Monday, September 3, 2007

Suboxone, a new treatment paradigm: Part Two

In Part One of this article I described the problems with
traditional treatment of opiate addiction. Suboxone is a
revolutionary alternative.

Suboxone consists of two drugs; buprenorphine and naloxone.
The naloxone is irrelevant if the addict uses the
medication properly, but if the tablet is dissolved in
water and injected the naloxone will cause instant
withdrawal. When suboxone is used correctly, the naloxone
is destroyed in the liver shortly after uptake from the
intestines and has no therapeutic effect. Buprenorphine
is the active substance; it is absorbed under the tongue
(and throughout the mouth) but destroyed by the liver if
swallowed. There is a formulation of buprenorphine without
naloxone called subutex; I have used this formulation when
the patient has apparent problems from naloxone, including
headaches after dosing with suboxone. I have also treated
addicts who have had gastric bypass, where the first part
of the intestine is bypassed and the stomach contents empty
into a more distal part of the small intestine. In such
cases the naloxone escapes 'first pass metabolism', the
process with normal anatomy where the drug is taken up by
the duodenum and transferred directly to the liver by the
portal vein, where it is quickly and completely destroyed.
After gastric bypass naloxone can be taken up by portions
of the intestine that are not served by the portal system,
causing blood levels of naloxone sufficient to cause brief,
relatively mild withdrawal symptoms.

Buprenorphine has a 'ceiling effect'-the narcotic effect of
the drug increases with increasing dose up to about one or
two mg, but then the effect plateaus and higher amounts of
buprenorphine do not increase narcosis. The average
patient usually takes 12-24 mg of suboxone per day, and
quickly becomes tolerant to the effects of buprenorphine
(buprenorphine does have significant narcotic potency, but
the potency usually pales in comparison to the degree of
tolerance found in active opiate addicts).. The opiate
receptors in the brain of the addict become completely
bound up with buprenorphine, and the effects of any other
opiate medication are blocked. Once the addict is tolerant
to the correct dose of suboxone, the buprenorphine that is
bound to their opiate receptors reduces cravings and
prevents the effects-and so the use--of other opiates.
Suboxone is very effective in preventing relapse; the
'choose to use' issue is effectively removed by the fact
that use would require the addict to go through several
days of withdrawal in order to remove the receptor blockade
and allow other opiates to have an effect. Given addicts'
attitudes toward withdrawal, the appeal of this 'choice' is
quite low. The only real problem with suboxone treatment
relates to specificity. With suboxone, the addict stays
off opiates, but there is nothing to prevent the
substitution of alcohol. On the other hand, naltrexone
reduces alcohol cravings by blocking opiate receptors, and
it is quite likely that suboxone, through its similar
mechanism, will reduce alcohol cravings as well. Such an
effect has been reported to me by a number of suboxone
patients, but has not been reported in the literature at
this point. The suboxone patients who move from one
substance to another will likely require an approach that
demands total sobriety. But for pure opiate lovers, other
benefits of suboxone are that only mild (and possibly
medicated) withdrawal is required to start treatment, the
drug is usually covered by insurers, prescribing
restrictions are minor, and there are fewer stigmas
associated with maintenance than there are with methadone.

As I stated in part one of this article, I predict that
suboxone will eventually be the standard treatment for
opiate addiction, and will change the treatment approach
for other substance addictions as well. My only
reservation with this statement is that it is unclear how
the current recovering community will respond to patients
treated with suboxone. If suboxone patients are rejected
by the recovering community, what will be the long-term
outcome of their addictions when the substance is removed
but the personalities and issues remain untreated? Is it a
given that all addicts have a disease that requires group
therapy? As things stand now, addicts maintained on
suboxone are often referred for addiction counseling. But
the exact message to deliver with counseling is debatable.
In many ways, a patient maintained with suboxone becomes
similar to a patient with hypertension treated for life
with medication-the underlying problem persists, but the
active disease is held in remission. If the uncontrolled
use of opiates is effectively treated, is that enough?
Should counseling be focused on removing the shame of
having the disease of addiction, and on encouraging the
treated addicts to get on with their normal lives? Or
should we continue to see addiction as a consequence of a
deeper problem or faulty character structure, which
requires groups and meetings if one hopes to become
'normal'? Unfortunately the use of suboxone runs counter
to successful adoption of sobriety through 12-step
programs, which in the first step require acceptance of the
fact that the addict is powerless over the substance-that
there is no amount of will power that will allow the addict
to control the deadly effects of the drug. By using
suboxone the addict may develop the impression that he/she
has control, particularly if suboxone becomes popular on
the street for self-medication of withdrawal.

