Microsoft word - newsome_paxil_edit.doc
Paxil Litigation Going Strong on Multiple Fronts
By C. Richard Newsome, Esq. and Jerri H. Coletti, Esq.
Litigation surrounding the antidepressant drug Paxil continues to develop and
evolve around the country. During the past year, Plaintiffs won a key victory in
the first case to go to trial alleging birth defects caused by Paxil. The second birth
defects case ended in dismissal. A large number of cases have been settled and
many more remain pending. Personal injury product liability cases continue to be
filed against GlaxoSmithKline (GSK), the manufacturer of Paxil, at a steady pace.
The initial cases against GSK alleged that the company misrepresented Paxil as a non-habit forming drug when, in fact, discontinuing the drug can cause very severe withdrawal symptoms. The next wave of Paxil litigation involved claims that the drug caused an increase in “suicidality,” especially among adolescents. Following a 2005 announcement by GSK that Paxil may cause birth defects, a third wave of cases were filed alleging that GSK knew of the teratogenic effects of the drug for a number of years and had concealed that information from the public.
There has also been significant consumer fraud litigation claiming that GSK misrepresented the safety and efficacy of Paxil. This article will discuss the drug and its common uses and side effects, the history and development of the litigation, and legal theories employed in the litigation.
History, Uses and Side Effects of Paxil
Paxil (chemical name paroxetine hydrochloride) was approved by the FDA and first marketed in the U.S. in 1992.1 The drug is currently approved to treat depression, panic disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder and premenstrual dysphoric disorder (PMDD). Common “off label” uses of the drug include treatment for tension headaches, premature ejaculation and diabetic neuropathy, among others.2
Paxil is one of many selective serotonin reuptake inhibitors (SSRIs) approved by the FDA to treat depression. SSRIs are believed to work by blocking the reabsorption (reuptake) of the neurotransmitter serotonin in the brain.3 Changing the balance of serotonin appears to help brain cells send and receive chemical messages, which in turn boosts the patient’s mood.4 Paxil comes in immediate and timed-release tablets in various dosages and an oral suspension. The oral suspension is frequently used to facilitate withdrawal from the drug by allowing
1 Paroxatine is also sold under the trade names Aropax and Seroxat, both of which are also manufactured by GSK.
2 Paxil: History, Uses, Side Effects, and Withdrawal. Associatedcontent.com. Feb. 3, 2009. Captured December 14, 2010.
3 Selective serotonin reuptake inhibitors (SSRIs). Mayoclinic.com. December 9, 2010. Captured December 15, 2010.
patients to take gradually lower doses. Common side effects of Paxil include nausea, somnolence or insomnia, dizziness, dry mouth and sexual side effects.5
Sales of Paxil vary from year to year, but in 2006, annual sales were estimated at $1 billion and Paxil was the fifth most prescribed antidepressant in the U.S.6 In 2007 annual sales dropped slightly but the drug continued to be the fifth most often prescribed antidepressant in the in the country. 7
Litigation Involving Paxil
The Paxil personal injury litigation has been unique in that it has proceeded on three separate tracks with the initial cases involving undisclosed withdrawal symptoms, followed by suicide cases, and finally birth defect cases. In addition to personal injury litigation surrounding those issues, GSK has also been involved in costly consumer fraud and antitrust litigation, as well as being subject to significant fines for violations of government regulations in connection with the marketing of Paxil. This section will include a discussion of these different types of litigation.
