Thursday, September 15, 2005

Buprenorphine Explainer:
Subutex and Suboxone

As I go about my days, I get the impression that there is a lot of confusion out there about the treatment of opiate abuse and dependence. Wes Clark (not that Wes Clark, the other one) has written an article to help us understand this nettlesome issue.

First, I summarize some point from his article, and a few others, then add a few bits of my own.

Dr. Clark provides us with some historical background in his article, Office-Based Practice and Opioid-Use Disorders (H. Westley Clark, M.D., J.D., M.P.H.: NEJM, Volume 349:928-930, September 4, 2003)
buprenophine structure, comparative
In the case of Webb v. United States, the U.S. Supreme Court ruled that the 1914 Harrison Narcotic Drug Act made it illegal for physicians to prescribe narcotics for the purpose of keeping a patient "comfortable by maintaining his customary use." For more than 80 years, it remained illegal in the United States for physicians to prescribe opioid medications for the treatment of opioid dependence. [...]

The Harrison Narcotic Drug Act and decisions such as Webb v. United States essentially gave the following message to physicians: "Treat an addict; go to jail." Physicians consequently were reluctant to address the medical needs of those with opioid-use problems. [...]

 On October 17, 2000, the Drug Addiction Treatment Act of 2000 was signed into law in the United States. This act allows Schedule III, IV, or V narcotic medications that have been approved by the Food and Drug Administration (FDA) for the treatment of narcotic-use disorders to be administered for either medically supervised tapering (detoxification) or long-term maintenance. On October 8, 2002, the FDA approved the use of buprenorphine (see Figure) and of buprenorphine in combination with naloxone — both Schedule III drugs — for either detoxification or maintenance. 

socially engaged poetryDr. Clark spares us the additional political dimension, that of the "War on Drugs." Those interested in that orthogonal may wish to review the commentary in the Blogosphere at Pornographical Physics and INDC Journal.

Those interested in yet another dimension may wish to see what the artistically inclined have to say about the subject.

Collapsing back to the Flatland of neurochemistry, let's review what is known about buprenorphine. It acts on the mu (µ) opioid receptors in complex way. It is a mixed agonist-antagonist (or partial agnonist), meaning that it partly stimulates the receptors, but prevents them from receiving further stimulation.

Buprenorphine is available in three formulations: Buprenex ®, is an injectable form of buprenorphine hydochloride that is suitable for treatment of acute pain in persons who are not opiate dependent; Subutex ®, a tablet for sublingual usage, contains buprenorphine hydochloride as the only active ingredient; Suboxone ®, also a sublingual tablet, contains two ingredients: buprenorphine HCl and naloxone HCl. (1, 2) For the purposes of this article, I will refer to Subutex and Suboxone collectively by the informal term, "Bup," which is short for buprenorphine.

Subutex and Suboxone are manufactured by Reckitt Benckiser Pharmaceuticals (whose main claim to fame is that they are the World's #1 producer of household cleaning chemicals.) What is the rationale for including Naloxone in the Suboxone formulation? Naloxone is a mu opiate antagonist. It is not active when taken by mouth, so it does nothing if the drug is used as intended. However, if someone attempts to abuse it via injection, the naloxone blocks the opiate receptors, preventing the buprenorphine from acting. If that person happens to be opiate dependent, it puts them into abrupt withdrawal. Few people do that more than once.

Subutex and Suboxone were developed specifically under the aegis of the National Institute on Drug Abuse's Medication Development Division; this involved collaboration between NIDA, the FDA, and private industry. It was developed in response to some practical difficulties that arose with the use of methadone. Every once in a while, good things happen when people sit down and talk to each other. As the FDA puts it:
Subutex and Suboxone are the first narcotic [usage note - ed.] drugs available for the treatment of opiate dependence that can be prescribed in an office setting under the Drug Addiction Treatment Act (DATA) of 2000. Until recently, opiate dependence treatments in Schedule II, like methadone, could be dispensed in a very limited number of clinics that specialize in addiction treatment. As a consequence, there have not been enough addiction treatment centers to accommodate all patients desiring therapy. Under this new law, medications for the treatment of opiate dependence that are subject to less restrictive controls than those of Schedule II can be prescribed in a doctor's office by specially trained physicians. This change is expected to provide patients greater access to needed treatment.
Indeed, Bup has been shown to be helpful for persons with heroin dependence. The NEJM article summarizing the seminal study is this one: Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone. The results actually were underwhelming, at least at first glance:
The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated.
So persons treated with placebo stayed straight about 5% of the time; whereas those who were treated were successful about 20% of the time. Like I said, that may not seem impressive. But when you consider the awful consequences of heroin abuse, any improvement in the rate of success is welcome. Note, however, that Bup is not limited to use in treatment of heroin dependence. It can be used for treatment of dependence or abuse of any opiate. Furthermore, it can be used in three ways. It can be used to detoxify patients, i.e., taper them entirely off the use of an opiate. It can be used for long-term maintenance of opiate abusers. Also, it can be used for long-term treatment of chronic pain, even if the patient was not actually abusing whatever opiate they were treated with initially.

