Memorandum by APRIL (Adverse Psychiatric
Reactions Information Link) (PI 60)
The charity collects and collates information
from health professionals, the public and from medical literature
about psychiatric and neuropsychiatric adverse drug reactions
(ADRs), and alerts doctors and professors to inquiries such as
The chair Mrs Millie Kieve who, as part of a
Millennium Award in 2000, studied suicide prevention and attended
meetings and conferences in the UK and the USA. Many leading specialists
in the field of ADRs support the charity by speaking at conferences
and offering advice and information. All the information in this
submission is from knowledge and information gained since Karen
Kieve died following a series of adverse reactions to a variety
of medicines and anaesthetics in 1995.
The charity held a major conference in 2001
and will hold one 4 November 2004.
Meetings are planned at the House of Commons
and the Royal Society of Medicine. All this work is done with
little funding and no paid staff.
1. DRUG INNOVATION
(a) The pharmaceutical industry had a higher
that expected trade surplus of £3.6 billion in 2003 (ABPI
Press Release 19 May 2004) The industry spends very little of
their profits on new drug development.
(b) A great deal of money is spent on producing
what are known as "Me Too" drugs to break into the market
of competitors. Ingredients of established drugs may be altered
or just the name changed. Sometimes old drugs may be directed
at new conditions not included in the original licence application.
For example Duloxetine was used for urinary tract infection and
will be marketed as an antidepressant. Prozac became Sarafem and
Wellbutrin became Zyban.
Recommendation for action by the Government
(a) There should be a mandatory obligation
for the industry to spend a designated proportion of profits on
research for treating rare disease and finding cures for iatrogenic
disease and other long-term medical conditions.
(b) New licences could be restricted to drugs
proven in clinical trials to be more effective or safer that similar
drugs already on the market. Only drugs with improved efficacy
or safety in comparison with existing licensed drugs. at equivalent
doses, should be considered.
2. THE CONDUCT
(a) Favourable results of clinical trials
have been selectively published and unfavourable results suppressed.
(b) Serious adverse drug events (SAEs) during
clinical trials are not disclosed.
The SAEs that occur during the clinical
trials are the confidential information of the pharmaceutical
company. James Wright, Professor of therapeutics and pharmacology
at the UBC Canada presented some startling information from clinical
trial data that he has researched for Zyban, cox 2 inhibitors
and statins. I have his presentation and he has given me permission
to share this information so it could be viewed by the Health
Information about the agitation suffered
by people withdrawing from Seroxat in a pre licence trial, was
not disclosed by GSK in pre licensing data. Dr David Healy found
this evidence in the GSK files in their premises, during his research
when he was allowed access for legal reasons.
(c) There is no research into why adverse
drug reactions (ADRs) occur and no research to discover the causes
of iatrogenic disease.
(d) There are no NHS clinics offering specialised
help for iatrogenic illness or support for medication withdrawal.
Such clinics could run research trials into ADR causes. NECA was
the only dedicated withdrawal clinic run by Professor Heather
Ashton to support people withdrawing from benzodiazepines.
(e) Too little research is carried out in
the area pharmacogenetics.
Recommendation for action by the Government
(a) All clinical trials should be pre-registered
and ALL results given to the regulators. All clinical trial data
should be in the public domain. Freedom of information should
apply. Undisclosed information leading to harm of patients should
lead to legal proceedings.
(b) Serious Adverse Events (SAEs) should
be disclosed to the regulators.
(c) Research into ADRs should be mandatory.
(d) Clinics for medication withdrawal support
and for monitoring sufferers of iatrogenic disease should be government
funded. Information and data from these clinics could provide
valuable research material.
Professor Heather Ashton estimates 200,000
involuntary benzodiazepine addicts in the UK. Many people need
support to withdraw from SSRI antidepressants.
(e) Enzyme deficiencies lead to ADRs and
death, yet the "one size fits all" method of drug prescribing
is costing the NHS a great deal of money due to the damage to
health of thousands of patients. Patients suffering ADRs could
be tested for enzyme deficiencies.
Preventative initiatives could include enzyme
and endocrine tests, which could possibly identify groups liable
to suffer ADRs.
