Opioids, a personal journey

I found this article on Kevin MD

20 or so years ago I started treating chronic pain in a University Pain Clinic.  Actually it was just me and the Day Ward nurse who drew the short straw in a corner of the Day Ward that nobody else wanted to use but we called it a pain clinic.  I like to bore people by telling them how we used to treat patients with chronic pain in those days.  I basically had 3 tools:  needles, amitryptiline and carbamazepine.

Needles actually worked in more patients than should have been scientifically possible but didn't work in everybody.  Amitryptiline and carbamazepine work well in randomized double blind trials and in meta-analyses but work poorly in the real world  I started exploring other anti-depressants and anti-convulsants.  A patient brought me the article on the first case series of 9 patients treated with gabapentin and I still look on that moment as  a milestone in chronic pain management.  Gabapentin also only worked in a small fraction of patients.

I started sending patients to the hospital psychologist who, when she realized what was going on, rationed me to one patient a month; the physiotherapy department refused to see chronic pain patients.  Don't worry, I was told any time now we are going to get a big multidisciplinary pain clinic.  Fortunately I didn't hold my breath on that one.

Quite a few of the patients that came to the pain clinic were taking fairly substantial doses of narcotics.  In fact that was the primary reason for referral for most of them.  This was usually tylenol with 30 or 60 mg of codeine or tylenol with oxycodone.  There were the other standbys, talwin, darvin and fiorinal and quite a few patients were on injectable meperidine either thru their doctors office, the emergency department or some actually self-injected.

At this point I should back-track to what I knew about narcotics in chronic pain which was not very much.  I believe we had one lecture in medical school in first year.  This lecture was by someone  from the College of Pharmacists talking about prescription drug abuse.  I don't remember many lectures in medical school; I remember this one vividly if only because it was the first and last time I heard patients referred publicly as assholes.  Other than pharmacology we didn't get much teaching on how to order narcotics either in acute or chronic pain.  The use of narcotics in palliative care was only just starting.  During my first surgical rotation, the surgery resident told me how to write the post-op orders which consisted mostly of:  "Demerol 75-100 mg IM q3h PRN."  (I would like to think this has improved except I don't think is has, except that Demerol is hard to come by.)

When I started in general practice and covering the emergency it became apparent that a lot of patients had chronic pain.  Except we didn't call them chronic pain patients then, we called them addicts and drug seekers.  In the emergency quite a few docs didn't even bother seeing them.  "Oh so and so is here again," they would say as they wrote an order for the nurse to give 100 mg of Demerol.  Some GPs just phoned it in or left a standing order so they wouldn't have to come in from home in smaller hospitals where there wasn't on site coverage.  I remember in my first locums being alarmed at just how much narcotics and sedatives people were being prescribed.  Nobody told me about that in medical school.  To be sure, a lot of them were abusing their drugs.  There were stories about doctors being threatened by patients for not prescribing what they wanted.  I was never threatened but a friend of mine was by somebody just passing through town when my friend wouldn't prescribe the patient's choice of oral narcotic.  A lot of them however especially when you got to know them had legitimate pain problems, they had had multiple back surgeries or suffered from intractable migraines and while there was a lot of tut-tutting about their narcotic use, there wasn't a lot of effort being made to see if they could be helped in another way.

There were a lot of valid reasons why I fled general practice (like not being very good at it) but I have to think that seeing those patients day after day and night after night and knowing I really had nothing to offer them that pushed me just a little bit.

So it was that 7 or so years removed from general practice my opinion of narcotics in chronic pain both from   training and experience was pretty dim.  They were never appropriate and patients who used them inevitably became addicted which was a bad thing even if they did seem to help some people's pain.

The tide was changing.  Use of narcotics in palliative care had become accepted, it was noted that patients could tolerate high doses with reasonable function and long acting oral forms were  available freeing patients from injections.  Because nobody wanted to see chronic pain patients, a lot of palliative care physicians reluctantly saw these patients and used what they were familiar with which was long acting oral narcotics  And some patients actually got helped.  Around 1993 our provincial college (Medical Board) actually published guidelines on the use of narcotics in chronic pain.

