This is the emailed comment (reproduced
in full without their permission) to Dr Murray from
the Pharmacovigilance Division at the Medicines Control
Agency on her letter (below) to the British Medical
MCA ref: HPO2690 8 July 2002
Dear Dr. Murray,
Thank you for the copy of your response to the article
by Davies et al in the BMJ 324:1519-1521 entitled 'Discontinuation
of thioridazine in patients with learning disabilities:
balancing cardiovascular toxicity with adverse consequences
of changing drugs' published on June 22 2002.
The wording which was issued from the Medicines Control
Agency (MCA) can be found as follows: 1) MCA Press release,
2) Message from Professor Alasdair Breckonridge, Chairman
of CSM, 3) Advice on prescribing information and 4)
DOH on the following web links:
The website which you have cited in your response (http://www.doh.gov.uk/cmo/cmo00_18.htm)
is the only one to contain the garbled english that
you have highlighted. As all the others are consistent
with the original communications cascaded from the MCA
we do not know how this has happened. We will notifiy
the DOH of this dichotomy in their website.
The points that you have raised in your response about
gradual withdrawal and that were also highlighted in
the original BMJ article are well made. Should any similar
issues arise in the future then such points and suggestions
will be taken into account when seeking advice from
the CSM and will be important features of future communications.
The communication issues arising from the restriction
of thioridazine have provoked numerous comments for
future consideration and we are grateful to you for
Dr. A. Horsfall
Post Licensing Division
Dr Murray's letter to the BMJ on abrupt withdrawal of
Committee on Safety of Medicines'
gave bad advice on "gradual" withdrawal 30
Dinah KC Murray, Tutor Distance Education Dept /WebAutism
Birmingham University B15 2TT
Davies et al are right to raise concerns about the discontinuation
of thioridazine in patients with learning disabilities.
However, there are reasons for questioning some of their
interpretations of the problems which have arisen in
carrying out advice from the Committee on Safety of
Medicines. Thioridazine's high anticholinergic activity
may be associated with severe withdrawal syndromes for
some people. The Chief Medical Officer refers to these
as "nausea, vomiting, gastric upset, trembling,
dizziness, anxiety, agitation and insomnia, as well
as transient dyskinetic signs or the re-emergence of
psychotic symptoms." 'Gradual' withdrawal is advised
in pursuance of their avoidance.
Unfortunately, prevalent definitions employed by prescribers
refer to periods of between one week and four weeks
as "gradual withdrawal". For drugs which may
have been taken for decades this is an abrupt and not
a gradual change. In my own observation, discontinuing
Thioridazine in people with learning disabilities after
longterm use without a long taper can have catastrophic
effects . Dramatic weight loss, severe disruption
of sleep patterns, pronounced almost incessant agitation
and restlessness with distressed vocalisations are features
of these abrupt withdrawals which may last for months
after rapid onset coinciding with drug discontinuation.
Sovner found a similar pattern in his cases of thioridazine
withdrawal, with anxiety and insomnia prominent .
Here is what a veteran pharmacist who spent decades
specialising in psychiatric drugs says about antipsychotic
withdrawal, "All the problems, like benzodiazepines,
occur when withdrawal is attempted in a few days or
few weeks" .
There are a number of reasons for suspecting that a
proportion of the patients who had problematic withdrawal
from thioridazine in the study by Davies et al were
undergoing withdrawal reactions, with or without eventual
re-emergence of a baseline pathology. One reason is
the speed of onset of disturbed behaviour, one is the
appearance of psychotic like symptoms in people who
did not initially have a diagnosis of psychosis, one
is the cases where switching to another antipsychotic
did not curtail the problem behaviours, one is the case
of NMS , and finally it would be surprising if nobody
experienced a withdrawal syndrome when after only 37
weeks of antipsychotic treatment even monkeys show disturbed
behaviours after discontinuation for as long as seven
weeks before beginning to return to baseline . This
view is also supported by the findings of May et al
that "of 23 severely and profoundly mentally retarded
adult male patients undergoing slow "diagnostic"
neuroleptic taper, it was determined that at least 60%
could eventually be managed without psychoactive medication.
