Safety of antipsychotics in heart patients

name removed 23 Oct 2012 made this Freedom of Information request to Medical Research Council This request has been closed to new correspondence. Contact us if you think it should be reopened.

The request was refused by Medical Research Council.

name removed 23 Oct 2012

6 February 2012

Dear Medical Research Council,

I am making a Freedom of Information Request regarding Frontal Lobe atrophy and sinus tachycardia and right atrial enlargement.

1. What precisely is "right atrial enlargement"?

2. Can a "trial" of antipsychotic medication - in this case 8 weeks of Olanzapine - cause "right atrial enlargement" where an ECG a few weeks earlier there is no sign of "right atrial enlargement"?

3. Can a "trial" of antipsychotic medication - in this case Olanzapine - cause regular pattern of sinus tachycardia?

4. How dangerous is untreated "right atrial enlargement"?

5. How dangerous is untreated "sinus tachycardia" that has gone on for 77 days without a doctor seeking an ECG and then finds that not only is there sinus tachycardia as regularly found on standard observations by nursing staff but at 11 weeks an ECG then shows that there is now "right heart enlargement"?

6. How can sinus tachycardia and right atrial enlargement be treated? What is the gold standard treatment? Are antipsychotic drugs contraindicated where such a patient is "trialled" on Section 3 first for Olanzapine and then is cross-titrated onto Amisulpride and suffers rapid weight loss over a few weeks? Should these drugs be removed?

7. Where a patient who has been found to have sinus tachycardia and right atrial enlargement on antipsychotic medication with rapid weight loss and parkinsonism and frontal lobe atrophy as found on CT scan should this patient be optimally considered for Clozapine - where a doctor believes that the person has untreated paranoid schizophrenia / undifferentiated schizophrenia of 25 years duration - or is this contraindicated - but where in the alternative the patient had been previously diagnosed hitherto with clinical Depression for a quarter of a century and latterly overlaid with possible chronic PTSD? Where the doctors' medical opinion is so divergent how safe is antipsychotic medication in any event?

8. Where a patient who has multiple co-morbidities including frontal lobe atrophy, sinus tachycardia, right atrial enlargement,parkinsonism, loss of proprioception in the foot following a fractured leg surgery leaving a major recurvatum of 18.1 degrees on healing, akithesia, fine tremor, should Clozapine be discontinued?

9. What long-term consequences are there for a person who is being medicated for a heart problem - sinus tachycardia and right atrial enlargement - with Bisoprolol, is this then optimally encouraged to continue with the Clozapine notwithstanding that the Bisoprolol lowers blood pressure and Clozapine can increase heartbeat? Is there a danger of polypharmacy? Is there a longer-term danger in one, two, three, four, five years' time as I understand that the effects of Clozapine can take a long time to emanate but that there can be fatalities?

10. When the Coroner's Decision of December 2011 declared that Catherine Bell's death was linked specifically to Clozapine, what has the Medical Research Council done to investigate the safety of Clozapine? Will the Medical Research Council be investigating the safety of Clozapine specifically with regards not only to agranulocytosis but also heart disease such as right atrial enlargement?

11. I have requested details from other bodies but nobody is able to give me the full details I am requesting. I do hope that you will be able to assist me and direct me in the right direction.

Thank you so much,

Yours sincerely,

[first name removed] [last name removed]

Campaigner for Liberty, Truth and Justice

Dear [first name removed] [last name removed],

Thank you for your Freedom of Information request.

We will look into what information we have available and get back to you.

Yours Sincerely,

Tiffany

Tiffany Lay
Senior Information Officer
Medical Research Council

www.mrc.ac.uk

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name removed 23 Oct 2012

3 March 2012

Dear Ms Lay, Medical Research Council,

I am hoping that you have been able to find something to assist me in my search for information.

As you actually research, you are possibly the most likely people to be able to help me.

I do hope so.