The network of genetic centres in which the
Government has invested, to investigate disease, should not just
be to facilitate tests for genetic disease as at present. They
could test patients for enzyme deficiencies to assess drug tolerance.
3. THE PROVISION
I. Patient Information Leaflets (PILs) do
not contain enough information and are often unclear with ADRs
being hidden in the small print. The fact that a drug may cause
depression or suicidal ideation is often not stated.
II. Consent forms would ensure that the prescribing
clinician explained the risk benefit to a patient, and the advisable
safeguards for taking and withdrawing from medication.
III. Newly discovered ADRs from Yellow Card
signals or Prescription Event Monitoring (PEM) studies are not
put on the PILs, for many years or not at all in some cases.
IV. Drugs dispensed from bulk supply are
often given to the patient in a brown bottle without a PIL. Hospital
patients are seldom given information.
V. PILs do not disclose previous names under
which the same drug was marketed.
VI. Hospital libraries have been found from
personal research to lack vital ADR manuals and books. Even small
publications such as the Consumer Assn Drug and Therapeutics Bulletin
and the CSM Latest problems in pharmacovigilance are unavailable
to most medical and nursing students.
VII. There is currently no system to keep
coroners regularly informed about new ADR alerts or lists of drugs
which affect a person's driving ability.
VIII. Patients receiving dental treatment
are not given PILs for drugs used during treatment.
Recommendation for action by the government
I. PILs from all manufacturers for the same
or similar products, should be compiled and approved by independent
scientists and not by sales people. Information and class warnings
should be standardised, with nothing missed out that could be
detrimental to the patient's health. If a drug may cause suicidal
feelings the PIL should state this. If a drug causes depression
it should state this. "Tell your doctor if you have ever
suffered from the following" does not explain that a drug
can CAUSE the following . . .
The PILs should be reviewed by patient groups
as well as specialists. The colour and size of print should be
readable. It should be available in different languages, with
a clear heading "POSSIBLE ADVERSE EFFECTS" on every
WARNINGS ABOUT THE RISK OF ALCOHOL with
medicines should be put on PILs, in the box and also on the outside
of the box. Any food or fruit juice that is contraindicated should
be shown on the box and marked clearly on the PIL.
PILS should include the need to drink a
full glass of water at least with medicines. The reason for this
should be given which is to prevent damage to the oesophagus or
kidneys and help prevent blood disorders.
II. The provision of consent forms in several
languages should be considered for all long term medication. People
are still informing APRIL of the fact that they have been taking
cortico-steroids having received no warning about the risk of
osteoporosis or the risk of suddenly stopping steroids. Mental
depression caused by medication is being regularly treated with
antidepressants without patients being informed their depression
is medication induced. Depression is a serious condition and often
triggered by medication ADRs. APRIL can provide testimony from
hundreds of patients who in most cases failed to persuade their
doctors to send in Yellow Card reports. Many of whom were prescribed
antidepressants without having the original drug stopped. (Zoton
and Dianette are often named as drugs causing depression, which
lifts once the drug is stopped.
Marketing departments change the wording
on PILs and adverts, without consulting the medical staff, I was
informed by an MP who used to work for an advertising agency and
by a pharmacist working for pharmaceutical companies.
III. Prescription Event Monitoring Studies
(PEMs) ignored by MHRA and the manufacturer.
The Pharmacovigilance of Mirtazapine: results
of the DSRU prescription event monitoring (PEM) study on 13,554
patients in England. This showed evidence of serious ADRs which
are still not on the drug information or included in the CSM bulletin
"Current Problems in Pharmacovigilance". The following
results: Agitation (73), aggression (70), rash (20), hallucinations
(13) and abnormal dreams (31). were all unlabelled AES. The Drug
Safety Research Unit (DSRU) PEM Journal of Psychopharmacology
Doctors should be informed individually
by the pharmaceutical companies of such information as found in
the DSRU PEM study and in other studies highlighting ADRs.
The Committee on Safety of Medicines (CSM)
should include signals of unlabelled ADRs information from DSRU
PEM studies in their publication "Current problems in pharmacovigilance".
The MHRA should have mandatory power to
add information to Patient Information data and PILs, the ADRs
reported in studies, or on Yellow Cards reporting forms. Dr June
Raine told me that the initiative has to come from the pharmaceutical
company and this is not a satisfactory arrangement.
