Memorandum by Dr Reg Peart
EXECUTIVE SUMMARY:
This submission concerns the nature and causes
of 40 years of Benzodiazepine dependency and is a skeletal outline
of chronological events, circumstances and consequences, plus
suggestions to improve the current situation and prevent such
a problem in the future with other drugs. The objective is to
present an overview, and to provide a framework for more detailed
submissions on specific areas by other organisations and individuals.
It is requested that a separate inquiry be set up for the Benzodiazepine
health problem.
PROCEDURES RELATING TO ADVERSE CLINICAL INCIDENTS
AND OUTCOMES IN MEDICAL CARE (ACI 159)
THE BENZODIAZEPINES
1. This submission is by Dr R F Peart, National
Co-ordinator of Victims of Tranquillisers (VOT) and concerns the
nature, causes and consequences of 40 years of Benzodiazepine
dependency, arguably the biggest medically induced health problem
of the 20th Century.
2. My purpose is to present an overview
of this problem, to provide a framework for the more detailed
submissions on specific areas made by other organisations and
individuals. In the absence of a national organisation, strategy
or funding for this problem, VOT has attempted to fill this gap
by liaising, co-ordinating with and providing information to various
support groups and individuals in the UK and overseas (a list
of some of these is given in Appendix 1).[3]
For convenience, I have enclosed two previous submissions by myself,
"Tranquillizer Addiction—A Medically Induced Epidemic",
and "A Submission to Phil Woolas MP with regard to a Health
Select Committee inquiry into the Benzodiazepines".
3. The VOT archives contain many thousands
of documents from the UK and overseas, including over 150 lever
arch files of medico/legal information. It also has over 2,000
papers on Benzodiazepine problems, cross filed in chronological
order, author, alphabetical order and subject matter, along with
pharmaceutical data sheets from about 30 countries, and documentation
from the WHO, the FDA and other organisations from countries which
have Freedom Information Acts (USA, Canada, Sweden, Australia).
VOT activities also include supporting and supplying information
to claimants pursuing legal cases at the European Court of Human
Rights, against prescribers, drug manufacturers, for DLA Tribunals
and complaints to the Parliamentary Ombudsman.
4. Assessment of the medical literature
and other documents clearly shows that there are three root causes
of the Benzodiazepine epidemic—a catalogue of misprescribing,
misdiagnosis and mistreatment which has cost this nation billions
of pounds.
(2) Absence of an effective system for dissemination
of information to prescribers and patients.
(3) The education, training, attitudes and
beliefs of prescribers.
5. I believe that the nature, magnitude
and consequences of this health problem warrants a separate inquiry
and request that it not be subsumed into the above enquiry.
6. The following is a skeletal outline of
the events, circumstances and consequences of Benzodiazepine dependency
and suggestions to ameliorate the current situation and prevent
such a problem in the future.
STATE OF
KNOWLEDGE PRE
UK DATA SHEETS
(1960-1973)
7. VOT has made an assessment of the state
of knowledge and consensus of medical opinion on prescribed drug
dependence in general, and on Benzodiazepine dependency per-se.
The first UK data sheets were published in 1973-74. Sources of
information used were:
(1) Drug company clinical trials and studies;
(2) Commercial information;
(3) Independent medical research and opinions;
(4) Pharmaceutical data sheets from overseas;
(5) Physicians Desk Reference (USA) and the
British National Formularly (UK);
(6) World Health Organization (WHO) and the
Food and Drug Administration (FDA, USA).
8. It is clear that there was a general
acceptance that all sedative/hypnotic drugs could produce dependence.
There was a high awareness of the problems with the barbiturates
and meprobamates and very specific recognition that Librium and
Valium were dependence producing drugs (WHO). In 1970, the WHO
declared that 10 other Benzodiazepines should be considered as
having the same potential as Librium and Valium. All the key indicators
for dependence were well documented eg high cross-tolerance with
other sedative/hypnotic drugs, tolerance with use, withdrawal
symptoms of the barbiturate alcohol type and the reinforcing nature
of these drugs.
