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.








   

Why The Binge Eating Disorder Banner Ad Is Good Marketing

I noticed a new banner ad for Binge Eating Disorder in my Yahoo pages last night for the first time.  It is one of those sophisticated ads that becomes a video clip when you click on it.  The main message of the video clip is that "Binge Eating Disorder is a real medical disorder" and it provides a link to the web site bingeeatingdisorder.com.  If you go to that site and click on the health care professionals link, you are taken to what is essentially a massive infographic on binge eating disorder with descriptions of  what is known about the epidemiology and theory of B.E.D.  There is no mention of treatment or the specific FDA approved medication from this pharmaceutical company that has been approved for B.E.D.  My speculation is that is coming once the advertisers analyze their web traffic and see how well the ad campaign is accepted.  Specifically will there be the usual outcry that pharmaceutical companies are making up diagnoses in order to sell drugs and of course the evil psychiatrists that are involved.  If a lot of that blowback occurs it would be easy to cancel the campaign, take down the web site and either come up with another campaign or go with more traditional advertising to a much less politically adept audience, namely physicians through medical journals.  I admit, the brain graphic with a slice of pizza replacing the parietal lobe is eye catching.      

This ad allows me to make a couple of points.  The first is the reason that we have epidemics of addictive drugs.  The general process is an increase in availability and exposing more people to the drug.  We do not know the genotypes at risk but in general a significant part of the population will have euphorigenic responses to addictive drugs.  Wider availability generally equates to larger numbers of users and people at risk for addiction.  An example I like to use is growing up in northern Wisconsin.  Back in the 1970s, even though it was the hippie generation, the main exposure in remote areas was alcohol and marijuana.  Flash forward 40 years and now there is widespread availability of practically all drugs of abuse in rural areas, including intravenous heroin.  Anytime an addictive drug comes into the marketplace there is a risk that level of availability will lead to more addiction and complications of addiction.  In the case of the first amphetamine epidemic, it was marketing and general use for a number of disorders that did not respond to the medication and marketing products like benzedrine inhalers that could be easily abused.  In the end there were thousands of amphetamine containing products until all of them were moved to Schedule II and under much tighter regulation.

The second point is that the FDA clearly does an inadequate job of preventing addiction and complications of addiction.  There should be no doubt that the main objective of the FDA is to get pharmaceuticals out into the marketplace as soon as possible.  Although politicians like to grandstand on the idea that the FDA prevents the release of life-saving drugs or builds regulatory hurdles that lead to unnecessary expense there appears to be less and less evidence that is true.  Those same politicians seem to favor quicker release and less regulation.  It is fairly clear that the FDA has minimal scientific requirements.  The release of multiple new opioids during the time of an opioid epidemic of overdose deaths and against the recommendations of the Scientific Committee would be a case in point.  A further case in point is that none of these new opioid drugs is a unique compound.  They are all basically mixes and matches of old compounds in patentable dose sizes and various possibly tamper proof formulations.   Even as I type this note I am being informed that the FDA has accepted an application for reviewing a new drug that is a combination of extended release oxycodone and naltrexone.

The FDA clearly has a lax approach to potentially addictive compounds and they cannot depend on post marketing surveillance or their so-called REMS (Risk Evaluation and Mitigation Strategies).  A reasonable approach would be to use a gatekeeper strategy and monitor those physicians for complications from prescribing controlled substances.  Since agencies and regulators at all levels seem to believe that they can teach all physicians to prescribe controlled substances with an equal low level of skill, the time of the gatekeeper option is in the past.  The main FDA approach is post marketing surveillance or basically waiting to see what happens.  In the case of addictive drugs this is even a worse idea than with other risky medications.  The post marketing surveillance depends on reports from physicians, patients or other health care professionals.  Reporting a complication from a controlled substance is much less likely to happen for a number of reasons.  Physicians working in the addiction field may be working in settings where there is a higher standard for confidentiality than typical medical records.  Any time there is the potential interpretation of diversion or inappropriate prescribing reporting is less likely.  For these reasons post marketing surveillance is not a good approach to monitor a new pharmaceutical to see if it is being overprescribed and abused.