However, many of these demonstrated a remarkably long,
but nonetheless transient, period of worsening"
Davies et al remark that, "Although the adverse
consequences for the seven patients who stopped taking
thioridazine could be viewed as being attributable to
poor management of change, the clinicians involved felt
they had little option but to follow the Committee on
Safety of Medicines' advice". A significant defect
in that advice was its characterisation of "gradual
withdrawal". Strangely, when that advice appears
as from the Committee's Chair, Professor Alan Breckenridge,
(online) it is thus: "When discontinuing thioridazine
a gradual reduction in dosage over several weeksone
to two weeks is recommended "[sic] . Did someone
alter the original statement and replace "several
weeks" with "one to two"? If so, they
may be responsible for widespread distress, often leading
to "prescribing cascades" . An ideally
slow taper would be no faster than 10% every two to
three months, especially after chronic use of thioridazine
or other neuroleptics.
1.Murray DKC 1999, "Potions Pills and Human Rights",
Good Autism Practice April 1999, pp.1-13.
2.Sovner,R. 1995, "Thioridazine withdrawal induced
behavioral deterioration treated with clonidine: Two
case reports". Mental Retardation, 33, 221-225.
3.Stuart Baker http://www.apana.supanet.com/links.htm
4. Amore M, Zazzeri N. 1995 Neuroleptic malignant syndrome
after neuroleptic discontinuation. Prog Neuropsychopharmacol
Biol Psychiatry ;19(8):1323-34
5. May P, London EB, Zimmerman T, Thompson R, Mento
T, Spreat S. 1995 "A study of the clinical outcome
of patients with profound mental retardation gradually
withdrawn from chronic neuroleptic medication."
Ann Clin Psychiatry. Dec;7(4):155-60.
7. See Webb, OJ. 1996, Medication use patterns in IHC
community homes. NZ Fam Physician; 23: 4-6. and Murray
DKC 1999, "Potions Pills and Human Rights",
Good Autism Practice April
|This is the
reply from the National Autistic Society, received in
Director of Services
Bristol BS34 7BD
|David N Andrews
Dear Mr Andrews,
The Chief Executive has asked that I respond to your
recent letter. On examination of my
files I discovered that I did draft a response to a
letter from Mrs Kehala in November
2000. I am afraid that I am at a loss as to what subsequently
happened to that draft and
can only apologise for the delay in response. I am happy
to reproduce the content of that
draft here and on reviewing it conclude that what I
said then still pertains although we
have recently been made aware of further concerns around
the use of Melleril and
Chlorpromazine that I am following up with a colleague.
The main approach the NAS takes to the management of
autism spectrum disorders is
that of the SPELL framework, an ecological means of
understanding and responding to
autism which places the individual at the centre of
all processes. It is essentially about
assisting the individual by reducing the disabling effects
of the condition. We would
contend that autism per se may not be amenable to treatment
pharmacological agents but there may be other associated
conditions, for example seizure
disorders, depression or anxiety states that are.
It is the major tranquillisers, particularly the phenothiazines
that are most problematic in
that they are the drugs most frequently misused to control
those behaviours that may best
addressed by environmental, cognitive or other behavioural
approaches. Of course, many
people with autism reside within settings with low levels
of understanding of specialised
practice in autism or there may be acute health or safety
emergencies in which the only
practical short-term alternative to serious restriction
of liberty has been the use of the
1t is also the case that some people with autism themselves
tell us that they can only cope
with overwhelming obsessive/ compulsive behaviours,
panic or anxiety attacks with that
aid of antidepressant / tranquillising medication, particularly
the more modern SSRI
drugs. We do of course share the concern around the
indiscriminate use of the major
tranquillisers in autism where there is little clinical
rationale for so doing and where the
long-term effects point to serious detrimental physical
effects, including irreversible
neurological damage. The problem is particularly serious
in the case of younger children.
We understand that the newer atypical neuroleptic drugs
developed since the mid 1990s
may have fewer adverse side effects than earlier versions
but even then we have a
concern that many health professionals in the UK will
not have appropriate awareness of
the specific needs of people with autism spectrum disorders
and may be prescribing
inappropriate medication. The NAS raised this in its
report "Ignored or ineligible? The
reality for adults with autism spectrum disorders".
This called for [inter alia];
þ A national strategy of training to be developed
for all primary care practitioners,
health visitors and mental health professionals in identifying
conditions. þ Psychiatrists working with adults
in particular to be targeted for
training to expand their expertise in developmental
disorders. This will avoid the
treatment of people with autism and Asperger syndrome
for acquired conditions
such as mental health problems without reference to
their underlying diagnosis.