Withdrawal Syndrome Litigation
GSK’s marketing materials for Paxil advertised the drug as “non habit forming” for many years; however, in the U.K. where GSK is based, the U.K. Committee on the Safety of Medicines reported withdrawal symptoms upon discontinuation of Paxil as early as 1993.8 It was not until 2002 that the U.S. FDA issued a warning regarding “paroxetine withdrawal syndrome.” Package information for Paxil now acknowledges the possibility of serious symptoms upon discontinuation of the drug.9
The most commonly reported withdrawal symptoms for individuals who discontinue Paxil include irritability, anxiety, insomnia, headaches, dizziness, fatigue, and nausea.10 Although withdrawal symptoms are known to occur upon discontinuation of any of the SSRI drugs, there is research suggesting that the incidence and severity of symptoms are higher upon withdrawal from Paxil compared to other approved SSRIs.11
In addition to the effects of withdrawal on individuals who take Paxil, in 2001 the World Health Organization reported that taking any SSRI during pregnancy may also cause withdrawal symptoms in the newborn children of women who used
5 Paxil Prescribing Information. GlaxoSmithKline, Research Triange Park. February 2007. Fda.gov. Captured Dec. 14, 2010.
6 Top 200 generic drugs by units in 2006. Top 200 brand-name drugs by units. Drugtopics.com. Mar. 5, 2007. Captured December 15, 2010.
7 Top 200 generic drugs by units in 2007. Drugtopics.com. Feb 18, 2008. Captured December 14, 2010.
8 Gelenberg AJ, ed. Postmarketing watch: paroxetine in the UK. Biol Ther Psychiatry 1993;16:25-8.
9 Paxil Prescribing Information. GlaxoSmithKline, Research Triange Park. February 2007. Fda.gov. Captured Dec. 14, 2010.
10 Depression (major depression). Mayoclinic.com. September 10, 2010. Captured December 14, 2010.
11 Anti-depressant addiction warning. News.bbc.co.uk. June 11, 2001. Captured December 16, 2010.
Paxil during pregnancy.12 The WHO’s data indicated that, of 93 cases of apparent SSRI withdrawal syndrome in newborn infants, 64 of the mothers had taken Paxil, 14 Prozac, 9 Zoloft, and 7 Celexa."13
According to a 2001 BBC report, approximately 5,000 consumers had filed suit
against GSK claiming that they were not sufficiently warned in advance of the
drug's side effects and addictive properties in the nine years following the drug’s
entrance in the U.S. market.14 Many of the cases alleging undisclosed withdrawal
symptoms were consolidated in the Central District of California in MDL 1574.15
In its 2008 annual report, GSK officials said that in January 2006, it had reached
a conditional settlement agreement with the MDL 1574 plaintiffs. That MDL was
closed one month later in February 2006. One estimate of the amount paid in
settlements in connection with Paxil withdrawal syndrome is $50,000 per case to
resolve about 3,200 cases16 or $160 million. Suicide Litigation
The time frame in which GSK became aware of a link between Paxil and an
increased risk of suicide has been the subject of much litigation. A June 11, 2008
letter from Senator Chuck Grassley to the FDA cites a report by Harvard
University professor Dr. Joseph Glenmullen that concluded, based on documents
from GSK and the FDA, “GSK officials knew back in 1989 that Paxil is associated
with an increased risk for suicide.”17 That would suggest GSK became aware of
the connection during clinical trials leading up to the 1992 approval of Paxil by
the FDA. The same letter indicated that, following a four-year investigation,
Britain's Medicines and Healthcare Regulatory Authority (MHRA) concluded that
GSK had been aware since 1998 that Paxil was associated with a higher risk of
suicidal behavior in adolescents.18
On June 9, 2003, the FDA issued its first Talking Paper to healthcare
professionals regarding increased “suicidality” in pediatric patients using
antidepressant medications, including Paxil.19 The Paper called attention to
“reports of the occurrence of suicidality (both suicidal ideation and suicide
attempts) in clinical trials for various antidepressant drugs in pediatric patients
with major depressive disorder (MDD)” and called for additional data, analysis
and public discussion.20
15 In re: Paxil Product Liability Litigation MDL 1574, C.D.Cal. 2001.
16 Glaxo Said to Have Paid $1 Billion Over Paxil Suits. Bloomburg.com, July 20, 2010. Captured December 13, 2010.
17 Press Release, Grassley seeks FDA scrutiny of Paxil and suicide risk, June 12, 2008. Finance.senate.gov. June 12, 2008. Captured December 15, 2010.