Over the next few days, I plan to go into more detail about these various uses of bup. In the meantime, if you find yourself craving more medical writing, check out the 51st Grand Rounds at Sneezing Po.

 usage note: the term narcotic is actually a legal term, under law that defines certain drugs as drugs of abuse; it is not really a medical term. The term narcotic referes to a pharmacologically diverse group of drugs, including heroin, cocaine, and cannabis. The more precise term for morphine-like drugs is opiate.

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Monday, September 12, 2005

Time for Investigative Journalism?

Something reminded me of a couple of old chapters in my life.  I've been thinking about that, and I realized that there are two stories here.  One is personal, and not very interesting to anyone who does not know me.  The other is important to everyone who lives in Michigan.  

In 1976, having just finished my freshman year at college, I needed a summer job.  I had no job experience to speak of, but some decent skills.  Specifically, I had learned photography, and was good at electronics.  There was an opening for a student extern at the Center for Forensic Psychiatry (1 2), in their audio-visual department.

The CFP is basically a state hospital for persons with mental illness, who are in trouble with the law.  It also serves as a training site for the University of Michigan, primarily their Department of Psychiatry.  The AV Dept. produced educational material for use in orientation of patients and staff, as well as for the training program.  

Back, then, the Government actually thought it was appropriate to provide jobs for people, and I was lucky enough to get one of them.  Unemployment in the area was still pretty high, because the auto industry had taken a big hit during and after the OPEC oil embargo.

In 1976, there were plans to build a new CFP, but the plans were put on hold because the State economy was not so good.  In 1977, I worked there again in the summer.  The economy was still improving, but the plans were still on hold.

In 1989 and 1990, I worked there again, although in a different capacity.  I was a fourth-year medical student, and they had some externships for M4's.  Basically, we would go there in the evening, perform and write up two admission history-and-physical exams (H&P's) , then sleep the rest of the night.  If any medical problems arose, I'd have to get up and triage them, then call a report to the attending.  It only paid something like $9/hr, but I pretty much got paid for sleeping.  It was close enough to my townhouse that I could ride my bike to work.  A pretty good deal, actually.  

Both of those jobs required me to go to every unit in the place, so I got to see most of it.  It was in pretty bad shape, in 1976; by 1990, it was much worse.  

By 1990, the need for a new CFP had gotten so acute, that plans to build a new one were underway in earnest.  The old one was really just a cordoned-off part of the Ypsilanti Regional Psychiatric Hospital, otherwise known as "Ypsi State."  

A sociological aside: "Ypsi State" had an Ypsilanti mailing address, and CFP had an Ann Arbor mailing address, even though they both were on the same land; yet, both actually are closer to Milan, than to either Ann Arbor or Ypsilanti.

No community wanted its name associated with a state psychiatric hospital.  Ypsilanti, being lowest on the prestige scale, got that dubious privilege.  CFP, by virtue of its association with UM, deserved the more prestigious address.

None of that has anything to do with a need for investigative journalism.

After 1990, the State decided to save money by eliminating the student externships.  But due to various regulations, the job still needed to be done.  Since there were no more externships, they hired, not medical students, but residents.  That ended up costing a lot more.

But that is routine government stupidity; if that were all there was to it, it would not call for investigative journalism.