IV. Bulk supplies leads to many drugs being
dispensed and given to the patients without advice or information
due to lack of PILs being supplied by the manufacturer.
Pharmaceutical companies should supply enough
PILs for every patient to receive one with their prescription
from bulk supply dispensing.
Hospitals should provide the patients or
their families with information about the drugs they intend to
prescribe. Patients should always be provided with PILs to take
home from the hospital.
V. Zyban also known as buproprion and wellbutrin
has been documented for years as a drug that may cause seizures.
Anyone prescribed this drug as an anti-smoking aid, in England
would not necessarily know they were being given a well know antidepressant
known as wellbutrin. This information is not on the patient information
Prozac being re licensed for PMT under the
name Sarafem may be given inadvertently to someone who should
not be given SSRIs. All names that the drugs were previously marketed
under should be on the PIL.
VI. The Government should make it a requirement
by law that all available information on ADRs should be in every
hospital library and kept up to date. Libraries should be inspected,
possibly by patient volunteers who could be given a list of books
to look for. Medical and nursing students should have easy access
to the information available.
VII. Coroners should have access to information
and independent advice about the role medication may have played
in a sudden death. This charity APRIL is a resource but there
should be an official resource for all coroners, many of whom
have no medical knowledge.
VIII. A coroner informed me of a dental
death where the fact that dental treatment was involved, was not
even put on the death certificate. All dentists should be informed
that patients are entitled to a PIL by law.
I. The Royal Institution of Great Britain
has been holding a series of talks and meetings sponsored by Novartis
at 21 Albermarle St London W1 aimed at audiences consisting of
the general publiic, since 2001. These are still continuing, so
must be of benefit to Novartis. The publicity for the talks may
not mention specific drug promotion, or the fact that Novartis
are sponsoring the talk, but the picture in the lecture theatre
my be different.
I attended one of the Novartis meetings
on 24 May 2001 titled "Schizophrenia". At the side of
the speakers was a large promotional poster.
The meeting was promoting early diagnosis,
early drugging and specifically was singing the praise of Clozapine,
the Novartis blockbuster drug for schizophrenia.
I heard Dr Adreanne Revely state that Clozapine
has no side effects. I also heard her state that the earlier you
administer drugs the better the outcome. The emphasis was on finding
evidence of schizophrenia in children and starting Clozapine as
early intervention. She said there is a better outcome the earlier
you administer the drugs. Professor Robin Murray was there to
support her statements.
I was with psychologist Rufus May and will
be willing to give oral evidence of the content of this meeting
which was blatant drug promotion to the masses. Novartis had intended
to use a film of the meeting as promotional material, on the internet
but this intention was apparently thwarted by the close detailed
questioning by Rufus May and myself.
II. "Europe's premier forum for marketing
and communications professionals in the pharmaceutical industry"
was held in London on 10 and 11 May 2004.
The Forum brochure was quite disturbing
and illuminating about the marketing tactics of the pharmaceutical
industry. and gives a hint of how unscrupulous the industry is
in promoting drugs and disease awareness.
On Day One talk titles included:
10.20 "PATIENT RELATIONSHIP MARKETING-"
The new DTC?
* Understanding and segmenting patient populations.*
Building profitable long term patient relationships etc
13.45 "MARKETING TO LOWER SOCIO
* Why your marketing to consumers needs to be
trashy, have a reading age of 9, lots of bold colours and still
On Day Two Tuesday talk titles included:
11.20 "THE POWER OF STRONG BRANDING
IN LIFE CYCLE MANAGEMENT"
* Brands as business assets; brand development
and its role in the pharma industry
* The Zantac-Tagamet example: optimisation of
a blockbuster etc
14.20 "WORKING TOWARDS SYNERGY
BETWEEN PROFESSIONALS AND PATIENT GROUPS" (themed luncheon
A profile for speaker Philip Atkinson International
Consumer Marketing Manager for Roche Pharmaceuticals, Switzerland
it states at the end of the paragraph. "Philip's specific
interest is how to drive patient demand for healthcare products."
