin, heparin, recombinant tissue plasminogen
activator, warfarin, NSAIDS, drugs metabolised by P450 2C9
incl phenytoin, tamoxifen, tolbutamide, fluvastatin.

TABLETS
Rx Clopidogrel hydrogen
anhydrous; pink f-c [film-coated]

sulfate;

lactose

Pack 75 mg [28]: Authority- PBS/RPBS (Rp 5)
[Approved indication(s) for authority: Secondary prevention of
ischaemic stroke and transient cerebral ischaemic events in
patients (1) with a history of cerebrovascular ischaemic
episodes while on therapy with low-dose aspirin; or (2) where
low-dose aspirin poses an unacceptable risk of gastrointestinal
bleeding; or (3) where there is a history of anaphylaxis,
urticaria or asthma within four hours of ingestion of aspirin,
other salicylates, or NSAIDS.
“Secondary prevention of myocardial infarction or unstable
angina in patients (1) with a history of cardiac ischaemic events
while on therapy with low-dose aspirin; (2) where low-dose
aspirin poses an unacceptable risk of gastrointestinal bleeding;
or (3) where there is a history of anaphylaxis, urticaria or
asthma within four hours of ingestion of aspirin, other
salicylates, or NSAIDS]
Dose 75 mg once daily
Refer MIMS Annual 1999 p 2-203”

Not having a copy of the MIMS Annual 1999 at hand, I am
required to turn back to the “product review”, which I assume
will have a full copy of the prescribing information including
risks and dangers included at the back of the document. This is
customary and required by the Pharmaceutical Industries Code
of Practice. This information is likely to be closer to the truth
about Plavix, provided one still reads between the lines.

Under “adverse reactions”:
“Clopidogrel has been evaluated for safety in more than
11,300 patients, including over 7,000 patients treated for one
year or more
Clopidogrel was well tolerated compared to aspirin in a large
controlled clinical trial (CAPRIE). The overall tolerability of
clopidogrel in this study was similar to aspirin, regardless of
age, gender and race. The clinically relevant adverse effects
observed in CAPRIE are discussed below.
Haemorrhagic. The overall incidence of any bleeding in
patients treated with either clopidogrel or aspirin was similar
(9.3%). The incidence of severe bleeds was 1.4% in the
clopidogrel group and 1.6% in the aspirin group.
Gastrointestinal haemorrhage was significantly less frequent
with clopidogrel (1.99%) compared to aspirin (2.66%). The
incidence of intracranial haemorrhage was 0.35% for
clopidogrel compared to 0.49% for aspirin.”

Intracranial haemorrhage is, like cerebrovascular thrombosis
or embolism, a cause of “stroke”, or cerebrovascular accident
(CVA). The results above suggest that 3.5 out of every 1000
people treated by Plavix will actually have a stroke because of
it, and 4.9 out of every 1000 treated with aspirin will suffer the
same fate, even though the drugs are being promoted for the
prevention of strokes and heart attacks. In addition to the
bleeding risk, it becomes clear that there are many other
dangers associated with both Plavix and aspirin, including the
risk of the potentially fatal allergic reaction of “anaphylaxis”.

Under “adverse reactions” is reported:
“The post-marketing experience confirms the safety
profile defined
during
the
clinical development:
hypersensitivity reactions have been reported; these mainly
include skin reactions (maculopapular or erythematous rash,
urticaria) and/or pruritus. Very rare cases of bronchospasm,
angioedema or anaphylactoid reactions have been observed.”

In addition to these risks, the following list of adverse effects
which occurred in greater than 2.5 percent of people receiving
Plavix is reported in the full prescribing information from
Sanofi-Synthelabo:
“Chest pain (8.3%), accidental injury (7.9%), influenza-like
symptoms (7.5%), pain (6.4%), fatigue (3.3%), hypertension
(4.3%), headache (7.6%), dizziness (6.2%), abdominal pain
(5.6%), dyspepsia (5.2%), diarrhoea (4.5%), nausea (3.4%),
hypercholesterolaemia (4.0%), arthralgia (6.3%), back pain
(5.8%), angina pectoris (10.1%), coronary artery disorder
(6.2%), purpura (5.3%), epistaxis (2.9%), depression (3.6%),
infection (4.7%), upper respiratory tract infection (8.7%),
dyspnoea (4.5%), rhinitis (4.2%), bronchitis (3.7%), coughing
(3.1%), rash (4.2%), pruritus (3.3%), urinary tract infection
(3.1%), claudication intermittent (3.8%), peripheral ischaemia
(3.2%) and cerebrovascular disorder (2.6%).”

The review article by Professor Donnan and doctors Conner
and Taylor have less to say about these adverse effects and

essentially ignores any meaningful discussion about them in a
short section titled “tolerability and safety”, described before.

