Author Topic: What You Need to know About Depression Medication  (Read 4827 times)

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Offline Anonymous

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What You Need to know About Depression Medication
« on: December 02, 2009, 12:15:54 AM »
Antidepressants
What You Need to know About Depression Medication

http://helpguide.org/mental/medications_depression.htm
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Offline Anonymous

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Re: What You Need to know About Depression Medication
« Reply #1 on: December 02, 2009, 04:47:33 AM »
There is a lot of good information in this piece. I especially like the part that states that there is no way to measure serotonin levels in the brain and that the "chemical imbalance" idea is a "theory".

Thanks to "off label" marketing and the changing of the laws on what can be prescribed for what ailment over the past few years, I was given an SSRI for insomnia, not even for depression. By law now, no tests are needed for prescribing medications for conditions the drugs were never tested for. I would like to see more info like this in the piece.
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Offline Anonymous

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Re: What You Need to know About Depression Medication
« Reply #2 on: December 03, 2009, 12:36:46 AM »
More proof...  Long read but full of interesting information:

http://www.bloomberg.com/apps/news?pid= ... yV1nYxCGoA
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Offline Anonymous

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Re: What You Need to know About Depression Medication
« Reply #3 on: December 03, 2009, 12:47:16 AM »
Quote
One of Pfizer’s units had been pushing doctors to prescribe an epilepsy drug called Neurontin for uses the Food and Drug Administration had never approved.

I was under the impression the FDA approved Neurontin for all epilepsy related uses.
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Offline Ursus

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Neurontin
« Reply #4 on: December 04, 2009, 01:05:32 AM »
Quote from: "Joel"
Quote
One of Pfizer's units had been pushing doctors to prescribe an epilepsy drug called Neurontin for uses the Food and Drug Administration had never approved.
I was under the impression the FDA approved Neurontin for all epilepsy related uses.
That may be so (I'm just not sure about the "all epilepsy related uses" part), but the FDA sure as hell didn't approve it for pain management and bipolar disorder, and yet those markets were targeted and generated substantially more prescriptions than the epilepsy market ever did for Warner–Lambert (later bought out by Pfizer Inc.).

Moreover, given that one of Neurontin's side effects happens to be suicidal ideation, I would think that prescribing it for folks who may be at risk for being in a not so good emotional state would be counterintuitive. Yet that is exactly what happened.
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Offline Ursus

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The Neurontin Legacy
« Reply #5 on: December 04, 2009, 01:17:04 AM »
New England Journal of Medicine
360;2 pp103-106 / January 8, 2009

The Neurontin Legacy — Marketing through Misinformation and Manipulation

C. Seth Landefeld, M.D., and Michael A. Steinman, M.D.

Old drugs usually fade away. Sometimes, however, they leave surprising legacies. In 1997, for example, a study comparing the effects of brand-name and generic formulations of levothyroxine led to an uproar over the discovery that the manufacturer of the brand-name product suppressed publication of the result that the two formulations were equivalent. Recently, lawsuits alleging damages from illegal marketing of another old drug, gabapentin (Neurontin), have yielded remarkable discoveries about the structure and function of pharmaceutical marketing.

Patented in 1977 and approved by the Food and Drug Administration (FDA) in 1993 in doses of up to 1800 mg per day as adjunctive therapy for partial complex seizures, Neurontin became a surprise blockbuster for Parke–Davis, a division of Warner–Lambert, which was purchased by Pfizer in 2000. U.S. sales rose from $98 million in 1995 to nearly $3 billion in 2004 before Neurontin faced generic competition and lost most U.S. sales.

The rise of Neurontin would have been unheralded except for a quirk of fate: a young biologist, David Franklin, went to work for Parke–Davis on April 1, 1996. Fresh out of postdoctoral training at Harvard, Franklin soon grew concerned that he was participating in illegal marketing. At a training seminar for "medical liaisons" on April 16, 1996, Franklin and his peers were told that FDA regulations required a fair and balanced presentation and prohibited promotion of a drug for off-label uses, selling by medical liaisons, and soliciting of inquiries from physicians. Six days later, a Parke–Davis executive reportedly told Franklin,

    I want you out there every day selling Neurontin. . . . We all know Neurontin's not growing for adjunctive therapy, besides that's not where the money is. Pain management, now that's money. Monotherapy [for epilepsy], that's money. . . . We can't wait for [physicians] to ask, we need [to] get out there and tell them up front. Dinner programs, CME programs, consultantships all work great but don't forget the one-on-one. That's where we need to be, holding their hand and whispering in their ear, Neurontin for pain, Neurontin for monotherapy, Neurontin for bipolar, Neurontin for everything. I don't want to see a single patient coming off Neurontin before they've been up to at least 4800 mg/day. I don't want to hear that safety crap either, have you tried Neurontin, every one of you should take one just to see there is nothing, it's a great drug.1[/list]

    Three months later, Franklin left Parke–Davis and filed a suit (ultimately, United States of America ex rel. David Franklin vs. Pfizer, Inc., and Parke-Davis Division of Warner-Lambert Company) alleging that off-label marketing of Neurontin constituted "false claims" designed to elicit payments from the federal government. On May 13, 2004, Warner–Lambert agreed to plead guilty and to pay more than $430 million to resolve criminal charges and civil liabilities. A class-action suit was filed the next day in federal court on behalf of private parties who had paid for illegally marketed Neurontin; this case (now known as In Re: Neurontin Marketing, Sales Practices, and Products Liability Litigation) remains active.

    The Franklin case placed more than 8000 pages of corporate documents in the public domain; these documents are now available in a searchable digital library at the University of California, San Francisco (http://www.dida.library.ucsf.edu). The class-action suit also generated detailed testimony and reports that are available through the Federal Judiciary's Public Access to Court Electronic Records Service Center (e.g., https://ecf.mad.uscourts.gov/doc1/09502786849).

    The Neurontin cases have revealed the mechanisms of action of a comprehensive marketing campaign — its goals and strategies, tactics and programs, and the participation of particular physicians and institutions.2 The campaign involved the systematic use of deception and misinformation to create a biased evidence base and manipulate physicians' beliefs and prescribing behaviors. These marketing methods were not found to be illegal in themselves; they were illegal insofar as they promoted off-label prescription. Thus, the importance of the cases lies largely in the light they shed on marketing methods that may be widespread but remain unseen because companies are rarely prosecuted for illegal marketing.

    The Neurontin marketing plan consisted of both general strategies — such as the promotion of Neurontin use among high-prescribing physicians and cultivation of thought leaders — and tactical programs.2 Local physicians were recruited, trained, and paid to serve as speakers in "peer-to-peer selling" programs, which the company saw as "one of the most effective ways to communicate our message." Academic leaders were solicited with educational grants, research grants, and speaking opportunities; some received up to $158,250 over a 4-year period. Advisory boards and "consultants" were convened so that the firm could cultivate relationships with them and deliver "a hard-hitting message about Neurontin."

    Marketing "tactics" included education, publications, and research whose promotional intent was disguised, in addition to more transparent activities, such as advertising and sales visits.2 "Educational programs" reflected the belief that "medical education drives this market!" Teleconferences involving practicing physicians were moderated by physicians who were paid as much as $176,100 over 4 years. Parke–Davis formed speakers bureaus and sought "strong Neurontin advocates and users to speak locally for Neurontin." "Unrestricted educational grants" were made to for-profit medical-education companies that produced programs to discuss unapproved uses of Neurontin and to grant credit approved by the Accreditation Council for Continuing Medical Education.

    A "publication strategy" was designed to increase the use of Neurontin for neuropathic pain and bipolar disorder, off-label indications with great revenue potential. Parke–Davis contracted with medical-education companies to produce articles on prespecified topics, target journals, titles, potential authors to be "chosen at the discretion of Parke–Davis," and "a consistent message" in keeping with promotional goals; some articles were ghost-written.

