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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by Pacha on June 6, 2001, at 9:22:29
Buprenorphine: Treatment for detoxification, maintenance and
Major depressive disorders?Buprenorphine: Treating Narcotic Abuse With A Unique Opiod
The development of Buprenorphine, an Opiod with reduced dependence and abuse potential, has made possible the reevaluation of specific opiods for the treatment of depressive disorders as well as a first line treatment for the detoxification of Opiate/Opiod DDPs. This is significant for patients who are unresponsive or intolerant to conventional antidepressant agents including SSRI's (Prozac, Paxil, Zoloft, Wellbutrin), Tri-Cyclics, or MAO Inhibitors (Monoamine Oxidase).Buprenorphine was developed in the UK in 1972 and has approval there as a primary treatment for pain relief and opiate detoxification. France recently (1996) added Buprenorphine under the trade name Subutex as its primary therapeutic tool for opiate detoxification. The French utilized data elicited from a joint NIDA-FDA study which has taken place from 1994 through the present at 12 VA
Hospitals in the US as its main evidence in making this decision.This moves treatment of opiate abuse from the stigma of the methadone clinic into the office of the primary care physician. The US is
looking into this option themselves as the French model has been incredibly successful.Recently, Drug Czar McCafferty has stated publicly his advocacy of this action.
As an analgesic, Buprenorphine is currently accepted for use in the US, UK, France, Japan, Germany, Russia, China, Taiwan, Korea, Thailand,: Portugal, Belgium, New Zealand, Holland, Luxembourg, : South Africa, Mexico, as well as numerous countries in south and Central America and Canada.
Highly effective (35 times as powerful as Morphine by volume) as an analgesic, Buprenorphine's unique pharmacological profile of PARTIAL mu agonist and as a full binding kappa receptor antagonist offer an Opiod with virtually NO ABUSE POTENTIAL,
LITTLE TO NO RESPIRATORY DEPRESSION, NO EUPHORIA, and therefore an end to the phenomena known as
physician "opiophobia"With significantly lower abuse potential than the status quo (Schedule V on the controlled substance list as opposed to Methadone -a Schedule II) referenced further in the preceding paragraph, we are experiencing a paradigm shift in the opiate abuse treatment armamentarium as well as a major discovery and treatment potential for refractory depression and other panic and anxiety psychiatric disorders.
The enkephalins, dynorphins, and endorphins are endogenous opiods which function as neurotransmitters, neuromodulators, and hormones and are involved in the perception of pain, and the modulation of behavior.
Pharmacological studies have defined three classes of Opiod receptors where these endogenous opiods bind; delta, kappa, and mu.
The mu receptor is most commonly associated with euphoria and pain relief.
The kappa receptor is most commonly associated with sedation ( nodding often seen in Heroin addicts).Underproduction or over-removal (severe re-uptake) of these endogenous opiods can be the cause of many psychiatric disorders ranging from Bipolar Personality disorders to major depressive disorders that often times manifest themselves in severe drug abuse.
Unbeknownst to them, these patients use Opiod medications either illicit or pharmaceutical because they are compelled to attempt to replace the endorphins, dynorphins, and enkephalins (endogenous opiods) that naturally occur in their systems at insufficient levels.When taking these patients into account, a better term than the word "addict" or DDP (drug dependent person) would be opiate receptor deficie
Buprenorphine's superior efficacy when dealing with these disorders is due to the aforementioned unique pharmacological profile as a PARTIAL MU RECEPTOR AGONIST combined with a FULL KAPPA RECEPTOR ANTAGONIST.
FACT: Buprenorphine is the strongest kappa receptor antagonist currently legal to use anywhere throughout the world. There is a large body of evidence that implicates mu agonists in anxiety and depressive disorders
Fink et al 1970, Kline et al 1977, Angst et al 1979, Pickar et al 1981
Pfeifer et al 1986, Schmauss and Heimrich et al 1988, Frecksa et al 1989,
Matussk and Hoehe et al 1989.)Reviewing these clinical studies by the aforementioned internationally renowned experts in this field leave little doubt that
mu agonists are powerful anxiolytic and calming agents.
Prior to the development of Buprenorphine, MD's have avoided opiod use in the area of psychiatric disorders since the late 1950's due to the overriding issues of addiction, abuse, sedation, and respiratory depression.