Our State Government, at the time, decide to do the taxpayers another favor.  They took the lowest bidder -- an out-of-state contractor -- for the construction of the new CFP.  So instead of having millions of dollars stay in Michigan, they shipped much of that money away, where it does no good for Michigan residents.  I'm no economist, but I know that was a dumb thing to do.  But that is not all.  The outstate contractors botched the job rather badly.  That led to a two-year delay in the construction, and massive cost overrun.  

The land that the old CFP was sitting on was bid on by Toyota, a deal which held the promise of many new, high-paying jobs for the area.  The deal was almost lost because of the delay.  Even with the deal finally going through, those jobs are not here yet.  

The new CFP finally opened, earlier this year.  

click for more info

One might wonder why the new CFP needs that massive glass part in the middle.  One might be annoyed to learn that it leaked terribly, and was one of the things that led to the delay and cost overrun.  It wouldn't have been so bad if it had been a necessary part of the design, but the fact that it was wasteful to begin with, makes the additional waste much more regrettable.  

I don't know much about the specifics.  In fact, most of what I know is hearsay; it may not be reliable.  Therefore, I tried to get more reliable information.

Oddly, a Google News search on "Michigan Center for Forensic Psychiatry" turned up only four hits: none interesting; none informative.  Yet there is a story there that should be told.  We just need someone who knows how to do real journalism, instead of mere blog journalism, to look into it.

categories: rants, politics

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Sunday, September 11, 2005

Bertrand Russell on Transition;
Real Risk of Totalitarianism in a Democracy

In The History of Western Philosophy, Bertrand Russell makes makes interesting comments on the transition from the end of thoughtful contemplation of St. Thomas Aquinas to that philosophically bankrupt era known as the Dark Ages. I am going to write about that, as soon as I either find my copy of the book, or get a new one.  
I wrote that a week ago, but never actually posted it; instead, I wrote this.  (You may need to read the older post  to put this one in context.) Now that I actually have the book and have read the chapter, I can proceed to write what I had planned all along.

I received The History of Western Philosophy a few days ago.  Becoming reacquainted with it, I am surprised it did not make the list of Ten Most Harmful Books of the 19th and 20th Centuries.  Maybe the people who made up that list are not as well-read as they like to think they are.

The passage in Russell that I was trying to remember is this, at the end of Part I, Chapter IV:
It is strange that the last men of intellectual eminence before the dark ages were concerned, not with saving civilization or expelling the barbarians or reforming the abuses of the administration, but with preaching the merit of virginity and the damnation of unbaptized infants.  Seeing that these were the preoccupations that the Church handed on to the converted barbarians, it is no wonder that the succeeding age surpassed almost all other fully historical periods in cruelty and superstition.1
I first read that in 1975.  The book is over 800 pages long, and I am not blessed with a photographic memory.  So one may wonder why, in 2005, that passage would come to mind; and come to mind with such an emotional overtone that I would feel compelled to buy another copy of the book.  That is exactly the sort of introspective observation that fascinates me.  

Sometimes these seemingly random recollections do have meaning.

No doubt, the passage came to mind because of a similarity to our current times.  The parallel is not exact.  For one thing, I do not mean to imply that we are about to enter another Dark Age, although we must not forget that such a thing is possible.

The parallel is not exact, because it would be difficult to argue that the current political leadership in the USA consists of "men of intellectual eminence."  Moreover, they do seem to have a concern with expelling "the barbarians;" although "barbarian"  has come to hold a judgmental implication that I would not apply myself; rather, I use it to express the Administration's view of illegal immigrants, poor people, and certain political refugees.

I would say, however, that a case could be made for the view, that the Administration is not particularly concerned with saving civilization, nor with reforming their own abuses; clearly, they do have a preoccupation with preaching the merit of virginity.2  

Perhaps it is not obvious why a casual blogger would advance the notion that the Administration of the United States of America is not concerned with saving civilization.  Is this merely a partisan snipe?  Hardly.  The Corpus Callosum is much more interested in promoting dialog, forming connections, and advocating compromise.  Plus, I happened to notice that a moderately conservative blogger (an American living in China, which no doubt gives him an interesting perspective) at Banana Oil has expressed some of the same concerns, taking care to point out that a dictatorship could arise in either party, with de facto single-party rule being the primary risk. 