POST UK DATA
SHEETS EVENTS
(1973-1984)
9. The first data sheets in the UK (1973-74)
were extremely limited in scope. Much information given in those
of other countries was omitted, and the main thrust appeared to
avoid litigation, with pre-emptive strikes against the users and
prescribers rather than information for the benefit of the patients.
10. This position remained relatively unchanged
until the mid 1980s when a few minor additions were made after
years of discussions between the drug companies and the Committee
of Safety of Medicines(CSM)/Committee of Review of Medicines(CRM).
11. During this period there was a very
active campaign by the pharmaceutical industry and sections of
the medical profession extolling the virtues of the Benzodiazepines
over Barbiturates. This campaign, led by Roche Products Ltd included
1,000 visits per week by medical representatives to doctors, letters
to all GPs and consultant psychiatrists and over 10,000 copies
of a book on Benzodiazepines by J Marks the ex Director of Clinical
Research for Roche. The nature, methodology and conclusions of
this "research" were severely criticised in the medical
literature and the author recanted in 1983. The prescribers were
not notified of this.
12. There has been very little comparative
research assessing the merits of the Benzodiazepines over the
Barbiturates. The few studies made suggest that the benefit/risk
ratio is very similar and some are in favour of the Benzodiazepines.
The risk of toxicity in overdose appears to
be the only significant difference between these drugs. Home Office
Statistics give about 300 deaths per year caused by the Benzodiazepines
over the last decade. The 760 million prescriptions for Benzodiazepines
since 1960 suggest over 10,000 deaths were caused by these drugs.
Over the last two decades the Benzodiazepines have become the
"drug of choice" for those attempting suicide by overdose.
This is probably a reflection of the higher suicidal ideation
caused by the Benzodiazepines. Some observers believe that the
changes in personality and brain chemistry produced by the Benzodiazepines
are responsible for some of the increase in senseless violence
in recent years. In this context, all of the students involved
with the schools shootings and killings in the USA were on prescribed
drugs. Estimates of the number of patients per million prescriptions
dependent on the Barbiturates are about one third of those for
the Benzodiazepines.
13. The combination of little information
in data sheets plus the campaign resulted in a rapid increase
in prescribing levels which reached just over 30 million in 1979.
The rate of prescribing in the USA was about half of this and
supports the observation of an inverse correlation between the
amount of information in data sheets and prescribing rates.
POST UK DATA
SHEETS (1984-98)
14. The prescribing rates in the UK have
steadily decreased from 1979 to about 18 million in 1997, about
2 per cent per year. The factors responsible for this include
public protests, reports in the press and media and mandatory
measures such as the restricted prescribing list imposed by the
NHS in 1985, the banning of Halcion (Triazolam) in 1991 and the
prescribers fear of prosecution. Awareness by the prescribers
appears to be a minor factor.
15. In 1988, the CSM issued guidelines severely
restricting the indications and length of time for prescribing
of Benzodiazepines. The prescribing, several years before and
after these guidelines were issued, shows a similar rate of decrease
suggesting no significant reduction due to this action alone.
It is more likely that the continual decrease was due to extensive
publicity given to the litigation against the CSM, Health Authorities,
prescribers and the drug companies which began in 1988.
16. In 1993-94 the Benzodiazepine Litigation
ended owing to the withdrawal of Legal Aid Board funding. Over
£50 million pounds was spent on legal aid and by the drug
companies. Since this event the number of prescriptions for all
Sedative/Hypnotic drugs has increased by several per cent overall,
and that for Valium has increased by 15 per cent (1994-97). The
prescribing of the new Sedative/Hypnotic drugs Zolpidem and Zopiclone,
which act on the Benzodiazepine receptors has risen dramatically
and is now about two million per year. It is very significant
that the number of adverse reactions (No/yr/106 pres.) reported
for these drugs is very much greater (x100) than for any of the
Benzodiazepines. This coincides with many reports to support groups
of dependency on these drugs. It appears that the lessons of history
have not been learnt and there is an additional dependency epidemic
in the making.