One of the drug side interactions to be expected with new
Plavix occurs when phenytoin is used concomitantly with the
new drug. This is because clopidogrel interferes with the
important cytochrome P 450 enzyme pathway, an important
drug detoxification pathway in humans and other animals.
Phenytoin is the generic name for the crippling antiepileptic
drug “Dilantin”, marketed in Australia by Parke-Davis who also
sent me information about the brain today, in the form of a
personalised letter offering educational materials, hopefully of
a higher standard than the enclosed “newsletter” titled
“epilepsy, driving and safety”.

The letter, which is addressed to Dr R B Senewiratne, 257
Tucker Road, ORMOND reads:
“Epilepsy may affect 1 out of 50 Australians. Whilst a
serious condition, it can be treated in a variety of ways so that
the sufferer is able to maintain quality of life.

Epilepsy Society of
Australia benefits
from continued support
from Parke Davis.

One important factor in treating this condition is education.
Providing medical professionals with the latest developments
on epilepsy and informing their patients and carers about
quality of life issues help to promote better health outcomes.
To this end, Parke Davis has joined forces with the Epilepsy
Society of Australia to support their endeavours and to
distribute the Society’s special release on epilepsy and
assessing driving fitness. This has been achieved through an
unrestricted educational grant from Parke Davis.

More

educational

materials available now.

For over 40 years, we have sponsored clinical trials and
collected information relating to epilepsy, Dilantin (phenytoin)
and Neurontin (gabapentin). We now invite you to ‘tap into’
our libraries and utilise our resources to gain additional
knowledge and insight into this condition.

Currently in production are case study videos that will be
available in the near future. To register your interest in
receiving a copy, please refer to the attached Request Form.
We also offer new abstracts, copies of the “Neon” paper plus
practical tools such as Seizure Classification and Drug
Interaction Charts.

To ensure prompt delivery of the materials you request, please
post your request before Friday, 17 December 1999.

Should you have any other requests or suggestions on how we
can assist you, please enclose a separate letter with the
Request Form.
We look forward to hearing from you
Sincerely
Danielle Mayne
M ARKETING A SSISTANT ”
The reverse side of this personalised mass-produced letter
gives details of the offer from Parke Davis. One has the choice
of selecting “New in Epilepsy”(a “bulletin containing abstracts
of recently published papers”), a “seizure classification chart”,
the “Neon Paper”, a “Drug Interaction Chart” and a “Neurontin
Dosage Chart”. The “Neon Paper” is explained as “Bruni J on
behalf of the “Neon” Study investigators group. Outcome
evaluation of gabapentin as add-on therapy for partial
seizures. Can J Neorol Sci 1998; 25: 134-40.”

As an “optional” section at the bottom of the page five
questions are listed:
1. How many epileptic patients are currently under your care?
2. Are any of your patients taking Neurontin now?
3. Would like [sic] to receive patient information material about Neurontin?
4. Would you be interested in attending an education meeting next year?
5. Are you interested in receiving information about Parke Davis sponsorship for

Clinical trials
Overseas meetings
Local meetings
Other, please specify

In small print at the bottom of the page is printed:
“Dialantin and Neurontin are registered trademarks of
Warner Lambert Co, USA”

Is the last line a deliberate or accidental misprint of the well
known name “Dilantin”?
Brain attack?

Dilantin has been a “benchmark anticonvulsant” for several
decades now, and in that time it has become clear that the
drug can cause horrendous side-effects, including deformity of
the face, teeth and gums with prolonged exposure. It can also
cause nervous system and brain damage when the level of the
drug in the blood is excessive. Because of the toxicity of
phenytoin (Dilantin) regular blood tests need to be done if the
drug is used for the treatment and control of epilepsy. This is
also the case with other toxic anticonvulsant drugs such as
Tegretol (carbamazepine) and Epilim (sodium valproate).

The adverse effects of Dilantin listed in the 1993 MIMS annual
were listed as follows:

Central nervous system. The central nervous system is the
most common place where manifestations with Dilantin
therapy are encountered. These include nystagmus, ataxia,
slurred speech and mental confusion. Cases of dizziness,
insomnia, transient nervousness, motor twitching and
headache, have also been reported. These side effects may
disappear by continuing therapy at a reduced dosage level.
Gastrointestinal. Dilantin may cause nausea, vomiting, and
constipation. To prevent gastric irritation due to alkalinity,
Dilantin should be taken with at least half a glass of water.
Gastric irritation may often be minimised by administering
Dilantin during or following meals or by using Dilantin
Suspension.
Dermatological. Manifestations sometimes associated with
fever have included scarlatiniform or morbilliform rashes. The
latter case is the most common with other types of dermatitis
being more rare. In general, rashes are more common in
children and young adults. More serious forms which may be
fatal have also been reported and they include bullous,
exfoliative or purpuric dermatitis, lupus erythematosus and
Stevens-Johnson syndrome.
Haematological. Some fatal haemopoietic complications have
occasionally been reported in association with the
administration of phenytoin. Included in these are
thrombocytopenia,
leucopenia,
granulocytopenia,
agranulocytosis and pancytopenia. Although macrocytosis and
megaloblastic anaemia have occurred, these conditions are
more a consequence of folic acid deficiency.
Other. Gingival hyperplasia occurs frequently and its incidence
may be reduced by good oral hygeine, including gum massage,

frequent brushing, and appropriate dental care. Occasionally,
polyarthropathy and hirsuitism as well as potentially fatal
cases of toxic hepatitis, liver damage and periarteritis nodosa
may occur.”