Theoretically, it is true that this could happen with either of the major political parties.  If either party came to hold an irrepressible dominance, it could lead to totalitarianism.  But of course, at this time, the actual risk comes from the Republican party.  This risk will not be perceived, readily, by the (shrinking) number of citizens who still trust the individuals who lead the Republican party at this time. The problem is, that if such a concentration of power develops and matures to the point that there is no credible challenger, it is only a matter of time before some truly ruthless people maneuver themselves to the center of power.   Such an entity obviously would not be concerned with reforming its own abuses.

I believe that it is more accurate to say that humans are fundamentally good, than to say we are fundamentally evil; even so, I am aware of the fact that some people truly are evil.  Some of them are politicians.

Given that one-party rule is possible, and that truly evil persons do exist, there really could be a risk to civilization.  Our political system was designed with the explicit purpose of diminishing the probability of a dictatorship emerging here.  That was the rational for most of our electoral system, the Bill of Rights, and the system of checks and balances between the branches of government.  Until now, the system has worked fairly well.  However, there have been developments that could not have been anticipated by our Founders, developments that threaten the effectiveness of the safeguards against totalitarianism.

The current Administration has an explicit policy of gaining and keeping control of all four branches of government: The White House, Congress, The Supreme Court, and K Street.  Not only is this contrary to the conceptual foundation of our democracy, it is an incredibly foolhardy policy.  I would oppose this regardless of which Party controlled the four branches.  Simply put, that is too much power for any one group to have.  Such a concentration of power does threaten civilization.  Indeed, in this post-Hiroshima age in which we live, it threatens not just civilization, but all of human life.  Although the United States of America never has had such a leader as 김 정일 (Kim Jong-il), we must not forget that such a thing is possible.   

Dictatorship within the United States is possible, because the safeguards within our political system are outdated.  

When the Constitution and Bill of Rights were written, there were 13 states, each semi-autonomous.  The tensions inherent between the states acted as part of the safeguard.  Now, although states still have individual agendas, the divisions are not so great.  Therefore, it is more likely that a block of states could form in such a way as to exert a dominating force.  

Similarly, in the eighteenth century, rapid travel and communication across large distances were not possible.  This made it much more difficult for large coalitions to form, and to remain stable.  Now, communication is essentially instantaneous, and travel is pretty quick.  Moreover, mass communication has been refined to an art form.  (Not that is always is used for aesthetic purposes.)

Advertising and other forms of marketing have been refined, such that they now are both more powerful, and more predicable in their effects.  Coupled with information technology, it is possible to derive fairly accurate lists of likely voters, and to anticipate their likely voting habits.  It also is possible to direct political marketing efforts precisely where it is most likely to have the greatest impact.

Information technology has another important impact: it has made gerrymandering much more dangerous.  Tom DeLay's redistricting of Texas included some very strange geometrical configurations.  The configurations were so complex, that they must have used computerized mapping and modeling to generate them.  This made the resulting districts more predictable and secure than they could have been otherwise.  

Economic stratification and economic mobility are other factors to consider.  The more rigidly stratified a society, the more stable the gerrymandered districts will be.  As it happens, in the USA, within the past five years, there is more economic stratification and less economic upward mobility than there used to be.  There is more home ownership; this makes people less likely to move from one place to another.  There also is more homelessness, but that is not important: homeless persons rarely vote.

In order to really make the case that there is a risk of totalitarianism here, it is necessary to show, not just that there are structural problems with our political system, and that there are evil people in the world; it is necessary to show that some of those evil people really could manage to get elected.  

The usual conception of an evil person corresponds roughly to the psychiatric definition of antisocial personality disorder.  The psychiatric definition includes seven personality traits that, statistically, tend to come together as a package.  Note that, in common usage, the term antisocial is sometimes substituted for asocial.  To clarify: an asocial person is a person who avoids social interaction.  An antisocial person is a person who actively disrupts social harmony, causing harm to others.

Another such statistical clustering of maladaptive personality traits is called narcissistic personality disorder.
In the political realm, narcissistic personality traits are not only common, they seem to be preferred.  Some of these folks are real charmers.  In contrast, most antisocial types are not particularly appealing, and would be unlikely to get elected to anything.  In addition, persons with antisocial personality disorder tend to accumulate enough of a criminal history that they could not hide it from a sufficiently determined opponent.