Similarly, we raised the key areas of concern of psychopharmacology,
the absence of
review of treatments and inexperience in recognition
of side effects in people with autism
with the Department of Health in our response to the
consultation on a new Mental
The proposal of a natural health clinic with a rehabilitation
centre could prove a welcome
step forward for many families with individuals affected
by autism. We wish you well in
your efforts to secure funding for this.
Director of Services
|Here is APANA's letter to the Secretary
of State for Health:
|30 June 2001
Alan Milburn, M.P.,
Secretary of State for Health,
Department of Health,
London SW1A 2NS.
Dear Mr Milburn,
Re Medical Research Council
(MRC) Study into Autism
APANA members believe it is vital for
questions about autism to be addressed from a non-medical
perspective, for a number of reasons.
In the Department of Health sponsored
London Learning Disabilities Strategy it is clearly
stated that the social model of disability will be applied.
The disability to which this model most clearly applies
is autism. Autism is a neurological and cognitive difference,
sometimes extreme: to be distributed at the edge of
the normal distribution curve is to be not sick, just
atypical. Autism is not an illness. The fact that autism
is correlated with, for example, a disposition to epilepsy
may be put forward as evidence for the medical view.
However this is no more valid than an argument that
the high correlation of fair skin and skin cancer means
that to be fair skinned is to have a medical condition.
The onus of the question about the causes
of autism thus shifts to the question of what causes
this particular cognitive variant to be dysfunctional.
As a spectrum condition, there has always been an area
of uncertain diagnosis in which the appearance of autism
as a dysfunction depended on the current view of normality.
It has equally always been true that certain aspects
of the environment such as calm, stability, formality,
and ritual have reduced the dysfunctionality of autism.
Other aspects of the environment, including its rate
of change and the behaviour of the people in it, have
the opposite effect. And there is evidence that it is
just this environmental influence that largely causes
the "problem" of autism.
A major additional cause of difficulty
and dysfunctionality for people on the autistic spectrum
in our society derives directly from the application
of the medical model to the autistic condition. Doctors,
who are central to the current process of identifying
Autism Spectrum Differences, may also be expected to
provide cure or palliation. Unfortunately doctors are
not able to help, although they are able to write prescriptions.
The prescriptions they write tend to be for toxic psychiatric
drugs which, though they may reduce some unwanted behaviours
through short-term sedation, have numerous unwanted
effects such as tremors, uncontrollable muscle spasms
and eye movements, reduced tongue and mouth control,
reduced cognitive function, incontinence, obesity, depression,
anxiety, and mania. Some of these are irreversible,
and all of them are damaging to the individuals' social
acceptability and self esteem. Such drugs have never
been appropriate for use
in cases of autistic spectrum conditions, and were certainly
not designed for that purpose. Such treatments cannot
alleviate autism, and can worsen many of its attendant
difficulties. This is something that some of our members
Historically, doctors including psychiatrists
have received minimal education in autism, if any, and
may even have been taught to see Asperger's syndrome
as a psychosis, which it is not. Understanding autism
takes time and experience not usually available to members
of the medical profession. Expertise in autism is pre-eminently
to be found among parents and carers and among people
themselves on the autistic spectrum, also among specialist
teachers, speech therapists, clinical psychologists
and educational psychologists. Members of all these
groups are in a much better position to acquire a deep
knowledge of the condition than any doctors (unless
themselves parents). APANA therefore applauds the panel's
intention to solicit views from the widest possible
range of informants and looks forward to being included
among them, but deplores both the choice of the Medical
Research Council as the base for this research and the
choice of a psychiatrist to chair the prospective inquiry,
however distinguished her career in schizophrenia. The
fact that Dr Johnstone has a specialty in schizophrenia
is a major factor in our objections to her appointment
to the post. Why would, for example, a social psychologist
not have been considered?
APANA members hope that you will take
these points into account in the appropriate manner,
and we look forward to your kind reply in the not too
David N Andrews
|This is APANA's letter to the National
Autistic Society in July 2000
31 July 2000
Ms Virginia Harvey
Parliamentary Liaison Officer
National Autistic Society
393 City Road
London EC IV 1NE
Dear Ms. Harvey,
In response to suggestions via the media (i.e. "Public
to have Say on the NHS Reform",Daily Telegraph
24.4.2000, copy enclosed), it is opportune to present
relevant views of the "Submission by the National
To quote: Mission Statement: "The NAS exists to
champion the rights and interests of all people with
autism and to ensure that they and their families receive
quality services, appropriate to their needs."