    "Research" was designed and commissioned specifically to promote Neurontin use. A large seeding trial was conducted to "teach physicians to titrate Neurontin to clinical effect" and "to give neurologists the opportunity to titrate to higher doses [up to twice the FDA-approved limit] when needed." In a recently unsealed 318-page analysis of research sponsored by Parke–Davis, epidemiologist Kay Dickersin concluded that available documents demonstrate "a remarkable assemblage of evidence of reporting biases that amount to outright deception of the biomedical community, and suppression of scientific truth concerning the effectiveness of Neurontin for migraine, bipolar disorders, and pain."3 For example, publication was delayed for a report on a multicenter, placebo-controlled study that found no effect of Neurontin on the primary outcome measure for neuropathic pain because "we [Parke–Davis employees] should take care not to publish anything that damages neurontin's marketing success." Ultimately, ghost-written manuscripts downplayed the lack of effect on the primary outcome and emphasized other outcomes and subgroup analyses that favored Neurontin. Although guest authorship and commercial bias in research are a well-recognized threat to scientific integrity, the documentation of comprehensive manipulation of research and publication related to Neurontin is remarkable.

    What is Neurontin's legacy? First, we have learned that pharmaceutical marketing can be comprehensive, strategic, well financed, disguised as "education" and "research," influential, and very effective. Promotion of Neurontin was neither discrete, compartmentalized, nor readily apparent; instead, it was intercalated in nearly every aspect of physicians' professional lives, from the accoutrements of practice to lectures, professional meetings, and publications. Although some pharmaceutical marketing may be less opaque, deceptive, and manipulative, evidence indicates that drug promotion can corrupt the science, teaching, and practice of medicine.4

    Second, such comprehensive marketing involved many people and institutions that apparently failed to recognize the serious ethical and legal problems with their actions. Employees of Parke–Davis, the medical-education companies it hired, and many physicians (consultants, advisors, educators, and researchers) all participated knowingly. Universities, hospitals, professional organizations, and foundations also participated, and oversight agencies such as the FDA and the Department of Justice did not intervene quickly. Apparently, there was a shared acceptance that Parke–Davis's marketing was simply business as usual.

    Finally, these cases substantiate the emerging conviction that "drastic action is essential" to preserve the integrity of medical science and practice and to justify public trust.4 We believe that such action should include the routine placement of legally discovered documents in the public domain, the study of such documents to inform strategies for minimizing abuses, the establishment of penalties that eliminate the profit to be gained through illegal marketing, and the independent public funding of peer-reviewed pharmaceutical research through a National Institute for Pharmaceutical Research that might be funded by a tax on all drug sales.5

    Will our profession soon feel compelled to advocate for such actions to preserve our integrity, our social contract, and ultimately our privileges? Neurontin's most important legacy may be promoting our discussion of these issues and perhaps pushing us beyond the tipping point to action.


    Drs. Landefeld and Steinman report serving as unpaid consultants to the plaintiff's attorney in United States of America ex rel. David Franklin vs. Pfizer, Inc., and Parke-Davis Division of Warner-Lambert Company and participating in the creation of the Drug Industry Document Archive by the University of California, San Francisco, Kalmanovitz Library, an effort that was funded in part by Thomas Greene, whose law firm represented David Franklin in the case. Dr. Steinman also reports receiving support from an educational grant funded by the Attorney General Settlement Fund that arose from the Franklin case. No other potential conflict of interest relevant to this article was reported.

    The views expresssed in this article are those of the authors and do not necessarily reflect the official views of the Department of Veterans Affairs.


    -----------------------------------------------------------------
    Dr. Landefeld is a professor of medicine and chief of the Division of Geriatrics at the University of California, San Francisco (UCSF), San Francisco; associate chief of staff for geriatrics and extended care at the San Francisco Veterans Affairs Medical Center (SFVAMC), San Francisco; and a fellow at the Center for Advanced Study in the Behavioral Sciences, Stanford University, Stanford, CA. Dr. Steinman is an assistant professor of medicine at UCSF and a staff physician at SFVAMC.


    1. Disclosure of information by relator David P. Franklin pursuant to 31 U.S.C. § 3730 b(2), page 11. (Accessed December 16, 2008, at http://dida.library.ucsf.edu/pdf/rab00a10.)

    2.  Steinman MA, Bero LA, Chren MM, Landefeld CS. The promotion of gabapentin: an analysis of internal industry documents. Ann Intern Med 2006;145:284-93.

    3. Dickersin K. Reporting and other biases in studies of Neurontin for migraine, psychiatric/bipolar disorders, nociceptive pain, and neuropathic pain. August 10, 2008. (Accessed December 16, 2008, at http://www.pharmalot.com/wp-content/upl ... rsin-2.pdf.)

    4. DeAngelis CD, Fontanarosa PB. Impugning the integrity of medical science: the adverse effects of industry influence. JAMA 2008;299:1833-5.

    5. Landefeld CS. Commercial support and bias in pharmaceutical research. Am J Med 2004;117:876-8.




    Downloaded from http://www.nejm.org by on January 14, 2009.
    Copyright © 2009 Massachusetts Medical Society. All rights reserved.
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    Offline Anonymous

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    Re: What You Need to know About Depression Medication
    « Reply #6 on: December 04, 2009, 02:16:56 AM »
    The comparison between this big pharma "medication" deception and the deception in marketing behavior mod programs and the so-called "treatment" they provide is amazingly similar, if not identical.

    The foundation of both of these "solutions" is based on lies and intentional deception. And those who perpetuate these lies have no conscience. I thought that people who had no conscience and hurt people or killed people or robbed people went to prison.

    Instead we put people in prison for smoking a little weed. If you're going to be a career criminal, big pharma or the troubled teen industry is a safe haven for you.

    And this part of the article sounds just like a cult leader:

    I want you out there every day selling Neurontin. . . . We all know Neurontin's not growing for adjunctive therapy, besides that's not where the money is. Pain management, now that's money. Monotherapy [for epilepsy], that's money. . . . We can't wait for [physicians] to ask, we need [to] get out there and tell them up front. Dinner programs, CME programs, consultantships all work great but don't forget the one-on-one. That's where we need to be, holding their hand and whispering in their ear, Neurontin for pain, Neurontin for monotherapy, Neurontin for bipolar, Neurontin for everything. I don't want to see a single patient coming off Neurontin before they've been up to at least 4800 mg/day. I don't want to hear that safety crap either, have you tried Neurontin, every one of you should take one just to see there is nothing, it's a great drug.
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    Offline Ursus

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    Re: What You Need to know About Depression Medication
    « Reply #7 on: December 04, 2009, 12:04:21 PM »
    Quote from: "scamerica"
    The comparison between this big pharma "medication" deception and the deception in marketing behavior mod programs and the so-called "treatment" they provide is amazingly similar, if not identical.

    The foundation of both of these "solutions" is based on lies and intentional deception.
    I fully concur! They are both driven by greed, putting profits over people, in industries producing products or therapies allegedly designed to "help" people.
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    Offline Ursus

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    Pfizer Broke the Law by Promoting Drugs for Unapproved Uses
    « Reply #8 on: December 04, 2009, 06:25:01 PM »
    Quote from: "scamerica"
    More proof...  Long read but full of interesting information:

    http://www.bloomberg.com/apps/news?pid= ... yV1nYxCGoA
    A long and excellent read! This article discusses the Pfizer Inc. / Neurontin marketing scandal as well as highlighting a number of other cases. Big Pharma is rife with this kind of stuff. And these are just the people who got caught with their pants down in public!  :D

    Copy of that 2009 article for posterity's sake:

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    Bloomberg.com
    Pfizer Broke the Law by Promoting Drugs for Unapproved Uses

    By David Evans

    Nov. 9 (Bloomberg) -- Prosecutor Michael Loucks remembers clearly when lawyers for Pfizer Inc., the world's largest drug company, looked across the table and promised it wouldn't break the law again.

    It was January 2004, and the attorneys were negotiating in a conference room on the ninth floor of the federal courthouse in Boston, where Loucks was head of the health-care fraud unit of the U.S. Attorney's Office. One of Pfizer's units had been pushing doctors to prescribe an epilepsy drug called Neurontin for uses the Food and Drug Administration had never approved.

    In the agreement the lawyers eventually hammered out, the Pfizer unit, Warner-Lambert, pleaded guilty to two felony counts of marketing a drug for unapproved uses.

    New York-based Pfizer agreed to pay $430 million in criminal fines and civil penalties, and the company's lawyers assured Loucks and three other prosecutors that Pfizer and its units would stop promoting drugs for unauthorized purposes.

    What Loucks, who's now acting U.S. attorney in Boston, didn't know until years later was that Pfizer managers were breaking that pledge not to practice so-called off-label marketing even before the ink was dry on their plea.

    On the morning of Sept. 2, 2009, another Pfizer unit, Pharmacia & Upjohn, agreed to plead guilty to the same crime. This time, Pfizer executives had been instructing more than 100 salespeople to promote Bextra, a drug approved only for the relief of arthritis and menstrual discomfort, for treatment of acute pains of all kinds.