Some might consider the above a good reason to ban the use
of this chemical, especially in children.

EPILEPSY
Epilepsy is a medical term used to describe a condition
characterised by seizures affecting the brain and nervous
system. These seizures involve uncontrolled electrical
discharges which form “short circuits” in the brain and a
spread of the “epileptic focus” to other parts of the brain
resulting in different clinical presentations of epilepsy. These
are named according to the type of epileptic seizure that
results, such as “grand mal”, “focal seizures”, “petit mal”, and
“temporal lobe epilepsy”. The recommended drugs for the
treatment of different types of epilepsy depend, to a point on
the type of seizure, and other factors such as duration of each
seizure and the frequency of seizures. The drug Dilantin is
recommended for grand mal and psychomotor seizures. In the
1993 MIMS Annual the indications are described as:
“Control of grand mal and psychomotor seizures.
Dilantin will prevent or effectively decrease the incidence and
severity of convulsive seizures in a high percentage of cases,

with patients exhibiting little tendency to become resistant to
its action. Besides its effectiveness in controlling seizures,
Dilantin frequently improves the mental condition and outlook
of epileptic patients, and there is also increasing evidence that
Dilantin is valuable in the prevention of seizures occurring
during or after neurosurgery, and in the treatment of certain
cardiac arrhythmias.” (p.3-228)

An important factor to consider in the holistic medical
management of epilepsy is identification of seizure triggers,
and several of these have been clearly identified over the
years. These are variable between individuals, but several
common triggers can cause epileptic convulsions in different
people who share a tendency to epilepsy. These include
flashing artificial lights and other repetitive visual experiences
involving electrovisual stimuli. Particular music with artificial
repetitive rhythms can also trigger convulsions in the
susceptible. Hypnotic induction into seizures can also be done,
and this can be done via videos and television, computer
games and video games. Fatigue and sleep deprivation can
also trigger epilepsy, especially if combined with drug and
alcohol intoxication. Even small intakes of alcohol can lower
the seizure threshold and trigger seizures in susceptible
people. Drugs such as amphetamines, methyl phenidate
(Ritalin) and other stimulants are notorious for causing
seizures, and seizures can also occur during withdrawal from
these and other drugs and during withdrawal from alcohol.

Damage to the brain from trauma and infection can also cause
seizures, including seizures during the acute insult and later,

when scar tissue has formed in the affected area of the brain.
Trauma can be accidentally or deliberately inflicted on the
brain. In Australia and Canada there has occurred a recent
resurgence of popularity for operations on the brain to treat
neurological and psychiatric abnormalities, particularly for an
interesting condition termed “temporal lobe epilepsy”.

In The Brain (1997), an Oxford University Press publication, a
paper was written by doctors from the Montreal Neurological
Hospital and Institute, Quebec, Canada titled, “Results of
surgical treatment in temporal lobe epilepsy with chronic
psychosis”. The summary of the paper reads as follows:
“The combination of psychosis and refractory temporal
lobe epilepsy is not rare. However, patients with chronic
interictal psychosis and refractory epilepsy are rejected from
many epilepsy surgery programmes purely on psychiatric
grounds. It is often assumed that disturbed behaviour will
prevent adequate preoperative evaluation or that the patients
are unable to provide informed consent for preoperative
investigations and for surgery. The observation that the
psychosis usually does not improve after operation and fears of
an exacerbation of psychosis with post-surgical seizure
remission, analogous to ‘forced normalization’, are further
deterrents to surgery in these patients. We describe five
patients with the dual diagnoses of medically intractable
temporal lobe epilepsy and chronic psychosis who underwent
temporal lobe resection. The patients were able to provide
informed consent and were easily managed during
preoperative investigation. Seizure outcome has been excellent
in all. Neither temporal lobe resection nor remission of seizures

influenced the nature or evolution of the psychosis. Subjectively
the patients functioned better in activities of daily living and
freedom from seizures improved integration into psychiatric
treatment facilities. With appropriate psychiatric intervention,
patients with chronic psychosis and refractory epilepsy can
participate in presurgical investigation successfully, and can
undergo surgery uneventfully.”