In 1995 at the Canadian Pain Society Meeting, I first saw OxyContin advertised.  My experience with patients who were taking oxycodone/acetaminophen preparations in Canada, lead me to believe that the oxycodone molecule had some special properties that other opioids didn't have.  I remember telling the rep manning the booth that OxyContin was going to be huge drug.  Occasionally I am right about things.

I don't remember when I wrote my first long acting narcotic script.  It should have been a memorable experience but it wasn't.  I do know that it took two years for my to write my first 50 triplicate prescriptions and I was seeing a lot of patients in that era.  What I do remember is that when I wrote these prescriptions for people who had failed needles, amitryptiline, carbamazepine and even gabapentin, a significant number of patients actually seemed to improve.  It was actually fun seeing them for their follow-up visits because they were actually happy.  This wasn't everybody of course and many people who aren't satisfied with their treatment just don't show up for follow up visits.  (I always assumed they didn't show up because they were better but of course I know that usually isn't true.)  I got a methadone licence and started prescribing methadone with great gusto as well.

I started even feeling dirty when I did a block on somebody instead of whipping out my triplicate pad.

I started seeing people at meetings talking about their experiences treating chronic pain with opioids.  What I noticed was that they presented the same small group of cases again and again as if this was maybe their only success.  It didn't matter, I drank their Kool-aide; after all we had very little left to treat the majority of our chronic pain patients.  Pretty soon I got approached to start doing those talks locally.  I was still evangelical about pain and to Big Pharma's credit, I was never told what to say and while they provided slide kits, they never minded.when I modified their slides when I didn't agree with what the content.

The gospel my fellow travelers and I preached was:

1. You cannot be addicted to your pain meds if they are prescribed for legitimate pain.
2. There is no maximum dose of opioids.
3. Opioids are safe and there is no end-organ damage.
4. Opioids are efficacious in chronic pain.
5. Controlled release opioids are preferable to short-acting opioids.

You cannot be addicted to your pain meds if they are prescribed for legitimate pain.

This was a reaction against the conventional wisdom of the day which was you would always become addicted to your opioids.  The answer was somewhere in between that.  Addiction unfortunately is not a black and white condition.  It is difficult to find any definition that doesn't have a lot of "yes buts".  The most extreme people defined anybody who took opioids for more than a day as addicted.  We took the opposite.  Many of the signs traditional attributed to  opioid mis-use like dose escalation, double doctoring, buying meds, visiting the emergency room we excused as pseudo-addiction or a cry for help by the patient. 

 After a few years of wild prescribing some of us realized that yes, people could become addicted to their meds and the practice of universal precautions came into being whereby using various questionnaires and tools and urine drug screening we could pick out the high risk patients and deal with them.  Never mind that all these tools had huge false negative and false positive rates.  Therefore the little old lady with pain from compression fractures got the same UDT as the biker with back pain.  The biker of course knew how to beat urine drug screens.

Clearly people can have pain and still be addicted.  Some were already addicted when we saw them, some we introduced a drug they could be addicted to into their lives.

There is no maximum dose of opioids

This was preached by many of the pain specialists who started out in palliative care.  This was expanded by the concept of a therapeutic window for narcotics, whereby patients would get relief but only at the right dose.  If the patient came back and said he was getting no relief, the answer was more higher doses.  There is no denying that patients do develop a tolerance to their medications although this clearly does not seem to be a universal phenomenon.  

I remember watching two of the uber-disciples presenting a case (actually I saw this case presented 3 times) of a lady whose pain was only a control at doses of hydromorphone to the point where every second molecule in her blood must have been hydromorphone.

Of course because we all believed that patients couldn't get addicted when the patient phoned you up saying he had taken a month's worth of drugs in a week, you response was to up his dose.

Part of this came from chasing the patient's pain scores.  Unfortunately most chronic pain patients routinely report scores of 8 or 9/10.  This depressed me until instead of asking them what their score was, I started asking them whether they really felt that the drug was helping.  In a lot of cases it was and I stopped chasing the pain score.

Opioid hyperalgesia was something our palliative care colleagues had observed for some time and I still see this in many patients I see, usually other people's patients but sadly a few of my own. It is hard to tell them that the answer to their pain is less rather than more opioid.  Strangely many of my colleagues continue to disbelieve that this exists; some of them get out right hostile if you discuss it.

