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Wednesday, September 18, 2013

Why Was the Japanese Paxil Pediatric Study Terminated?

Regular readers of this blog will know how I broke the news back in 2009 regarding GlaxoSmithKline's attempts to push Paxil [known as Seroxat in UK] on kids in Japan.

I was so outraged at this that I wrote to the Japanese Embassy and the Japanese Ministry of Health, more or less to give them a detailed view of how GSK had previously claimed Paxil was safe for kids to take...when in actual fact they knew that it wasn't.

I never heard back from either one of them.

I also contacted GlaxoSmithKline in 2010, you can see the email I sent to them here.

In 2008, one year before I broke the news, Glaxo were recruiting kids for a clinical study. I say Glaxo, they, in actual fact were sponsoring the study.

The study was designed to compare the efficacy of oral paroxetine 10 to 40 mg/day (initial dose:10 mg/day) versus placebo administered once daily.

Oral paroxetine is a sickly orange syrup, I've been on it myself. It was the only safe way to taper from this highly addictive antidepressant.

And just who were being used as the guinea pigs in Japan?

One look at the inclusion study criteria would have showed you.

Ages Eligible for Study:7 Years to 17 Years.

Yup, that's right folks. Despite being dragged through numerous courts in the US where evidence was shown that Glaxo manipulated previous clinical trials in children, here they were again back in 2008 recruiting more kids.

A marketing campaign went out in the form of a poster... which I just happened to obtain from a source at Medwatcher Japan. Medwatcher were also furious at this particular clinical trial involving kids and Paxil.

Take a good look at the imagery used in the recruitment poster.

If a picture paints a thousand words, eh?

Well, folks... **drum roll** - the trial has been terminated.

**Cue a spectacular display of fireworks**

According to GSK's clinical trial database the study was terminated in 2011. They give no reasons as to why this study was terminated.

What we do know is that 56 kids were enrolled. 29 were in the Paxil group whilst the remaining 27 were in the placebo group.

The study results claimed that there were 3 reports of suicidal ideation in the placebo group but none in the Paxil group. [More about this later]

The subjects enrolled had to have a diagnosis of a depressive disorder before being allowed into the study.

So, it would appear that 3 of the kids taking placebo had suicidal ideation. Not one report in the Paxil group. Glaxo must have loved this.

Unfortunately for the Glaxo sponsored trial, Paxil didn't really show much efficacy.

Open the Outcome Measures on the Clinical Trials website and it tells us how Paxil failed.

Paxil didn't reduce the depression scores of the children sufficiently to be considered effective and the primary purpose of this study was efficacy. In this study all participants had to have a depression score of 45 or greater to be included. A 50% reduction on the CDRS-R is required to consider children have responded to treatment.

So, not only did Paxil not reach the standard for efficacy but in comparison to, let's say, fluoxetine, it would be seen to be less effective.

In the Fluoxetine studies [1] [2] the average decrease was 28.9%. In this Japanese study, the decrease was only 16.9% therefore the kids would not be considered to have responded to Paxil treatment.

No wonder the study was terminated, right?

It would appear that GlaxoSmithKline didn't want to expose the fact that Paxil is less effective than that of their competitor.

Another interesting finding from the Japanese study was the participants only had to have been free from any antidepressant for 1 week prior to the trial commencement.

Anyone who's anyone will know that one week off an antidepressant is hardly a time to get the champagne corks popping and decorate rooms with bunting and balloons. Any number of these participants could have been suffering withdrawal even before they were entered into the Japanese trial. Any of these patients suffering withdrawal, which remember can mimic depression, would have had immediate relief if they were selected for the Paxil arm of the trial. As the phases of the trial progressed they would have, obviously, reaped the benefits of Paxil but not for their apparent depression, their benefits from Paxil would have merely meant they would not be going through withdrawal anymore.

Take the three patients from the placebo arm of the study who, according to the results, suffered suicidal ideation, and we may just find that these three were also taking antidepressants a week or so before they entered the Japanese study.

Could their suicidal ideation have been caused by the withdrawal effects of the medication they were taking prior to the Japanese study?

Glaxo pretty much shot themselves in the foot with this study, a study that should never have taken place given the findings of the Paxil 329 study.

So, once the Japanese trial was over did the sponsors, GlaxoSmithKline, do any follow-up to see if these kids were okay? The doses used in the study were between 10mg and 40mg, the latter being enough to put a horse into a coma.

The withdrawal phase of the Japanese study lasted three weeks. Two weeks later the participants were contacted to see how they were.

Can you imagine a 7 year old child on 40mg of Paxil a day just having three weeks to taper? Even if the 7 year old was on a lower dose it's still mind-boggling how one adult human could give someone so young a pill known to increase suicidal thoughts, known to increase completion of suicide.

What on earth were GlaxoSmithKline thinking by using kids in a study for Paxil?

The Japanese public, particularly the children and adolescents, just don't know what a lucky escape they've had from this truly awful abomination of an antidepressant.

Bob Fiddaman

[1] Psychometric Properties of the Children's Depression Rating Scale–Revised in Adolescents - J Child Adolesc Psychopharmacol. 2010 December; 20(6): 513–516.
[2] Early Prediction of Acute Antidepressant Treatment Response and Remission in Pediatric Major Depressive Disorder - J Am Acad Child Adolesc Psychiatry. 2009 January; 48(1): 71.

Back stories:

Thursday, January 15, 2009 - Email to Japanese Embassy regarding New GSK paroxetine study in Children. Identifier: NCT00812812

Friday, April 03, 2009 - Japan/GSK - 329 All Over Again!

Friday, April 03, 2009 - Email to Ministry of Health - Japan

Friday, May 21, 2010 - Email To GlaxoSmithKline Re; Paxil Study In Children

Friday, September 24, 2010 - HEY, GLAXO!... LEAVE THOSE KIDS ALONE

Friday, May 13, 2011 - Glaxo remain tight-lipped on new Japanese Paxil study in children.

Wednesday, May 18, 2011 - GSK Japan, Paxil Study in Kids Update