19 Reports of Suicidality in Pediatric Patients Being Treated with Antidepressant Medications for Major Depressive Disorder (MDD) fda.gov October 27, 2003. Captured December 13, 2010.
The Talking Paper was followed by an FDA advisory committee meeting before the Psychopharmacologic Drugs Advisory Committee and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee on February 2, 2004. Following that meeting, in March 22, 2004, the FDA requested label changes to include a recommendation of close observation of adult and pediatric patients to detect worsening depression or signs of suicidality.21 The label change was applicable to nine antidepressants, including Paxil.22 Later that year, on October 15, 2004, the FDA ordered the manufacturers of 32 antidepressant drugs to give healthcare providers the results of pediatric studies and to revise their labels to include a “black box warning” about the increased risk of suicide in children.23 While the warning applies to all SSRIs, the concern began with reports of suicidal behavior in paroxetine trials, as well as recommendations from the United Kingdom Medicines and Healthcare Products Regulatory Agency urging that paroxetine not be used in individuals younger than 18 years of age.24 In June 2005, the FDA issued an FDA Alert for the first time, extending the warning about increased risks of suicidal behavior to adults being treated with antidepressants.25 GSK’s revised prescribing information states, in part, “Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of PAXIL or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need
pediatric patients.”26 The first Paxil-related suicide case tried in the U.S. involved an adult patient. The trial, which took place in federal court in Wyoming resulted in an $8 million verdict in favor of family members of Don Schell, who killed his wife, daughter and granddaughter before taking his own life after using Paxil for two days.27 Attorneys for GSK had argued that the drug had not had enough time to work. During the trial, Plaintiffs’ attorneys introduced a GSK clinical study of 2,963 patients who took Paxil that showed some subjects, including ones who had only used Paxil for a short time, experienced agitation, hallucinations, psychosis, suicidal thoughts and behaviors.28 The jury assigned 80 percent of the fault in the
21 Warning Depression and Suicidality in Patients Being Treated with Antidepressants, fda.gov March 22, 2004. Captured December 14, 2010.
23 Press release, FDA, Oct. 15, 2004. Fda.gov/newsevents. Captured December 18, 2010.
24 Press release, CHMP meeting on Paroxetine and other SSRIs, European Medicines Agency. 9/12/04 emea.europa.eu. Captured Dec. 16, 2010.
25 Suicidality in Adults Being Treated with Antidepressant Medications, FDA Alert, June 30, 2005. Fda.gov. Captured December 16, 2010.
26 Prescribing Information, GlaxoSmithKline, Research Triangle Park, NC 27709. October 10, 2010, us.gsk.com. Captured December 18, 2010.
27 Tobin v. GlaxoSmithKline, 164 F.Supp.2d 1278 (D.Wyo. 2001); Wyoming Eagle-Tribune, June 7, 2001.
deaths to GSK and 20 percent to Schell, resulting in a net payment of $6.4 million to the family. 29 Significant litigation ensued throughout the U.S following the Schell trial, with the great majority of cases being settled. It has been estimated that, as of December 2009, GSK had paid approximately $390 million in settlements and verdicts in suicide or attempted suicide cases.30
Birth Defects Litigation
When Paxil was introduced in 1992, it was classified as a drug with no known link
to increased birth defects. That changed in September 2005 when GSK notified
doctors of a potential link between use of Paxil during pregnancy and certain
birth defects, particularly heart defects.31 According to the notice, a study
undertaken by GSK had suggested an increased risk of congenital malformations
associated with the use of Paxil during early pregnancy.32 GSK advised doctors
to “carefully weigh the potential risks and benefits of using paroxetine therapy in
women during pregnancy” and to “discuss these latest findings . as well as
treatment alternatives, with their patients." 33
Following GSK’s letter to healthcare providers, in September 2005 the FDA
issued a statement saying that Paxil may be associated with birth defects. The
FDA strengthened the warning in a December 2005 Public Health Advisory.34
According to the FDA’s December 8, 2005 Advisory, exposure to paroxetine in
the first trimester of pregnancy could increase the risk for congenital
malformations, particularly cardiac malformations.