Opioids are safe and there is no end-organ damage.

Clearly while in the acute phase opioids can depress respiration causing death which doesn't really happen in tolerant patients (unless they take an accidental or intentional overdose combined with other CNS depressants) this seemed a fairly safe thing to say.  Certainly they weren't nephro and cardiotoxic like the NSAIDs or hepato-toxic like acetaminophen.   

But:

Narcotics do depress endocrine function.  This was actually known in the 1960s with heroin addicts but we rediscovered it when patients showed up asking for Viagra prescriptions and we measure their testosterone levels.  Low testosterone is fairly easy to treat, although treating it never seemed to help them much; women whose endocrine systems are way more complicated were very difficult to assess or treat and I never succeeded in getting an endocrinologist to take an interest in this.  

Methadone can prolong the QT interval leading to Toursades de Pointes.  I have seen about 5 cases of this. This is usually associated with anti-depressants most of which also prolong the QT and motility agents which likewise prolong the QT.  Cocaine use was a factor in at least one case.

Some studies are now showing grey matter changes in patients started on opioids.  Nobody knows what the significance of this is.

We tend to minimize constipation as a symptom but the odd patient develops an obstruction leading in some cases to a perforation.

Opioids can cause or exacerbate sleep apnea which a lot of chronic pain patients already have.

Nausea, constipation and sedation were minimized as side effects but usually require the prescription of medication to counteract the side effect, each with its own set of side effects and drug interactions.

Opioids are efficacious in chronic pain

There are lots of studies and meta-analyses which "prove" this to be true.  The only problem is that almost all of these studies were short-term studies and most of them had high drop-out rates because of side effects or lack of efficacy.  Almost all were Pharma sponsored but that of course is a problem not limited to opioid trials.  Clearly if we looked at the patients who told us that the drug wasn't working as we pushed the dose higher and higher or that simply just didn't come back for follow-up we knew that this wasn't universally the case.

Controlled release opioids are preferable to short-acting opioids.

Controlled release opioids were originally intended for palliative care patients as a convenience so that they wouldn't be taking meds every 3 hours.  They were introduced into chronic pain practice by palliative care physicians but took off like gang-busters in the chronic pain world.  This is despite lack of much evidence that they are really any better than short acting opioids which are cheaper and in many cases preferred by the patient either because they don't mind taking their meds every 3 hours or because they prefer to take them only when their pain is severe.  This is not to say that somebody taking 20-30 doses of acetaminophen/codeine or oxycodone per day is a good thing but there are pure short acting opioids available. 

We originally believed the the CR opioids were less prone to abuse.  OxyContin showed us this wasn't the case although we knew even before OxyContin that MS Contin could also be abused, it's street name was  "red peelers".  We also believed there was less tolerance if a CR opioid was used, without any evidence.

Patients told us otherwise, they frequently used CR Opioids as PRN meds or took them 3-6 times a day because that was what they said worked.  We didn't even trust the CR opioid that much ourselves, we always prescribed a short acting medication as breakthrough medication.  This was supposed to be for exacerbations but our patients more or less took as much as they were allowed (and when they wanted more, we gave them more because there was after all no maximum dose of opioid.)

Published guidelines supported (mandated) the use of controlled release opioids so if you prescribed short acting opioids because that was what seemed to work, you could face discipline.

Controlled release opioids were, of course, more expensive and less likely to be generic.

And so a new era in pain management began

With all this in mind my fellow pain specialists and I began prescribing with great gusto.  Many family docs who attended our talks also took this up.  Many of course steadfastly refused to have anything to do with what was supposed to be the future of pain management.  We knew they would eventually come around.  I acquired more colleagues who had done pain fellowships in the US and were versed in the gospel of oral narcotics.  They were for the most part against interventions so I began to feel guilty when I did a procedure.  Besides it was so much easier to whip out the old triplicate pad.

Even the local entrepreneurial physiatrist  with the "multi-disciplinary" pain clinicwho had previously preached against opioids got in on the act.  He realized that it was much more cost-effective to prescribe methadone than to have to pay for physiotherapists and  psychologists.