NATURE, MAGNITUDE
AND CONSEQUENCES
OF BENZODIAZEPINE
DEPENDENCY
17. The Benzodiazepines like all Sedative/Hypnotic
drugs are depressants of the central nervous system with marked
dis-inhibitory properties. They are fat soluble, accumulate and
are stored in the body and brain. These properties produce extensive
toxic effects causing a multi-symptom illness with a wide range
of physical, mental and sociological problems. VOT files contain
thousands of papers on these eg 420 on Addiction/Dependency/Withdrawals,
158 on Illegal Use, 130 on paradoxical Reactions, 112 on Pregnancy/Neonates
and Children, 96 on Deaths/Toxicity and Poisoning, 90 on Accidents
and Injuries, 58 on Geriatric/Elderly, 42 on Muscular Skeletal
and 36 on Heart/Respiratory problems. A complete list of about
70 topics is given in Appendix 2. The number of papers probably
represents less than 50 per cent of the total in the medical literature.
18. Dependence on the Benzodiazepines occurs
quickly and frequently ie in a few days or weeks. The Institute
of Psychiatry recognises that it can occur within four weeks—hence
the time limit on prescribing in the 1988 CSM Guidelines. Various
estimates of the percentage of patients dependent on these drugs
are 20-45 per cent after 6 months and 50-90+ per cent for 1-2
years. All longer term users including some who have been on these
drugs for over 30 years are dependent (addicted) on them. It is
now generally accepted that Benzodiazepine withdrawals are far
worse and last much longer than those for alcohol, heroin or the
barbiturates. Estimates for long term users of alcohol suggest
only about 5 per cent become dependent. Hence it is arguable that
the Benzodiazepines are as addictive as any other legal or illegal
drug.
19. Estimates on the number of people using
prescribed Benzodiazepines vary from 10-17 per cent of the adult
population with from 1-3 per cent on these drugs for over 12 months.
The current 18 million prescriptions for Benzodiazepines (UK)
equates to about 2.5 million people using them for periods greater
than one month as specified in the guidelines. Consideration of
all sedative/hypnotic drugs give significantly higher figures
eg over 1 million of the elderly take sleeping pills regularly
at night (MIND 1995). These figures suggest that there has been
only a small improvement in the long term problem over the last
decade with the possibility that it is getting worse again.
20. The very wide range of physical and
mental problems caused by these drugs is very well documented
but the sociological problems and denial of basic human rights
is less so. These are summarised in the following extract from
an affidavit to the Benzodiazepine Litigation 1995 by R F Peart
"includes loss of family, colleagues, work, reputation, respect,
personality and character. We have also lost rights such as freedom
to think, talk, act, or react normally and to experience the normal
range of human emotions" "Many have lost the rights
to choose friends or have normal relationships, to marry and to
have children. Some have had babies terminated or borne addicted
to these drugs suffering from physical and other mental problems.
Many have lost the right to work and to support themselves and
their families financially". Many have been stripped of their
dignity, lost meaning of life and most aspects of what it means
to be a human being.
ROLE OF
THE DRUG
COMPANIES
21. The pharmaceutical industry has a long
history of convictions for illegal activities on a world wide
basis. In 1950, Hoffman La Roche were convicted in the USA of
failure to warn of the hazards of a drug. As a result of a Department
of Health initiative a Monopolies Commission in 1973 into un-competitive
practices and profiteering by Roche Products Ltd resulted in the
payments of several million pounds to the UK Government. Very
recently (May 1999) Roche has been fined $500 million in the USA
for a global price fixing conspiracy.
22. The root cause of the Benzodiazepine
problem is the suppression of information by the drug manufacturers.
They knew of the probability that these drugs would cause dependence
by 1960 and all the information currently given in the UK data
sheets and Patient Information leaflets was known prior to the
first data sheets in 1973-74. VOT archives contain extensive material
demonstrating these propositions. It has all been supplied to
Mr Ian Caldwell who is a litigant against Roche Products Ltd in
the Scottish Courts. He has written to the Health Committee under
separate cover.
23. n 1968, Wyeth Lab Inc were convicted
in the USA with failing in its duty to warn of the dangers of
a drug and in more recent times the FDA in a letter to Wyeth in
1989 stated that "Wyeth has an intolerable record of compliance
with the law on drug promotion". Wyeth were issued with 18
motions of violation of drug advertising and labelling laws over
a two year period. One violation was that Wyeth had disseminated
promotional material clearly false and misleading indicating a
general and wilful disregard for legal and regulatory limitations
on drug promotions. The information in VOT files shows that Wyeths'
activities in the UK follows the same pattern as those for Roche.