Buprenorphine's development compels reevaluation of this specific Opiod in this armamentarium as we now have a mu agonist that deals directly with these concerns and issues.The kappa antagonism of Buprenorphine also offers a new approach in the treatment of depressive disorders. Clinical studies have shown that the overproduction or under-removal of the endogenous kappa agonist dynorphin can have a direct causal relationship with various depressive disorders.
Therefore, a kappa antagonist would be of great clinical value in this treatment paradigm.
Buprenorphine is the strongest kappa antagonist currently available for clinical use.
Buprenorphine's unique pharmacological profile referenced earlier make it the only medication that offers this concurrent treatment alternative.
Additionally, clinical studies suggest that Buprenorphine increases the levels of the neurotransmitter dopamine in the brain pathways that control pleasure indicating a third method of effect. (See reference 3 below)Conventional antidepressants and antipsychotics work gradually over a period of weeks or months, whereas maximal benefit is
apparent with Buprenorphine in a matter of days and in some cases hours.
After undergoing treatment with Buprenorphine, patients report an almost immediate improvement in function, an elevation of mood, and a general feeling of contentment. The fact that a rapid alteration in mental state can be produced by a pharmacological agent suggest an alternate theory to that of treatment with conventional antidepressants and the slow adaptive changes that are associated with simultaneous psychotherapeutic treatment.A recent clinical study at Johns Hopkins University Dept of Psychiatry of Buprenorphine and its efficacy in psychiatric disorders, a number of patients received a complete remission of the symptoms of depression based on the universally used Hamilton Rating Scale for Depression. (See reference 2 below)
REFERENCES:
(1) DR's-Walsh, Preston, Bigelow, Sitzer, Cone
Department of Psychiatry and Behavioral Sciences
Johns Hopkins University School of Medicine, Baltimore MD.
Journal of Clinical Pharmacotherapy May 1994 Volume: 55 Pg. 569-580(2) DR's- Spangel R et al: "The Effects of Opiod Peptides on Dopamine Release in the Nucleus
Acumbens" Journal of Neurochemistry Volume 55 Pg. 1734-1740 (1990)(3) DR's-Bodkin, Zornberg, Lukas, Cole-McClean Hospital Department of
Psychiatry
Harvard School of Medicine, Belmont, MA. "Buprenorphine Treatment of
Refractory Depression" Journal of Clinical Psychopharmacology February 1995(4) DR's- Levin, Mendelsohn, Holman, Teoh, Garada, Schwartz, Mello
Dept. of Radiology, Brigham and Womens Hospital, Boston, MA USA
"Improved Cerebral Regional Blood Flow in Chronic Polydrug Users
Treated With Buprenorphine" Journal of Nuclear Medicine- July 1995(5) DR Kosten TR
"Depressive Symptoms During Buprenorphine Treatment of Opiate
Abusers"
Journal of Substance Abuse Treatment Volume 7 (1) Pg. 51-54 1990(6) Emrich H M MD
"A Possible Role of Opiods in Depression"
Developments in Psychiatry Series V5 B-Sevier (1981) Pg 380-385
Posted by Elizabeth on June 6, 2001, at 21:55:06
In reply to Buprenorphine- check this great article out !!, posted by Pacha on June 6, 2001, at 9:22:29
> Buprenorphine was developed in the UK in 1972 and has approval there as a primary treatment for pain relief and opiate detoxification. France recently (1996) added Buprenorphine under the trade name Subutex as its primary therapeutic tool for opiate detoxification.
It seems to work very well for a lot of people. Because of a ceiling effect (above a particular dose it becomes ineffective), however, it's not adequate for a lot of people who have heavy heroin habits.
> This moves treatment of opiate abuse from the stigma of the methadone clinic into the office of the primary care physician. The US is
> looking into this option themselves as the French model has been incredibly successful.Weird that the US would look into something that actually works, huh? < g > MMT as it's done in the US is hard to implement and, as a result, isn't available to most of the people who need it. Letting primary care doctors prescribe buprenorphine for maintenance treatment of addiction would make help available to many more people.
> Recently, Drug Czar McCafferty has stated publicly his advocacy of this action.
That was Clinton's drug czar (that sounds like a Russian variant on the Latin American _narcotrafficante_, not a government position!).
> As an analgesic, Buprenorphine is currently accepted for use in the US, ...
But it is only available
> Highly effective (35 times as powerful as Morphine by volume)
By mass, not volume. Volume depends on the medium (morphine is available in many forms in the U.S.; buprenorphine is in an injectible 5% dextrose solution that contains 0.3 mg buprenorphine per mL solution). 0.3 mg of IV buprenorphine is supposed to be equivalent to about 10 mg of IV morphine.
