“Paxil turned me into a monster:” The still-unfolding story of GlaxoSmithKline’s Study 329
“I tried killing myself thirty times”
So says Vickie, a young nurse from Philadelphia who was first prescribed Paxil at the age of ten.
Vickie recalls her life before she began taking psychiatric medication. “I had a pretty nice life. I grew up with money, I was never deprived of anything, my parents were very supportive of me. I had a great upbringing.” But she had a tendency towards shyness, and her parents became concerned.
“I was just shy,” Vickie remembers. “I had friends but I liked to be home, and I liked to watch TV, and I liked to read, and I actually liked to be alone.” Nevertheless, her mother took her to see a psychiatrist, and after a forty-five minute consultation, during which her mother did most of the talking, the psychiatrist diagnosed her with “social anxiety disorder” and prescribed Effexor.
After six months, there didn’t seem to be any improvement in her condition, so her mother brought her back to the same psychiatrist, who prescribed Paxil.
The effects were devastating, Vickie recalls. “I really just wanted to die. I cried all the time. Almost daily I would sit in my room and cry.” Once more her mother took Vickie to the psychiatrist, who doubled her prescribed dose of Paxil.
Vickie found her condition worsening. “It was a downward spiral that I got into and couldn’t get out of.” She felt compelled to harm herself—starving herself, binging and vomiting, pulling her own hair out, cutting herself, and obsessively picking at the scabs. She also tried to dozens of times to end her own life. “I tried slitting my wrists, overdosing on Tylenol PM, I tried hanging myself, I tried drowning myself. I even considered jumping off a bridge at one point. It wasn’t a cry for help. I just wanted to die.”
“Remarkable efficacy and safety”
SmithKline Beecham’s Study 329 of Paxil may well be the single most infamous drug trial ever, and its history is instructive.
Paxil is one of several brand names for paroxetine, a drug developed in 1975 by the Danish pharmaceutical firm Ferrosan, which in 1980 sold the rights to the drug to the Beecham Group. (In 1989, the Beecham Group merged with SmithKline Beckman to form SmithKline Beecham, which in 2000 merged with Glaxo Wellcome to form GlaxoSmithKline, at the time the largest drug company on the planet.) Paxil, which was approved by the FDA at the end of 1992, is one of a class of antidepressants called Selective Serotonin Reuptake Inhibitors, or SSRI’s. Despite its alleged selectivity, this drug has been approved for a dizzying variety of human woes, including major depressive disorder, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, posttraumatic stress disorder, hot flashes, and something called “premenstrual dysphoric disorder.”
The plans for Study 329 were drawn up in 1992. The study itself began two years later, and was completed in 1998. In July of 2001, the results of Study 329 were published in the Journal of the Academy of Child and Adolescent Psychiatry, which has the highest impact rating of any journal in child psychiatry. The article, titled “Efficacy of paroxetine in the treatment of adolescent major depression: A randomized controlled trial” listed Doctor Martin B Keller of the Department of Psychiatry and Human Behavior at Brown University as first author, along with 21 others.
Study 329 was the largest study ever conducted on the effects of an SSRI on a pediatric population. The study subjects consisted of a group of adolescents, between 12 and 18 years of age, each of which was diagnosed with major depression of at least eight weeks in duration. 93 of these youths were given paroxetine, while 87 of them received placebo. Dropout rates were similar in both groups. Subjects were assessed by means of the Hamilton Rating Scale for Depression, a questionnaire consisting of 21 items, with possible scores ranging from 0 to 60; the higher the score, the more severe the depression.
The paper listed two primary outcome measures: 1) change in HAM-D total score and 2) response, defined as a HAM-D score of 8 or less or a 50% reduction in HAM-D scores. For the first outcome, there was no significant difference between those treated the paroxetine and the placebo groups. For the second, 63% of patients treated with paroxetine were judged to have “responded,” as opposed to 50% of the placebo group. In plain English, an additional one out of eight patients given paroxetine “responded,” compared to those given placebo. Nevertheless, this difference was judged to be statistically significant.
In addition, the paper listed six secondary outcome measures; for three of these, patients given paroxetine were judged to have done better than those given placebo, while for three there was no difference.
Serious adverse events were reported for 11 patients given paroxetine, as opposed to 2 for those given placebo. The serious adverse events for youths given paroxetine included emotional lability (5 patients), conduct problems or hostility (2 patients), euphoria (1 patient), and headache (1 patient). The authors stated “Only headache (1 patient) was considered by the treating investigator to be related to paroxetine treatment.” The logic underlying this conclusion was not explained.
The paper concluded “Paroxetine is generally well tolerated and effective for major depression in adolescents.”
This was an auspicious moment for GlaxoSmithKline. Eli Lilly’s blockbuster drug Prozac was scheduled to go off patent in August of that year, clearing the field for any of several would-be successors to the title of the best-selling antidepressant in America. A 2001 internal memo GSK circulated to its drug reps proclaimed “Paxil demonstrates REMARKABLE Efficacy and Safety in the treatment of adolescent depression.”
On 7 October of the following year, Newsweek, which already had published not one but two laudatory cover stories on Prozac, weighed in with yet another cover story, “Young and depressed,” which warned readers “Without treatment, depressed adolescents are at high risk for school failure, social isolation, ‘self-medication’ with drugs or alcohol, and suicide – now the third leading cause of death among 10-to-24-year-olds.” Fortunately, the article advised, help was on the way, in the form of “another NIMH study looking at newer medications, including Effexor and Paxil, that may help kids whose depression is resistant to Prozac.” Paxil went on to become the best-selling antidepressant in the world, with annual sales in excess of three billion dollars.
Not everyone was so sanguine about all this. Even before the JAACAP paper came out, storm clouds had begun to gather on the horizon for GSK.
Next: Part 3: “An effective drug treatment”
List of Sources
- Buus-Larsen, J. 1980. Introduction to the development of paroxetine, a novel antidepressant.—Acta Psychiatrica Scadinavica 80 (Supplement 350):13.
- Bloomberg Business News 1993. British drug shares get lift. New York Times January 1 1993.
- Keller, M. et al. 2001. Efficacy of paroxetine in the treatment of adolescent major depression:—A randomized, controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry 40:762-772.
- Wingert, P. et al. 2002. Young and depressed. Newsweek October 7 2002.
- Moynihan, R. and A. Cassels 2005. Selling Sickness: How the World’s Biggest Pharmaceutical Companies Are Turning Us All Into Patients. Nation Books.