    Record High Fine

    For this new felony, Pfizer paid the largest criminal fine in U.S. history: $1.19 billion. On the same day, it paid $1 billion to settle civil cases involving the off-label promotion of Bextra and three other drugs with the U.S. and 49 states.

    "At the very same time Pfizer was in our office negotiating and resolving the allegations of criminal conduct in 2004, Pfizer was itself in its other operations violating those very same laws," Loucks, 54, says. "They've repeatedly marketed drugs for things they knew they couldn't demonstrate efficacy for. That's clearly criminal."

    The penalties Pfizer paid this year for promoting Bextra off-label were the latest chapter in the drug's benighted history. The FDA found Bextra to be so dangerous that Pfizer took it off the market for all uses in 2005.

    Across the U.S., pharmaceutical companies have been pleading guilty to criminal charges or paying penalties in civil cases when the U.S. Department of Justice finds that they deceptively marketed drugs for unapproved uses, putting millions of people at risk of chest infections, heart attacks, suicidal impulses or death.

    $7 Billion in Penalties

    Since May 2004, Pfizer, Eli Lilly & Co., Bristol-Myers Squibb Co. and four other drug companies have paid a total of $7 billion in fines and penalties. Six of the companies admitted in court that they marketed medicines for unapproved uses.

    In September 2007, New York-based Bristol-Myers paid $515 million -- without admitting or denying wrongdoing -- to federal and state governments in a civil lawsuit brought by the Justice Department. The six other companies pleaded guilty in criminal cases.

    In January 2009, Indianapolis-based Lilly, the largest U.S. psychiatric drug maker, pleaded guilty and paid $1.42 billion in fines and penalties to settle charges that it had for at least four years illegally marketed Zyprexa, a drug approved for the treatment of schizophrenia, as a remedy for dementia in elderly patients.

    In five company-sponsored clinical trials, 31 people out of 1,184 participants died after taking the drug for dementia -- twice the death rate for those taking a placebo. Those findings were reported in an October 2005 article in the Journal of the American Medical Association.

    'Don't Respect the Law'

    "Marketing departments of many drug companies don't respect any boundaries of professionalism or the law," says Jerry Avorn, a professor at Harvard Medical School in Boston and author of "Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs" (Random House, 2004). "The Pfizer and Lilly cases involved the illegal promotion of drugs that have been shown to cause substantial harm and death to patients."

    The widespread off-label promotion of drugs is yet another manifestation of a health-care system that has become dysfunctional.

    "It's an unbearable cost to a system that's going broke," says Avorn, who heads the pharmacology economics unit of Brigham and Women's Hospital in Boston. "We can't even afford to pay for effective, safe therapies."

    10 Million Prescriptions

    About 15 percent of all drug sales in the U.S. are for unapproved uses without adequate evidence the medicines work, according to a study by Randall Stafford, a medical professor at Stanford University in Palo Alto, California.

    He estimates that doctors write more than 10 million such prescriptions each year.

    As large as the penalties are for drug companies caught breaking the off-label law, the fines are tiny compared with the firms' annual revenues.

    The $2.3 billion in fines and penalties Pfizer paid for marketing Bextra and three other drugs cited in the Sept. 2 plea agreement for off-label uses amount to just 14 percent of its $16.8 billion in revenue from selling those medicines from 2001 to 2008.

    The total of $2.75 billion Pfizer has paid in off-label penalties since 2004 is a little more than 1 percent of the company's revenue of $245 billion from 2004 to 2008.

    $36 Billion in Revenue

    Lilly already had a criminal conviction for misbranding a drug when it broke the law again in promoting schizophrenia drug Zyprexa for off-label uses starting in 1999. The medication provided Lilly with $36 billion in revenue from 2000 to 2008.

    That's more than 25 times as much as the total penalties Lilly paid in January.

    Companies regard the risk of multimillion-dollar penalties as just another cost of doing business, says Lon Schneider, a professor at the University of Southern California's Keck School of Medicine in Los Angeles.

    In 2006, he led a study for the National Institute of Mental Health of off-label use of drugs, including Zyprexa, for the treatment of Alzheimer's disease.

    "There's an unwritten business plan," he says. "They're drivers that knowingly speed. If stopped, they pay the fine, and then they do it again."

    Shareholders Unmoved

    Schneider has been paid both by Lilly as a consultant and by plaintiffs suing the company.

    Big Pharma's off-label transgressions didn't trigger a rush for the doors by shareholders. From Jan. 26, when Pfizer announced that it would pay billions in penalties, to Oct. 12, Pfizer's share price increased 9.3 percent, just shy of the 11.2 percent rise in the Standard & Poor's 500 Health Care Index.

    From Oct. 21, 2008, when Lilly said it would pay its penalties, to Oct. 12, the company's stock value went up 0.6 percent; the S&P index gained 6.9 percent in that time.

    In pushing off-label use of drugs, companies find ready and willing partners in physicians. Under the fragmented system of medical regulation in the U.S., it's legal for doctors to prescribe FDA-approved drugs for any use.

    The FDA has no authority over doctors, only over drug companies, regarding off-label practices. It's up to the 50 states to oversee physicians.

    "I think the physician community has to take some ownership responsibility and do their own due diligence beyond the sales and marketing person," says Boston's former U.S. Attorney Michael Sullivan.

    Off-Label Benefits

    Loucks says prosecutors realize that patients can benefit when doctors use drugs for off-label purposes based on science and not on false marketing claims.

    Doctors generally don't tell people that they're prescribing drugs pitched to them by pharmaceutical salespeople for unapproved treatments, says Peter Lurie, deputy medical director of Public Citizen, a Washington-based public interest group.

    Most physicians don't keep track of FDA-approved uses of drugs, says Lurie, a physician who has published articles in "The Lancet" and the "Journal of the American Medical Association."

    "The great majority of doctors have no idea; they don't even understand the distinction between on- and off-labeling," Lurie says.

    Pharmaceutical companies have showered doctors with cash to persuade them to use drugs off-label, according to their guilty pleas.

    'Buying Access'

    Pfizer's marketing program offered doctors up to $1,000 a day to allow a Pfizer salesperson to spend time with the physician and his patients, according to a whistle-blower lawsuit filed by John Kopchinski, who worked as a salesman at Pfizer from 1992 to 2003.

    "By 'pairing up' with a physician, the sales representative was able to promote over a period of many hours, without the usual problems of gaining access to prescribing physicians," Kopchinski says. "In essence, this amounted to Pfizer buying access to physicians."

    Pfizer spokesman Chris Loder says the company stopped what it calls "mentorships" in 2005. He says Pfizer paid doctors $250 per visit.

    It used to be legal for companies to promote drugs for any use in the U.S. Congress banned the practice in 1962. The catalyst was Thalidomide, a morning sickness drug taken by pregnant women outside the U.S. that caused severe birth defects.

    Recouping Investments

    The 1962 law required pharmaceutical companies to prove their drugs were safe and effective for specific uses. Before that, a drug company could market an approved medicine for any illness.

    If the law is clear, why do drug companies keep breaking it? The answer lies in economics. Pharmaceutical companies spend about $1 billion to develop and test a new drug. To recoup their investment, the companies want doctors to prescribe their drugs as widely as possible.

    Pfizer's Neurontin is a case in point. The FDA approved the drug as a supplemental medication in treating epilepsy in 1993. Pfizer took in $2.27 billion from sales of Neurontin in 2002. A full 94 percent -- $2.12 billion -- of that revenue came from off-label use, according to the prosecutors' 2004 Pfizer sentencing memo.

    Pfizer, which bought Wyeth on Oct. 15 for $68 billion, put itself at the center of illegal off-label drug marketing with an acquisition frenzy a decade earlier. From 1995 to 2005, Pfizer purchased more than 20 companies.

    Guilty Pleas

    Since 2004, companies that are now Pfizer divisions have pleaded guilty to off-label marketing of two drugs. Pfizer continued off-label promotions for these medications after buying the firms, according to Pfizer's Sept. 2 guilty plea and FDA correspondence with Pfizer.

    Pfizer first stepped into an off-label scheme in 1999, when it offered to buy Morris Plains, New Jersey-based Warner-Lambert Co. Prosecutors charged that Warner-Lambert marketed Neurontin off-label between 1995 and 1999.

