TRANSPARENCY OF MHRA

This is my final communication with the MHRA. It is a fruitless task people. I recently disputed a set of answers they gave me regarding a Freedom of Information request and they wrote back. I have now realised writing to them is pointless. I've had my fill after 3 years of probing only to be given answers that Tom Hanks' character in the Da Vinci Code would have trouble understanding. I am sure somewhere along the line they will be investigated and hauled to task over their lack of transparency but for now I have just about had enough. As one highly respected psychiatrist put it to me: "Bob, I don't think much of their answers but I do think they're on a wicket they can defend and I don't think you can land a knockout blow"

Here is the email I recieved and my response to it (blue) that has made me come to this decision.

Names have been removed to protect the guilty



Dear Mr Fiddaman,

I copied in Ingrid Cal**rt and Muriel Pa***ore because they log the MHRA responses to FOIs and this was by way of letting them know that the FOI had been dealt with. They are both Executive Assistants in Licensing Division of the MHRA.

Dear Mr Ber**dge,

I am copying in my MP, Gi**la St**rt to show her just how 'transparent' the MHRA really are... more on that later.

Your first point regarding Ingrid Cal**rt and Muriel Pa***ore - It seems rather odd that you choose to disclose who they are to me - why not throw the exemption rule at me (Information accessible by other means). I know who they are - I googled their names after my second email to you was not answered!

Regarding whether or not depression is associated with low levels of serotonin. Since my last correspondence I have had the opportunity to look into this further and also to consult further with colleagues and I present the following evidence.

Evidence in support of the PIL statement for paroxetine

‘People who are depressed or anxious have lower levels of serotonin than others. It is not fully understood how Seroxat and other SSRIs work but they may help by increasing the level of serotonin in the brain’Please note that in wording the text for PILs, the requirements of the Guideline on the Readability of the Label and Package Leaflet of Medicinal Products for Human Use (European Commission, Pharmaceutical Committee, September 1998) must be followed. The EC guideline states that ‘The text must be phrased so that it is readily understandable by patient.’

So a member of the public can understand the following taken from the Seroxat PIL:'It is not fully understood how Seroxat and other SSRIs work'?

If information on the leaflet cannot explain how Seroxat works then how on earth do you expect the patient to understand?

The rest of your email highlights the fact that the MHRA ARE NOT transparent and merely try to blind members of the public with science. I have continued in my reply after the biochemestry lesson.

The aetiology of depression is multifactorial and scientific work to elucidate it has been ongoing for many years. Psychological approaches include psychoanalytical and cognitive theories. Cognitive theories emphasise negative biases in information processing, leading the depressed patients to make unrealistically negative judgments about themselves and the world.. The neurobiological approach to the aetiology of depression includes factors such as monoamines (serotonin, noradrenaline, dopamine), endocrine abnormalities, cytokines, neurotrophins such as brain-derived neurotrophic factor (BDNF) etc, as aetiological factors.

There is good evidence for abnormalities in serotonin (5-hydroxytryptamin) neurotransmission in depression.

Plasma tryptophan:
The synthesis of serotonin in the brain depends on the availability of its precursor L-tryptophan. Plasma tryptophan levels are decreased in untreated depressed patients.

Studies in cerebrospinal fluid
There is evidence that depressed patients who have made impulsive and more dangerous suicide attempts have low CSF 5-hydroxyindolic acid (5-HIAA) levels.

Studies of post-mortem brain
Such studies have suggested that suicide victims have increased expression of 5-HT2A receptors and decreases in serotonin transporters in pre-frontal cortex.

Neurochemical brain imaging studies
Neuroimaging techniques such as single-photon emission computed tomography and positron emission tomography have demonstrated evidence of a wide-spread modest decrease in 5-HT1A receptor binding throughout cortical and subcortical regions and decreased brainstem 5-HT reuptake sites.

Neuroendocrine tests
Studies in unmedicated depressed patients have demonstrated that 5-HT-mediated endocrine responses are blunted in depressed patients.

Tryptophan depletion
As mentioned above, the synthesis of serotonin in the brain depends on the availability of L-tryptophan. Acute tryptophan depletion lowers brain serotonin synthesis and results in a transient, but striking, clinical relapse in recovered depressed patients.