Prior to the December 2005 FDA action, paroxetine was categorized as
“pregnancy category C,” meaning that comprehensive studies of its effects on a
pregnancy had not been performed.35 As a result of the new information from
GSK, the FDA requested that GSK change the pregnancy category from C to D
and add new data to the paroxetine prescribing information. A category D drug is
described as a drug having “positive evidence of human fetal risk based on
adverse reaction data . . . but potential benefits may warrant use of the drug in
pregnant women despite potential risks.”36
In July 2006, the FDA issued another Safety Alert, this one relating to the whole
30 Glaxo Said to Have Paid $1 Billion in Paxil Suits (Update2). Bloomberg.com, December 14, 2009. Captured December 16, 2010.
31 Paxil Birth Defects Warning Strengthened, Sept. 27, 2005. Webmd.com. Captured December 18, 2010.
34 Press Release. FDA Advising of Risk of Birth Defects with Paxil
Agency Requiring Updated Product Labeling. December 8, 2005. Fda.gov. Captured December 16, 2010.
category of SSRI drugs.37 The FDA indicated that two new studies had provided information regarding the risks of treating pregnant women with antidepressants. The second study had suggested that babies whose mothers used antidepressants after the 20th week of pregnancy were found to be six times more likely to experience persistent pulmonary hypertension (PPHN) shortly after birth than babies whose mothers did not use antidepressants in that stage of their pregnancies. PPHN is a condition that causes a newborn's arteries to the lungs to remain constricted after birth, resulting in an abnormal blood flow through the heart and lungs, insufficient oxygen and, in some cases, death. The baby's circulation does not make the normal transition from fetal circulation to newborn circulation, because of the pressure in the arteries to the lungs.38 The agency indicated that the study was too small to compare the risk of one antidepressant versus another.39 For many parents whose children had been born with congenital heart defects, this new information finally shed light on a possible cause for their child’s condition. Lawsuits were filed around the U.S., but most cases gravitated to a state court consolidation in the Common Pleas Court in Philadelphia. Philadelphia is home to one of GSK’s two U.S. headquarters.
The first Paxil birth defects case to be tried was Kilker v. SmithKline Beecham Corp. dba GlaxoSmithKline
, which was included in the Philadelphia consolidation.40 Lyam Kilker’s mother used Paxil during her pregnancy. He was born in October 2005 with an atrial septal defect, a ventricular septal defect, and an interrupted aortic arch, one month after GSK and the FDA first warned the public about the risk that using Paxil during pregnancy could cause birth defects. The Kilker
case resulted in a plaintiffs’ verdict for $2.5 million in October 2009. The jury in Kilker
voted 10 to 2 that GSK negligently failed to warn of the risk and that Paxil could cause heart conditions such as Lyam’s. However, the jury found that GSK’s actions were not “outrageous,” thereby eliminating the possibility for an award of punitive damages against the company in that case.
The primary theories of liability against GSK in the birth defects cases are negligent and strict liability failure to warn, negligent "pharmacovigilance"—a drug company's duty to continue testing its products even after receiving government approval, breach of warranty and unfair trade practices. The verdict in the Kilker
case was based on a failure to warn claimants. Lawyers in the Kilker trial argued that adverse events reports started to come in the late 1990s and
37 SSRIs and Treatment Challenges of Depression in Pregnancy. July 19, 2006. Fda.gov. Captured December 18, 2010. 07/19/2006.
38 Persistent Pulmonary Hypertension of the Newborn (PPHN), thechildrenshospital.org. Dec. 2001. Captured Dec. 17, 2010.
39 SSRIs and Treatment Challenges of Depression in Pregnancy. July 19, 2006. Fda.gov. Captured December 18, 2010. 07/19/2006. 40 Case No. 2007-001813, Court of Common Pleas, Philadelphia County, PA.
GSK had enough information to warrant product warnings much sooner than 2005. The Plaintiff in Kilker
also claimed that Glaxo urged in-house scientists to withhold data on side effects from a GSK company report on Paxil.