    Warner-Lambert admitted doing so for one year in a May 2004 guilty plea for which Pfizer paid $430 million in fines and penalties.

    Neurontin, which was invented by Warner-Lambert, was first tested in humans in 1987. When the FDA approved it in 1993 to be used only along with other epilepsy drugs, the agency wrote that a side effect of the drug can be that it induces depression and suicidal thoughts in patients.

    Whistle-Blower

    Much of what prosecutors learned about Warner-Lambert's marketing of Neurontin comes from a former employee.

    David Franklin, who holds a Ph.D. in microbiology from the University of Rhode Island, left his job as a pediatric researcher at Harvard University's Dana-Farber Cancer Institute in 1996 to work for the Parke-Davis unit of Warner-Lambert in Boston.

    He says he hoped the salary boost -- to $55,000 annually from $18,000 -- would help him pay off student loans and better support his family.

    Franklin's title at Warner-Lambert was medical liaison. He says he soon realized his new employer viewed his doctorate as a badge that would allow him to strike up conversations with physicians.

    Franklin, 48, says his job involved more salesmanship than science. He told doctors that Neurontin was the best drug for a dozen off-label uses, including pain relief, bipolar disease and depression.

    'What I Did Was Wrong'

    "Technically, I had responsibility for answering physician questions about all of Parke-Davis's drugs," Franklin says. "In practice, my real job was to promote Neurontin for off- label indications heavily -- to the exclusion of just about everything else."

    Franklin, whose wife is a lawyer, says he knew such uses of the drug had no scientific support for effectiveness and safety.

    "I was actually undermining their ability to fulfill the Hippocratic oath," Franklin says, referring to a physician's pledge to "first, do no harm."

    Franklin says he was horrified when he learned from a doctor that a child had a behavioral outburst at school for the first time after taking Neurontin.

    "Don't we have an obligation to tell physicians about this?" Franklin says he asked his manager, Phil Magistro. His boss tried to reassure him, Franklin says.

    'Total Disregard'

    " 'Don't worry about this stuff,' " he says Magistro told him. " 'It can never get back to us.' "

    Franklin was stunned.

    "I realized at that moment, looking into his eyes, that there was an absolute total disregard for the patient," he says.

    Magistro, who now works at drug marketing adviser Atom Strategic Consulting LLC in Randolph, New Jersey, didn't return calls seeking comment.

    Franklin saved phone messages from Magistro to his sales team urging them to market Neurontin for off-label uses, including pain relief. During one such call, on May 23, 1996, at 5:48 p.m. in Boston, Magistro told his staff, "You're supposed to be pushing on Neurontin," according to a transcript of the tape filed in federal court.

    "When we get out there, we want to kick some ass. We want to sell Neurontin on pain," Magistro said. "All right?"

    Quit the Job

    After working for Warner-Lambert for three months, Franklin grew concerned about his own liability. He quit the job and talked with Boston attorney Thomas Greene, who helped him file a lawsuit against the company.

    Franklin acted as a whistle-blower, suing on behalf of taxpayers to recover money the government paid for illegally promoted drugs. Under federal and state whistle-blower statutes, he stood to collect as much as 30 percent of any settlement the company made with the government.

    Franklin had to wait four years -- until 2000 -- before the Justice Department began a criminal investigation. In November 1999, Pfizer made its public offer to buy Warner-Lambert. In January 2000, a federal grand jury in Boston issued subpoenas to Warner-Lambert employees to testify about the marketing of Neurontin.

    That March, Warner-Lambert's annual report disclosed that prosecutors were building a criminal case. Undeterred, Pfizer bought Warner-Lambert in June for $87 billion. It was the third-largest merger in U.S. history.

    'Misleading and in Violation'

    A year after the acquisition, the FDA discovered that Neurontin was still being marketed off-label. In a letter to the company on June 29, 2001, the agency wrote that Pfizer's promotion of the drug "is misleading and in violation of the Federal Food, Drug and Cosmetics Act."

    The agency asked Pfizer to stop such promotions of Neurontin. The FDA said Pfizer had distributed brochures -- known as "slim jims" because they're small enough to put in a jacket pocket -- improperly claiming that the drug could improve energy levels and memory.

    "Immediately discontinue the use of this slim jim and any other promotional material or practices with the same or similar messages," the FDA wrote.

    Pfizer marketed Neurontin off-label after receiving that letter, agency records show. For 2001, Pfizer reported revenue of $1.75 billion from Neurontin sales, making it the company's fourth-largest-selling drug that year, ahead of impotence pill Viagra, which Neurontin topped for four years.

    Marketing Violated Rules

    As Neurontin sales soared to $2.27 billion in 2002, the FDA found that Pfizer was improperly claiming that the drug was useful for a broader range of brain disorders than scientific evidence had established.

    The agency sent a letter dated July 1, 2002, that said the company's marketing practices were in violation of FDA rules. It asked Pfizer to stop using misleading promotions. Pfizer reported $2.7 billion in revenue from Neurontin in 2003. Overall, the drug has provided Pfizer with $12 billion in revenue.

    In a response to Bloomberg News, Pfizer spokesman Chris Loder said, "Regarding the 2001 and 2002 FDA letters, we do not believe that they were suggestive of any continuing off-label promotion."

    For blowing the whistle on his employer, Franklin collected $24.6 million under the False Claims Act.

    Prosecutors Loucks and Sullivan got involved in the case after Franklin filed his suit, relying on information from Franklin and their own investigation. Before 2004, prosecutions for off-label marketing were rare.

    'Everybody Does It'

    "Until a couple of these cases became public, companies were probably saying, 'Everybody does it this way,' " Sullivan says.

    Loucks had a track record in off-label prosecutions. He gave up private practice at Choate Hall & Stewart LLP in Boston in 1985 to join the U.S. Attorney's Office.

    In 1994, he negotiated a $61 million settlement with Murray Hill, New Jersey-based C.R. Bard Inc., which pleaded guilty to promoting off-label use of a heart catheter that led to patient deaths.

    In 2002, he co-authored, with Carol Lam, "Prosecuting and Defending Health Care Fraud Cases" (BNA Books).

    In the January 2004 settlement negotiations with Loucks, Sullivan and two other prosecutors, Pfizer's lawyers assured the U.S. Attorney's Office that the company wouldn't market drugs off-label.

    'Those Promises'

    "They asserted that the company understood the rules and had taken steps to assure corporate compliance with the law," Loucks says. "We remember those promises."

    What Pfizer's lawyers didn't tell the prosecutors was that Pfizer was at that moment running an off-label marketing promotion using more than 100 of its salespeople. They were pitching Bextra, a Pfizer sales manager admitted when she pleaded guilty to misbranding a drug on March 30, 2009.

    Jeff Kindler, who became Pfizer's general counsel in 2002, supervised the lawyers who made the promises to prosecutors. By 2004, Kindler increased the compliance budget 12-fold. He became chief executive officer in 2006. In Pfizer's ethics guide, he says stories about misbehaving companies and executives abound.

    "Pfizer truly stands apart," he says. "I am proud of our record." On Oct. 1, Kindler was elected to the board of the Federal Reserve Bank of New York. Kindler declined to comment.

    Peapack, New Jersey-based Pharmacia & Upjohn Inc. developed Bextra, which was approved by the FDA only for the treatment of arthritis and menstrual discomfort in 2001.

    Sales Manager Pleads Guilty

    P&U and Pfizer had by then already crafted a joint marketing agreement to sell the drug. In November 2001, Mary Holloway, a Pfizer regional manager for the Northeastern U.S., began illegally training and directing her sales team to market Bextra for the relief of acute pain, Holloway admitted in a March 2009 guilty plea.

    On Dec. 4, 2001, Pfizer executives sent Holloway a copy of a nonpublic letter from the FDA to the company. The agency had denied Pfizer's application to market Bextra for acute pain. Clinical trials had shown Bextra could cause heart damage and death.

    Pfizer bought Pharmacia & Upjohn in April 2003. From 2001 to the end of 2003, P&U, first as an independent company and then as a unit of Pfizer, paid physicians more than $5 million in cash to lure them to resorts, where salespeople illegally pitched off-label uses for Bextra, P&U admitted in its Sept. 2 guilty plea.

    'Golf, Massages'

    "Pharmacia paid targeted physicians both airfare and two to three days' accommodations at lavish resorts in the Bahamas, Virgin Islands and across the United States and further entertained these physicians with golf, massages and other recreation activities," according to prosecutors' findings.

