Letter from Dr June Raine, Vigilance & Risk Management of Medicines, Medicines and Healthcare products Regulatory Agency to John Perrott (08 December 2010)

To clarify my previous statement on the results of the 14 CAT scans included in the correspondence with the MRC – there is no consistent trend in the type of abnormality observed or the duration of use of benzodiazepines within these cases on which to establish a causal relationship.

Professor Lader subsequently published an article in 1984 in the journal Psychological Medicine which included 19 patients on benzodiazepines (including 12 of the original 14 patients).  This paper included more detail about the dose and specific benzodiazepine taken by each patient, but indicated that definite abnormalities were only observed in 3 of the 19 patients and concluded that the clinical significance of the findings were unclear and therefore further research was required.  The MHRA is not aware of conclusive evidence that either confirms or refutes a relationship between benzodiazepines and brain damage.

You have request clarification of the statement “but does (not) make any further reference to brain damage”  I meant that although the published literature considered by the Committee in relation to their assessment of withdrawal reactions included information about the abnormal CAT scans, the resulting update to the product information for benzodiazepines on withdrawal reactions did not include any information about potential brain damage. I am sorry if this was unclear.

You have suggested that this data should trigger regulatory action. As the licences for all benzodiazepines are currently restricted to short-term use and the product information contains warnings about tolerance, dependence and withdrawal reaction, we do not consider further regulatory action to be justified at this time.

You have also requested a copy of the correspondence between Professor Lader and the MHRA referred to in my email of the 3 November.  Prior to the Committee on Safety of Medicines’ assessment of withdrawal reactions, comments were sought from expert advisors on the content of the Data sheet (data sheets were the original licence document and were subsequently replaced by the Summary of Product Characteristics) in relation to withdrawal reactions. A copy of his response is provided as an attachment to this email.

Yours sincerely

DR J M RAINE CBE
Vigilance & Risk Management of Medicines

(Attached Letter):

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