Thank you very much for your help,

Yours sincerely,

[first name removed] [last name removed]

Campaigner for legal reform in mental health, liberty, truth and justice

Dear Ms [last name removed],

Further to my message of 06 February 2012 acknowledging your Freedom of
Information request.

The Medical Research Council (MRC) are currently pursuing one further avenue
to determine whether any of the information that you have requested is held
by the MRC. I will contact you again by the end of the week with an update
on this.

Yours Sincerely,

Tiffany

Tiffany Lay
Senior Information Officer
Medical Research Council

www.mrc.ac.uk

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name removed 23 Oct 2012

MONDAY 5 MARCH 2012

Dear Ms Lay, MHRC, Mr Lansley Secretary of State for Health, Lord Howe Parliamentary Under Secretary to the Department of Health and Mr Turner MP for the Isle of Wight,

Thank you very much for all your help.

Yours sincerely,

[first name removed] [last name removed]

1 Attachment

Dear Ms [last name removed],

Thank you for your Freedom of Information request and your questions
regarding Frontal Lobe atrophy and sinus tachycardia and right atrial
enlargement.

The Medical Research Council (MRC) is a publically funded organisation
dedicated to improving human health through world-class medical research.
We support research across the entire spectrum of medical sciences, from
fundamental laboratory-based science to clinical trials, and in all major
disease areas, in universities and hospitals, in our own units and
institutes in the UK, and in our units in Africa.

The MRC provides funding for research through a range of grants and personal
awards to scientists in universities, medical schools and other research
institutes. Applications for MRC funding are generally submitted by the
scientific community in 'response mode', the MRC always welcomes high
quality applications for support into any aspect of human health but does
not normally commission research to address specific questions. Details of
how the MRC funds research can be found at:
www.mrc.ac.uk/Fundingopportunities/index....

You have asked a number of questions regarding the definitions of
conditions, outcomes of trials and links between various drugs and medical
conditions. The MRC is not currently funding any work that is examining the
precise relationship between the use of the drugs you have identified and
cardiovascular complications, and the provision of advice relating to
medical conditions is outside of the remit of the MRC. Therefore no
information is held by the MRC that would address the specific points that
you have raised. You may find some of the information that you seek within
scientific articles published in a number of journals. Two databases of
these articles that you may wish to search are UK PubMed Central
(http://ukpmc.ac.uk) and Google Scholar (http://scolar.google.com). The
articles that you find may include work supported by the MRC in the past,
for example the findings of a study conducted in 2007 by the MRC funded
General Practice Research Framework (GPRF) which showed heightened rates of
cardiovascular diseases in schizophrenic patients. Please note: this work
did not specifically look at patients who had been prescribed
antipsychotics.

As noted above the MRC is not currently funding any work that is examining
the precise relationship between the use of antipsychotics and
cardiovascular complications, however the MRC are funding three projects
that are looking at the long term effects of antipsychotic use. The details
of these projects can be found in the attached Excel file: 2012-03-05_WDTK
request 104771-469556f3. The MRC also funds a Centre for drug Safety
Science at the University of Liverpool. This centre investigates the
fundamental mechanisms of clinically important adverse drug reactions with
the overall aim of preventing such reactions by improved drug selection,
drug design and more informed patient selection. Further information on the
work of this centre can be found at: http://www.liv.ac.uk/drug-safety/.
Information on other research funded by the MRC can be found at:
http://www.mrc.ac.uk/ResearchPortfolio/i....

You note at Q11 that you have contacted a number of other organisations
seeking information on these issues, you have not mentioned which
organisations these are however your questions regarding the safety and
suitability of drugs would be better answered by the Medicines and
Healthcare products Regulatory Agency (MHRA) or the National Institute for
Health and Clinical Excellence (NICE). The MHRA is the government agency
which is responsible for ensuring that medicines and medical devices work,
and are acceptably safe and further details can be found at:
http://www.mhra.gov.uk. The NICE develop evidence-based guidelines on the
most effective ways to diagnose, treat and prevent disease and ill health
and further details can be found at: http://www.nice.org.uk.

