Researchers said a popular antidepressant was safe for teens. It was actually deadly.

For years, the drug company GlaxoSmithKline was illegally persuading doctors to prescribe paroxetine, sold under the brand name Paxil, as an antidepressant for children and teenagers. They did so by citing what’s known as Study 329 — research that was funded by the drug company and published in 2001, claiming to show that Paxil is “well tolerated and effective” for kids.

But now here’s the horrifying news: A major new analysis of the raw data behind Study 329, published in BMJ, suggests that the original conclusions were wildly wrong. Not only is Paxil ineffective, working no better than placebo, but it can actually cause serious side effects, including self-injury and suicide.

Unlike the original study, this follow-up research isn’t funded by the drug manufacturer. And the researchers found that GSK had manipulated their data and selectively downplayed the harms of the drug in their analysis.

This isn’t the first controversy around Paxil — or this study. The FDA originally approved Paxil in 1992 for use as an antidepressant for adults, not for adolescents. But between 1998 and 2003, GSK illegally tried to persuade doctors to prescribe the drug to adolescents anyway, using Study 329.
The New York State Attorney General’s office eventually found out what was going on with Paxil (and fraudulent activities related to other GSK drugs), sued GSK, and the company pleaded guilty to the wrongdoing, paying out $3 billion in fines. Through legal discovery, it became clear that the company knew their data on Paxil for teens was problematic, even hiring a PR firm to ghostwrite Study 329. In 2004, the FDA added an explicit “black box warning,” recommending against Paxil’s use in adolescents.

This latest research casts that whole episode in an even more appalling light. Not only was GSK illegally marketing the antidepressant for “off-label” uses, but the new research shows exactly how horribly flawed and misleading Study 329. And the end result was that doctors were prescribing an antidepressant — to kids — that doesn’t work any better than placebo and could lead to suicide.

Under current US law, drug companies can only advertise or market their products for FDA-approved indications. When GSK pushed Paxil for teenagers, it was breaking the law and had to pay a big fine.

The logic of this rule is that companies should only be able to promote products for uses that have solid science behind them. Other uses may not be evidence-based and could pose a danger to public health.

Lately, though, drug companies are trying to get this law changed. Two companies have recently sued the FDA over this rule, claiming that it violated their First Amendment right to free speech.

The first, Amarin, was seeking to promote its prescription fish oil for off-label uses. On August 7, a federal court in New York ruled in favor of the company. Then, this month, Pacira Pharmaceuticals filed a similar lawsuit, arguing that it should be allowed to promote its post-surgery pain drug for uses that are much broader than those authorized by FDA.

“Beyond matters of constitutional law and governmental oversight, the pharmaceutical industry is clearly angling to boost prescription sales,” Ed Silverman explained at the Boston Globe. “Of course, this would fatten bottom lines, a good thing if you happen to be a shareholder.”

If drug companies win the right to market drugs for off-label uses, it could have massive implications for public safety. The FDA will have a harder time cracking down on potentially misleading marketing practices. It’ll also be more difficult for doctors and patients to be able to tell which claims drug companies make are evidence-based, and which ones are nothing more than marketing spin.

When viewed through the lens of the Paxil saga, a future of more off-label peddling looks potentially dangerous.