Kilker was one of four “bellwether cases” selected by the Philadelphia Common Pleas judge to be tried first. The three remaining cases were settled before trial. In July 2010, firms representing approximately 800 plaintiffs settled all of their cases with GSK, leaving approximately 100 cases still pending in Philadelphia. 41 The average settlement value of the 800 birth defect cases settled was reported to be $1.2 million per case, for a total of more than $1 billion.42 According to Esther Berezofsky, an attorney who represents a number of plaintiffs in the Paxil birth defects litigation, "While a very significant number of cases have settled, GSK's strategy appears to be shifting more towards taking these cases to trial."
In October 2010, trial began in a second birth defects case on behalf of Plaintiff Anna Blyth.43 During trial on November 29, 2010, Judge Gary Glazer granted GSK’s Motions for Summary Judgment, which resulted in a final judgment against the plaintiff in the case.44 It is not anticipated that the ruling will have wide-ranging impact in the litigation because the ruling was very fact specific. The issue that resulted in dismissal was that the doctor who prescribed Paxil to Anna Blyth’s mother had died and could not testify as to whether he would or would not have prescribed the drug if he had been warned of the risks.
The judge in the Philadelphia cases had consolidated six cases and scheduled
them to be tried jointly in January. Since then, the court has “deconsolidated” the
cases, but attorneys involved in those cases anticipate that one of the six cases
will begin trial in January. Antitrust and Fraud Litigation and Government Action
GSK’s litigation woes have not been limited to personal injury lawsuits. The
following is a sampling of other legal proceedings involving Paxil.
GSK agreed in 2003 to pay $87.6 million to the United States and 49 individual
states in response to claims it repackaged and privately labeled Paxil and
another drug, Flonase, to a health maintenance organization at discounted
41 Glaxo Said to Have Paid $1 Billion Over Paxil Suits. Bloomburg.com. Jul 20, 2010. Captured December 17, 2010.
43 Case No. 07-3305. Court of Common Pleas, Philadelphia County, PA.
44 Docket Entry, Case No. 2007-001813, Court of Common Pleas, Philadelphia County, PA. fjdefile.phila.gov/dockets. Captured December 18, 2010.
In 2004 GSK agreed to pay $165 million to settle two antitrust suits related to Paxil. The theory of those cases was that the company engaged in sham patent infringement litigation to stall approval of generic versions of the drug manufactured by its competitors. In June 2004, New York Attorney General Eliot Spitzer filed a lawsuit claiming that GSK had committed fraud by withholding negative information and misrepresenting data in prescribing its antidepressant Paxil to children. The lawsuit also claimed that an internal 1999 GSK document indicated the company intended to “manage the dissemination of data in order to minimize any potential negative commercial impact.”45 The lawsuit was settled in August 2004 when GSK agreed to a schedule for releasing negative data relating to the safety and efficacy of its drugs, as well as to put summaries of all its studies since December 2000 in a clinical trial registry on its website. The settlement also included a payment of $2.5 million to the state of New York.46
On October 27, 2006, an Illinois consumer class action was settled. The theory of that case was that GSK had caused economic harm by misrepresenting Paxil as a drug that was useful in treating child and adolescent depression—after GSK’s own research had shown the drug was not effective in treating that group. The amount of that settlement was reported to be over $63 million. Two years later, in October 2008, GSK agreed to pay $40 million to insurance companies and third party payees to settle a national class action lawsuit.47 The plaintiffs’ claims in that suit were similar to the claims in the Illinois consumer class action, that is that they suffered economic harm by paying claims for Paxil prescriptions for child and adolescent insured’s when GSK knew the drugs lacked efficacy in treating that population.