VOT is using this information to support a complaint to the Parliamentary
Ombudsmen about the refusal of the MCA to release details of Wyeths
licence application for Ativan (lorazepam).
24. In 1992, Halcion (Triazolan) manufactured
by Upjohn was banned from sale in the UK. The reasons for this
included the failure of Upjohn to disclose, in the licence application,
information concerning frequent and disabling psychiatric adverse
reactions as given in the clinical trials.
ROLE OF
GOVERNMENT COMMITTEES
AND DEPARTMENTS
25. The CSM/CRM/MCA along with the Medicines
Act and the 1972 Medicines (Datasheets) Act have been severely
and extensively criticised over the years. The primary purpose
and responsibility of these committees is the health and safety
of the public. In practise, their primary function has been as
a protective shield for the pharmaceutical industry with their
action and activities shrouded by "official" secrecy.
It would be an insult to the intelligence of committee members
to assume that they were/are not aware of the consequence of their
actions.
26. With regard to the first data sheets
in the UK, there are two scenarios that require investigation:
(1) Did Roche and Wyeth declare all appropriate
information to the CSM and if so why did it not appear in the
data sheets?
(2) If Roche and Wyeth failed to disclose
this information, then why did the CSM members not query the submission
and ensure that the data sheets contained all information that
existed in the medical literature?
27. The Department of Health under successive
governments could have and should have intervened to diminish
the Benzodiazepine problem from the early 1970s onwards. When
they finally did in 1985 with the selected list of generic Benzodiazepine
they were, as with their previous initiatives, motivated by financial
considerations. Ironically it was this action that prevented thousands
of sufferers from suing the drug companies.
28. A major criticism of the CSM/MCA is
the overwhelming conflict of interest produced by financial links,
including consultancies with the drug companies. Recent changes
introduced in 1993 ensure that the MCA is financed by licence
application fees and other remuneration from drug companies. Such
financial links inevitably produce a strong bias and loss of independence
in the system. The establishment of truly independent committees
and the passing of a Freedom of Information Act (with teeth) are
both required to ensure that further health scandals do not occur.
29. The prescribing of drugs to the population
at large acting as a giant human laboratory with no adequate controls
on long term use or pharmacovigilance is both unethical and immoral.
The principle that the minority must suffer, with no practical
means of redress, for often dubious benefits to the majority,
can only be justified with blatant casuistry and sophistry. Redress
via legal action is a non-starter for group medical negligence
actions. No case in the UK against a pharmaceutical company has
reached the stage of a legal ruling. The failure of the Benzodiazepine
litigation is one more example of the inability and incompetence
of the English legal system, and those who operate it, to deal
with Group Medical Negligence claims. The strong conflict of interest
in the roles of consultant psychiatrists as case experts and prescribers
was a key reason for its failure. The basic problem of "inequality
of arms" can only get worse with the recent changes in the
law concerning legal aid.
30. After the Thalidomide tragedy (another
sedative/hypnotic drug), a number of official bodies looked at
compensation schemes for drug damage, eg a Royal Commission, the
Law Commissions for England, Wales and for Scotland. They recommended
that the law should change and that companies should be responsible
for compensating those injured without the victims having to prove
negligence in court. The EEC agreed but UK governments have failed
to implement the findings. There should be a mandatory requirement
that drug manufacturers finance and support ongoing research into
the causes of a treatment of long-term and permanent adverse reactions
caused by ingestion of prescribed drugs. Many victims have been
made unemployed and unemployable because of the long term effects
of Benzodiazepines. Because of the relatively few studies in this
area, lack of knowledge and denial by doctors, many are not receiving
Disability Living Allowance and other benefits they should be
getting.
ROLE OF
PRESCRIBERS
31. There are two factors which have heavily
influenced the attitudes and activities of prescribers and caused
the misprescribing, misdiagnosis and mistreatment over the last
40 years. Firstly the pressure of extensive promotion by the drug
industry in the 1960's and 1970's has produced a mindset in many
of the older doctors. A recent survey showed that over 70 per
cent of GPs and over 30 per cent of Psychiatrists had little or
no knowledge of the effects of Benzodiazepines on brain chemistry.