I hope that you find this information useful, if you have any questions, or
would like any further information, please let me know.

However, if you are not satisfied that this response has been handled
appropriately, you may appeal using the MRC's complaints procedure. Details
are on the MRC website at:
www.mrc.ac.uk/index/about/about-contact/....
You may contact the MRC Complaints Officer at:
The Complaints Officer, Medical Research Council, 14th Floor, One Kemble
Street, London WC2B 4AN.
email: [email address]

If you remain dissatisfied with the handling of your request or complaint,
you have a right to appeal to the Information Commissioner at:
The Information Commissioner's Office, Wycliffe House, Water Lane, Wilmslow,
Cheshire, SK9 5AF.
Telephone: 0303 123 1113
Website: www.ico.gov.uk

I apologise for the delay in getting our final response to you.

Yours Sincerely,

Tiffany

Tiffany Lay
Senior Information Officer
Medical Research Council

www.mrc.ac.uk

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name removed 23 Oct 2012

7 March 2012

Dear Medical Research Council, Mr Turner MP for the Isle of Wight, Lord Howe Minister for Health, Mr Lansley Secretary of State for Health

I am most grateful to the Medical Research Council for the information given to me.

I note that these are only the ABSTRACTS, please may I request the FULL versions as I am very concerned about the way in which people with mental health are treated, and in particular the toxicological effects of Clozapine, Olanzapine and Amisulpride on the heart.

I note that there has been no acknowledgement of my specific request for information about Right atrial enlargement at all, and I do wish to know how serious is this condition as nobody as yet has informed me - nobody.

And the issue of regular Sinus Tachycardia - how dangerous is this?

And the issue of significant atrophy of the frontal lobes how significant is this?

Should a person who has a combination of all these presentation features EVER be given antipsychotics in the first place?

This is a real, live issue, and one which I have been seeking answers from psychiatrists, the Department of Health, the Secretary of State for Health and the MHRA as well as the NHS and NHS Direct.

Could you please tell me what is the significance of this condition.

It is vital for me to know please.

Thank you very much for your help,

Yours sincerely,

[first name removed] [last name removed]

Campaigner for legal reform, liberty, truth and justice

MRC projects identified in the area of antipsychotic research, current (March 2012), by project.

MRC Reference Funding Stream Research Organisation Principal Investigator Title Start Date End Date Amount Awarded (£k) Abstract
G1100574/1 Research Grant King's College London Andrea Mechelli Predicting drug response in schizophrenia: are clinical & cognitive tests a cost-effective alternative to neuroimaging? TBC TBC £205

G1002198/1 Research Grant King's College London Shitij Kapur
Effects of antipsychotics: linking brain structural imaging changes to cellular alterations and evaluating mitigation st 01/08/2011 31/07/2014 £820

Although antipsychotic drugs are effective in the treatment of schizophrenia, the response to medication varies considerably from one patient to another, both in terms of therapeutic and adverse effects, and is unpredictable. As a result, finding the most suitable antipsychotic for a given patient often involves a trial-and-error approach which prolongs patient suffering and increases health care costs. There is therefore an urgent need for a better understanding of how we can best predict response to treatment in a given patient. Neuroimaging measures may be useful in predicting antipsychotic response, but scanning is a relatively expensive investigation that is not routinely used in clinical practice. Demographic, clinical and cognitive measures may provide a more practical, cost-effective alternative, but their predictive value at an individual level has yet to be tested. The aim of the present project is to examine how to best predict the response to antipsychotic medication in a given patient with first episode schizophrenia. We will compare three classes of predictors: (i) structural MRI scans; (ii) demographic and psychopathological measures which are routinely acquired in a clinical setting; (iii) cognitive measures which are not part of a routine clinical assessment, but could be acquired at relatively little extra cost. Two hundred patients with first episode schizophrenia will undergo a structural Magnetic Resonance Imaging (MRI) scan and receive a comprehensive demographic, clinical and cognitive assessment. All of them will be given the same antipsychotic (amisulpride) and will be clinically assessed over a period of 4 weeks; this will allow us to examine treatment response, both in terms of symptom remission and side-effects. We will then use Support Vector Machine to investigate the value of pre-treatment neuroanatomical, demographic, clinical and cognitive information for predicting treatment response. Our main hypothesis is that the combination of demographic, psychopathologi