One of the most important of the narcissistic personality traits is that called entitlement.  Persons with narcissistic personality disorder believe that there is something special about them, such that they deserve to bend (or break) the rules.  In actual practice, this trait tends to be cloaked in some socially presentable form.  There are many different ways in which this is done, but a full treatment of that would require a small textbook.  Such persons tend to believe, quite earnestly, that it really is OK for them to expect special treatment.  Sometimes, their conviction in this belief is convincing to others.

Of course, in nature, personality traits are assorted in a variety of ways; nature apparently has not read our textbooks.  It is common to encounter persons with an assortment of features from both the antisocial and the narcissistic categories.  

The most dangerous people, in a political context, are those that have just the right mix of antisocial and narcissistic traits.  They have enough narcissism to be charming, and to overshadow their sociopathic tendencies.  Yet, at the core, they are antisocial.  They act with casual disregard for social order, and take delight, either quietly or openly, in causing harm to others.  They may even claim that they are doing good, on some level.  (See Confessions of an Economic Hit Man, for examples.3)  

Bertrand Russell's commentary implies that it was the tunnel vision of the predominant power in the fifth century that led to the Dark Ages.  Rather than keeping their eye on the broad, critical issue of saving civilization, they focused on the overvalued specifics of sexual repression and proselytizing.  This is strikingly reminiscent of the gay marriage ban, the suppression of OTC emergency contraception, the push for faith-based initiatives, and the false-flag operation known as Intelligent Design.  

Although the majority of persons involved in these specific religious initiatives think they are saving civilization, I would argue the opposite.  Rather that saving anything, they are focusing too narrowly, thereby missing the real threat.  The real threat comes from the possibility of unchecked power, concentrated in the hands of a few, armed with nuclear weapons, elected by a people who are unable to discern the difference between a genuinely nice person and a clever antisocial narcissist.  

There are three problems here: the weakening of the protection against concentration of power, the supply of evil persons, and the inability of the population to recognize a certain kind of evil.  We can do nothing about the supply of evil persons.  We can do something about the other two problems.  

We can initiate change in our political system.  It would have to be a fundamental change in order to be effective.  This would be difficult.  However, if I am correct about the nature of the forces that are weakening our system, the problem and the threat will only grow worse unless change is undertaken.  Examples of such changes would include proportional representation, and instant-runoff voting.  

We can improve our ability to recognize evil politicians.  I would add, at this point, that anyone who takes part in any social system that creates or concentrates power, has an obligation to be sure that the power is used appropriately.  Since we all take part in such organizations, we all share this obligation.  Those who participate in religious organizations have a particular challenge, in light of the following:
When fascism comes to America, it will be wrapped in the flag, carrying a cross.
— Sinclair Lewis
I've seen that quote on somebody's sidebar, and would like to give her or him credit, but now I can't find it.  In any case, recall that the clever antisocial narcissist will have a cloak for his or her sense of entitlement.  The cloak does not have to be a flag and a cross, but it could be.  That seems to be a popular costume, these days.  Note that I am explicitly stating that not all patriotic Christians are suspect, just that within that group, there may be a few dangerous ones.  

There are many Christians (1 2 3 et. al.)who are upset by their perception that their religion is being hijacked.  I encourage them to remain vigilant.  I can't argue that religious persons should forget the specific issues that concern them, although it perplexes me that gay marriage and contraception should be such a big deal.  I just don't want anyone loosing sight of the real threat.

Like the concern seen among moderate Christians, there are many patriots who have expressed concern that there is more to being a patriot, than slapping a magnetic flag on the rear of your vehicle.  They, too, are encouraged to remain vigilant.

1 Russell, Bertrand, (1945) The History of Western Philosophy.  New York: Simon and Schuster. p. 366
2 The reader is hereby informed that the Corpus Callosum does not deny the merits of virginity; under certain circumstances, it is highly desirable.  However, it is an error to preach the merits of virginity to the exclusion of the merits of latex condoms.
3 Note that I am not claiming that the author, John Perkins, has a personality disorder. The behaviors described in his account are suggestive of the type of narcissistic/antisocial character that I am describing, but the act of true confession would not be consistent with a clinical diagnosis of a personality disorder.  Besides, I never met him, so cannot claim to be able to diagnose him.  

Categories: politics, armchair musings

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