I suffer from a congenital connective tissue disorder called Marfan syndrome.  This syndrome is caused by a faulty gene (FBN1) on the 15th chromosome pair, and is autosomal dominant (if one parent has the syndrome, each child that the parent brings into the world stands a 50% chance of presenting with this syndrome).  The fault in FBN1 causes this gene to code for a damaged version of a key protein called fibrillin-1 (this protein is a key component of connective tissue).

As a direct result of this genetic defect, my connective tissue (the “glue” that holds the body together) is insufficiently elastic.  This syndrome, if left untreated, is highly lethal.  As in so many patients who suffer from Marfan syndrome, I have an ascending aortic aneurysm.  In my case, the aneurysm is not quite large enough to warrant the brutal surgery that may one day become necessary – furthermore, the aneurysm has shown absolutely no indication of increased size since I was first diagnosed as suffering from this condition back in 1995.  It appears that I may be one of the lucky patients who will never require the surgery to which I allude above.  This surgery involves replacement of the aortic root and the aortic valve with a Dacron tube and artificial valves – this procedure is highly effective, but requires that the patient take warfarin sodium (Coumadin) for the rest of his or her life.

Currently, the standard of care consists of putting the patient on beta blockers (e.g. metoprolol 100 mg twice daily) for life – beta blockers reduce both blood pressure and heart rate.  This in turn places less strain on the aneurysm, lessening the chances of the aneurysm ever dissecting (slowly coming apart over a period of hours) or rupturing (in which case the patient usually dies within seconds).  The standard of care also calls for regular echocardiograms with complete visualization of the heart, or CT scans (an echocardiogram performed by a talented radiologist is as good as a CT scan, and has the advantage of enabling the radiologist to detect and measure any aortic valve incompetence (which causes regurgitation of blood back into the heart)).

Recently, Dr. Harry Dietz (a world authority on Marfan syndrome and related conditions) discovered that the faulty FBN1 gene also potentiates the action of a hormone named Transforming Growth Factor beta (TGF-beta).  This discovery has completely revolutionized the treatment of Marfan syndrome.  When TGF-beta is overactive, the patient presents with symptoms such as unusual height  (in my case, 6’6”), unusually long arms and legs, a highly arched palate, a “crowded mouth” (too many teeth for too small a mouth), a tendency for some joints to dislocate spontaneously, and other problems that cannot be attributed to the bad version of fibrillin-1 acting alone.  Dr. Dietz theorized that drugs that block the action of TGF-beta may arrest the condition.  He therefore placed several infants who had very severe cases of Marfan syndrome on a drug named losartan (which inhibits the action of TGF-beta).  This theory appears to be correct – Dr. Dietz noted not just arrest of the syndrome in pediatric cases, but in several cases, complete reversal of the aortic wall abnormalities that give rise to the aortic aneurysms!  In short, Dr. Dietz identified another factor in the pathogenesis of Marfan syndrome – as a direct result of his work in pediatric patients, and the successes he has documented in these patients, he is now conducting a Phase III clinical trial involving adults, using losartan combined with beta blockers, irbesartan combined with beta blockers, and beta blockers alone.  I decided not to wait for the results of this clinical trial, and my doctor now prescribes losartan for me every month on a repeat prescription.

Without getting too technical, I suffer from chronic pain.  My back, knees, and arms are badly damaged – phrases such as spur formation, levoscoliosis, annular bulge, Schmorl’s node formation, bone marrow signal changes, degenerative changes, etc. jump out from the CT scan reports.  My doctor in New York City (where I lived and worked until about two years ago) treated the chronic pain with OxyContin as the mainstay of my pain management regimen, and Norco 10 / 325 (hydrocodone 10 mg and acetaminophen 325 mg) for breakthrough pain.

I now live in the UK, where hydrocodone is not marketed – instead, I take OxyNorm 10 mg and 20 mg capsules, and the UK equivalent of Tylenol #3 with codeine (known as Co-codamol in the UK) for the treatment of breakthrough pain.  I continue to take OxyContin 160 mg twice daily as the mainstay of my pain management strategy.  I am therefore on OxyContin, OxyNorm, and Co-codamol for pain management.

Yes – thank you, I am well aware of the fact that oxycodone (the active ingredient in OxyContin and OxyNorm) is a very powerful opiate!  A French study concluded that, on a gram for gram basis, 100 mg of oxycodone packs the same analgesic punch as about 150 mg of oral morphine (making oxycodone considerably stronger than morphine); another study concluded that oxycodone is roughly equianalgesic to diamorphine (heroin, which is a legal painkiller in the UK, often used in the treatment of cancer pain and in palliative care contexts).  Yes, you read that correctly – heroin (known to doctors as diamorphine) is a legal drug in the UK when dispensed by doctors who know what they are doing, and oxycodone is roughly equianalgesic to diamorphine.

