Sept, 9 2000
Go to More Wellbutrin/Zyban Bio- Neurological Side-Effects
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Let the Games Begin - "Buyer Beware" (continued)
Companies are seeing to it that research focuses on comparisons of drugs or drugs versus placebo. Not only can these practices endanger the health and well-being of consumers, but, as Angell contends, other practices are distorting the very practice of medicine and medical education. Companies present themselves as educating medical students, interns, house officers and young doctors. Articles from symposiums sponsored by drug companies have been proven to illustrate more favourable outcomes than articles without company support. Companies "troll the halls of the academic medical centers. They give away free samples," also giving lectures to students, claims Angell. All these factors contribute to distortion in what medicine actually is, resulting in very serious long-range consequences. A study cited in The Boston Globe, May 20, found that information provided by drug reps was inaccurate at least 11 percent of the time - promoting a more favourable view of their drug - and that most residents failed to recognize the misinformation. Even Trewhitt, of Pharmaceutical Research and Manufacturers of America, acknowledges growing criticism about drug industry violations of ethical guidelines.
Angell contends drug companies increasingly design studies, keep the data, analyse it and don't even let researchers view it. They make the decision if they are going to publish the data and sign contracts with researchers and medical centers that prohibit them from publishing their work without prior company permission. She asserts that during her tenure, more and more company supported manuscripts were trying to put a positive spin on what really may have been negative studies. A contract research organization (CRO) executive maintains obstruction of negative findings in clinical trials by the pharmaceutical industry is another big problem, revealing "They are nervous if bad data comes out and gets into the mass media," threatening their well orchestrated control.
The manufacturer of bupropion abruptly pulled a study on Wellbutrin SR in August of 1994 before completion due to the development of such "bad data. The study, which took months to uncover, was found in the Fedrip Database, National Technical Information Service (NTIS). It was conducted at the Department of Veterans Affairs/Medical Center, Charleston, SC, where it was examining the SR formulation's use as an antidepressant. Out of patients enrolled, over 25% were unable to tolerate the drug due to adverse effects, an even higher percentage, just over 40%, did NOT find the drug effective, others were withdrawn due to non-compliance/self-withdrawal, leaving a dismal 14.89% showing any positive effect. Serious adverse events occurred in 3 individuals, which revealed seizure, chest pain (assumed to be associated with a panic attack), and sleep apnea/hypersomnia. Bupropion is known for its seizure risk, the manufacturer maintaining the risk to be at .4% (4/1000) for the Wellbutrin immediate release (IR) formulation and .1% (1/1000) for the Zyban/Wellbutrin SR formulation. In regards Glaxo's warnings of seizure risk, they neglect to inform patients that seizures can pose a very grave risk for those who experience them. Seizures have been illustrated to cause death in and of themselves, as well as death by drowning and by asphyxiation. Reports of car accidents, serious burns, brain damage and fractures due to falls have been reported in connection with seizure activity, specifically in connection with bupropion. Continuing seizure activity has yet to be explored, once one has had the misfortune of having experienced an episode that is drug induced.
According to this aborted study, the seizure rate proved to be over 2% (2/100), a substantially higher risk factor than claimed by Glaxo, with far reaching, unknown negative implications for those exposed to the drug. In regards the panic attack cited in the deeply buried study, it has been scientifically documented that initial presentations of panic attacks can, in fact, be manifestations of a seizure. It is highly conceivable that the individual reported to have experienced chest pain assumed to be related to a panic attack was in fact experiencing seizure activity. Were this to be the case, it would raise the seizure percentage findings exponentially. When all findings are weighed, drug induced adverse events and drug ineffectiveness combined far outweighed the actual efficacy of the drug. It is important to note that facilitation of Zyban's approval was based in part on safety and efficacy claims of the SR formulation. A pro-bupropion published study cited the drug's purported efficacy in treating depression as a plus for those who use it as a smoking cessation aid, claiming that many smokers have symptoms of depression or develop them when attempting smoking cessation.
Providing support to the Veteran's study are findings revealed in one of the few published studies showing negative results of bupropion exposure in regards metabolite concentrations. The study illustrated certain metabolites of bupropion predominate over the parent compound in plasma and cerebrospinal fluid at a steady state. Higher plasma metabolite concentrations were proven to be associated with poor clinical outcome, asserted to be the possible result of toxic effects involving dopaminergic systems.
One particular metabolite not mentioned in the study, but referred to in the US Zyban Drug Product Monograph (DPM), is the glycine conjugate of meta-chlorobenzoic acid, deserving of serious attention. There are multiple limitations in the metabolism of meta-chlorobenzoic acid (MCBA), a neurotransmitter, however, it can also decrease bioavailability of the glycine needed to facilitate its metabolism and elimination from the body. MCBA has been shown to induce myotonia (tonic spasm of a muscle or temporary rigidity after muscular contraction) in laboratory animals. It is known to be a free radical generating agent, that will enter into the mitochondria of cells, where it can either be metabolized or can interact with copper centered hemes to produce hydroxyl radicals.