We are a group of people on the autistic spectrum and
parents with adults sons and daughters on the autistic
spectrum. Several of our children have become innocent
victims who have experienced tremendous pain and suffering,
inflicted upon them by the medical profession's ignorance
and failure to recognise the symptoms of autism. The
destructive nature of these mood and mind-altering substances
have caused chaos and despair in our lives.
Aware of the persistent cognitive deficits associated
with neuroleptics (such as personality deterioration,
lack of initiative and spontaneity, drive, motivation
and will) to non-autistic persons, the impact on autistic
people will be increasingly severe, some of whom are
already affected by these drawbacks to varying degrees.
Neuroleptics in any amount and for any length of time
are potentially dangerous to non-autistic individuals,
therefore more harmful to autistic persons. The disastrous
side-effects of these toxic substances can be the equivalent
of a "mental cosh", sedating people into "zombies",
immobilised for lengthy periods during the day, preventing
normal function for sometimes months or years, destroying
any possibility of coping with life's difficulties.
Challenges which need to be resolved require a lucid
train of thought. Instead problems are masked (covered)
by drugs - intractable, become permanent, restricting
motivation and development, undermining self-esteem,
producing apathy and helplessness, a hopeless situation
for the victim, making progress impossible.
See: "Draft Code of Good Practice on Prevention
of Violence Against Persons with Autism". (Autisme-Europe,
September 1998, page 40).
No.1 No. There is no drug to treat autism.
No.3 3rd line. There is no treatment for autism and
drugs are likely to complicate even more the situation.
No.9 There are no psychiatric drugs without side effects.
See also: Autisme-Europe - "Charter for Persons
Item 16 THE RIGHT of people with autism to freedom
from fear or threat of unwarranted incarceration in
psychiatric hospitals or any other restrictive institution.
Item 17 THE RIGHT of people with autism to freedom
from abusive physical treatment or neglect.
Item 18 THE RIGHT of people with autism to freedom
from pharmacological abuse or misuse.
The European Law on Human Rights is to be incorporated
in our legal system in October 2000.
See also: Potions, Pills and Community Care for People
with Learning Difficulties" by Dinah Murray. BA
MA PhD. (Ing Ap. Vol.1 No.1).
There are many extremely dangerous :Life-threatening
side-effects from these anti-psychotic drugs, such as
Neuroleptic Malignant Syndrome (can be fatal) and Tardive
dyskinesia, an insidious drug-induced iatrogenic disease,
a chronic/irreversible condition damaging the central
nervous system, preventing people from achieving their
full potential and proving an asset to society, which
can cause serious physical and mental dysfunction in
non-autistic people, and is inevitably more devastating
to autistic persons. This
disease is incurable. There is also catatonic decline.
Therefore your "Mission Statement" cannot
produce effective and advantageous results for the benefit
of autistic people within the present National Health
Service System. Indeed, we would state emphatically
that Mental Health Services are not only totally inappropriate
for the needs of autistic spectrum individuals but can
be extremely harmful.
We wish to present the following proposal:
That a "Natural Health Clinic" be inaugurated
for autistic spectrum persons, specialising in a range
of alternative/complementary therapies and integrated
medicine; to include access to socia1 skills training,
cognitive behavioural therapy, awareness/aptitude profiles,
combined with a variety of projects, possibilities for
knowledge/schemes for full/part-time employment where
applicable. Supportive employment schemes. Many of the
following approaches have shown strong evidence in their
favour: homeopathy, herbal, nutritional approach; Allergies
(a very prevalent factor) and diet; Orthomolecular Medicine;
to name but a few. Also, of course, essential vitamin/mineral
supplements etc. Careful monitoring essential. In addition,
last but not least - a very needy "Rehabilitation
Possibilities of funding: NHS (now requesting public
suggestions/consultations); full or subsidised lottery
grants, plus doubtless massive moral/financial support
from members and associates, finance producing groups,
charities, e.g. The Shirley Foundation.
With goodwill and enthusiasm, an entire new productive
and successful system can be established to replace
the present anachronistic treatment methods and to herald
in the new century.