    In her guilty plea, Holloway said her team had solicited hospitals to create protocols to buy Bextra for the unapproved purpose of acute pain relief. Her representatives didn't mention the increased risk of heart attacks in their marketing.

    They told doctors that side effects were no worse than those of a sugar pill, Holloway admitted in her guilty plea.

    In 2003, Holloway reported her unit's off-label promotions of Bextra up the corporate ladder at Pfizer, according to a pre-sentencing memo to the judge written by Robert Ullmann, Holloway's attorney. Top managers didn't attempt to halt the illegal conduct, the memo said.

    "Corporate tracked this information, and at no time did it inform Ms. Holloway that any of the reported protocols were inappropriate," he wrote. "Instead, the instruction was to get more protocols."

    Blockbuster Status

    By the end of 2004, Bextra reached blockbuster status, with annual sales of $1.29 billion. Holloway promoted Bextra until the FDA asked Pfizer in April 2005 to pull it from the market for all uses, evidence in her case shows.

    The agency concluded that the drug increased the risk of heart attacks, chest infections and strokes in cardiac surgery patients. In June 2009, Holloway, 47, was sentenced to two years on probation and fined $75,000. She didn't return phone calls seeking comment.

    Ronald Rainero, a Pfizer district sales manager and employee for more than 20 years, says he was responsible for promoting Bextra in New York from 2001 to 2005. In September 2007, Rainero, 47, began cooperating with federal prosecutors on the Bextra case.

    Hotel Meetings

    He says he met monthly with his fellow managers at a Hilton hotel in Staten Island, New York, to discuss sales methods of promoting Bextra off-label. As a whistle-blower, Rainero was awarded $9.3 million as part of the September settlement.

    In the same time period that Pfizer was marketing Bextra off-label, the company's sales force was promoting another drug, Zyvox, improperly, Pfizer admitted at the time of its September plea agreement.

    Zyvox was approved in 2000 by the FDA for treating MRSA-caused pneumonia and skin infections. Raniero told federal prosecutors that Pfizer began the Zyvox campaign in 2001. The company admitted to falsely claiming that the drug was better than other medications for treating MRSA pneumonia.

    Pfizer told doctors to use Zyvox rather than vancomycin, a generic antibiotic that cost $18 a day. Pfizer sold Zyvox for about $150 a day. A table on page 30 of a 35-page fact book produced by Pfizer for Zyvox says the drug is less effective than vancomycin for MRSA pneumonia.

    'Misleading Promotion'

    On July 20, 2005, the FDA sent a letter to Hank McKinnell, then Pfizer's CEO, saying, "Your misleading promotion of Zyvox, and in particular your unsubstantiated implied claims regarding its superiority to vancomycin, poses serious health and safety concerns."

    The agency ordered the company to stop the promotion. In response, Pfizer told the FDA it would stop saying Zyvox was more effective against MRSA pneumonia than vancomycin.

    Despite its 2005 pledge to the FDA, Pfizer continued to tell hospitals and doctors that Zyvox would save more lives than vancomycin, the company admitted in the September settlement.

    By 2007, the criminal and civil cases against Pfizer, its employees and its subsidiaries had started to mount. The tally of drugs cited by federal prosecutors for off-label promotion reached six by 2009. In April 2007, P&U pleaded guilty to a felony charge of offering a $12 million kickback to a pharmacy benefit manager.

    $2.2 Billion in Penalties

    Pfizer paid a criminal fine of $19.7 million. Thomas Farina, a Pfizer district sales manager, was convicted in federal court in March 2009 for destroying records during the Bextra investigation. Farina, 42, was sentenced to three years on probation, including six months of home confinement. He didn't return calls seeking comment.

    Pfizer itself was called to account on Sept. 2, when it agreed to pay the $2.2 billion in fines and penalties. P&U pleaded guilty to a felony charge of misbranding Bextra with the intent to defraud. After the settlement, Pfizer general counsel Amy Schulman said the company had learned its lesson.

    "We regret certain actions we've taken in the past," she said. "Corporate integrity is an absolute priority for Pfizer."

    One reason drug companies keep breaking the law may be because prosecutors and judges have been unwilling to use the ultimate sanction -- a felony conviction that would render a company's drugs ineligible for reimbursement by state health programs and federal Medicare.

    "It's potentially a death sentence for a drug company," prosecutor Sullivan says.

    Fig Leaf

    A legal fig leaf allows a parent company to continue to participate in government programs even after its subsidiary has pleaded guilty.

    Pfizer maintains its good standing with such agencies because its subsidiaries, Warner-Lambert and P&U, and not the corporation itself, entered the guilty pleas to felony charges.

    A felony conviction of a pharmaceutical giant could lead to disaster for shareholders, Loucks says, adding that's a step that may have to be taken for repeat offenders.

    "I think it's something the trigger will get pulled on," he says from his ninth-floor office in the federal courthouse, with a sweeping view of Boston Harbor. "It's just a question of when."

    At Pfizer's Pharmacia sentencing on Oct. 16., U.S. District Court Judge Douglas Woodlock said companies don't appear to take the law seriously.

    "It has become something of a cost of doing business for some of these corporations, to shed their skin like certain animals and leave the skin and move on," he said.

    Eli Lilly

    Lilly's rap sheet goes back to 1985. That's when the company pleaded guilty to 25 federal misdemeanor charges related to its misbranding of Oraflex, an arthritis drug.

    Lilly stopped selling the drug four months after U.S. sales began in 1982, following the company's failure to tell the FDA about illnesses and deaths tied to the medication. Lilly paid a $25,000 fine.

    Twenty years later, in 2005, Lilly paid $36 million in a guilty plea to one federal misdemeanor for off-label marketing of Evista, a drug the FDA had approved for bone strengthening.

    In 1997, the agency had rejected Lilly's application to market the drug to reduce the risk of breast cancer. Yet beginning the next year, Lilly adopted an Evista marketing plan that included a seminar with doctors designed to appeal to women's breast cancer concerns, Lilly admitted in its 2005 guilty plea.

    In 2007, the FDA approved Evista for preventing breast cancer in two limited groups.

    Back in Court

    In January 2009, Lilly was back in federal court. Prosecutors in Philadelphia accused the company of earning hundreds of millions of dollars by illegally promoting its schizophrenia drug Zyprexa for the unapproved treatment of dementia from 1999 to at least 2003.

    In 2001, Lilly's senior management decided not to seek FDA approval for Zyprexa to treat dementia because of what they viewed as mixed results in clinical trials and safety risks, according to admissions by Lilly in its 2009 guilty plea. In its marketing, Lilly promoted the drug as effective.

    Zyprexa has been Lilly's best-selling drug for the past decade.

    "Eli Lilly undertook this illegal off-label promotion for its own financial gain despite the potential risk to patients' health and lives," prosecutors wrote in their sentencing memo.

    Lilly Chairman and CEO John Lechleiter said after the settlement that the company was devoted to acting responsibly.

    'Deeply Regret'

    "We deeply regret the past actions covered by the misdemeanor plea," he said. "Doing the right thing is nonnegotiable at Lilly."

    In a written response to questions from Bloomberg News, Lilly said, "Lilly entered into a very narrow guilty plea. Even though the company disagrees with and does not admit to the allegations, Lilly agreed to settle the dispute."

    Lilly paid $1.42 billion for a fine and penalties in the January settlement with federal and state governments. That included the largest criminal fine in U.S. history -- until Pfizer pleaded guilty in September.

    The Justice Department could have charged Lilly with a felony. Prosecutors decided that it wouldn't be fair to innocent Lilly employees, shareholders and pensioners to potentially shut down the company, according to the sentencing memo.

    'All the Factors'

    "The government considered all the factors in its decision," prosecutors wrote. "Those factors included other persons not proven personally culpable."

    Federal regulators have detected a similar pattern of dishonesty by other pharmaceutical firms. Schering-Plough Corp. drug salesmen pitched off-label uses of a cancer drug called Temodar at the American Society of Clinical Oncology's annual conference in San Francisco in May 2001.

    Schering-Plough representatives said Temodar compared favorably to a placebo in clinical trials for the off-label uses and was approved by the FDA for first-line use in treating brain tumors.

    An FDA employee attending the conference took note. The next month, the FDA accused Schering of lying.

