The Saga Of Study 329 – A Chronology

Selective serotonin re-uptake inhibitors (SSRI) antidepressants burst on to the scene in 1988 with the introduction of fluoxetine/Prozac, hailed as a wonder drug that will make people feel “better than well” with no side effects. This Eli Lilly blockbuster is soon followed by similar medications:

  • Sertraline/Zoloft for Pfizer,
  • Paroxetine/Paxil/Sexoxat for SmithKline Beecham (SKB, later to become GlaxoSmithKline, or GSK*),
  • Celexa for Forest Labs,
  • Effexor for Wyeth,
  • and others.

Blurring the line between marketing and science

The line between marketing and science blurs as drug makers try to expand both the uses for these medications and the populations taking them. They do pretty well, in a lax regulatory environment.  In 2000-01, GSK is the second fastest growing drug company, and Paxil is its #1 seller at $2.68 billion US worldwide. With Prozac now off patent, Paxil is also the #1 selling SSRI, beating out Zoloft by sales of $340 million. This is a true tribute to GSK’s marketing prowess.

Study 329 boosts sales

The publication of Study 329 in July 2001 provides a major boost to this cause. This Keller et al article includes data that is obviously incompatible with the conclusion reached. It may represent the greatest divide in all of medicine between what the academic literature says and what the data show. The data show an ineffective medication with many serious side effects, some deadly, yet the Study 329 conclusion, used to promote use of the drug for children and adolescents, is that Paxil is safe and effective.

In the same year that Study 329 was published, Paxil rose to be GSK’s bestselling drug, and became the #1 antidepressant in the United States with sales of $340 million by the close of 2001, the year Prozac’s patent expired. GlaxoSmithKline lost its patent on Paxil in 2003. This was an event of concern to market analysts. Not so the laying of the consumer fraud charges the following year, which barely rated a mention. Sales of the drug continued to climb; brand name Paxil sales dropped to $172 million in 2004 in the United States, but the newly available generic version sold about four times that much.

The truth leaks out

Increasing scrutiny of Study 329 focuses attention on the regulatory process and then on other studies and other medications. Bit by bit, the commercially unpalatable truth starts to leak out: SSRIs are powerful drugs, with potentially harmful side effects, requiring expert judgement to identify the few people who will benefit from them, and vigilance when they are taken. To reach the average citizen, it is essential that this knowledge become known to the broader medical community.

In 2012, a US Department of Justice lawsuit against GSK involving Paxil (and two other drugs, Wellbutrin and Avandia) was settled, costing GSK $3 billion, then the biggest fine in corporate history. The following year, the number of prescriptions for paroxetine in the United States increased by 3%, and the number for Wellbutrin increased by30%[1].

Why did the FDA, the agency that protects consumers from harmful drugs with questionable benefits, not put a stop to this outrageous situation? First, the conflicts of interest of senior FDA staff have long been known. Second, the FDA seems to have accepted drug company propaganda over the evidence. As Robert Temple MD, Director of the FDA Office of Medical Policy, told a Senate Subcommittee in Sept, 2004: “…the poor effectiveness results [of SSRI antidepressants]…make it very difficult for practitioners to know what to do to treat a very serious, life-threatening illness. While we believe that these drugs may be effective in children, studies have not shown this to be true.”

Still no retraction

All parties involved with the publication of Study 329 have refused to request retraction. Re-publication of the data with a valid interpretation and conclusion will generate awareness of the truth, through the article and the surrounding debate.

Good science demands access to the data

There are many lessons to be learned from Study 329. The many deaths and other harms caused by Paxil/Seroxat can be traced to inaction due to conflicts of interest. It seems surprising that nobody saw the danger in handing over to drug companies the right to test their own products for effectiveness and safety, without at the same time demanding complete transparency.