Gene polymorphism studies
There is evidence that gene variants in sequences of serotonin pathway proteins may be associated with susceptibility to depression and suicidality in response to stressful life events and to response to antidepressive treatments.

Response to treatment with SSRIs
Antidepressants that increase serotonin in the brain have demonstrated efficacy in their licensed indications in adequately designed clinical trials. There is evidence that treatment with an SSRI reduces negative bias and increases positive bias in tasks involving social perception and emotional memory.

In conclusion, it is considered that the simple information given in the Patient Information Leaflet is in line with the available evidence.

Please note that the literature regarding the aetiology of depression is in the public domain. You may wish to refer to textbooks such as the New Oxford Textbook of Psychiatry available from the British Library or perform literature online literature searches on databases such as PubMed.

In addition, it is apparent from the literature that depression may be associated with low levels of serotonin (e.g. see link ). (http://otl.georgetown.edu/industry/inventions/sian428501.html).




I am well aware of the investigation being conducted by the MHRA into GSK clinical trials.

Yet you point me to their website for the information I requested. That is like asking me to phone Dr Harold Shipman because my mother is ill!

You previously asked:
Please forward me documents that GSK supplied the MHRA during the application procedure for Seroxat that relate to the 'correcting effect' regarding people with lower levels of serotonin.

GSK have published on their website a list of trials that they have conducted on paroxetine. As you will see from the number of trials it would be very time consuming for me to check if their list is exhaustive and to extract the data that you require.

To answer your request fully will require considerable extra work, for which we will need to make a charge. We estimate that meeting your request will require 40 hours work. The Freedom of Information Act allows us to make a charge for the costs of finding, sorting, editing or redacting the material you have requested, if this cost would exceed £600, calculated at £25 per hours’ work. We have therefore decided to charge you £1000 for providing the information you have requested.

If you wish us to go ahead with the work, please send a cheque or postal order made payable to the "Medicines and Healthcare products Regulatory Agency" quoting the above reference to: The Cashier, Medicines and Healthcare products Regulatory Agency, Market Towers, 1 Nine Elms Lane, London SW8 5NQ.

Unfortunately, due to the problems Seroxat has left me with I am in no position for employment therefore could only dream of having £1000 and I certainly wouldn't waste it on the MHRA to carry out an investigation.... It's taken you nigh on 4 years to investigate Glaxosmithkline and we (the public) still have no idea whether or not the drugs we take (in this case Seroxat) are safe. Read Dr Pete Breggin's report (http://www.breggin.com/courtfiling.pbreggin.2006.html)
it's as simple as that, then criminal prosecutions should follow and the MHRA should not stop at GSK they should then turn their attention to it's own members who knowingly allowed this drug to be 'peddled' despite knowing it's dangers (see http://whale.to/a/brook.html)

When someone wants to learn about a drug they take these days, a common port of call is the internet. One only has to type the word 'Seroxat' into a search engine to read horror story after horror story, lawsuit after lawsuit and yet YOU (MHRA) continue to robustly deny that it is harmful in adults. I'm an adult and I had severe withdrawal effects on this drug - 18 months to get off a drug is not 'mild' withdrawal. The patient information leaflet slightly touches on this:

When stopping Seroxat, your doctor will help you to reduce your dose slowly over a number of weeks or months –this should help reduce the chance of withdrawal effects. One way of doing this is to gradually reduce the dose of Seroxat you take by 10 mg a week. Most people find that any symptoms on stopping Seroxat are mild and go away on their own within two weeks. For some people, these symptoms may be more severe, or go on for longer.

May I guide you to here: http://www.paxilprogress.org/forums/ one of countless support sites for people having difficulty with the drug the MHRA think is safe. These are adults posting in these forums... and Yes they are over 30 years of age

Finally, regarding copyright please see the following link (http://www.mhra.gov.uk/home/Idcplg?IdcService=SS_GET_PAGE&nodeId=412).

I think this is rich coming from a body who have articles on their webpage with my full name and address on for all and sundry to see. I will continue to disseminate information that I think is in the public interest, in particular FOI requests

I hope this answers your query adequately.

I'd need a degree in biochemistry and you know it. It's a pity The EC guideline ‘The text must be phrased so that it is readily understandable by patient.’ doesn't apply to the MHRA because the email you sent me was sent purely to blind me with science. Clever Mr Be**idge, very clever

Mr Fiddaman