    There had been no such clinical trials and the agency had not approved Temodar as the salespeople had claimed, the FDA said in a June 28, 2001, letter to Mary Jane Nehring, Schering's senior director of marketed products. The agency ordered the company to immediately cease illegal promotion of Temodar.

    Kenilworth, New Jersey-based Schering-Plough was quick to respond. On July 12, 2001, it wrote back to the FDA, assuring regulators that the San Francisco activity was an isolated incident.

    'Certainly Inconsistent'

    "It was certainly inconsistent with the direction provided by the home office," the drug company wrote, according to prosecutor's records.

    The FDA told Schering-Plough three weeks later that it had closed its investigation.

    Schering-Plough didn't stop pitching the drug for unapproved uses. At the direction of top management, Schering ordered widespread off-label marketing of Temodar and Intron A, another cancer drug, until December 2003, the company admitted in an August 2006 guilty plea.

    Schering, which agreed in March to be acquired by Merck & Co., earned a pre-tax profit of $124.2 million from the illegal sales after promising the FDA in 2001 it would stop marketing for off-label uses, the company admitted.

    Schering-Plough pleaded guilty in August 2006 to conspiring to make false statements to the FDA. The company agreed to pay $435 million to settle the case.

    'Upsetting to Me'

    U.S. District Court Judge Patti Saris, who had presided over the Neurontin whistle-blower case before the Pfizer probe, accepted Schering's plea in her Boston courtroom in January 2007. She expressed dismay with the drug industry.

    "It's been upsetting to me how many of the big pharmaceutical companies have engaged in what I view as clearly illegal behavior in terms of off-label marketing," she said. "It almost seems as if the pharmaceutical companies said 'Yeah, yeah, yeah' to the FDA and then went and did it anyway."

    Brent Saunders, a Schering-Plough senior vice president, said after the settlement that his company had made great progress in putting integrity at the center of its work.

    "With this agreement, we are putting issues from the past behind us," he said. Schering declined to comment further.

    As prosecutors continue to uncover patterns of deceit in off-label marketing by pharmaceutical companies, millions of patients across the nation remain in the dark. Doctors often choose the medications based on dishonest marketing by drug company salesmen.

    'A Morass'

    "It's a morass of undifferentiated information out there," Public Citizen's Lurie says. "And the doctors, let alone patients, aren't able to distinguish the good from the bad."

    One thing all people should do, Lurie says, is ask whether their prescriptions are for FDA-approved uses, and if not, whether strong evidence supports using the drug, particularly if it can be dangerous.

    Loucks says that putting an end to the criminal off-label schemes by the pharmaceutical industry is more difficult. As drugmakers repeatedly plead guilty, they've shown they're willing to pay hundreds of millions of dollars in fines as a cost of generating billions in revenue.

    The best hope, Loucks says, is that drug companies actually honor the promises they keep making -- and keep breaking -- to obey the law of the land.

    To contact the reporter on this story: David Evans in Los Angeles at davidevans@bloomberg.net

    Last Updated: November 9, 2009 00:01 EST


    ©2009 BLOOMBERG L.P. ALL RIGHTS RESERVED.
    « Last Edit: December 31, 1969, 07:00:00 PM by Guest »
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    Offline Anonymous

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    Re: What You Need to know About Depression Medication
    « Reply #9 on: December 04, 2009, 08:57:05 PM »
    My personal favorite website for everything you wanted to know about crazy meds.

    http://www.crazymeds.us/

    They have a pretty good blurb on the bullshittery that is neuontin/gabapentin.

    I tried that shit after a particularly traumatic event, and it was awful. The shit made me totally manic. I felt like I was on ritalin or something.
    « Last Edit: December 31, 1969, 07:00:00 PM by Guest »

    Offline Anonymous

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    Re: What You Need to know About Depression Medication
    « Reply #10 on: December 04, 2009, 09:31:45 PM »
    So do you support the drug war or don't you? If you want marihuana legalized then you have to let Prozac be legal too, otherwize you are a hippo critter. All drugs should be legal from Meth to Prozac to Crack to Ephedrine to MDMA , and we should be able to buy it from the local convenience store. If you don't believe that you are a commie bastid. My beef with anti depressants is they are not strong enough, I'd rather do drugs that work. pity insurance will not cover those.
    « Last Edit: December 31, 1969, 07:00:00 PM by Guest »

    Offline Anonymous

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    Re: What You Need to know About Depression Medication
    « Reply #11 on: December 04, 2009, 10:03:30 PM »
    I’m kind of with you on that. On the one hand I’m sick of these drug companies being so poorly monitored by the FDA and that we the sheeple seem so accepting that. Some people do have organic brain illnesses that are managed well on chemicals, legal or otherwise. I’ve heard quite a few ringing endorsements for Marijuana as effective treatment for PTSD…though it’s not for me.
     
    Others flit from one medication to another wondering why they never feel better. I’ve been there. It’s worth considering just what it is that we’re trying to medicate. Are there really so many of us in this freeborn nation of clean running water and consumerism that are really so stressed and beset by sorrows that we are truly need pills to cope?
     
    I think most of the off label uses and drug hybrids are symptoms of greed and we accept this, because we the sheeple are so desperate for a panacea for what in many cases amounts to symptoms of the human condition. Maybe I'm jaded from knowing so many who have had negative experiences with medications, including my own.

    On the other hand I like pharmaceutical stimulants, benzos and treat myself to the occasional diverted Vicodin. ?I recognize that it is an indulgence.and yet I never drink alcohol.

    Maybe we are culturally sick and the stuff of antidepressants, mood stabilizers, anxiolytics and stimulants are to widely sought and given, perhaps far more than is actually indicated. If we were not capable of physical pain we’d have lives as hindered as suffers of CIPA (congenital analgia) have. If we were not capable of emotional pain we’d all be like whotroll.
    « Last Edit: December 31, 1969, 07:00:00 PM by Guest »

    Offline Ursus

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    Suicide Risk of Neurontin Kept Hidden for Years
    « Reply #12 on: December 05, 2009, 02:39:26 PM »
    Man... reading about the lengths to which this Big Pharma company went, when it came to milking the public for all they could, really reminded me of the stuff that got unearthed during the Big Tobacco trials...

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    OpEdNews February 19, 2007 at 21:24:34
    Suicide Risk of Neurontin Kept Hidden for Years

    By Evelyn Pringle

    The all-time poster child for a drug illegally promoted for off-label uses, is Neurontin, marketed by Warner-Lambert, and its Parke-Davis division, until Pfizer acquired the company in 2000.

    The term "off-label" means prescribing a drug for indications not listed on the label, upping the recommended dose, prescribing a drug in combination with other medications, or using a drug with a patient population, such as children, not listed on the label.

    As part of the approval process, the FDA reviews the drug's labeling, which must include the proposed claims about the drug's risks and benefits, as well as the directions for use.

    If an indication is not listed, it means the drug maker has not submitted the required studies to prove the drug is safe and effective for that use. While physicians may prescribe a drug approved by the FDA for an unapproved use, it's against the law for a drug maker to influence doctors to prescribe a drug for uses outside the label.

    Pfizer completed the acquisition of Warner-Lambert in June 2000, and four years later in May 2004, Pfizer pleaded guilty to illegally marketing Neurontin for unapproved uses and agreed to pay a $430 million, the second-largest settlement ever in a health care fraud prosecution, to settle charges brought by the US Department of Justice that included defrauding public health care programs.

    The case specifically sought to recover the losses to public programs resulting from the off-label promotion of a drug and focused primarily on Medicaid, which spent an estimated $422 million on Neurontin between 1994 to mid-2000.

    In the end, Pfizer paid $83.6 million to the federal government and $68.4 million to the 50 states and the District of Columbia. In addition, Pfizer agreed to pay the states a total of $38 million to settle liabilities under state consumer protection laws, and a $240 million criminal fine, according to the DOJ.

    However, the settlement with the DOJ did not include damage awards for patients who may have been injured by Neurontin and many patients, or families representing deceased Neurontin victims, have filed lawsuits against the company.

    Many of the cases are wrongful death actions based on the company's failure to warn about the risk of suicidality associated with the drug. In 2004, attorneys Derek braslow and Harris Pogust of the Pennsylvania law firm, Pogust & Braslow, began filing lawsuits on behalf of victims who became suicidal.

    Pogust & Braslow represent plaintiff, Natalie Biedenbender, whose husband Mark committed suicide on July 9, 2005, at age 39, after being prescribed Neurontin off-label for back pain, in a wrongful death lawsuit.