(You can download the pdf brochure at http://www.pmc.access-events.com
then click on Programme and when the programme page shows the
participants, click on the small blue arrow which states "
click here to download brochure as a pdf.)
III. FREE HOLIDAYS AND ENTERTAINMENT are
provided and doctors feel obliged to order expensive products
from their host. Direct promotion of drugs to health professionals
is a reason for the provision of perks in the way of free food,
entertainment, holidays in luxury hotels and trips abroad. This
is still happening yet well hidden.
IV. PATIENT SUPPORT GROUPS are sometimes
set up by pharmaceutical companies and others are financially
supported by them. This leads to the promotion of drugs in the
groups journal and meetings where the drugs are promoted and little
attention paid to warnings about ADRs. On a web site of a leading
charity dealing with anxiety and supported by two pharmaceutical
companies, there is a list of drugs used to treat the condition,
no link to discussions about risk benefit or ADRs. Named doctors
and professors on the anxiety site I viewed are known declare
that they receive income from pharmaceutical companies.
V. CME SEMINARS AND MEETINGS sponsored by
pharmaceutical companies should be reviewed. Clinicians are sometimes
paid to promote drugs in meetings and conferences.
VI. CONFERENCES are so heavily sponsored
by the pharmaceutical industry and the representatives are everywhere
promoting and standing around looking at the doctors who, I believe
feel intimidated and therefore do not ask relevant questions
about ADRs during conference sessions. Very little discussion
of risk benefit or ADRs took place at the British Association
of Psychopharmacology annual conference, I attended. In a talk
about suicide and antidepressants, I was the only person to ask
about incidents of akathisia (drug induced physical and mental
agitation that often leads to suicide).
VII. FREE FOOD IN THE GP PRACTICE
The provision of free lunch for GP practice
staff in return for listening to information about a drug still
goes on I am told by a local health professional.
VIII. DRUG PROMOTION to POLITICIANS and using
Pharmaceutical companies employ lobbyists
to influence politicians for the purpose of selling their products
to the NHS.
One example of FREE FOOD AND DRUG PROMOTION
IN THE HOUSE OF COMMONS
Conservative Party Mental Health Summit Wednesday
29 October 2003 Portcullis House, Palace of Westminster FOOD PROVIDED
BY ELI LILLY
I attended a recent Conservative Mental
Health Summit meeting at the House of Commons, the lunch was provided
by Eli Lilly. The Mental Health Bill will promote the use of drugs
and yet Tim Loughton MP or Liam Fox MP could not see this compromised
the meeting at which Eli Lilly representatives were present.
DRUG PROMOTION at the meeting by a speaker.
At the same meeting, a person, ostensibly chosen
as a patient spokesperson, promoted a drug in an obvious way during
his talk. At the moment he said the name of the drug which he
said had "helped his condition" I saw the Lilly reps
of the look at each other smiling. The talk being about his experience
as a mental health patient had no reason to include a drug name
co-incidentally manufactured by Eli Lilly.
IX. The Promotion to and influence on the
THE NATIONAL SUICIDE PREVENTION STRATEGY
FOR ENGLAND contains no reference to medication induced suicide
or akathisia. The risk of suicide is 2.2 times greater for those
taking SSRI antidepressants (stats from all clinical trials in
the UK and USA Dr David Healy)
THE NATIONAL SERVICE FRAMEWORK FOR DEPRESSION
THE ELDERLY AND MENTAL HEALTH promotes the discovery of depression
yet contains no reference to medication induced depression.
ABPI Framework Will Help NHS And Pharmaceutical
Industry To Work In Partnership To Help Patients
A framework to guide joint working arrangements
between the pharmaceutical industry and the NHS to benefit patients
has been launched today by the Association of the British Pharmaceutical
Industry (ABPI) in association with the NHS Alliance.
The announcement comes as a survey shows
that more than half of Primary Care Organisations (PCOs) now work
in partnership with the pharmaceutical industry, rating medicines
management projects as the most helpful area of working. Other
top-rated areas are in team building and communication skills,
implementing NICE guidelines and national service frameworks,
and the training of nurses.
"This survey shows how timely the issue
of the framework guidelines is," said Dr Trevor Jones, Director
General of the ABPI. "The NHS Plan and other recent publications
from the Department of Health all point to the benefits that can
come from a constructive engagement with the private sector.
