http://www.timesonline.co.uk/article/0,,2099-1703380,00.html

The Sunday Times July 31, 2005

Investigation

Death of the magic bullet
We have learnt to place our faith in pills. But at what cost? As more
and more prescription drugs are withdrawn because of adverse side
effects, new figures suggest that the medicines we take are killing up
to 20,000 people a year in the UK - six times as many as die on
Britain's roads. Rose Shepherd reports

Mark's death in March 2004 was horrific. He'd been feeling low and
losing sleep, and his doctor had prescribed promazine, an
antipsychotic, although Mark, 49, had no symptoms of psychosis -
until he took the drug. After two tablets he started to act oddly,
saying he felt he could control things with his mind. After a third
tablet, James, his partner of six years, saw him stepping agitatedly
from foot to foot as he talked strangely on the phone, and then he
fell.  "He said he was okay," recalls James, "but I went with him to
the surgery and we saw a different GP, who took the tablets off us and
said Mark should be all right."

That evening, as James tried to go into the kitchen, Mark blocked his
way and scuffled with him in the hall. James pushed him out of the
front door, and Mark, "the quietest person", lobbed a paving slab
through the window.

"He calmed down, so I let him in, then phoned 999. The police and
ambulance came and asked Mark if he was okay, and left us to it. When
Mark had gone to bed, I phoned the duty doctor, who said some people
react that way to medication. He didn't feel a need to come out. I fell
asleep but was woken by Mark screaming. He had locked himself in the
bedroom. I called and he came to the door. He was trying to say
something, but the words weren't coming. Then he fell on his back,
really screaming. It looked like he was having an electric shock."
James was on the phone to the emergency services when the screaming
stopped. He found Mark lying on the stairs. There was blood in his
mouth. The paramedics arrived promptly, but too late.

James was summoned to the police station, not to talk about the drug
that might have killed Mark, but to raise the possibility that he had.
"The inquest seemed mainly about establishing it was an accident. They
said they believed Mark died of postural asphyxia after falling
downstairs. Promazine was mentioned, but they never went into what
caused him to have a fit. It is just my opinion that the promazine
killed him."

According to the mental-health charity Mind's booklet Making Sense of
Antipsychotics, adverse drug reactions (ADRs) to these drugs can
include restlessness, unease, rocking from foot to foot, muscle spasms,
aggression and, rarely, potentially fatal neuroleptic malignant
syndrome, characterised by "sweating or fever... rigidity or loss of
movement, difficulty in speaking or swallowing, changes in
consciousness from lethargy and confusion to stupor or coma". Who
knows, then, if it was the promazine, or perhaps an interaction between
the promazine and other medication Mark had had? But shouldn't the
possibility have been countenanced? There is a system in place for
logging suspected ADRs.

The fact is, if someone you know is suffering from ADRs, you and they
may not know it, and it may not be immediately obvious to your GP or
even to a hospital consultant.

Allopathic medicine is founded on the belief that drugs are, all in
all, a good thing; but we are now in a society awash with medications,
and we have ushered in a killer. In a report in July 2004, the
department of pharmacology and therapeutics at Liverpool University
suggested ADRs account for 5,700 deaths a year on admission to
hospital. If adverse reactions after admission were added, this could
suggest a total of 10,000 deaths, while deaths from ADRs among those
not admitted to hospital could be as many again. To put this in
perspective, 3,221 people were killed on Britain's roads in 2004, and
six times as many were killed by a legally prescribed drug, according
to this study's conservative reckoning.

It has always been accepted that medicines can have dangerous side
effects - hence the so-called "risk-benefit" trade-off. Even drugs in
long and common use can cause ill in a susceptible few. And, with an
industry under economic pressure to produce new drugs, these are
prescribed without knowledge of their long-term side effects. It may
take years for unwanted consequences to be known. They could even show
up a generation later, as was the case with the synthetic oestrogen DES
(diethylstilbestrol), prescribed to prevent miscarriage from around
1950 until 1975 in the UK, when it was found to cause a rare form of
vaginal cancer in one in 1,000 girls exposed to it in the womb.

Most of us take pills at times, and we need clear information as to
possible side effects. Yet packet inserts are skimped, small-print
affairs, while in medical schools there is a paucity of teaching of
clinical pharmacology and therapeutics. Much of doctors' knowledge
comes from advertisements, sales reps' spiel, industry-sponsored
seminars, and a medical press seeded with ghosted articles that
emphasise the positive.

The need to monitor drugs more closely became evident after the
thalidomide debacle in 1964. Here in Britain, Sir Derrick Dunlop,
chairman of the new Committee on Safety of Drugs (CSD), circulated a
letter to doctors asking them to report promptly "any untoward
condition in any patient that might be the result of drug treatment".
Thus began the yellow-card scheme, implemented by Bill Inman, formerly
with the medical department of the pharmaceuticals division of ICI.
Under this voluntary reporting scheme, doctors were to notify the
committee of suspected ADRs.

The Medicines and Healthcare products Regulatory Agency (MHRA) now
collects yellow cards - submitted by health-care professionals and
coroners, and by pharmaceutical companies under statutory obligations
- assisted by the Committee on Safety of Medicines (CSM) and the
Medicines Commission within the Department of Health. It is funded
entirely by the pharmaceutical industry, and how it goes about its
business is not for us to know. The Medicines Act, 1968, prohibits the
disclosure of any information "obtained by or furnished in pursuance of
this act". Professor Inman demurred. "I believe," he has written, "that
all information about the effects of drugs should be available to any
bona fide research worker from the first moment that the first dose is
taken by a human being."

In 1965, Inman took home nearly 1,000 yellow cards relating to ADRs
among women on the contraceptive pill. He arranged and rearranged them
on his living-room floor, sorting and resorting them according to age,
time on the pill, and whether or not the patient had died, until it
became "glaringly obvious" that certain preparations of the pill caused
thrombosis. Inman spent hours performing analyses that, he noted, "I
would now have completed in minutes on a home computer".

The MHRA, under the chairman Professor Sir Alasdair Breckenridge
(formerly of Glaxo's scientific advisory committee), enters yellow-card
reports onto its Adverse Drug Reactions On-Line Information Tracking
(Adroit) database. Doctors, pharmacists and scientists within the
Pharmacovigilance Group of the Post-Licensing Division use this
information and other sources to assess causal links between drugs and
reported reactions. But is the authority performing any more
effectively than did Inman, grubbing around on his carpet 40 years ago?

Not to judge by a recent inquiry by the Commons health select committee
into the influence of the pharmaceutical industry, which describes a
"lack of effective discipline and regulation", a "pervasive and
persistent" industry, a "failing system of pharmacovigilance" and an
"extremely passive" process of drug surveillance. The MHRA is, says the
inquiry report, "oblivious to the critical views of outsiders and
unable to accept that it has any obvious shortcomings... [its] attitude
to its public health responsibilities suggested some complacency and a
lack of requisite competency".

cont. page 2

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Google "pharma magic bullet". Lots of interesting results. This was one
of them.

TC