    According to the lawsuit, from July 1995 through at least August 5, 2002, the company engaged in a marketing program "to induce physicians to prescribe Neurontin, for medical conditions for which the FDA had not approved Neurontin to be used."

    That program, the complaint charges, included (a) illegally promoting the sale and use of Neurontin for a variety of conditions "for which defendants had not performed the required FDA testing or established safety and efficacy;" and (b) offering and paying illegal remuneration to doctors, "either directly or through third parties, to induce them to promote and prescribe Neurontin for off-label uses."

    On May 17, 2004, Andrew Finkelstein, of the New York law firm of Finkelstein & Partners, submitted a citizen's petition to the FDA requesting that a black box suicide warning be added to the label and that a Dear Doctor letter be sent out to instructing physicians to be on alert for increased depression in patients taking the drug.

    Mr Finkelstein also continued to remind the FDA about the rising number of suicides. In a March 21, 2005, letter to Dr Russell Katz, he wrote in part: "Enclosed you will find two hundred fifty eight MedWatch forms ... Each represents a suicide of an American who was on Neurontin when he or she took his or her own life."

    "Many of these suicides likely could have been prevented," he said, "had both the treating physician and unsuspecting families been armed with full knowledge of the risks of suicide that was known to both the FDA and the manufacturer."

    But as it turns out, the FDA was fully aware of the suicidality risk when Neurontin was recommended for approval in 1992, and Dr Katz oversaw the FDA's analysis of the clinical data provided to support the New Drug Application.

    According to Mr Finkelstein, the evaluation of serious adverse events during the original clinical trials showed the risk of suicide was known and a major concern. In the letter to Dr Katz, he pointed out that an FDA reviewer specifically stated in December, 1992:

      Serious adverse events may limit the drug's widespread usefulness. Depression, while it may not be an infrequent occurrence in the epileptic population, may become worse and require intervention or lead to suicide, as it has resulted in some suicidal attempts during clinical trials.[/list]

      In fact, in the clinical trials, Neurontin was attributed to four people actually attempting suicide, two more having depression with suicidal ideations, and 22 participants reporting depression so severe it required pharmacologic intervention. Most alarming was that 19 of the 78 participants who reported depression had no prior history of depression.

      "Clearly," Mr Finkelstein told Mr Katz, "the FDA did not approve this drug with any expectation of use beyond the approved indication."

      Documents that surfaced in litigation also show that the FDA was aware of the off-label marketing scheme eight years before the DOJ settlement. In July, 1996, FDA official, Lesley Frank, wrote to Parke-Davis and said in part:

        Parke-Davis may be promoting Neurontin for 'off-label' uses ... in printed promotional materials, in detail or sales presentations to physicians, and through the use of company-solicited physician participation in a series of teleconferences.

        These promotions of Neurontin for off-label uses included, but were not limited to, its use in chronic pain, bipolar disorders, and other psychiatric conditions. As you are aware, Neurontin's only approved indication was for adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults with epilepsy.
        [/list]

        The documents show that after 11 months, Parke-Davis sent a written response denying all the allegations and the FDA accepted the denials and the matter was dropped.

        In reality, $430 million was chickenfeed to Pfizer, considering that at the time of the settlement, Neurontin sales were up 32% from 2003, and the 2004 sales were expected to exceed the $2.7 billion mark set in 2003. In actuality, the settlement amounted to only about 15% of the gross sales of Neurontin in 2003.

        By 2002, a full 94% of Neurontin sales were for off-label use and according to the August 16, 2004, USA Today, when Pfizer settled the lawsuit, the Wall Street firm Lehman Bros estimated that 90% of the sales were still off-label.

        At the time, Pfizer issued a statement that said the illegal practices took place before Pfizer acquired Warner-Lambert. However, sales figures clearly show that Pfizer was still reaping the benefits of the illegal promotion of Neurontin at the time of the settlement.

        "Although Neurontin is prescribed for scores of off-label indications," Attorney Braslow reports, "since 2000 off-label use continues to be most common in the areas where the company focused its illegal marketing efforts such as bipolar disorder, peripheral neuropathy and migraine headaches."

        "This increase," he points out, "is most likely a direct result of sales representatives and leading physicians, who were paid by the company recommending its use for these conditions."

        According to Attorney Pogust, "there are no scientific studies that support Neurontin's use for pain disorders."

        "But as a result of the company's previous promotional activities," he says, "tens of thousands of patients who could use other pain killing drugs whose effectiveness has been established, are given Neurontin."

        "These prescriptions for pain," Mr Pogust notes, "are still being written, as a direct result of past illegal promotional activities."

        "Likewise," he points out, "the off-label prescriptions of Neurontin for bipolar disorder, attention deficit disorder, and depression are also without any scientific evidence supporting such uses."

        The off-label scheme was first revealed by whistleblower, David Franklin, a former Park-Davis employee who worked as a medical liaison, in a lawsuit against Warner-Lambert and its Parke-Davis division filed under the federal False Claims Act.

        By Mr Franklin's estimates, as much as 90% of prescriptions for Neurontin were written off-label as a result of the illegal scheme which prosecutors claim dates back to1995. To back up his allegations, Mr Franklin offered a voicemail he saved from his boss that stated:

          I want you out there every day selling Neurontin... holding their hand, whispering in their ear, Neurontin for pain, Neurontin for monotherapy, Neurontin for bipolar, Neurontin for everything. I don't want to see a single patient coming off Neurontin before they've been up to at least 4,800 milligrams a day.[/list]

          His boss concluded by stating: "I don't want to hear that safety crap either. It's a great drug"

          As a whistleblower in a case to recover federal funds, Mr Franklin was entitled to a percentage of the settlement and received $24.6 million

          The Drug Industry Document Archive (DIDA), created by the Center for Knowledge Management at the University of California San Francisco Library in collaboration with faculty members, contains roughly 1,000 documents drawn primarily from the case titled, United States ex rel David Franklin vs Parke-Davis, Division of Warner-Lambert, which describe all the specific details on the Neutontin off-label marketing scheme.

          In settling the charges, Pfizer pleaded guilty only to conduct occurring before August 21, 1996, even though the DOJ determined that illegal activities had occurred much later, making it possible for Pfizer to continue to participate in federally funded health care programs despite a health care fraud law that went into effect on August 21, 1996, that would have required its exclusion from public programs.

          Pfizer escaped the severe penalties, that many critics say would have sent a clear message to companies engaging in such conduct to knock it off or risk losing the most treasured customer base of all public health care programs, even though Warner-Lambert had been convicted of a felony in 1995, for failing to report failures concerning other drugs, which meant the new charges were second offenses "punishable as felonies without regard to proof of intent to defraud or mislead."

          Initially, Neurontin was approved only to treat epilepsy in combination with another drug, and at a maximum 1800 mg daily dose. But the DOJ found the drug was being promoted for a multitude of pain uses, psychiatric conditions such as bipolar disorder and anxiety, social phobia, and general mood stabilization, as well as certain unapproved uses within epilepsy treatment. According to the DOJ, the list of unapproved uses became so long that company employees called it the "snake oil" list.

          Over all, the DOJ listed the potential harm caused by the illegal scheme as: (1) public health care programs paid more in reimbursement; (2) consumers paid for ineffective, experimental use and may have been improperly medicated; (3) patient's unnecessary exposure to adverse side effects; and (4) improper medication may have resulted where Neurontin was not as effective as another approved drug.

          The DOJ listed six tactics involved in carrying out the off-label scheme as: (1) Detailing by sales representatives; (2) Use of Medical Liaisons; (3) Preceptorships; (4) Consultant meetings, speakers bureaus and advisory boards; (5) Series of teleconferences to disseminate off-label uses; and (6) Control of Purportedly Independent Medical Education.

          Another element of the overall scheme to increase profits was to convince doctors to prescribe Neurontin at substantially higher doses than the maximum approved dose.

          The DOJ produced evidence to show that Parke-Davis had arranged hundreds of teleconferences, meetings, and educational seminars, in addition to the detailing of individual doctors by sales representatives, to promote the off-label use of Neurontin.

          In 1996, a Parke-Davis sales representative created a document that said sales representatives could ask doctors if they ever used other antiepileptic drugs for painful neuropathies and then mention that approximately 35% of all Neurontin use is non-seizure. This same document, entitled "Neurontin Can Do/Can't Do," also stated that sales representatives could present lunch programs on Neurontin and pain.