“Patient 1” in this paper is described as a 30 year old man
“with severe schizoaffective disorder” and “medically
intractable right temporal lobe epilepsy” who “underwent a
selective amygdalohippocampectomy for control of his
seizures”. This man’s seizures apparently began at the age of 2
years when he had a prolonged febrile convulsion followed by
transient paralysis of his left side, after which he developed
“temporal lobe seizures at the age of 4 years”. This man’s
“psychiatric history” is described as follows:
“The patient completed grade 10 at school and has
never been employed. In early adolescence, he became
non-compliant with anticonvulsant drugs, attempted suicide
with impulsive drug overdoses and refused psychiatric help. He
made no lasting emotional attachments, began to use street
drugs and drove without a license despite uncontrolled
seizures. He developed thought blocking and a sense of being
possessed by the devil. At the age of 27 years, at the behest of
auditory hallucinations commanding him to exorcise himself,
he doused himself with coal oil, mutilated himself with an axe
and set himself alight. Having sought no help, he was
discovered by his family a day later, lying in bed severely
burned and cut. He required admission to an intensive care

unit and received extensive skin grafts. A diagnosis of
schizoaffective disorder was made. Neuroleptic treatment was
started and antidepressants added later. There was never a
clear temporal relation between exacerbations of psychosis
and seizures.”

This tragic story of religious confusion, drug addiction and
psychiatric abuse has an ending which is described as a success
by the authors of the article, but sounds much like a chronic
invalid state, the resultant of torture and a broken spirit in a
young man who had earlier shown anger towards the medical
profession who had started drugging him with anticonvulsants
and other drugs when he was still a young child. His
“postoperative course” is described as follows:
“Two years after surgery, the patient lives in his own
home, works in a supervised workshop for chronically ill
psychiatric patients and complies with ongoing out-patient
psychiatric follow-up. He no longer takes antidepressant
medication but is now treated with chlorpromazine
(75mg/day), risperidone (8 mg/day) and loxapine (100
mg/day). He continues to take carbamazepine (800 mg/day)
and clonazepam (2 mg/day) and has had only one
postoperative seizure.”

Prior to the surgery on his limbic system and temporal lobes,
this unfortunate man was being treated with the following
drugs: phenytoin (300 mg/day), carbamazepine (1200 mg/day)
and clonazepam (2 mg/day) for his “temporal lobe epilepsy”

and haloperidol (12.5 mg/day), fluvoxamine (100 mg/day) and
procyclidine (10 mg/day) for his “chronic psychosis”.

A major difficulty encountered in understanding this case and
where the medical profession failed this young man is the lack
of proper neurological, social and psychological assessment,
analysis and historical presentation. Of what racial and cultural
background is this man? What reasons did he have for
rejecting anticonvulsant drugs and psychiatric treatment when
he was younger? What did he look like? Where and why did he
develop the idea that he was possessed by the devil? What
was his religious, political and philosophical background? What
was his family background and sibling relationships like? What
music and television programs influenced his thinking? What
“street drugs” did he “experiment with” and how did these
affect his health, mental state and chronic epilepsy? What was
he interested in and why? What skills and talents did he have?

A difficulty with understanding this man’s problems is that
symptoms attributable to “temporal lobe epilepsy” overlap
with symptoms attributable to “psychosis”. Temporal lobe
epilepsy associated with distinctive electroencephalogram
readings can result in trance or fugue states, visual and
auditory hallucinations, visions, and dissociative states of
various sorts. Such states can also result from drug intoxication
and toxicity.

A clear example of the latter is given in the second case
described in this article, which is of a 42 year old women who,

in the course of her treatment developed visual hallucinations
and uncharacteristically aggressive behaviour as a direct result
of Dilantin (phenytoin) toxicity:
“On one occasion, paranoid hallucinations became
unusually florid and she was uncharacteristically aggressive
and socially inappropriate. This exacerbation coincided with
excessive plasma phenytoin levels and resolved with cessation
of the drug.” (p.1931)

The actual manifestations of what was considered to be the
result of temporal lobe epilepsy is unclear from the paper, and
only a brief description of vague symptomatology from the
man’s childhood are given:
“In the seizures an initial feeling of fear and a sensation
of pressure in the lower abdomen was followed by cessation of
activity, a blank stare and loss of awareness.” (p.1930)

This could be a description of terror, and it is important to
differentiate a loss of awareness from a loss of consciousness,
which would be more suggestive of a genuine epileptic cause
for these episodes, which do not sound serious or severe
enough to warrant the extraordinarily aggressive treatment
that the man received prior to and following the surgery.

It would be interesting to speculate about how this man could
have been better treated by understanding his religious views
and beliefs in an effort to understand the “psychosis” which
was subsequently diagnosed as “schizoaffective disorder”

according to criteria of the American Psychiatric Association’s
DSMIV (1994). The DSM IV is also used in Australia to make
diagnoses of this and other psychotic illnesses, although it
makes few recommendations for treatment. It is a book of
labels, devoid of cause and cure.

