Well I know I haven’t… but I can tell you that the head of the Seroxat Secrets legal department has – and he has made some interesting observations. (Thanks for this Matt!)
From: Matthew Holford
Subject: Report of the CSM EWG on the Safety of SSRIs
Date: 6 April 2007 01:26:46 BDT
To: info@mhra.gsi.gov.uk, Simon.M.Bicknell@gsk.com
Cc: BOSWELLT@parliament.uk, GRIEVED@parliament.uk, bobsmith@cix.co.uk, STEENA@parliament.uk, VARAS@parliament.uk
Dear Sir or Madam,
I was interested to take the opportunity to skim through the above tome, in an odd moment, which presented itself. I regret that my comprehension of the learned opinion represented there were beyond the scope of my meagre appreciation.
However, as is the tendency with lawyers, I suppose, I flicked fairly promptly to the back pages, to see what had been drawn in the way of conclusions, and made in terms of recommendations. The EWG concentrated on reports of a select group of adverse reactions, particularly suicide and withdrawal. I was interested to note the 5th bullet of Section 8.5, which deals with the key findings of the Group, pertaining to withdrawal. There, it states:
“There is no clear evidence that the SSRIs and related antidepressants have a significant dependence liability or show development of a dependence syndrome according to internationally accepted criteria, either DSM-IV or ICD-10.”
Although, the first bullet in that section claims:
“All SSRIs may be associated with withdrawal reactions on stopping or reducing treatment. Paroxetine and venlafaxine seem to be associated with a greater frequency of withdrawal reactions than other SSRIs. A proportion of SSRI withdrawal reactions are severe and disabling to the individual.”
Now, at first glance, to the uninitiated, such as myself, that might appear to be a contradiction in terms, until one begins to appreciate the complexity of language on display, here. Upon re-reading, am I to understand that while SSRIs have the potential to cause significant distress to the patient, but that, at the same time, the patient will have no great desire to start using them, again?
I was also interested to read the DSM IV’s definition of “Substance Dependence”, which I took from PsychiatryOnline “There is a pattern of repeated self-administration that can result in tolerance, withdrawal, and compulsive drug-taking behavior.”
While I understand that the compulsion to take a particular drug may be absent, I note that DSM IV claims that not all factors need be present for Dependence to be a established. Dependence, then, is not the sum of the three parts, as far as DSM IV is concerned. Thus, for example, withdrawal is not a feature of hallucinogens, I understand:
“The symptoms of Dependence are similar across the various categories of substances, but for certain classes some symptoms are less salient, and in a few instances not all symptoms apply (e.g., withdrawal symptoms are not specified for Hallucinogen Dependence). Although not specifically listed as a criterion item, “craving” (a strong subjective drive to use the substance) is likely to be experienced by most (if not all) individuals with Substance Dependence.”
It then goes on to require that three criterion be demonstrated by the user, within any 12-month period, with tolerance being the first criteria, for its definition of Dependence to be met. My question, then, is a simple one: does one need to demonstrate tolerance, craving and withdrawal, in order to be Dependent, in the view of the MHRA, or does one not?
I was also interested in the Key Findings at Section 7.7, which deals with adult suicide. It seems that there is a greater risk of emotional liability [sic] around the time of “presentation to the medical services,” (please see the first bullet, under the above section). Aside from the taking of SSRIs, has any research been undertaken into patient experience, at this apparently key time? I understand, from comments made elsewhere in the document, that this view is limited to “young adults”, ie, those in the 18-30 age group, however.
I note that responsibility for patient monitoring is passed to carers and healthcare professionals, in light of the perceived risk. I am concerned that that might be perceived as an attempt to limit liability for pesonal injury, on the part of a manufacturer, should it be minded to include such advice on the PIL, for example. The inference that one might draw, were one of such a bent, would be that, in the event of a worst case scenario, representation might be made to the effect that the carer or healthcare professional concerned had failed in their duty to carefully and frequently monitor patients, particularly given that I understand that the model of monthly appointments and repeat prescriptions is regarded as therapeutically efficient. Assuming that this monitoring duty is accepted as the desired model, may I ask what provisions have been established, in the interregnum, to ensure that monitoring is indeed “careful and frequent”?
Howsoever it may be, I note also that there is assessed to be no notable increase in rates of suicide, since the introduction of SSRIs, although the rider that attends that observation (that such statistics are almost impossible to analyse accurately), renders the initial claim valueless, in my view.
Now, in the fourth bullet of that Section “a modest increase in the risk of suicide and self harm… cannot be ruled out.” However, in the sixth bullet “There is no clear evidence of an increased risk of self-harm and suicidal thoughts in young adults of 18 years or over.” May I ask, which of these two statements the EWG wishes to pin its colours to?
My apologies for deliberating so closely, and at such length, on this somewhat turgid subject matter. However, it was quite a long report.
Best regards
Matthew Holford
