Brompton Cocktail - The Magical Qualities of Addictive Drugs....

I was talking to a colleague today about problems in the addiction field.  She was referring to problem with opioids and suddenly I had the association: "Brompton Cocktail."  The Brompton Cocktail was a mixture of alcohol, cocaine, morphine and other ingredients that had purported superior pain alleviating qualities compared with any other available medication at the time.  I first encountered the term on a medicine rotation as a medical student.  Our attending physicians at the time were two very bright hematologist-oncologists.  One was older and more cerebral with many publications.  The other was younger, outspoken and generally edgier.  He had just completed his fellowship.  When the conversation turned to pain relief for patients with cancer pain he made it very clear that his preference was "Brompton's Cocktail" but that it was not available in the United States.  He railed against the regulations in this country that prevented him from providing Brompton's to his American patients.

That piqued my interest at the time.  The natural question is why Americans were being denied a superior analgesic?  The second question was - why all of the polypharmacy?  Alcohol was an analgesic out of the old west - why would it need to be mixed with morphine and cocaine?  And why the cocaine?  It could certainly be a local anesthetic that could restrict blood flow in ENT procedures - but would it really provide widespread pain relief if it was ingested and systemically absorbed?  Further research in the matter showed that in addition to gin - vodka and whiskey were being used as the alcoholic beverage.  Some people added tincture of cannabis.  Others added anti-nausea medication like phenothiazines or antihistamines.

These combinations in elixir form were popular in Europe where their original use was in mainstream surgery in the late 1890s.  They became widespread in the 1920s and 1930s when many formulations were listed in the medical literature and practitioners often had their own custom formulations.  One of the references I read suggested that the patient could be given a choice in terms of the alcohol component (vodka, whiskey, or gin) and it gave them a sense of control over their medication.  There were some modifications of the original formula based on economic considerations - like the cost of cocaine.  The most striking feature of this mixture is that it persisted in use in medical facilities for nearly 100 years!  My medical school professor was telling me it was the ultimate pain medication in 1982.  Available evidence accumulating in the 1970s eventually illustrated that for pain relief there was no advantage of an exotic mixture over morphine monotherapy (1).   And that (in addition to more permissive use of opioids) brings us into the current period of opioid and nonopioid treatment of chronic pain, although the Brompton mixture was used almost exclusively for severe postoperative pain or pain associated with malignancy.

One of the strong themes in medical care as in the rest of American culture is the lack of appreciation of how past history factors into current medical care.  Although there were probably two biases in the early 20th century leading to the use of Brompton - the lack of manufactured pharmaceuticals and the potent effects of both cocaine and morphine, the same biases exist today.  The common bias noted on this blog has been the idea that opioids are universally effective for acute and chronic pain.  We are seeing an emphasis on cannabis as a treatment for pain and tincture of cannabis was an element of Brompton a century ago and it was eventually eliminated.  Unusual combinations of prescription medications are combined with the hope that they will provide some pain relief including opioids, sedative-hypnotics for sleep, benzodiazepines for anxiety and muscle spasm, muscle relaxants, gabapentinoids, and antidepressants.  I see patients who are taking extended release forms of opioids who are also given immediate release forms of the same opioid and told that they are "rescue" medications in the event that they have breakthrough pain not treated by their maintenance extended release medication.  I see people with implanted opioid pumps who are given immediate release medications for the same reason.  In both cases they tell me that their pain is the same but they continue using the rescue medication.

In a previous post on medical cannabis, I posted that some physician advocates talk about the entourage effect and why the whole plant needs to be smoked for pain relief.   The uniting thread in all of these approaches is that there is a predominance of potentially addictive drugs.  Addictive drugs always seem to be imbued with magical qualities - whether it is pain relief or the recent push to use psychedelics for whatever ails you. That always leads me to ask - is this medication working for pain or is it just reinforcing its own use?

All of these approaches strike me as being not much more scientific than Brompton Cocktail.  Like all historical lessons about addictive drugs and their purported effects - Brompton is nearly forgotten.

I nearly forgot it myself.


George Dawson, MD, DFAPA




References:

1: Melzack R, Mount BM, Gordon JM. The Brompton mixture versus morphine solution given orally: effects on pain. Can Med Assoc J. 1979 Feb 17;120(4):435-8. PubMed PMID: 376079.








   

Insights From the UK: Prescribing Addictive Drugs

From the British National Formulary (BNF): under the heading prescribing drugs likely to cause dependence or misuse (p. 9):

1.   To avoid creating dependence by introducing drugs to patients without sufficient reason (2).

2.  To see that that the patient does not gradually increase the dose of the drug, given for good medical reasons, to the point where dependence becomes more likely (2).

3.  To avoid being used as an unwitting source of supply for addicts and being vigilant to methods for obtaining medicines (2).