Schizoaffective disorder is described in this book in the
following manner:
“The essential feature of Schizoaffective Disorder is an
uninterrupted period of illness during which, at some time,
there is a Major Depressive, Manic, or Mixed Episode
concurrent with symptoms that meet Criterion A for
Schizophrenia (Criterion A). In addition, during the same
period of illness, there have been delusions or hallucinations
for at least 2 weeks in the absence of prominent mood
symptoms (Criterion B). Finally, the mood symptoms are
present for a substantial portion of the total duration of the
illness (Criterion C). The symptoms must not be due to the
direct physiological effects of a substance (e.g., cocaine) or a
general medical condition (e.g., hyperthyroidism or temporal
lobe epilepsy) (Criterion D).” (p.292)

In the Montreal Neurological Hospital and McGill University in
Montreal, however, while claiming an adherence to the DSM
classification, brain surgery is being done on people with
known temporal lobe epilepsy who have been additionally
diagnosed with “schizoaffective disorder” in direct
contravention of the criteria in the DSM. At the same time as
claiming that these people are “chronically psychotic” the

authors of the article claim that they are also capable of giving
“informed consent” for surgery to their brain. Did the surgical
candidate understand that the surgery was not intended to
cure his psychiatric condition, and was only intended to treat
the “temporal lobe epilepsy”?

Brain attack?

STROKE
The clopidogrel (Plavix) MIMS Product Review is credited to
two doctors and a professor. The professor is Professor
Geoffrey Donnan of the Department of Neurology at the
Austin Hospital in Heidelberg, Melbourne. This hospital is also
home to Professor Graham Burrows, chairman of the drug
promoting “Mental Health Foundation” and several other drug
promoting organizations. Professor Burrows is also a senior
editorial consultant for the MIMS organization, and consults at
the Austin Hospital (for his public patients). At this hospital, as
in Canada, neurosurgery for temporal lobe epilepsy has been
done in recent years.

During a recent visit to this hospital to visit a friend who had
just had surgery to excise part of her bowel, I picked up a
series of public education pamphlets in several languages
about the diagnosis, treatment and prevention of stroke. The
pamphlet in English is titled “STROKE IS A BRAIN ATTACK”.

The front cover announces:
“Answers to the top ten questions about stroke (Brain
attack)” credited to the “National Stroke Foundation”. These
questions are:
1. What is a stroke?
2. Does a stroke “just happen”?
3. How common is a stroke?
4. What are my chances of having a stroke?
5. What risk factors can I control?
6. Are there warning signs of stroke?
7. What happens after a stroke?
8. Can stroke be prevented?
9. Can a stroke be cured?
10. What sort of research into stroke is taking place?

Under the final question is given this rather intriguing answer:
“Australia is one of a number of countries undertaking
major research studies into the causes and prevention of
stroke.

“The National Stroke Research Institute Laboratories (NSRI) are
located at the Austin and Repatriation Medical Centre. The
research projects are being conducted by the Director,
Professor Geoffrey Donnan. Professor Donnan and his staff of
researchers are continuing to provide valuable insights in the
process and treatment of stroke, or “brain attack”, in our
community.
“The National Stroke Foundation seeks to raise funds to
support this world-class research activity. NSF also provides
leadership and offers to act as a coordinator when joint
research programs involve several hospitals.
“As the lead agency for Brain Attack nationally, the National
Stroke Foundation seeks to raise much needed funds for
research, prevention, treatment, education and awareness
into Brain Attack, so as to improve stroke health for all
Australians and help reduce the morbidity and mortality rate
from stroke.”

Morbidity and mortality from stroke refers to illness and death
from stroke respectively. Illness from stroke includes both
residual disability from the acute injury as well as the
long-term illness that treatment for stroke can cause. The
latter is ignored completely in the pamphlet, which states
categorically that stroke cannot be cured. Question nine, titled
“can a stroke be cured” is answered thus:
“Once the stroke has occurred, the short answer is
“NO”. There is no known drug which can completely eliminate
the possibility of a stroke or offer a guaranteed “cure”.
However, early diagnosis and quick action when a stroke does

occur can reduce its severity. For Brain Attack patients
suffering loss of speech, movement, thought processes or
sensory reaction, rehabilitation is also possible with the
assistance of physical, occupational or speech therapists.”

In other words, the medical profession cannot aid in recovery,
but the “allied health professionals” can. This may hold true
for Professor Donnan and his drugs, but it certainly does not
apply to the entire medical profession, which can do a great
deal to assist in the rapid and complete recovery from
“stroke”, provided it is not too extensive. Many people make
complete recoveries from cerebral infarctions as far as their
brain function is concerned, although histologically
irretrievable loss of neurones and other brain cells may have
occurred. The reason for this is probably that connections
between undamaged cells compensate for those which are
lost. New axonal and dendritic processes are known to form
and atrophy throughout life, and it seems clear that active use
of the brain facilitates new connections. The people who make
a complete recovery from stroke tend to be those who believe
it to be possible, and work towards regaining lost function
whilst adapting to the current disability by developing new
skills. The development of new skills requires active use of the
brain and mind, and it is obvious as to why this aids in
recovery. Management that results in such recovery is
necessarily holistic and aimed at identifying risk factors and
remedying them together with maximising the brain’s capacity
to heal itself and regain function after injury, regardless of
cause.