"In the spirit of this developing relationship,
the ABPI has produced this document to introduce NHS managers
and decision-makers to the benefits of partnership with the pharmaceutical
An NHS Confederation Diary for 2005 has
on the front cover the words "supported by Wyeth"
Within the diary it states "The
confederation aims to bring industry and the NHS closer and to
The delegate pack for the NHS Confederation
conference June 2004 is also sponsored.
RECOMMENDATION FOR ACTION by the Government
I. The film of the Novartis meeting should
be available and the Health Committee could review the film. The
Royal Institution and other such "respected" bodies
should be informed of their ethical duty to protect the public
from blatant drug promotion by Novartis. A person I spoke to in
the events department said they could not exist without Novartis
and was not aware of the content of the meeting I attended. The
government should provide funds to cover the cost of independent
meetings at the Royal Institution so that a balance could be provided
for the members and the public who attend RI meetings.
Such promotional conduct should be carefully
monitored and government representatives should attend all meetings
sponsored by pharmaceutical companies to hear and see the blatant
promotion of drugs to innocent audiences. Clozapine causes serious
blood disorders, far from having "no side effects" as
stated by Dr Revel, the patient has to have regular blood tests
while on Clozapine. The drugs cause diabetes, obesity and heart
problems and a young person may be helped by counselling and may
not need long-term medication.
The Government should look at the school
curriculum which could include time to help children learn how
to deal with life events and teach about life style, healthy living,
the importance of healthy diet etc. Relaxation techniques and
perhaps good breathing techniques and yoga could help people cope
with life events.
Politicians concerned about the breakdown
of values and decent behaviour in society should look towards
the top of industry and in particular to the pharmaceutical industry
where such bad examples trickle down into society as a whole.
The Government should halt the medicalisation
of society. The promotion of disease should be stopped. New diseases
such as "social phobia" are promoted to create a market
II. Such conferences should be monitored
by government "watch dog" representatives. The fact
that no one hesitates to put such a blatantly crude marketing
brochure on the Internet is a reflection of the complacency of
the industry. The medicalisation of society is costing society
in huge sales of medication and huge bills to pay for the damage
The cost of ADRs may be up to 70,000 deaths
a year in hospitals according to the NPSA. The cost runs into
billions for extra bed days and no one has estimated the cost
to society of ADRs in Primary Care.
III. DRUG PROMOTION TO DOCTORS DURING LUXURY BREAKS
& FREE TRIPS
I have been told by one entertainer that
the provision of his services was furtively hidden in fake invoicing
for lighting and other such needs for so called "therapy"
weekends where 120 people, GPs and their partners or practice
nurses were feted in the best luxury hotels, given free drink
and top class entertainment.
The GPS had to attend one 10 or 15 minute
talk on a topic such as asthma or migraine and had to sign a form
saying that they had attended a "therapy weekend".
The pharmaceutical company sales reps told
my contact that they always got orders for the product the following
week as the GPs could hardly refuse after being plied with food,
as much drink as they could take and entertainment. For a few
The products being promoted were very expensive
as in the case of an inhaler for asthma costing £22 as compared
to the NHS blue one at £1.96.
The entertainer was told not to invoice
the pharmaceutical companies but to invoice a small lighting company.
The pharmaceutical companies were providing
so many luxury trips that the lighting company originally doing
the invoicing to the pharm company, as lighting, then paying the
entertainers, could not cope. So this entertainer was actually
put on the books of the pharmaceutical company and was provided
with a supply number for the invoices.
This stopped about six years ago and he
knows that now the way the companies continue to entertain the
doctors, is by employing professional entertainers with some kind
of medical or health qualification such as therapist.
So a person with a background in entertainment
now ostensibly employed as a therapist/speaker but who, if you
attend a therapy weekend will be found doing stand up or some
other entertainment for far longer than the actual 10 or 15 minute
listed therapy talk. The fees are substantial for such entertainers
with medical qualifications.
My source, has the same fear that so many
in the medical profession and businesses have, that if he is identified,
his current livelihood could be affected. He would be willing
to be interviewed and produce evidence, if his identity could
IV. Patient Groups should be told to display
how much they receive from the pharmaceutical industry on their
literature. A "health warning" should be mandatory to
go on all literature from such groups as Depression Alliance who
receive support from the industry.
