The Corpus Callosum

This is an archived post from September, 2005, posted here and now because I am away on vacation.

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, rev="review" href="http://content.nejm.org/cgi/content/full/349/10/928">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)

alt="buprenophine structure, comparative"
title="buprenophine structure, comparative"
src="http://content.nejm.org/content/vol349/issue10/images/medium/04f1.gif"
align="right" border="0" height="440" width="186">
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. 

alt="socially engaged poetry" title="socially engaged poetry"
src="http://www.poetsagainstthewar.org/header/logo.gif"
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width="262">
Dr. 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 href="http://physicsofporn.blogspot.com/2005/08/we-cannot-win-war-on-terror-without.html">Pornographical
Physics
and href="http://www.indcjournal.com/archives/001986.php">INDC
Journal
.

Those interested in yet another
dimension may wish to see what the artistically inclined href="http://www.poetsagainstthewar.org/report_medellin.asp">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: href="http://www.rxlist.com/cgi/generic2/buprenorphine.htm">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. ( href="http://www.drugs.com/pdr/subutex_tablets.html">1,
href="http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a605002.html">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 href="http://www.reckittbenckiser.com/newsroom/news_article1.cfm?pressreleaseid=641">Reckitt
Benckiser Pharmaceuticals (whose main href="http://www.reckitt.com/">claim to fame is
that they are the World’s #1 producer of household cleaning chemicals.)
What is the rationale for including href="http://www.rxlist.com/cgi/generic3/naloxone.htm">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 href="http://www.drugabuse.gov/NIDA_Notes/NNVol10N2/Meddev.html">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 [ href="#usage_note">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: href="http://content.nejm.org/cgi/content/short/349/10/949">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.

———-
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 refers
to a pharmacologically diverse group of drugs, including heroin,
cocaine, and cannabis. The more precise term for
morphine-like drugs is opiate.