refining our “No”… »
« grown-up stuff…
scarlet bullets…

Posted on Thursday 14 November 2013

Yesterday, I wrote about what we heard about the current goings-on with GSK and Paxil Study 329 [how that should work…, grown-up stuff…]. Today we get yet a new puzzle piece from David Healy –
  • an FDA letter to GSK from 2003 approving Paxil for use in children and adolescents.
Yeah, you heard that part right. Here are the operative lines from that letter:
Who knew? But speaking of new information, that second highlighted paragraph is something in its own right. It appears that GSK and the FDA had been chatting about the fact that
  • Study 329 "failed to demonstrate the efficacy of Paxil in pediatric patients with MDD"
[along with Studies 377 and 701].
  • And they were in agreement that there wasn’t any need to put that on the package label?
Dr. Healy goes on to assemble some more pieces of the story into the timeline:
The House of GSK
by Dr. David Healy
November 14, 2013

…Study 329 began to unravel because a journalist, Shelley Jofre, working for BBC’s Panorama, accidentally left to her own devices, begin to dig. She went to the American Psychiatric Association Meeting in Philadelphia in May 2002, clutching the Keller-Laden paper. She was interested to interview some of the “authors”. One of her questions was “What is emotional lability?” There was a surprising number of children in 329 who became emotionally labile – what’s this? she asked. No-one seemed to know.

At APA, she approached one of the 329 authors Neal Ryan, who gave a non-answer and quickly got in touch with GSK to let them know a journalist was asking questions. A few weeks later in July and again in August, GSK send a dossier to FDA seeking approval for Paxil for children. A few weeks after that, on October 7th, to coincide with World Mental Health day [October 10th], Newsweek hit the streets featuring a depressed teenager on the front cover and a strapline Teen Depression: 3 million kids suffer from it. What you can do. The message inside was that Prozac was already being marketing for children and Paxil and Zoloft were about to be. What you can do – is get children on Prozac, Paxil and Zoloft.

Celebrating World Mental Health Day

Three days later, on October 10th, World Mental Health Day, and the 40th anniversary of the passage of the 1962 amendments to the Food and Drugs Act, FDA sent GSK a letter saying Paxil was approvable for kids. Among other things, the letter notes that GSK had already told FDA that Study 329 showed that Paxil doesn’t work for depressed children. FDA were happy to go along with GSK’s suggestion that this should not be mentioned in the labeling of the drug. Given that the Study 329 publication majored on how effective Paxil was, it would have been inconvenient if the label said otherwise. There are many notable things in this approvable letter. Perhaps the most interesting is FDA asking GSK to clarify just what emotional lability meant.

FDA have later spun this into a story that their reviewers detected there was an increase of emotional lability events in Study 329 that needed looking at. In fact this idea came on their radar after conversations between Jofre and third parties led to a visit to FDA on August 28th and a suggestion to FDA that they explore the issue of emotional lability. FDA at the time had a few weeks to respond to GSK’s request to market Paxil for children. Neither Jofre nor the third parties knew at the time that GSK were seeking pediatric approval for Paxil…
Pardon my heavy handed scarlet bullet formatting, but I wanted to convey outrage. Yesterday, I was reading that letter from GSK swatting away Jon Juriedini’s request for Study 329 to be withdrawn, saying "GSK does not believe it appropriate to request retraction of the article" – an article which had said "paroxetine is generally well tolerated and effective for major depression in adolescents." And now today I read that ten years ago, GSK and the FDA were openly talking about Paxil study 329 being a negative study that "failed to demonstrate the efficacy of Paxil in pediatric patients with MDD," and that the FDA said "we agree that it would not be useful to describe these negative trials in labeling." But it is apparently fine to leave the article that itself is a part of the proof that Paxil is not effective in pediatric patients with MDD but says the opposite intact in a major psychiatric journal for child psychiatrists around the world to read as if it is true? Scarlet bullets aren’t close to enough.

We’re left dangling by Dr. Healy’s post because this revelation that the FDA was declaring Paxil "approvable" for OCD in Children and Adolescents is something I sure didn’t know. What happens next? And what about the biggest question of all. Whether it’s effective in OCD kids or not, there’s the question of akathisia, agitation, hostility, suicidality – those adverse effects that stay on the table with SSRIs in kids and adults, but particularly with kids. My crude analysis of Paxil Study 329 last year suggested that it was a real danger [the lesson of Study 329: uh-oh!…]. What was the FDA thinking about that? The FDA letter said:
To which Dr. Healy responded [above]:
FDA have later spun this into a story that their reviewers detected there was an increase of emotional lability events in Study 329 that needed looking at. In fact this idea came on their radar after conversations between Jofre and third parties led to a visit to FDA on August 28th and a suggestion to FDA that they explore the issue of emotional lability.
I expect we’ll hear more about this thread in the story [Healy leaves us with a crypyic "to be continued"]. I’ve chopped up Dr. Healy’s post and the FDA letter to make my own points, but there’s another thread in his narrative that I lost along the way. This story has a hero – journalist Shelley Jofre. I thought I’d make up for that omission by reposting her Panorama program for those of you that may not have seen it:

And here is Shelley’s later series – posted for American viewers who don’t know this part of the story:
  1.  
    Nick Stuart
    November 15, 2013 | 1:01 AM
     

    I want to convey absolute total outrage too. How can I express this productively? Who should I write to? How should I act and what should I do? I feel a little helpless now because of my agnosia.

  2.  
    Altostrata
    November 16, 2013 | 2:23 PM
     

    Shelley Jofre should get a Pulitzer.

Sorry, the comment form is closed at this time.