G0700477/1 Research Grant University of Oxford John Geddes CEQUEL-FA: Comparative evaluation of quetiapine plus lamotrigine vs quetiapine monotherapy, and folic acid vs placebo 01/10/2007 30/09/2012 £1,735
CEQUEL-FA is a randomised controlled trial investigating the efficacy of combination lamotrigine plus quetiapiane in people with bipolar depression. The trial is a 2x2 factorial design with patients additionally being randomised to folic acid or placebo. The trial outcomes are remission from depressive symptoms at 12 weeks and maintenance of improvement by 12 months. A number of secondary analyses will be conducted which should yield valuable knowledge about the neurobiology of folic acid in mood disorders.

The results of CEQUEL-FA will guide therapy for people with bipolar disorder for many years to come and will inform the development of future clinical practice guidelines

I am writing to request an internal review of Medical Research Council's handling of my FOI request 'Safety of antipsychotics in heart patients'.

A full history of my FOI request and all correspondence is available on the Internet at this address:
http://www.whatdotheyknow.com/request/sa...

Dear Ms [last name removed],

Thank you for your correspondence regarding my response to your Freedom of
Information request.

You have requested an Internal Review and this has now been initiated, we
will be in touch once this has been completed. In the response to your
initial request I confirmed that the Medical Research Council (MRC) held no
information that would address the specific points that you raised. This was
on the basis that the MRC was not currently funding any research examining
the precise relationship between the use of the drugs identified and
cardiovascular complications, and, that the provision of advice relating to
medical conditions is outside of the MRC's remit.

In my response I provided information on three research grants examining the
long term effects of antipsychotic use as an illustration of the type of
research that has been supported in this broad area. I forwarded you
information on these funding awards including an abstract of the research.
The abstract that I provided to you was the scientific abstract that was
submitted as part of the research proposal. As you have now requested
further information about these grants and I will take this forwards as a
separate request under the Freedom of Information Act.

To help us take your request forward please can I ask you to clarify what
information about these grants you would like. For example, would you like
the details of the research plan submitted at the time of application or is
there other information from the application that you like to access?
Details of the information submitted to the MRC as part of the application
process can be found at:
http://www.mrc.ac.uk/Fundingopportunitie...
ookannexes/index.htm, and this document may help you to identify what
information is available.

I will not be able to take your additional request forward until I have
received clarification from you on the information required.

Yours Sincerely,

Tiffany

Tiffany Lay
Senior Information Officer
Medical Research Council

www.mrc.ac.uk

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name removed 23 Oct 2012

12 March 2012

Dear Ms Lay, MRC, Mr Turner MP for the Isle of Wight, Mr Lansley Secretary of State for Health, Mr Cameron Prime Minister of Great Britain and Northern Ireland, MHRA, Department of Health,

Thank you very much for your response and for explaining that the Internal Review has been initiated.

And for informing me that my request for the 3 current programs will be a new FOI Request.

For completeness, may I request everything that the MRC has on these 3 programs.

I believe that expenditure may well be a consideration when determining whether or not a patient receives psychotherapy, or arts programs or skills parograms or pharmaceutical therapies, and, as such, the MRC's own grants needed to investigate issues is also a factor, especially with the radical overhaul of the NHS and Social Care system and Mental Health reforms.

If you have any OLDER completed programs on antipsycotics which the MRC has available for public viewing, would it be possible to give me these links, as I know that there was fierce debate in medical and scientific papers available online as to whether or not clozapine is actually a safe drug at all.

And it is the safety of these drugs that worries me considerably.

I note that one of the programs about which I requested information when I received your response was about scanning people to find out how their brains reacted.