“Strokes” are a popular term for “cerebral infarctions”, which
can be caused by either haemorrhage into the brain, or
obstruction to the blood flow of the brain. For this reason,
another term used by the medical profession has been
“cerebrovascular accidents” or “CVAs”. The term “brain
attack” is as appropriate as “heart attack” and implies the
urgency of the situation more so than “cerebrovascular
accident” does. It is, indeed a medical emergency if the
delicate tissue of the brain is being deprived of blood or being
compressed by it, as occurs with intracranial haemorrhages.

The cause of cerebral blood flow obstruction includes blockage
of blood vessels in the neck and head, and embolism, when a
blockage is caused by a solid object such as a piece of blood
clot that travels to the brain through the arterial circulation.
Common aetiological processes that can underlie blockage of
different sorts include atherosclerosis and atherothrombosis
affecting arteries in the neck, hypertension and diabetes.
These conditions also cause susceptibility to haemorrhagic
strokes, following rupture of blood vessels in the brain.

Some of these aetiological processes are referred to in the
“brain attack” pamphlet, which explains:
“The most common form of stroke is the result of a
sudden disruption in the flow of blood to parts of the brain.
“When blood cannot reach parts of the brain, the
oxygen supply to those areas is cut off and the brain cells die
(infarct). Less frequently, blood vessels burst and blood
spreads into nearby brain (haemorrhage) and as a result of

either of these processes, functions normally controlled by
these damaged areas become affected. In many cases,
unconsciousness and/or partial paralysis may occur. This is
often the immediate “outward sign” that a stroke has
occurred.”

Embolic strokes are not mentioned, and question two is
answered with a refutation of the term “cerebrovascular
accident”:
“…even though a stroke is often referred to by doctors
as a “cerebrovascular accident”, the term is not an accurate
one, since stroke is rarely an “accident”.

Is “brain attack” a more accurate term? Who is attacking
whom? Where is the attack coming from? Is it coming from the
“National Stroke Foundation”?

The advice given in the pamphlet regarding “Risk factors that
cannot be controlled” include gender, family history, individual
history, diabetes and irregular heart beat. The “risk factors
which can be controlled” are listed as “high blood pressure”,
“high cholesterol level”, “diet”, “alcohol”, “obesity”,
“smoking”, “exercise” and “birth control pills”. Stress is
mentioned only in the context of “controlling blood pressure”:
“Controlling high blood pressure, whether by a
low-sodium diet, weight control, stress management and/or
medication will reduce your risk of stroke.”

In actuality, all but a person’s gender can be “controlled” by
physicians capable of the holistic management of stroke and
cardiac risk factors. Even family history can be altered by
addressing problems in communication between family
members, since they can influence each other to improve their
health and wellbeing generally, including their cardiovascular
and cerebral health. Diabetes and irregular heart beats are
readily treatable with modern drugs and good dietary advice
combined with stress management. The latter is essential for
the successful management of coronary and cerebral risk
factors generally. This definitely includes the lowering of
elevated blood pressure, but also the management of
diabetes, eating disorders and obesity, cigarette smoking,
alcohol abuse, and high plasma cholesterol levels.

CHOLESTEROL
Aggravation of elevated LDL cholesterol levels by stress is not
mentioned in the pamphlet, which instead gives outdated and
misleading advice regarding treatment of elevated cholesterol
levels with diet:
“a high cholesterol level is a contributing factor to
arterial disease, which often leads to a predisposition for
stroke. Try to avoid foods which have excess fat, cholesterol,
or have been fried. Choose lean meats and low-fat dairy
products. Limit your intake of eggs.”

In truth, the link between cholesterol and cardiovascular
disease is much more complex than the pamphlet makes out.

Total cholesterol includes subfractions of low density (LDL)
cholesterol and high density (HDL) cholesterol. While an
elevated LDL cholesterol level has been associated with
increased rate of blockage of arterial blood vessels, a high HDL
cholesterol level has an effect of protecting against such
disease. It is well recognised that fish, cereal and vegetable
fibre and exercise can raise HDL levels. A modest intake of
alcohol is also said to help raise HDL levels, but this possible
beneficial effect may be offset by concomitant rises in other
blood lipid levels.

Fresh fruits and vegetables, cereals, fish and other foods
widely accepted to be of benefit for persons suffering from
heart disease, obesity and diabetes are not mentioned at all in
the pamphlet, even in the rather bizarre section on “diet”
which, following the section on “high cholesterol level” reads:
“In addition to the above, avoid foods which have excess
salt. Try to eat fresh foods wherever possible. When buying
processed or canned foods, check the sodium content on the
list of ingredients which, by law, should be on the label.
Sodium can be in the form of disodium phosphate,
monosodium glutamate, sodium nitrate or any other sodium
compound. Avoid food with high sodium levels.”