          According to Mr Franklin, the company gave financial incentives to hundreds of doctors by inviting them to dinners, sports outings, and weekend trips to resorts where fellow-physicians were paid to speak about the use of Neurontin for unapproved indications.

          The company founded a speakers' bureau, as a method of making large payments to physicians who gave presentations and court documents show doctors were paid to listen to speeches that took place on a "Bus to Yankee Stadium," a "World Yacht Cruise," and the "Braves Stadium."

          During one trip in 1996, Parke-Davis paid for 18 doctors and their spouses to stay in Atlanta for 5 days to attend the Summer Olympics. The company paid for their meals, use of a resort, and travel to the games while the agenda for the seminar listed only 10.5 hours of business meetings, including one devoted to off-label uses for Neurontin.

          The DOJ determined that the company kept track of how well these marketing efforts paid off. For instance, in a memo dated June 26, 1995, a marketing executive reported that doctors who attended dinners and listened to speeches from other physicians, wrote 70% more off-label prescriptions than doctors who did not attend.

          Documents show that the company intentionally hired influential doctors from major teaching hospitals to speak at these events. For instance, Dr Steven Schachter, a professor at Harvard Medical School, received $71,477 between May 1994 and September 1997, and Dr B J Wilder, a former professor at the University of Florida, was paid more than $300,000, and other doctors received more than $100,000 each.

          The company also paid to disseminate papers and articles on off-label uses throughout the medical literature so that doctors would find themselves bombarded with information about the many uses for Neurontin, made to look like independent scientific papers.

          For some uses, like monotherapy, the research was used to support an attempt to obtain FDA approval. But in other cases, the company's goal was to disseminate the information as widely as possible to increase off-label prescribing for conditions like pain and bipolar disorder, without ever trying to obtain approval.

          To carry out this part of the scheme, Warner-Lambert hired two marketing firms to write the articles and then found doctors willing to sign on as authors. According to Mr Franklin, the PR firms were paid $12,000 per article and the doctors were paid $1,000.

          The DOJ found more than twenty 20 articles published in various medical journals that were fully paid for by Parke-Davis. Critics say this tactic still affects off-label prescribing today. According to Mr Braslow, "since 1999, the types of off-label are most likely weighted in the precise areas where the drug maker focused its illegal marketing efforts: bipolar disorder, peripheral neuropathy, migraine, depression, etc."

          "Because physicians were inundated with false information for years," Mr. Pogust says, "they continue to prescribe it for off-label uses for which there is no reliable scientific support."

          Parke-Davis also infiltrated the continuing education arena where doctors were misled into believing that seminars on the off-label uses for Neurontin were independent educational programs, when they actually were marketing events set up by Park-Davis.

          For example, prosecutors found an undisclosed relationship with a firm known as Physicians World where Parke-Davis employees transferred to the firm to run the company's speakers bureau.

          At the same time, the DOJ discovered that in a division of Physicians World, known as Professional Post-Graduate Services, which purported to be an independent education provider presenting programs on anticonvulsants for pain to thousands of US doctors, Parke-Davis employees actually planned and developed the programs.

          According to the DOJ, in late 1995, the company took the position that medical liaisons could discuss off-label issues with doctors, so long as the doctor asked a question about the topic first. Because physicians believed medical liaisons were persons with a scientific background and not employed to sell Neurontin, they were often able to gain access to doctors that the sales representatives could not.

          For example, Mr Franklin was trained to increase the rate of prescriptions of Neurontin as monotherapy, and one of the ways he was able to gain access to doctors was by fraudulently presenting himself as a neurology specialist conducting research on epilepsy and the actions of anticonvulsant drugs.

          Company records reveal an extensive pattern of misuse of medical liaisons. A January 31, 1996, memo describes a goal to "utilize the medical liaison group to target the Neurontin, Pain & Psychiatric market."

          "Objective to conduct twice weekly Pain Teleconferences moderated by key Neuro Consultants," the memo states. "Goals 250 Physician participants quarterly."

          One of the most alarming sales tactics identified during the DOJ's investigation was that sales representatives were allowed to review patient records, suggest an increase in Neurontin dosage, and "shadow" doctors while they examined patients, in exchange for paying the doctor a few hundred dollars a day.

          According to the DOJ, at various times Parke-Davis made a conscious decision to not seek approval for a new use because it would have required solid proof from clinical trials that could not be provided.

          Documents show that Parke-Davis even went to the trouble of determining how much could be made off Neurontin for a new approved use, compared to sales from marketing the drug off-label for the same use.

          For example, a May 19, 1995, Marketing Assessment forecast potential revenue from Neurontin for bipolar without approval at $6 million in 1997, rising to $36 million in 1999. On the other hand, with approval, forecasted sales were almost $12 million in 1997, to over $80 million in 2002, but the company still decided not to seek approval for bipolar.

          The DOJ found that similar projections were made for other uses including various types of pain but again, after evaluating the potential sales with and without approval, Parke-Davis decided to market Neurontin off-label instead of seeking approval.

          The company also kept track of doctor's prescribing habits for Neurontin's competitors. In October of 1995, Parke-Davis determined that two competing epilepsy drugs, Tegretol and Depakote, had total sales of 18-27% for bipolar disorder, and up to 9% for pain, while at the time, only 1-2% of sales for Neurontin were for pain and bipolar.

          The company continued to market the drug for bipolar even after studies showed it was ineffective for that use. The DOJ's sentencing Memorandum states: "One of the psychiatric uses for which Neurontin was promoted ... bipolar disorder, was particularly troubling because the Company had very weak evidence of Neurontin's efficacy in treating this condition."

          "Indeed," the prosecutor wrote, "in one study ... the placebo was as effective or more effective than was Neurontin."

          Yet with full knowledge of this study, medical liaisons told psychiatrists that early results from clinical trials indicated a 90% response rate for bipolar. Likewise, they told pediatricians that Neurontin was effective for children with attention deficit disorder, when no data other than occasional anecdotal evidence supported that claim.

          And although no studies existed to prove that Neurontin was even as effective as inexpensive pain killers already on the market, medical liaisons told doctors that clinical trials demonstrated that Neurontin was highly effective in treating various pain syndromes and reported once again that a 90% response rate was found in the treatment of pain.

          The DOJ also reports that the company continued to promote Neurontin for monotherapy even after the FDA refused to approve it. Parke-Davis sought approval in September 1996, but because one of the 2 clinical trials submitted with the application showed no demonstrable monotherapy efficacy, the application was denied.

          Nonetheless, the DOJ produced evidence showing that Parke-Davis continued to promote Neurontin for monotherapy through at least 2000, without ever mentioning the rejected application, and that at one 1998 event, Parke-Davis went so far as to state that Neurontin is "now approved as monotherapy for seizures."

          When caught red-handed promoting drugs for unapproved uses, drug makers always feign ignorance of the high rate of off-label prescribing. However in this instance, company documents show that Warner-Lambert regularly obtained detailed information on the number of prescriptions written for Neurontin and what indication they were written for.

          Neurontin sales did finally drop to $182 million in the first quarter of 2005, but as a result of new generic competition on the market, according to USA Today on April 20, 2005.

          Persons seeking information about Neurontin representation can contact the Pogust & Braslow law firm at 610-941-4204, or http://www.pogustbraslow.com/

          Evelyn Pringle
          evelyn-pringle@sbcglobal.net

          Evelyn Pringle is a columnist for OpEd News and investigative journalist focused on exposing corruption in government and corporate America.

          (This article is part of a series on Neurontin related litigation and is sponsored by the Pogust & Braslow law firm)

          The views expressed in this article are the sole responsibility of the author
          and do not necessarily reflect those of this website or its editors.



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          Offline Anonymous

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          Re: What You Need to know About Depression Medication
          « Reply #13 on: December 05, 2009, 03:21:14 PM »
          Ursus is the most annoying poster on this forum. Is ursus a undercover troll or just retarded?

          Protip: Post links instead copypasta! you are making pages impossible to navigate. on purpose?? hmmmmm
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          Offline Inculcated

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          Re: What You Need to know About Depression Medication
          « Reply #14 on: December 05, 2009, 03:26:34 PM »
          Previous poster, not everyone shares your opinion. Of course it’s perfectly understandable that you might feel that way considering it probably exceeds your reading comprehension skills to discern much out of the provided information.
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          “A person needs a little madness, or else they never dare cut the rope and be free”  Nikos Kazantzakis