| Buprenorphine is currently accepted for use in the US, UK, France, Japan, Germany, Russia, China, Taiwan, Korea, Thailand, Portugal, Belgium, Australia, 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 opioid 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 III on the controlled substance list as opposed to Methadone a Schedule II) referenced further in the preceding paragraph, we are experiencing a paradigm shift inn 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 opioids 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 opioid receptors where these endogenous opioids 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 (the nodding often seen in Heroin addicts). Underproduction or over-removal (severe re-uptake) of these endogenous opioids 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 opioid medications either illicit or pharmaceutical because they are compelled to attempt to replace the endorphins, dynorphins, and enkephalins (endogenous opioids) that naturally occur in their systems at insufficient levels.
Buprenorphine's superior efficacy when dealing with these disorders is due to the aforementioned unique pharmacological profile as a partial my receptor agonist combined with a full kappa receptor antagonist. As a matter of 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 world 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 opioid 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 Opioid 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 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:
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
DR's- Spangel R et al
“The Effects of opioid Peptides on Dopamine Release in the Nucleus Acumbens” Journal of Neurochemistry Volume 55 Pg. 1734-1740 (1990)
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
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
DR Kosten TR
"Depressive Symptoms During Buprenorphine Treatment of Opiate Abusers" Journal of Substance Abuse Treatment Volume 7 (1) Pg. 51-54 1990
Emrich H M MD
"A Possible Role of opioids in Depression" Developments in Psychiatry Series V5 B-Sevier (1981) Pg 380-385
DR Frecksa et al
"Prolactin Response to Fentanyl in Depression"
DR Walter Ling
University of California at Los Angeles (UCLA), Headed Clinical Trials of Subutex ® and Suboxone ® for the Painless Narcotic Withdrawal Program.
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Buprenorphine: Treating Narcotic Abuse With a new Opioid 