Having looked at more papers now and I am sure that Merck would have seen the problem that this drug could have caused in a minority of patients. The knowledge of genomics was in its infancy when the drug was developed but the association with prostatic hyperplasia was noted in the pre-clinical stages, i.e. the clinical trial stage. Some of the sexual dysfunctions and associated psychiatric problems will find significant potential hormonal and endocrine disruptions that could provide a key.
If this is looked at from the perspective of Vioxx, a drug licensed in 1999 (Isotretinoin was licensed in the UK in 2001) then it is easy to see why they hid the potentially severe ADRs. Vioxx was held responsible for 185,000 cardiovascular accidents (heart attacks and strokes) and killed more Americans than the Vietnam War did. Merck did not admit that they had hid vital negative results from the clinical trials and effectively blamed the patients lifestyles for their misfortune. A bit like blaming the PFS victims as being mentally unstable in the first place. Not that in law that is a defence, pre-existing mental health conditions are an added risk in prescribing since Page v. Smith (1996) UKHL 7 and not an escape clause.
Vioxx is a Cox2 inhibitor and they prolong the QT interval. The clinical trial group were all in an age group where that would not be so critical, the target patient group were predominantly elderly and taking polypharmacy regimens likely to involve other QT prolonging drugs. They must have known that the clinical trial cohort would not show that as a major risk factor and the trial cohort were definitely not matched with the patient target group.
The Americans call this wilful blindness and drug companies were notorious for it in the 1980’s and 1990’s. I have found trial data in data sheets that indicate adverse effects that never got into the formularies. I suspect that it would not take long if the Isotretinoin clinical trial data was scrutinised before a significant marker was discovered. There is every good reason to think that a rare effect associated with metabolism could have caused a very rapid toxic effect not unlike that experienced by those with anaphylactic reactions to nuts and wasp stings for instance. Not everyone is killed by a peanut and a wasp sting but some most certainly are.
Having studied how anti-cholinesterase inhibitors at extraordinarily low doses can kill, while these agents will kill indiscriminately it is quite feasible that some other agents will only severely injure those with particular rare genotypes. Anti-cholinergic drugs, the properties of which are found in many psychopharmaceuticals cause slowing of mental & physical functions, dizziness, disorientation and hallucinations along with skin flushing, increased heart rate urinary retention and constipation. In some patients these cause severe ADRs while not in all. It is hardly acceptable however to suggest that because that does not happen in all that is is not a serious risk.
The psychiatric profession love to refer to treatment resistant (refractive) patients, almost as if in some way they are doing this deliberately. Patients are treatment resistant because the cytochromes necessary for drug metabolism are poorly expressed. If they cannot metabolise the drug it is hardly surprising that they don’t get better when taking it. What is remarkable about this is that they want it both ways. They are happy to accept that a patients is resistant, necessitating a move to another drug (usually Clozapine) but stubbornly resist any further inquiry into other potential difficulties presented by P450 metabolism.
This dog-in-the-manger resistance to a proper investigation into rare ADRs, in many cases simply to protect drug company profits and prissy clinical reputations is a disgrace and an insult to medical science.
This is what we have experienced when it comes to the above as highlighted. It actually states in the files that Elizabeth is treatment resistant and a long list of the drugs, including Clozapine.
Now that there is the P450 liver enzyme tests available to everyone via the NHS, this needs to be widely known and further investigations into other potential difficulties presented by P450 metabolism should be thoroughly carried out.
Psychiatric Abuse UK 