Do you have ANY completed MRC programs or ones ongoing or will happen in the future regarding the following:

right atrial enlargement

atrophied frontal lobes of the brain

sinus tachycardia

pseudo parkisonian syndrome secondary to amisulpride

akithesia

fine tremor

Bisoprolol

Lewy bodies

Post-surgical cognitive dysfunction

Post-anaesthesia cognitive dysfunction

If these can be added to the FOI Request for the 3 programs and their details, I would be most grateful as there is very little available on the issue of Clozapine with a person who is a working age adult rather than old age patients who might have such a presentation or not as the case may be.

Thank you very much,

Yours sincerely,

[first name removed] [last name removed]

Campaigner for mental health reform, safety in prescribing, liberty, truth and justice

name removed 23 Oct 2012

22 March 2012

Dear Medical Research Council,

I am writing regarding the internal review of Medical Research Council's handling of my FOI request 'Safety of antipsychotics in heart patients'.

I have discovered a specific document regarding Clozapine produced by the MRC as follows:

"RISK ASSESSMENT FOR HAZARDOUS SUBSTANCES

Substance: CLOZAPINE
SYNONYMS: Clozaril, Leponex, Fazaclo, Froidir; Denzapine, Zaponex, Klozapol, Clopine

Hazard Signs

Risk Phrases
R22 R36/37/38
• Harmful if swallowed.
• Irritating to eyes, respiratory system and
skin.

Safety Phrases
S26
• In case of contact with eyes, rinse
immediately with plenty of water and seek
medical advice.

Hazardous Chemical Details
Chemical Form Amount Storage
Clozapine Powder (faintly yellow) 25mg Room temperature, Keep tightly closed

PROTECTIVE MEASURES TO BE ADOPTED
• Respiratory Protection: Use dustmask or work
in a fume cabinet or similar mechanical
exhaust ventilation system.

• Wear appropriate labcoat, gloves and safety
spectacles.

• Wash hands before breaks and at the end of
workday.

FIRST AID MEASURES
• INGESTION – wash out mouth with water. Seek
medical advice immediately

• Splashes on SKIN – Flush area with copious
amounts of water for at least 15 min

• Splashes to EYES – Flush eyes with copious
amounts of water for at least 15 min
All accidents must be reported to the Lab
Manager / Safety Supervisor or the
departmental first aid personnel, and CSC
Safety via an accident report form:
http://safety.csc.mrc.ac.uk/CSCAccidentR...

Emergency spillage procedure
• Spills (solid) – Sweep up, place in bag and
hold for waste disposal. Avoid raising dust.
Wash spill site with copious amounts of water

• Spills (liquid) – Wear appropriate protective
clothing. Ensure supply of fresh air in
enclosed rooms. Absorb on an inert
absorbent, transfer to a suitable container
and arrange for waster disposal. Wash site of
spillage thoroughly with water and detergent.

WASTE DISPOSAL
• Disposal to sink with running water to rinse,
as long as being used in concentrations of
less than 100uM

• Higher concentrations / volumes through
chemical waste route: contact CSC Safety to
arrange this

LEVEL OF CONTAINMENT:
A B C X D X E Other

Notes to accompany COSHH Assessment/Project Form

• All substances whether chemical or microbiological must be assessed as to their risk. Information about substances can be obtained from many sources including suppliers and various reference books. If there are any difficulties, the advice of the Safety Officer should be sought.

• The level of containment section should be filled by using the appropriate letters as detailed below:
A: No special precautions

B: Safe to use in well ventilated
area

C: Contact hazard gloves to be
worn

D: Inhalation/aerosol hazard
work in a fully functional
fume cupboard/safety cabinet

E: High risk work in specialised
laboratories only

RESPONSIBLE PERSON NAME SIGNATURE DATE
Person carrying out the assessment
Principal Investigator
Group Safety Supervisor
Annual Review

Due consideration should be made in this assessment for women of child-bearing years, and a full re-assessment should be carried out upon notification of pregnancy.