Secondly tradition and training makes it difficult for doctors
to appreciate adverse consequences of drug use. Most are not trained
to diagnose and to recognise the syndrome of addiction and its
adverse consequences and are unable to differentiate between normal
clinical pathology and that produced by drugs.
32. Many doctors propagate myths and fallacies
concerning addiction and drug side effects as a part of their
denial of the problem, eg the side effects are a resurgence of
a pre-existing or underlying problem, or its all in the mind,
or it shows the patient needs to be on these drugs for the rest
of their life and the patient has an addictive personality. The
reality is that most who become addicted to these drugs were put
on them for somatic symptoms, sleep problems or sociological reasons.
Only a very small minority had any diagnosed pre-existing mental
disorder. In a recent report by the Royal College of Psychiatrists
two important statements were made in this connection:
(1) No single underlying trait or unique
constellation of personality features can be identified as predisposing
to drug misuse.
(2) It is improbable that gross mental illness
is ever likely to make more than a marginal contribution to drug
misuse.
In addition the WHO (1993) categorically states
that all aspects of dependence can be explained by biochemical
factors.
33. The lack of recognition and acceptance
by prescribers of Benzodiazepine induced problems have many consequences
and impacts heavily upon the patient's endeavours to obtain appropriate
treatment. The non-recognition of depression and anxiety as major
side effects and part of the withdrawal syndrome has led to many
being given ECT inappropriately. Others have been misdiagnosed
as neurotic, psychotic, alcoholic, depressive, schizophrenic or
having senile dementia, multiple sclerosis or Parkinson's disease
and subjected to years of inappropriate multi-drug prescribing.
Both the counsellors and clients attending tranquillizer support
groups bitterly complain of the absence of interest or support
from the doctors, in their attempts to recover. Many would like,
and some really need, residential treatment to come off these
drugs but unlike the alcoholic or hard drug addict such treatment
is rarely available because of the high cost of the length and
severity of the withdrawal process. A system of help and recovery
that is independent of prescribing doctors is urgently needed.
RECENT REPORTS
34. There are a number of recent reputable
reports that are highly relevant to the Benzodiazepine problem
in the UK, those include:
(1) The International Narcotics Central Board
1998
"The Board requests to Governments of countries
with high levels of consumption of Benzodiazepine and their increasing
abuse to conduct, in co-operation with non governmental organisations
involved with treatment and rehabilitation, comprehensive surveys
to determine the size of the population abusing/and using these
substances. There are indications that some doctors prescribe
Benzodiazepine for unnecessarily long periods and for symptoms
that may not require such treatment. The Board invites the Governments
of countries in Europe to raise the awareness of medical practitioners
of the need to use those substances in a more rational manner."
(2) The International Society of Drug Bulletins
(ISDB, 1997). This report severely criticises the role and activities,
especially the lack of transparency, of drug regulatory authorities.
(3) A study by the Kings Fund health charity,
1998 "Informing Patients" concludes that information
materials contained out of date, inaccurate and sometimes misleading
information.
(4) The Erice Declaration resulting from
an international WHO sponsored conference on "Effective Communications
in Pharmocovigilance". This contains five key recommendations
all of which are pertinent to this submission (see Appendix 3).
(5) Medication for Older People (Royal College
of Physicians, 1997) "Adverse drug reactions remain an important
cause of morbidity even mortality in older people" . . .
"older people suffer much drug related iatrogenic disease
caused by inappropriate treatment which may be incorrect medication,
inappropriate polypharmacy and/or inadequate monitoring of therapy".
35. This submission is supported by further
information and factual evidence, in my previous report (attached)
to Phil Woolas MP, albeit that contains only token samples of
the total evidence available in VOT archives and other sources.
WORDS OF
WISDOM
— The only difference between a drug
addict and the rest of society is the drug—Krivanek, 1988.
— The level of science in psychiatry
lies between astrology and witchcraft—Anon.
June 1999
3 Appendices not printed. Back
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