I was asked to write a piece about benzodiazepines last week.  In the process, I went to look at guidelines in the UK, specifically the NICE guidelines.  In the process, I ended up getting a copy of the British National Formulary because it had some commentary on prescribing addictive drugs.  The section starts with three paragraphs that start with the above sentences.  I don't know how long these sentences have been included in this book but I took a few moments to ponder whether anything like this is written in papers or texts that American physicians read.  Americans may go about the prescription of addictive drugs in an entirely different manner.

Medical training in the US often matches trainees with a lot pf people on complicated polypharmacy for a lot of different conditions.  In a typical resident's clinic there will be people taking benzodiazepines, sleep medications, antidepressants, and in some cases pain medications including opioids.  There people generally expect to see a resident and get these prescriptions refilled.  In supervising residents, they generally have the same questions about this process from 30 years ago: "Wouldn't it be a good idea to see if we can get people off these medications?"

The only difference in my approach from that of my supervisors was to suggest an informed consent approach.  In other words, advise the patient about current guidelines that suggest time-limited use and open up a potential dialogue about how to taper and discontinue a drug.  Even that position can be controversial.  There are three main attitudes that I have encountered in that area.  The first is: "Maybe the patient needs it."  In the case of benzodiazepine maintenance, there is really no research guidance at all in this area - there rarely is for chronic medication use.  The underlying assumption is that here is the rare person that needs maintenance use of this medication - typically a benzodiazepine or sedative hypnotic.   

The second attitude is "As physicians we need to be able to help the patient and that is my orientation when prescribing these drugs."  The underlying assumption here is that this medicine is the only possible way to help the patient.  There is a more insidious underlying assumption that if you don't want to prescribe this addictive drug that maybe you as a physician don't want to help as much as the physician who does.  The other obvious limitation that if the patient believes the only way he or she can be helped is with a specific medication that will define what the physician does in this case.

A third attitude is more nihilistic and that is the patient has been on this medicine for years and seen new residents every one of those years.  What are the odds that they want to change it?  There may be a rational basis for the nihilism.  People are generally very resistant to tapering and discontinuing an addictive drug even if there is no indication that it is doing anything for them. In my days in resident clinic many people were taking triazolam at two and three times the maximum recommended dose for sleep.  They still complained of insomnia - often to the same degree before they started using this medication.  Any attempts to taper them off were fraught with problems.  It was often possible to get them down to maximum recommended dose only to find that they went back to the higher dose after a new resident came into the clinic.

The three lines from the BNF assume that the physician being advised is going to prescribe the addictive drug initially rather than maintain it.  That is a lesson that should not be lost on residents in these clinics or attending physicians in the field.   Every physician prescribing addictive drugs needs to have a plan in their head that incorporates the BNF guidelines.  There is plenty of evidence that is not the case.  Wide variability of prescribing patterns by physicians in the same setting provides a good illustration.   In a recent study (1) the range of opioid prescriptions across physicians varied from about 7 to 25% of emergency department visits with the odds of long term use correlating directly with the quartiles based on those frequencies.

There is another implicit dimension to the BNF guidelines and that has to do with neutrality.  There is generally far too much heat around the issue of addictive drugs in American training and practice.  That ranges all the way from the physicians just being uncomfortable with prescribing the drugs and transmitting that emotion to the patient to overt threats by the patient in order to get the drugs.  In the case of the former, I have had people who were both reliable and unreliable tell me that they felt they were being treated like a drug addict.  In the case of the latter, physicians (including myself) have been threatened with physical attack or blame for a patient's demise (suicide or accident due to recklessness) if they do not supply the desired addictive drug in the right dose and quantities.  There are the "dog ate my alprazolam calls"  to on-call physicians who typically are not seeing the caller as a patient.  All of these factors often lead to a contentious relationship between physicians in training and attending physicians and the people on addictive medications.  As these few pages in the BNF point out - that emotional intensity is really unnecessary.

I have found that to be a mistake in the training of American physicians.  We learn how to prescribe addictive drugs and come to dealing with the problem of addiction much later.  The most important aspect of those prescriptions is the personal relationship and emotional reaction to the patient.  Some physicians never really learn to deal with it.  We could learn a lot earlier by the basic focus that is in the BNF.    


George Dawson, MD, DFAPA



References:

1: Barnett ML, Olenski AR, Jena AB. Opioid-Prescribing Patterns of Emergency Physicians and Risk of Long-Term Use. N Engl J Med. 2017 Feb 16;376(7):663-673. doi: 10.1056/NEJMsa1610524. PubMed PMID: 28199807.    

2:  British National Formulary.  Published Jointly by the Pharmaceutical Press; Division of the Royal Pharmaceutical Society; 66-68 East Smithfield, London E1W 1AW, UK and BMJ Group; Tavistock Square, London, WC1H 9JK, UK; 2016: p. 9.


Attributions:

The cover of the BNF is the cover of my copy that I purchased from Amazon.  I consider the three lines that are quoted and referenced to this book to be fair use for scientific discussion on a non-commercial and not-for-profit blog.

I have no personal or business connection with the BNF.  Any references to it here are just for the scientific discussion of its content and potential importance in medical training.