CASE II - Paroxetine & GlaxoSmithKline (GSK)

Paroxetine (also known by the trade names Aropax, Paxil, Seroxat, Sereupin) is an SSRI antidepressant. The marketing of this drug began in 1992 by the pharmaceutical company SmithKline Beecham, which is now GlaxoSmithKline. Paroxetine is used to treat major depression, obsessive-compulsive disorder, panic disorder, social anxiety, and generalized anxiety disorder in adult outpatients.

In 2007, paroxetine was ranked 94th on the list of bestselling drugs, with over $1 billion in sales. In 2006, paroxetine was the fifth-most prescribed antidepressant in the United States retail market, with more than 19.7 million prescriptions. In 2007, sales had dropped slightly to 18.1 million but paroxetine remained the fifth-most prescribed antidepressant in the U.S.

In adults, the efficacy of paroxetine for depression is comparable to that of older tricyclic antidepressants, with fewer side effects and lower toxicity. Differences with newer antidepressants are subtler and mostly confined to side effects. Unlike two other popular SSRI antidepressants, fluoxetine and sertraline, paroxetine is associated with clinically significant weight gain. Pediatric trials of paroxetine for depression did not demonstrate statistical efficacy better than placebo and showed an increase in the risk of harmful outcomes, including episodes of self-harm and suicidal thoughts.

For 10 years, GlaxoSmithKline (GSK) marketing of the drug stated that it was "not habit forming," which numerous experts and at least one court found to be incorrect. In 2001, the BBC reported that the World Health Organization (WHO) had ranked paroxetine as the most difficult antidepressant to withdraw from. In 2002, the U.S. FDA published a new product warning about the drug, and the International Federation of Pharmaceutical Manufacturers Associations said that GSK had misled the public about the drug and hence breached two of the Federation's codes of practice. The fact that it could cause intolerable withdrawal symptoms of the kind that could lead to dependence was enormously important to patients, doctors, investors, and the company. GSK evaded the issue since it was granted a license for paroxetine over 10 years ago, and the drug had become a blockbuster for them, generating about a tenth of their entire revenue. The company promoted paroxetine directly to consumers as 'non-habit forming' for far too long. Paroxetine prescribing information posted at GlaxoSmithKline now acknowledges the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.

Since the FDA approved paroxetine in 1992, approximately 5,000 U.S. citizens have sued GSK. Most of these people feel they were not sufficiently warned in advance of the drug's side effectsparticularly

the withdrawal syndrome discussed above, after GSK had specifically advertised the drug as non-habit forming. In 2001, GSK increased its American TV advertising of Paxil after the September 11 attacks; in October 2001, GSK spent nearly twice as much as in October 2000. The difficulty of withdrawal from paroxetine, and GSK's concealment of it, was later reported on ABC.

Since 2001 in the UK, lawsuits have been filed representing people who have been prescribed Seroxat. They alleged that the drug had serious side effects, which GlaxoSmithKline downplayed in patient information.

In 2002, the U.S. Food and Drug Administration published a new product warning about the drug, and the International Federation of Pharmaceutical Manufacturers Associations (IFPMA) declared GSK guilty of misleading the public about paroxetine on US television. The British Medical Journal quoted Charles Medawar, head of Social Audit: This drug has been promoted for years as safe and easy to discontinue. The fact that it can cause intolerable withdrawal symptoms of the kind that could lead to dependence is enormously important to patients, doctors, investors, and the company. GlaxoSmithKline has evaded the issue since it was granted a licence for paroxetine over 10 years ago, and the drug has become a blockbuster for them, generating about a tenth of their entire revenue. The company has been promoting paroxetine directly to consumers as 'non-habit forming' for far too long.

In early 2004, GSK agreed to settle the charges of consumer fraud for $2.5 million (a tiny fraction of the over $2.7 billion in yearly Paxil sales at that time). The legal discovery process also uncovered evidence of deliberate, systematic suppression of unfavourable Paxil research results. One of GSK's internal documents had said, "It would be commercially unacceptable to include a statement that efficacy [in children] had not been demonstrated, as this would undermine the profile of paroxetine". In June 2004, FDA published a violation letter to GSK in response to a "false or misleading" TV ad for Paxil CR; FDA said that the ad was concerning from a public health perspective because it elongated the use of Paxil CR [beyond the conditions it was approved for] while also minimizing the serious risks associated with the drug. To this, GSK claimed that the ad had been previously reviewed by FDA, but said that the ad would not run again.

In March 2006, California Attorney General Bill Lockyer announced that "GlaxoSmithKline (GSK) will pay $14 million to resolve allegations that state-government programs paid inflated prices for the firms antidepressant drug Paxil because GSK engaged in patent fraud, anti-trust violations and frivolous litigation to maintain a monopoly and block generic versions from entering the market."

On 22 December 2006, a US court decided in Hoorman, et al. v. SmithKline Beecham Corp that individuals who purchased Paxil or Paxil CR (paroxetine) for a minor child may be eligible for benefits under a $63.8 million Proposed Settlement. The lawsuit stemmed from a consumer advocate protest against GSK. Since the FDA approved paroxetine in 1992, approximately 5,000 US citizens and thousands more worldwide have sued GSK. Most of these people feel they were not sufficiently warned in advance of the drug's side effects and addictive properties.

In January 2007, the BBC broadcast a fourth documentary in its Panorama series about the drug Seroxat. This programme, entitled "Secrets of the Drug Trials", focused on three GSK paediatric clinical trials on depressed children and adolescents. Data from the trials showed that Seroxat could not be proven to work for teenagers. Also, one clinical trial indicated that adolescents were six times more likely to become suicidal after taking it. The court documents released as a result of one of the lawsuits in October 2008 indicated that GSK "and/or researchers may have suppressed or obscured suicide risk data during clinical trials" of paroxetine. In January 2007, according to the Seroxat Secrets website, the national group litigation in the United Kingdom, on behalf of several hundred people who allege withdrawal reactions through their use of the drug Seroxat, against GlaxoSmithKline plc, moved a step closer to the High Court in London, with the confirmation that Public Funding had been reinstated following a decision by the Public Interest Appeal Panel. The issue at the heart of this particular action claims Seroxat has a propensity to cause a withdrawal reaction.

In March 2008 the Medicines and Healthcare Products Agency concluded that GSK should have warned of the effects of taking Seroxat a lot sooner. GSK could not be under the old legislation. As of 2008, GlaxoSmithKline's information acknowledges that "serious discontinuation may occur.

Regulatory possible ill prosecuted prescribing symptoms"