This assessment has been carried out by the person responsible for the work. A copy of this assessment has been sent to CSC Safety."

May I ask just how safe a drug can be that has to be ingested when the dust / liquid can be so very dangerous? Is this why people can experience such toxic side-effects, including death?

A full history of my FOI request and all correspondence is available on the Internet at this address:
http://www.whatdotheyknow.com/request/sa...

Yours sincerely,

[first name removed] [last name removed]

name removed 23 Oct 2012

3 April 2012

Dear Medical Research Council,

Please pass this on to the person who conducts Freedom of Information reviews.

I am writing to request an internal review of Medical Research Council's handling of my FOI request 'Safety of antipsychotics in heart patients'.

I was asked to clarify my outstanding requests for data, which I did, but thereafter have not heard anything from the Medical Research Council.

May I request that someone check that you received my requests for the data?

I am most grateful to you.

A full history of my FOI request and all correspondence is available on the Internet at this address:
http://www.whatdotheyknow.com/request/sa...

Yours sincerely,

[first name removed] [last name removed]

Dear Ms [last name removed],

Thank you for your further requests for information regarding the safety of
antipsychotics in heart patients. I do apologise for the delay in
responding to this request and to your internal review.

In the response to your initial request to the Medical Research Council
(MRC) we informed you (on 07 March 2012) that as the MRC was not currently
funding any research projects which aimed to investigate the precise
relationship between the use of the drugs that you had identified and
cardiovascular complications. We also informed you that the provision of
advice relating to medical conditions and on drug safety was outside of the
remit of the MRC. In relation to the MRC's remit we outlined the role of the
MRC in funding research proposals submitted by the scientific community.

Under the duty to advise and assist the MRC provided you with information on
related MRC-funded research, including three research projects relating to
the long term effects of antipsychotic use. You were also advised that
further information on research funded by the MRC could be found at:
http://www.mrc.ac.uk/ResearchPortfolio/i..., directed to other public
bodies that may potentially hold relevant information and also to a resource
where you might be able to access published research findings relating to
the issues identified in the request.

Following this response you submitted a second information request for 'the
FULL versions' of the three projects that we identified in our first
response. Whilst clarifying that you would like everything that the MRC has
on these projects, you also requested:
- any OLDER completed programs on antipsychotics
- ANY completed MRC programs or ones ongoing or will happen in the future
regarding the following:
right atrial enlargement
atrophied frontal lobes of the brain
sinus tachycardia
pseudo parkisonian syndrome secondary to amisulpride
akithesia
fine tremor
Bisoprolol
Lewy bodies
Post-surgical cognitive dysfunction
Post-anaesthesia cognitive dysfunction
The MRC are treating this as a third request for information under the
Freedom of Information Act (FOIA).

The MRC are aggregating the time taken to respond to the second and third
request for information that you submitted as the scope of the information
that you are requesting is wider than the focus of your initial request.
From our preliminary assessment, the MRC estimates that compliance with your
additional requests would exceed the appropriate costs limit under Section
12 of the FOIA 2000. This is currently £450.

Rather than refusing your request at this stage, I would like to explore
with you how the MRC may best assist you to request relevant information
which we hold. If you need assistance with this please do not hesitate to
contact me.

If you are not satisfied that this response has been handled appropriately,
you may appeal using the MRC's complaints procedure. Details are on the MRC
website at:
www.mrc.ac.uk/index/about/about-contact/....
You may contact the MRC Complaints Officer at:
The Complaints Officer, Medical Research Council, 14th Floor, One Kemble
Street, London WC2B 4AN.
email: [email address]

If you remain dissatisfied with the handling of your request or complaint,
you have a right to appeal to the Information Commissioner at:
The Information Commissioner's Office, Wycliffe House, Water Lane, Wilmslow,
Cheshire, SK9 5AF.
Telephone: 0303 123 1113
Website: www.ico.gov.uk

Yours Sincerely,

Tiffany

Tiffany Lay
Senior Information Officer
Medical Research Council

www.mrc.ac.uk

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