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 Journal:

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:
1. http://www.mca.gov.uk/whatsnew/pressreleases/thioridazinepressrelease.htm
2. http://www.mca.gov.uk/mca/csm/thiolet.pdf
3. http://www.mca.gov.uk/mca/csm/thisspc.pdf
4. http://www.doh.gov.uk/cmo/cemcmo200018.pdf

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 your contribution.

Yours sincerely,

Dr. A. Horsfall
Scientific Assessor
Pharmacovigilance
Post Licensing Division

Committee on Safety of Medicines' gave bad advice on "gradual" withdrawal 30 June 2002

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 [1]. 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[2] .
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"[3] .
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 [4]. 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" (my emphasis)[5].
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][6] . 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"[7] . An ideally slow taper would be no faster than 10% every two to three months, especially after chronic use of thioridazine or other neuroleptics.
footnotes
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.
6. www.doh.gov.uk/cmo/cmo00_18.htm
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

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 with particular 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 major tranquillisers.

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 autism spectrum 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 Health Act.

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.
Yours sincerely

Richard Mills
Director of Services

Alan Milburn, M.P.,
Secretary of State for Health,
Department of Health,
Richmond House,
79 Whitehall,
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 have experienced.

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 distant future.

Yours sincerely

David N Andrews

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 Autistic Society."

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 with Autism":

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 Centre."

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.

Yours sincerely,

A.P.A.N.A.