What is a good approach?  For decades there have been large databases that compile the prescriptions of all physician in the US.  This data was typically sold to pharmaceutical companies to gauge the success of their marketing efforts by the number of prescriptions written.  It is time that the FDA ran a database and looked at real numbers and trends in prescribing.  They would have first hand knowledge of how many new Vyvanse prescriptions were written for binge-eating disorders and where any potential prescription mills were located.  They could intervene before there was a years long or decades long problem.        

I conclude the Binge-Eating Ad is good advertising.  Someone once said that an addictive drug sells itself.  I think that is true in terms of the place that stimulants have in the collective consciousness of Americans.  They are seen as magical performance enhancing drugs that are good for whatever ails you.  I can see the pressure building in primary care clinics for Vyvanse prescriptions for Binge-Eating Disorder and patients expressing their severe disappointment if they hear their clinic will not prescribe it.  They will not understand that good advertising is not necessarily good medicine.

Creating demand for a medication with definite addictive potential seldom is.


George Dawson, MD, DFAPA

Why antidepressants are not addictive

I recently noticed that a blogger posted his theory on the addictive properties of antidepressants. He pointed out that people get "psychologically addicted" and that using the term "addiction" for physical addiction seemed too restrictive. His supporting evidence is a newspaper article about how Glaxo Smith Kline dropped its claim on a patient information pamphlet for paroxetine saying that the drug was "not addictive".  David Healy is quoted as saying "If there is withdrawal, then there is physical dependence. There will be some people who will never be able to halt this drug, there will be some for whom halting will not be awfully difficult and some for whom it is a real issue". The article goes on to say that although SSRIs are not like opiates they are "more comparable to the benzodiazepines such as diazepam, which is now prescribed only with great caution because of withdrawal problems".

Working in the addiction field this entire line of thinking is rhetorical. There is significant psychiatric comorbidity in people with addictions with anywhere from 40-75% having co-occurring disorders. Most of those co-occurring disorders are anxiety disorders and depression and they are well known triggers for relapse as well as initiating drug and alcohol use in the first place. Contrary to public denial,  addictive disorders have huge liabilities in terms of morbidity and they are often lethal illnesses.  My goal is to reduce the risk of relapse by treating the co-occurring disorder while the person is being treated for addiction. SSRI medications are one of the mainstays of treating anxiety and depression these days. They are effective medications. I would not be prescribing them if they caused "psychological addiction". Furthermore, many treatment programs for addiction teach the concept of cross addiction and nobody studying that concept would want to take an SSRI if it caused any kind of addiction.

A better starting point would be to look at more comprehensive definition of what an addiction is. That starting point would be the October 2011 definition issued by the American Society of Addiction Medicine.  Paragraph 2 of the short definition will suffice and reading those four lines should make it very clear that the use of antidepressant medications does not lead to addiction. The real hallmark of addictions is uncontrolled use and there is no evidence that modern antidepressants are used in an uncontrolled manner.  Additional evidence is that antidepressants have absolutely no street value and therefore are in the majority of 34 million chemical compounds listed in Chem Abstracts of which only about 322 are addicting.

If your doctor has recommended that you take an antidepressant medication certainly be aware of the fact that there may be discontinuation symptoms. Discontinuation symptoms are not an addiction.  Needing to take an antidepressant for a chronic mood or anxiety disorder is not an addiction.  Contrary to Dr. Healy's opinion there are a number of nonpsychiatric medications can be discontinued and cause severe discontinuation symptoms.  The term "physical dependence" suggests an addiction or the inappropriate use of a potentially addicting drug where in fact that is not the case with antidepressants.  Comparing antidepressants to other clearly addictive compounds like benzodiazepines or opioids is not an accurate comparison across any dimension.  I agree that any person considering an antidepressant drug needs to be aware of the fact that mild to moderate symptoms can respond to psychotherapy as well as medication.  ANY medication can lead to rare but very serious complications.  Any person considering treatment with medications needs to be working with a physician who is skilled in the use of these medications and who can address any potential side effects.  My personal experience in treating people who have severe anxiety and depression is that they reach a point that anyone with a severe chronic illness reaches in making a decision about medication. That point generally involves asking themselves: "What else am I going to do?".

As physicians we can never minimize the importance of that question.