It became common to see patients on very large doses of OxyContin or another narcotic, usually with another short-acting agent for breakthrough, sometime two long acting opioids.

And then of course the shit hit the fan

I am of course referring to OxyContin.  As I mentioned above, when I first saw OxyContin at a meeting, I predicted it would be a huge drug.  As soon as it became available, it became my first-line opioid (it still is).  It seemed to have a lower side effect profile and better efficacy than the other opioids.  If I prescribed it, I knew I was less likely to get phone calls or unhappy patients.

Now it is not like there was no prescription drug abuse before OxyContin.  During my time in general practice we knew patients abused codeine products, dihyrocodone(DH) cough syrups, and Talwin among others. Even during the worst of the OxyContin "epidemic" of drug abuse, Tylenol with Codeine was as popular on the street as was OxyContin.  OxyContin was different from other pills in that much higher doses of narcotic were packed into each pill, as much as 80 mg.  And then there was the supply.

Being a sub-specialist I never was exposed to how OxyContin was marketed at the primary care level.  I did however give a lot of talks to primary care, where without mentioning OxyContin specifically, I outlined the five points above on how appropriate, safe and efficacious it was to prescribe long acting opioids for chronic pain. And OxyContin was a very effective well tolerated narcotic which meant that it became the go to drug for family docs which meant that there was a lot of OxyContin around to leak onto the streets.

Pretty soon we heard about "hillbilly heroin", lives ruined through OxyContin and people dying of overdoses.  I have always wondered who is at fault when somebody lies to their doctor, buys or steals a drug to get high.  Is it the drug or it is the person?  I am sort of leaning towards the person.  I would see parents on TV talking about how their son's or daughter's life was ruined through OxyContin as if maybe the way they were raised didn't maybe have a little to do with it?

Nonetheless licencing bodies and governments clamped down.  Family docs read the stories and didn't want to prescribe OxyContin or for that matter any narcotic.  Pharmacies wouldn't carry them.  Patients refused to take them.

In Canada a mulidisciplinary group on opioid use published a document stating that 100 mg of oral Morphine was the "watchful" dose which means that that was the dose at which you were supposed to re-evaluate things but of course licensing bodies and insurance companies interpreted this as the maximum dose.

Companies responded by trying to make their drugs more tamper-proof or by adding naloxone to foil IV drug use.  This is partially helping.  I am told that since CR Oxycodone is now tamper-resistant, illicit oxycodone use has gone down, replaced (surprise, surprise) by heroin use.

So did we (I) learn anything from this?

I like to think so.  I screen for addiction a lot more now and I like to believe I am more cautious.  I don't  push the dose, I figure if they aren't getting relief at lower doses, it may be time to look at another medication or another therapy.  I'm not ashamed to do blocks if I figure they might work.  The bottom line is, I still prescribe oral opioids including controlled release Oxycodone.

A lot of doctors have however been scared off from prescribing narcotics in any form.  On top of this, because there is now a shortage of family docs, many family docs will not see any patient taking opioids, quite a few won't see any chronic pain patient just in case.  This of course puts more pressure on those of us doing chronic pain management and we all know that if we, after exhausting all options, trial the patient on oral opioids, we have more or less married them.

A few "experts" are also piling on stating that narcotics will inevitably lead to addiction (which given the rigid definition they use is an almost certainty).  I actually read somebody who wrote that palliative patients shouldn't be prescribed opioids.

Some of my fellow co-disciples from the old days don't seem to have learned.  I get some hostility at meetings when I suggest that the ways we practised and encouraged others to practise may not be appropriate anymore and we should maybe be a little judicious about prescribing opioids.

One of the advantages of getting old is of course seeing how heresy becomes dogma and dogma becomes heresy.  And of course oral opioids are just another medication fad that didn't work out as well as it should have.  For example:

Hormonal therapy for menopause

Vioxx

Flecainide and Tocainide

Aprotonin

The real issue here is that we don't really have very effective treatments for chronic pain and that many treatments that we do have aren't universally available.  A lot of people's lives may have been ruined by misusing prescription drugs; quite a few people I see in the Pain Clinic already have a life that has already been ruined.