I am lucky in that I have developed tolerance to oxycodone unusually slowly.  Back in 1995, my daily dose of OxyContin was 80 mg twice daily.  Now, 14 years later, my daily dose of OxyContin is 160 mg twice daily.  The development of tolerance and the manifestation of withdrawal symptoms when an opiate or opioid is abruptly discontinued are not indicative of addiction!  It was accepted wisdom for a long time that tolerance and withdrawal were indicia of addiction – pain management specialists now know that physiological dependence on an opiate or opioid is not the same as addiction.  Addiction is diagnosed clinically in terms of the behaviour of the patient and in terms of psychology: Does the patient hoard drugs?  Does the patient engage in deceptive techniques to acquire drugs (e.g. “doctor-shopping”)?  Does the patient refuse to travel unless he can bring his “stash” with him?  Does he engage in drug-seeking behaviour?  These are now the issues that pain management specialists take into consideration when determining whether nor not a patient is addicted.

The decision by the FDA advisory panel, if adopted by the FDA, could have tragic consequences.  It is now well established that doctors in the USA are notorious for undertreating chronic pain for fear of their patients becoming “drug addicts”.  The “war on drugs” has become enmeshed with the legitimate field of pain management, to the extent that many doctors in the USA (about 25% of them) don’t even bother to order the triplicate prescription blanks required in order to issue Schedule II prescriptions for drugs such as pure oxycodone, pure codeine, pure morphine, etc.  Pain management specialists have coined the phrase “opiophobia” to describe the attitude of so many doctors who do not specialize in pain management.  Up until now, doctors in the USA have always been able to fall back on Schedule III compound analgesics – e.g. Norco 10 / 325 (hydrocodone mixed with APAP), Tylenol #3 with codeine, Vicoprofen (hydrocodone mixed with ibuprofen), Darvocet (dextro-propoxyphene mixed with APAP), etc.  Schedule III prescriptions are not tracked to the same extent as Schedule II prescriptions, and doctors may issue up to five refills on all Schedule III prescriptions, whereas they may not issue any refills on Schedule II prescriptions.  All Schedule II prescriptions have to be written up on triplicate prescription blanks, and a new prescription has to be written for each month’s supply of the medication in question.  Given the well-documented tendency of doctors in the USA to undertreat chronic pain, I foresee a great sadness as those doctors who previously issued prescriptions for medications such as Norco, Vicodin, Tylenol #3, etc. simply stop issuing prescriptions for opioid / opiate analgesics, leaving their patients to suffer with NSAIDs and drugs such as acetaminophen and aspirin.

This is so typical of the reactionary and backwards mentality that informs the “war on drugs” – Americans have a shocking tendency to confuse the abuse of a drug with its legitimate usage.  The recent death of Michael Jackson has thrown this issue into sharp relief – already, people are blaming OxyContin and Demerol, instead of the dumb f—k who (allegedly) abused both of these drugs on a daily basis.  Those patients who suffer from chronic pain and who need aggressive treatment with mu-agonist opioids and opiates may now end up paying the price for the crass stupidity of people such as Michael Jackson and Rush Limbaugh (after his abuse of OxyContin, people started blaming OxyContin itself for his addiction, instead of blaming the gasbag who blackmailed his maid and who shovelled these tablets into his system as though they were pistachio nuts).  After Sonny Bono skiid into a tree whilst high on Vicodin, his wife blamed the Vicodin for his accident, not the idiot who took to the slopes in a semi-stupor.  Doctors in the USA are already afraid of falling victim to overzealous D.E.A. bureaucrats, who are uninhibited by wisdom, knowledge, or clinical experience and who substitute their own judgment for that of physicians who have studied medicine for seven or eight years before being permitted to prescribe!

Yes – some people abuse compound analgesics, mix them with alcohol, and damage their livers – but it is generally not sound public policy to throw away an entire class of drugs to accommodate the stupidity and ignorance of those patients who abuse such drugs!

The situation in the UK is precisely the reverse of that in the USA.  Doctors in the UK are entirely willing to prescribe powerful medications to those patients who can document a legitimate medical need for such drugs.  I had a good and caring doctor in New York City, and therefore never suffered the effects of opiophobia first-hand – but I heard of a doctor in Oregon who was disciplined for treating a terminally ill cancer patient with acetaminophen alone, for fear of turning that patient into a “drug addict” (the doctor was forced, as a condition of retention of his license to practice, to work side-by-side with a pain management specialist)!  These are not isolated incidents in the USA.  These tragedies occur with tragic frequency.  Fortunately, doctors in the UK treat chronic pain seriously and have not confused the legitimate usage of powerful opioids and opiates (including diamorphine!) with the abuse of such medications.  I doubt very much that the UK would follow the USA’s example should the FDA adopt the recommendation of its advisory panel – but even were the UK to do so, I don’t believe that UK doctors would stop issuing powerful opioids / opiates – instead of prescribing drugs such as Co-codamol, they would probably write separate prescriptions for codeine and APAP; instead of writing prescriptions for Co-dydramol, they would probably write separate prescriptions for dihydrocodeine and APAP.

Sadly, the FDA usually follows the recommendations of its advisory panel.  However, it does not have to do so, and there is still time to apply pressure on the FDA (in the form of angry public comment) to put a stop to this madness before it starts!

I very much hope that people will take this issue very, very seriously, and make the necessary noise to derail this grotesque proposal.