D

ear Dr. Gottlieb,

As you inch closer to becoming the new head of the Food and Drug Administration, your list of challenges must be swelling. Here is one more item to add: Whether to insist on a stronger warning label for the antidepressant Paxil.

For the past decade, Paxil’s label has not carried any information indicating the drug poses a statistically significant risk of suicidal behavior for anyone over 25. Yet there is scientific evidence that such a risk is real (see table 16 on page 26). A jury in Chicago recently decided that that a label warning could have prevented the death of a 57-year-old man who killed himself while taking a generic version of Paxil.

advertisement

For public health reasons, the FDA should pursue a warning.

“Even recognizing the limitations of the data (found in the relevant analysis), it’s hard to understand [why] the increased risk of suicidal behavior, or attempts, is not in the label,” said Dr. David Kessler, a former FDA commissioner and now a professor at the University of California, San Francisco, School of Medicine.

Here’s the backstory: Paxil is one of several antidepressants known as an SSRI, a group that includes Prozac and Zoloft. For many years, the drugs were mired in controversy over whether they increased the risk of suicidal behavior and thoughts. The FDA eventually ordered the companies to warn of such a risk for children and young adults.

But what about issuing a warning for adults older than 25? The opportunity was bungled.

Back in 2006, GlaxoSmithKline — which makes Paxil — actually offered to revise its label to indicate a risk existed for adults. But the FDA nixed that in favor of a class-wide warning, limited to children and young adults, for all SSRI drugs. This blunted the effect of the data Glaxo had submitted to the FDA — which showed that adults on Paxil faced a much higher risk than those on all but one other antidepressant.

Instead, the FDA suggested the company could submit a supplemental warning and schedule a meeting for review. This never happened because Glaxo did not follow up (see page 127). As a result, the Paxil labeling never included information about a risk to adults.

For its part, Glaxo does not deny that its studies showed an elevated risk for adults. But the company contends that it properly conveyed all the appropriate data to the FDA and says it was the agency’s call to create a common, class-wide label instead of developing a warning more specific to Paxil.

Now, let’s fast forward to a federal courtroom in Chicago, where documents detailing these developments have been filed.

A five-week trial recently took place over a legally complicated, but significant, question — whether consumers who suffer harm after taking a generic drug should be allowed to sue the company that makes the brand-name version of the medication. In this instance, the man who committed suicide took a generic version of Paxil, made by Mylan.

Glaxo was named in the lawsuit because Mylan had to use its label on the generic. Federal regulations do not allow generic companies to independently change labeling after learning of potential risks, unless a change has already been made to the corresponding brand-name drug. That regulation was upheld in 2011 by the Supreme Court.

As a result, consumers sometimes seek to hold brand-name drug makers responsible for injuries they suffer while taking generics, although more than 100 such cases have been tossed out by courts around the country. Only two survived and one is being appealed. This time, Glaxo was the loser and was ordered to pay $3 million to the man’s widow.

The company, however, plans to appeal, which raises the possibility that not much, if anything, will change. Meanwhile, countless adult Americans will continue to be prescribed a generic version of Paxil that does not contain a warning about the risk of suicidal behavior.

But this should not be the end of the story.

Sign up for our Pharmalot newsletter

Please enter a valid email address.

Most consumers may not realize this, but drug makers legally own the right to the labeling on their medicines. Yes, the wording is developed during talks with the FDA, but a company can certainly consider adding an additional warning.

Glaxo “had the option to go further, but chose not to do so,” said Dr. David Healy, a Bangor University psychiatry professor who helped spearhead a campaign to upgrade suicide warnings on antidepressants, and who served as an expert witness on behalf of the widow in the recent trial.

Perhaps Glaxo bet it would not face lawsuits from consumers who took the generic. Nonetheless, the possibility of harm has existed all this time. And that is something the FDA should have realized. (An FDA spokeswoman told me the agency would not comment.)

So, Dr. Gottlieb, as you look over your to-do list, consider the lack of information in the Paxil labeling. And move to fix it. You might save a life.

Leave a Comment

Please enter your name.
Please enter a comment.

  • Agree the damage has been done! Unfortunately in a fast passed “demanding from dawn to night” world, most overwhelmed afflicted prescribed patients would either disregard or not understand small print. Dear Doctor Gottlieb a bold visual symbol (Visual cliff) specific to the issue of induced feeling of suicide with a maximum days of use might save a few good people.

    Also take into consideration that Paxil is not the only drug with such adverse events. There are pain medicines that induce fear of falling, phobia and other type of side effects that could lead to undesired unconscious outcome.
    Only the strong and loved can sometimes seek help and maybe overcome such a adverse events, with additional medical intervention but some succumb in fear leaving their love ones behind.

  • This is only the tip of the iceberg on Paxil.
    Psychiatrists noticed significant problems with Paxil early on. To make up for the lost sales, Glaxo opted for a strategy to market Paxil to primary care physicians who would not be up to date in the kinds of experiences patients were having and treat it like “just another SSRI”.
    Over time, the problems finally caught up with Glaxo and many who took this drug. The tragedy is that many psychiatrists knew for years to only prescribe as a LAST resort, not first.
    This is a cautionary story of why Primary care physicians should stay out of the business of prescribing psych meds and certainly should not be authorizing refills long term.

Recommended Stories

Sign up for our
Daily Recap newsletter

A roundup of STAT’s top stories of the day in science and medicine — delivered straight to your inbox every weekday afternoon.