> With significantly lower abuse potential than the status quo (Schedule V on the controlled substance list as opposed to Methadone -a Schedule II)
> we are experiencing a paradigm shift in the opiate abuse treatment armamentarium as well as a major discovery and treatment potential for refractory depression and other panic and anxiety psychiatric disorders.
I hope so. (Some people find opioids helpful in panic disorder, OCD, and social phobia as well as depression.)
Another possibility is tramadol, an opioid with low intrinsic activity and mild monoamine reuptake inhibiting properties.
> Pharmacological studies have defined three classes of Opiod receptors where these endogenous opiods bind; delta, kappa, and mu.
A promising possibility exists that the addition of a delta antagonist could prevent tolerance to mu agonists. I hope that research continues in this direction.
> The kappa receptor is most commonly associated with sedation ( nodding often seen in Heroin addicts).
That's not so clear. Buprenorphine, a kappa *antagonist*, can cause nodding (but without euphoria) and is commonly sedating.
> Underproduction or over-removal (severe re-uptake)
Or metabolism -- there was some work in the early '80s or so on "enkephalinase inhibitors" (unfortunately it turned out that "enkephalinase" was a general polypeptidease, not specific to enkephalins, making these drugs non-viable for use in people).
> Buprenorphine's superior efficacy when dealing with these disorders is due to the aforementioned unique pharmacological profile as a PARTIAL MU RECEPTOR AGONIST combined with a FULL KAPPA RECEPTOR ANTAGONIST.
I'm not convinced that it works better than full agonists. Obviously there have been no head-to-head comparisons. Stadol, a kappa agonist/mu antagonist, is often experienced as dysphoric by depressives, but it's hard to conclude much from that.
> The kappa antagonism of Buprenorphine also offers a new approach in the treatment of depressive disorders. Clinical studies have shown that the overproduction or under-removal of the endogenous kappa agonist dynorphin can have a direct causal relationship with various depressive disorders.
Really? I haven't heard of clinical studies in this area.
> Buprenorphine's unique pharmacological profile referenced earlier make it the only medication that offers this concurrent treatment alternative.
Yes -- Dalgan (dezocine) is similar, but it was taken off the market recently.
> Conventional antidepressants and antipsychotics work gradually over a period of weeks or months, whereas maximal benefit is apparent with Buprenorphine in a matter of days and in some cases hours.
Intranasal buprenorphine works in about 1 hour. Intramuscular administration might produce more rapid effects. The effect I refer to is a complete reversal of all symptoms of depression (complete compared with MAOIs). Opioids have been found to work in a wide variety of subtypes of depression, too, which I find interesting.
> A recent clinical study at Johns Hopkins University Dept of Psychiatry of Buprenorphine and its efficacy in psychiatric disorders, a number of patients received a complete remission of the symptoms of depression based on the universally used Hamilton Rating Scale for Depression. (See reference 2 below)
? Reference 2 wasn't a clinical study in humans. Did you mean #1?
-elizabeth
Posted by Pacha on June 12, 2001, at 9:28:30
In reply to Re: Buprenorphine (comments) » Pacha, posted by Elizabeth on June 6, 2001, at 21:55:06
Hi,
What can you recommend for itching from Buprenorphine ? Are you still taking it ? hows it going ? I've been reading for hours your great postings on bup on the usernet groups, very interesting. any other advice you can give would be greatly apreicated.
thanks in advance
pacha
Posted by Elizabeth on June 12, 2001, at 16:43:47
In reply to Buprenorphine - elizabeth, posted by Pacha on June 12, 2001, at 9:28:30
> What can you recommend for itching from Buprenorphine ?
Antihistamines -- Claritin, Allegra, Zyrtec, Benadryl, ChlorTrimeton, Atarax, etc.
> Are you still taking it?
Yes. It's going fine (still working, side effects still manageable). I first used it a couple of years ago, so I have a pretty good idea of how it works for me.
I hope I've been of help. Always glad to answer questions if I can.
-elizabeth
Posted by Rob Halprin MSPhD on May 21, 2011, at 0:23:25
In reply to Re: Buprenorphine (comments) » Pacha, posted by Elizabeth on June 6, 2001, at 21:55:06
Pacha: I thank you again for posting a portion of my Doctoral Thesis!
This is the end of the thread.
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