The Finance Committee of the U.S. Senate held a series of hearings in 2008 to investigate whether drug companies had withheld or manipulated data regarding the safety and effectiveness of prescription drugs. That investigation included testimony that revealed extensive “consulting” payments from pharmaceutical companies to supposedly unbiased researchers hired by the National Institutes of Health to do clinical research on the very drugs those companies manufactured. Documents revealed that one of the investigators for the paroxetine clinical trials, a former psychiatry department chair at Emory University, reported to the University that he had received only $35,000 for clinical research he performed for GSK in 2006, when documents showed he had actually received payments totaling more than $960,000 from GSK that year.”48
45 Spitzer sues GlaxoSmithKline over Paxil. MSNBC AP updated 6/2/2004. Captured December 13, 2010.
46 Glaxo Settles Paxil Lawsuit, Drugmaker Agrees To Schedule For Release Of Clinical Trial Results. Cbs.com August 26, 2004. Captured December 13, 2010
47 Glaxo to Pay $40 Million in Paxil Settlement with Insurers. Lawyersandsettlements.com (Oct.2, 2008). Captured Dec. 14, 2010.
48 Top Psychiatrist Didn’t Report Drug Makers’ Pay, nytimes.com. October 3, 2008. Captured Dec. 16, 2010.
Reporting the actual income received from GSK would have required Emory to inform the NIH and take steps to deal with the conflict of interest or to remove Dr. Nemeroff as the investigator.49 On August 19, 2010, Dr. Maria Carmen Palazzo, a clinical investigator for GSK, pled guilty to 15 counts of failing to prepare and maintain records, with intent to defraud and mislead.50 The proceedings took place in federal court in New Orleans and related to actions taken by Dr. Palazzo during clinical trials to evaluate the safety and effectiveness of Paxil in children and adolescents.51 Dr. Palazzo was already serving an 87-month prison sentence after being convicted of 39 counts of defrauding Medicare and Medicaid in April 2008. According to court records, GSK paid Dr. Palazzo $5000 for each child she enrolled in the clinical study.
In October 2010, GSK agreed to pay $750 million to settle a civil lawsuit filed by the U.S. government.52 In the lawsuit, the government claimed that GSK caused false claims to be submitted to and payments to be received from various government health care agencies for four “adulterated” drugs, including Paxil CR.53 FBI representative Richard DesLauriers stated: “The completion of this investigation reflects law enforcement’s efforts to make companies like GlaxoSmithKline accountable for knowingly manufacturing and releasing defective products to millions of adults and children suffering from diabetes, depression, and skin infection. To avoid lost profits, GlaxoSmithKline intentionally disregarded the potential harmful effects of these defective drugs on consumers. The FBI will continue to work collaboratively with our law enforcement partners to identify individuals and companies who seek to line their pockets at the expense of the health care system and safety of each of us.”54
While cases continue to be filed on all three personal injury fronts, the birth defect cases are currently the most active and promising in terms of future litigation. Thanks to private and government litigation and investigations, a great deal of previously undisclosed information about GSK’s actions in connection with testing and marketing Paxil has become public. Both the information generated, and the heightened public awareness about this drug is likely to generate significantly more litigation in the coming years. While GSK must certainly be somewhat beleaguered by so much Paxil litigation on so many
50 Press Release: Jailed Psychiatrist Pleads Guilty and is Sentenced in Charges of Falsified Records of Clinical Trials Involving Children. Neworleansfbi.gov August 19, 2001. Captured December 17, 2010.
52 Press Release. U.S. Department of Justice, District of Massachusetts, October 26, 2010. www.usdoj.gov/usao/ma. Captured December 19, 2010.
different fronts, the company continues to make astounding profits from Paxil, as well as a number of other “blockbuster” pharmaceutical products.
INFECTION AND IMMUNITY, Feb. 2005, p. 1265–12690019-9567/05/$08.00ϩ0 doi:10.1128/IAI.73.2.1265–1269.2005Copyright © 2005, American Society for Microbiology. All Rights Reserved. Lactobacillus johnsonii La1 Antagonizes Giardia intestinalis In VivoMartı´n A. Humen,1 Graciela L. De Antoni,1,2 Jalil Benyacoub,3 Marı´a E. Costas,4Marta I. Cardozo,4 Leonora Kozubsky,4 Kim-Yen Saudan,3
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