Cholesterol is a ubiquitous bio-molecule that is the precursor
to all the steroid hormones, including cortisol, oestrogen,
progesterone and testosterone. It is essential for vertebrate
life and is found in the cell membrane of virtually every cell in
the body. Elevated serum cholesterol was one of the several

“risk factors” identified in the 1960s “Framingham Study” to
predispose to atherosclerosis and heart disease. Since then a
massive industry has grown based on frightening people about
“cholesterol” and selling treatments for “high cholesterol”.
Prominent amongst these treatments are drug treatments
with “cholesterol lowering drugs” such as the “statins” Zocor
(simvastatin) and Pravachol (pravastatin).

The MIMS Issue No 5 1999 lists 18 different cholesterol
lowering agents in section 2 (f) titled “hypolipidaemic agents”.
These include the following “HMG CoA reductase inhibitors”,
also called “statins”:
1. Lescol (fluvastatin) from Novartis
2. Lipex (simvastatin) from AMRAD
3. Lipitor (atorvastatin) from Parke Davis
4. Lipobay (cerivastatin) from Bayer
5. Pravachol (pravastatin) from Bristol Myers Squibb
6. Vastin (fluvastatin) from Astra
7. Zocor (simvastatin) from Merck Sharp & Dohme

The cost of these drugs is not mentioned in the MIMS Issue No
5, but these are very expensive drugs, and can bring a range of
adverse effects which are rarely written or spoken about by
the drug representatives or the companies advertisements.

In the section on hypolipidaemic agents are several glossy ads
for these expensive drugs. These include four for Lipitor, one
for Pravachol, one for Zocor, and two for Lipex. The slogans for
the ads demonstrate how far the drug companies have gone
down the road of commercial exploitation. The ad from the
American pharmaceutical giant Mercke Sharpe and Dohme
features a monolithic Z with the slogan “Zocor takes control of
the entire lipid profile”. At the three apexes of the Z are
printed “decreased trigs”, “increased HDL-C” and “decreased
LDL-C”. No evidence is presented to back up this claim in the
ad, which urges “before prescribing, please review Product
Information by referring to Section 2 (f).

This section has a “general statement for lipid lowering drugs
prescribed as pharmaceutical benefits”. This reads as follows:
“The following criteria, as recommended by the
Pharmaceutical Benefits Advisory Committee, qualify the
indications for the prescribing of atorvastatin calcium,
cerivastatin sodium, fluvastatin sodium, pravastatin sodium,
simvastatin and gemfibrozil as pharmaceutical benefits.
By writing PBS prescriptions for these drugs, the prescriber is
signifying that the drugs are being prescribed in accordance
with the criteria that follow.
Qualifying criteria for lipid lowering drugs. Note that the
registered indications for individual agents may differ. Refer to
the current product information.
Dietary therapy. All patients should receive dietary therapy,
typically for six weeks, before resorting to drug treatment.

For obese patients, a longer dietary period should be
considered.
In addition to dietary advice, specific advice should be
provided about lifestyle changes to modify risk factors such as
smoking, obesity, excessive alcohol intake and physical
inactivity.
Cholesterol/triglyceride levels. In addition to dietary therapy,
drug therapy is indicated in patients in accordance with the
information that follows, where patients must have both the
specified risk category and the stated lipid level.
Patients with existing coronary heart disease and cholesterol
level > 4 mmol/L.
Patients
with
diabetes
mellitus
and/or
familial
hypercholesterolaemia and/or family history of coronary hear
disease (first degree relative < 60 years of age) and/or
hypertension and/or peripheral vascular disease and
cholesterol level > 6.5 mmol/L or cholesterol level > 5.5
mmol/L with HDL < 1 mmol/L.
Patients with HDL < 1 mmol/L and cholesterol level > 6.5
mmol/L.
Patients without the risk factors described previously but who
are men aged 35 to 75 years or postmenopausal women aged
up to 75 years and who have a cholesterol level > 7.5 mmol/L
or a triglyceride level > 4 mmol/L.
Patients not included in any of the previous categories but who
have a cholesterol level > 9 mmol/L or a triglyceride level > 8
mmol/L.