There is increasing amounts of data that correlates free radicals with disruption of the bodily system as a whole. While there are entire journals devoted to this subject; two areas of particular interest are noteworthy. One area concerns free radicals' negative effects on the liver. Bupropion is extensively metabolised by the liver and any impairment of liver function can have deleterious effects upon the metabolism and elimination of the drug, to the point of inducing toxicity. Of particular interest is that free radicals have been shown to be involved in neurological porphyrias. (Bupropion has been linked to increased porphyrin accumulation when heme metabolism is impaired.) Chemically induced porphyria is a serious condition, attendant with a number of negative health repercussions, including, but not limited to serious neurological problems, life threatening drug reactions, and serious digestive problems. Radicals are also implicated in disruption of the central nervous system and disruption of peripheral cell membrane structure and function. Brain tissue is particularly sensitive to free radical assault, partially because of it's high content of oxidizable substrates and catalytically active metals. The nervous system may be especially prone to radical damage, certain disease states being linked to such damage as Parkinson's disease and Amyotrophic Lateral Sclerosis.
In regards purported positive bupropion efficacy findings in the area of smoking cessation, Dr. Ken Bassset, Chairman of the Therapeutics Initiative at the University of British Columbia, holds serious concerns about recently published Zyban clinical trials. He said patients were considered to have abstained if they had not smoked immediately prior to researcher examination and the final two examinations of patients were six months apart, with patients being noted as abstaining in the intervening months if they did not smoke before each exam.
Another little known, but highly disconcerting, fact concerning bupropion is it is revealed to be included in an FDA document listing of drugs deemed "Approved Drugs Not Listed in PDR (Physician's Desk Reference) as QT Prolonging, but Listed in Literature, in Other Drug Labels, or by Other Regulatory Agencies." QT prolongation causes a disorder in the electrical system of the ventricles, the lower and more powerful chambers of the heart. It is known to cause arrhythmias, blackouts, and death. Despite this FDA admission, a Journal of Clinical Psychiatry article comparing cardiac conduction effects of bupropion with amitriptyline states, "No significant changes were seen with bupropion in any of the ECG parameters measured", including QTc interval. The article cited the comparative drug as causing "a significant prolongation of PR interval", suggesting bupropion to be "less likely to cause cardiac conduction abnormalities in patients prone to such problems, or in those who overdose." QT prolongation also has a propensity to cause drop attacks, a type of seizure disorder coinciding with physical activity or emotional stress. If underlying QT prolongation is not diagnosed as precipitating this type of seizure disorder, a patient's health can be seriously jeopardized with potentially deadly consequences. A condition known as the long QT syndrome (LQTS) is known to be acquired by the use of QT-prolonging drugs. Further complicating the entire bupropion ADE picture, patients oftimes are misdiagnosed as having epilepsy when presenting with prolonged QT interval findings and syncope. When misinterpretation of epilepsy occurs, the negative repercussions of prognostic and therapeutic decisions can cause even further serious complications for patients on bupropion therapy. Other QT prolonging drugs have been pulled from the US market including Propulsid, a drug used for reflux, Seldane and Himanal, antihistamine drugs. According to Dr. Raymond L. Woolsey, Pharmacology Department Chairman at Georgetown University who served in the 80's on an FDA advisory committee, "It has been proven, over and over, that this QT prolongation predicts terrible events." The dangers concerning prolonged QT interval had been stressed for several years as of the Propulsid withdrawal, FDA Director Dr. Raymond J. Lipicky of the agency's cardiology division warning of its potentially lethal implications. According to his contentions in an issue of the American Journal of Cardiology, if a drug had such an effect with a benefit that was less than lifesaving…any risk of death would likely be considered unacceptable. Apparently, by some strange twist of logic (facilitated by secrecy) it has been deemed morally acceptable by both Glaxo and the FDA to risk one's death and/or serious disablement in the hopes of either aborting the chances of tobacco related disease or of treating depression related problems. It is ironic that the very charges levelled at the tobacco industry for its exercises in deceit and exploitation sit most squarely, and of equal weight, upon the shoulders of those who propose to deliver smokers from "all that ails them" - or, what has yet proven to ail them. Indeed, an ounce of bupropion "prevention" in truth all too often takes away even a chance of a "pound" of cure for its deleterious effects on many!
And yet, the beat goes on, as steady, rhythmic and intoxicating as the billions stacking like perfectly timed clockwork in the manufacturer's overflowing coffers, facilitated in part by drugs that maim and kill - we the invisible, casualties of such brilliantly calculated control and practices. We are the acceptable "statistics" all too conveniently accepted in the drug approval process, all too often denied and dismissed post-drug exposure, lest accountability be called for on the part of the powers that be - namely those that claim to benevolently provide "safe and efficacious" drug offerings and those who continue to abandon their morally demanded injunction to, "first, do no harm…"
Nevertheless, we leprous victims exude something very powerful by virtue of our very existence that cries out for vindication, acknowledgement, and justice, despite concerted efforts to deny it's invincible potency. It is the inescapable stench of the truth; the truth that we are being seriously harmed and in many cases killed, due to pomposity, ignorance, indifference or deceit on far too many fronts. Illustrated herein, it should prove to communicate it's far reaching effects in terms of avoidable human suffering and explore the reasons behind it's suppression in regards why we victims have and continue to experience extreme difficulty obtaining adequate medical care and accurate diagnoses subsequent to our exposure to and ensuing disabilities from bupropion…
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