Before suboxone, the only option for opiate addicts was to
lose a sufficient number of things-family, employment,
freedom, health-to cause them to accept treatment and
recovery. Only a small fraction of addicts recovered, and
only after significant losses-and relapse rates were high.
Suboxone is an amazing breakthrough; one that for the first
time allows treatment of addicts early in the course of
their illness, and that reliably induces remission in most
patients. But there are some things to be concerned about,
that have the potential to reduce the effectiveness of this
amazing new drug and treatment approach. First, some
insurers demand that the drug be used only short-term, in
some cases for only three weeks! This requirement totally
misses the nature of addiction, and ignores the known high
relapse rate after short-term use of suboxone (and why
wouldn't it be high?). Some physicians use the medication
in this short-term way; hopefully the motivations for this
ineffective treatment method are not related to the limits
placed on the numbers of maintenance patients per
physician. Other physicians will transfer their attitudes
toward opiate agonists to the use of suboxone, and place
constant downward pressure on the daily dose of suboxone.
This approach is not appropriate with suboxone; the value
of the drug requires adequate dosing to achieve the long
half-life and repression of cravings. At doses of less
than 8 mg, suboxone becomes more similar to a pure agonist;
one might as well be giving small doses of hydrocodone to
prevent withdrawal. There is no reason beyond drug cost to
reduce the dose, as tolerance is limited by the ceiling
effect that occurs with relatively low doses. In other
words, higher doses of suboxone do not result in eventual
higher degrees of withdrawal. Another issue is that the
medication is sometimes prescribed carelessly, without
emphasizing the need to dose once per day. Patients left
to their own devices will start using the medication
multiple times per day as a 'prn' medication, and will
remain in the same addiction behavior that brought them to
treatment. Once per day dosing is important because it
allows the addictive behavior to be extinguished over time.
Initially patients will have increased anxiety as they
lose the distraction and placebo effect of frequent drug
use. But over time the anxiety will fade, and the huge
void left by the removal of addictive obsession will allow
the development of relationships and other positive
character traits that were forced out by their addiction.

Given the time pressures and payment structures of modern
medicine, suboxone may eventually replace residential
treatment as a more reliable, less costly alternative. I
believe that the time has come to replace the 'recovery'
model with a new 'remission' model, which allows treatment
of a much higher percentage of users at an earlier stage of
disease. With time, will we find analogous agents that
provide a low level of intoxication in return for receptor
blockade? While not likely with alcohol, such an outcome
is certainly within the bounds of imagination for cocaine,
benzodiazepines, and barbiturates. While it is true that
daily use of a partial agonist would represent a reversal
from our current approach where all intoxicating substances
are to be avoided, it is also true that the current
approach has no bragging rights based on outcome. Finally,
perhaps the adoption of a remission model will lessen the
time until opiate and other addictions carry as much moral
stigma as hypertension or diabetes-two other diseases that
are generally treatable, but that require long-term use of
medications.


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Jeffrey Junig lives in Fond du Lac, Wisconsin. He has
worked as a neuroscientist and as an anesthesiologist, and
is a psychiatrist and pain physician in solo, independent
practice. Additional information can be found at
http://wisconsinopiates.com , the web site of his chronic
pain and addiction practice, or at http://fdlpsychiatry.com
. He is available for patient care, consultations, or
educational presentations.

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