C HOICE OF DRUG
Predominant hypercholesterolaemia. The preferred drugs are
the HMG CoA reductase inhibitors (‘statin’ drugs), bile acid
resins, gemfibrozil or nicotinic acis.
Mixed hyperlipidaemia. The preferred drugs are gemfibrozil,
HMG CoA reductase inhibitors or nicotinic acid.
Predominant hypertriglyceridaemia. The drugs recommended
are gemfibrozil or nicotinic acid.
Measurement of plasma lipids.
The decision to commence drug therapy should be based on at
least two measurements made at an accredited laboratory”

These criteria are routinely ignored by many doctors in
Australia, particularly by
cardiologists who are often
obsessed by lowering cholesterol levels despite the fact that
the drugs often cause impotence, muscle damage and pain,
gastrointestinal problems, fatigue, depression and other side
effects which can be avoided by good dietary and
psychological advice. The adverse effects listed under Liptor
are listed in the MIMS Issue No 5 as “rhabdomyolysis
(theoretical); myopathy; myalgia; GI upset; headaches;
insomnia; flu-like syndrome; sinusitis; other see MIMS Annual.”

These are ignored in the glossy ad for Lipitor which features a
metallic statue with arms raised superimposed over a line of
36 white-skinned people, mainly of middle age who appear to
be interacting socially with each other. Most are dressed
casually with a few male “executives” wearing ties. 23 of the

36 people are male, one of whom is engaged in a conversation
whilst wearing sunglasses. The people are all posing, and the
picture has been carefully crafted. The caption reads:
“ONCE…AND FOR ALL.” Subcaptioned under the slogan is the
lipitor logo below which is printed in italics “Once daily for all
cholesterol levels”.

The “Australian” company AMRAD have two full paged glossy
ad in the MIMS Issue No 5 for their HMG CoA reductase
inhibitor Lipex (simvastatin). This is their version of the original
statin drug marketed as Zocor by Mercke in the 1980s. The ad
for Lipex features a telescopic photograph of the sun, with the
slogan “SOME THINGS IN LIFE JUST KEEP ON DELIVERING”.
Below this is the caption:
The sun delivers power, day in day
out.
LIPEX delivers power too – the power of simvastatin

The second slogan, printed above the LIPEX logo claims:
“FROM LIPIDS TO LIFESTYLE, LIPEX
DELIVERS”

The Squibb ad for Pravachol features a photograph of Winston
Churchill with cigar in mouth giving his famous V for victory
sign (which ironically doubles as the “peace sign”) below the
slogan “IT’S OFFICIAL! NOW WITH TWO UNIQUE

INDICATIONS”. In the right hand lower corner if the Pravachol
logo beneath which is printed “POSITIVELY DIFFERENT”.

Ironically, amongst the drug ads is a full page glossy ad from
the Australian Dairy Corporation extolling the virtues of low fat
dairy products, despite the fact that dairy products are a major
problem for people with elevated blood fats. The ad reads:

Low fat dairy can help lower cholesterol

A low fat dairy diet is ideal for your high cholesterol patients. It
will reduce their intake of saturated fats, which lowers their
cholesterol levels and lessens their risk of heart attack. By
recommending low fat dairy food everyday your patients will
get the essential vitamins and minerals they need.”

At the bottom right hand corner is the caption:
“Dairy. Every day for life.”

It is true that saturated fats, which include most animal fats,
can raise the LDL fraction of the total cholesterol, and also
contribute towards obesity and diabetes. They can also worsen
hypertension, especially if mixed with alcohol and a high salt
intake. All of these dietary problems can be solved by a diet
rich in fresh fruits, vegetables and cereals, with the
predominant protein sources in the diet coming from legumes
(beans, lentils, chick-peas etc), nuts and fish. The bones in
canned fish are a good source of calcium as are various nuts. A
low fat dairy diet does not lower cholesterol, it just does not
do as much damage as a high fat dairy diet does.

The relationship between cholesterol and oestrogen should be
mentioned. Cholesterol is the precursor molecule for the
synthesis in the ovaries of oestrogen as well as progesterone,
the female sex hormones. It could be theoretically predicted
that drugs which block the synthesis of cholesterol will have an
effect on levels of these hormones. It is also thought that
oestrogen provides a protective effect against atherosclerosis
and known that it protects the bones against osteoporosis.
Osteoporosis is a common problem in older women, especially
after menopause, and the pharmaceutical industry and
gynecology profession have, for many years, been urging
women to take “hormone replacement therapy” to protect
themselves against calcium loss from bones, or
“demineralisation” as it is called.

On the page opposite the glossy Lipex ad in the MIMS Issue No
5 is a small green ad for Rocaltrol from Roche. Rocaltrol is a
drug treatment for osteoporosis.

Bone attack?

REFERENCES:

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders (Fourth Edition). APA:Washington, D.C.

2.

Brain Attack. Published by National Stroke Foundation, Australia (1999)

3.

MIMS Issue No 5 1999. Published by MultiMedia Australia (1999)

4.

MIMS Annual 1993. Published by MultiMedia Australia (1993)

5.

Neurology Care. Promotional material from Parke Davis (1999)

6. Reubens, D., Savard, G., Andermann, F., Dubeau, F., and Olivier, A.
Results of surgical treatment in temporal lobe epilepsy
with chronic
psychosis. The Brain (1997), 120, 1929-1936. Published
by Oxford
University Press (1997)