V. The CME and other educational courses
should be removed from the influence of the industry.
VI. The Government should develop guidelines
for ethical management of professional organisations and the Royal
VII. The practice of promoting drugs in GP
practices could be stopped.
VIII. The government will have to find ways
of halting the influence of the industry. It should be illegal
for politicians to accept free food, entertainment or money from
the pharmaceutical industry, either for themselves, for meetings
they organise or for party funds. Tony Blair had breakfast with
Paul Drayson (now a life peer). His company, Powderject, made
an estimated £20 million. The Government purchased a smallpox
vaccine from them. Drayson apparently gave a second £50,000
donation to the Labour party while the Government was deciding
who should be handed the contract.
Link to an article :http://politics.guardian.co.uk/foi/story/0,9061,1249440,00.html
IX. The National Suicide Prevention Strategy
and the National Service Framework have failed in not mentioning
that depression and suicide may result from ADRs. The Government
should establish how and why these omissions occurred.
The close partnership with the ABPI and
the NHS will result in greater than ever drug promotion. The Government
should make sure that the education of medical students, nurses
and health professionals balances the immense influence of the
industry in every sphere of their lives.
Chairs at universities in Drug adverse effects
and Toxicology should give an opportunity to medical and other
students to specialise. Education which currently rarely included
even and exam in pharmacology and therapeutics, let alone toxicology
and ADRs, should include the subject in all curricula.
A very worrying fact is that few medical
schools include any exam specifically in how drugs work, or how
to prevent, recognise or treat ADRs.
Southampton University has just dispensed
with their 12 days of pharmacology and therapeutics and replaced
this with alternative medicine. According to Professor Saad Shakir
of the DSRU.
The GMC produce guidelines on medical education
"Tomorrows Doctors" and only added a reference for the
need to include ADRs when I had pointed out their omission. They
thanked me for drawing their attention to this. Dr John Halliday
drew my attention to this and told me of the concerns of others
like himself who were teaching pharmacology in universities.
Patient Education is often biased
as it stems from support groups and disease campaigns funded by
the industry, as happens at the Royal Institution.
The refusal of the Dean of UCL to display
a flyer for a conference offering free places to medical students
to hear leading experts in ADRs in 2001 was a shocking reality.
He did not want to jeopardise his funding, he was reported to
have told the member of the students union who asked permission
for the flyer to be displayed.
Recommendation for Action by the Government
Government funding for medical education
should be increased to reduce reliance on the pharmaceutical industry.
All the universities where no specific pharmacology or ADR education
takes place should be warned not to let their major source of
funding be an industry that influences the standard of education.
The regulatory agency (MHRA) is also promoting
the pharmaceutical industry and therefore cannot be viewed by
the public as truly working in the interests of the patients.
It is known that drug licences are rushed
through and that pharmaceutical companies may be selective in
providing results of favourable clinical trials while withholding
unfavourable results. Clinical trials do not currently have to
include a cross section of population using varied age, gender
and ethnic origin. Withdrawal period is excluded from clinical
trials and reviews of patients, following cessation of drug,
are not mandatory.
Recommendation for Action by the Government
Efficacy should be assessed on the basis
of comparison with similar drugs using equivalent dosage and for
the age group that may be prescribed the drug.
Results of all the clinical trials should
be reviewed before licensing. No trial results should be hidden
and it should be a criminal offence if trial data is hidden or
ADR statistics should be centralised and
information from such as the Royal College of Anaesthetists should
be pooled centrally on an independent data base. Not, as now,
retained solely for their own purposes.
The collating and analysing of ADR data
should be funded by the government and should include data from
medical records of patients who suffer sudden unexpected death
due to organ failure, accident or suspected suicide. This data
could be analysed and interesting statistics could emerge without
recourse to expensive toxicity tests which fail to show all the
drug deposits that may be in the tissues or otherwise dispersed
from the blood soon after death.
The benefit to the Government would be to
win back the respect of the public and the savings for the NHS
would more than cover the cost in the long run.
6. PRODUCT EVALUATION,