Study 329 in Japan
Editorial Note: By 2002 GlaxoSmithKline had done 3 studies in children who were depressed and described all three to FDA as negative. As an old post on Bob Fiddaman’s blog reproduced here outlines, several years later they undertook another study in children in Japan.
Regular readers of this blog will know how I broke the news back in 2009 regarding GlaxoSmithKline’s attempts to push Paxil on kids in Japan. [See Here]
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.
The results
Well, folks… **drum roll** – the trial has been terminated.
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.
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.
Pharmaceutical companies will do anything to use children as guinea pigs for experimentation of their dangerous drugs as these children are considered “cheap” and it is all for the greed of these organisations. All children’s lives are valuable and need to be protected from this abuse for financial greed and power over many making innocent victims dependent on drugs they will never be able to come off after catching a disease created by the pharmaceutical industry which nature didn’t create. How many diseases are man-made by these organisations for dependency on the expensive drugs they manufacture?
John RJ,
If it is pharmaceutical companies using kids as guinea pigs, how do you explain prominent academic psychiatrists selling their names for bylines on ghost written articles?
How do you explain the prescribing habits influenced by these prominent doctors, who have almost nothing to do with the clinical trials and can’t be bothered to fact check the data before the results are published?
Pharmaceutical company execs do not have prescribing privs. Pharma reps do not see patients or monitor patients in a clinical setting.
The FDA in America would not approve a drug without input from a medical doctor.
Shouldn’t doctors protect kids from being exploited and harmed by greedy, powerful pharmaceutical company’s nefarious schemes?
EXCELLENT POINT! Integrity should begin with the researcher, but the DOCTOR is the guardian of human health. From whence does the ‘urge’ to prescribe a particular drug come from – the doctor’s due diligence and analysis or the pharm rep’s sales pitch?
I agree 100% John RJ.
ClinicalTrials.gov:
97 out of 136 (71%) of paroxetine studies (completion date before Oct 2010) => Unpublished.
EudraCT: Results: “Removed from public view”
EUCTR2004-004984-32-SE
EUCTR2005-002388-95-HU
EUCTR2004-004984-32-SE
…
Thanks for this re-post.
Heavy doses for kids, doncha think?
You really have to get inside these studies. The saddest thing is that we cannot poll the dead.
Julie
… we can honor the victims by publicizing their stories, many have already been shared by their loved ones — and
we can seek justice for their having been innocent victims;
for starters-
Thank you, Katie – honoring the victims by publicizing their stories is one way. I told my son’s story countless times before FDA Advisory Committees before realizing that the deck was stacked, and that I was sinking under the emotional weight of doing so – so I moved West to save my own skin. Though I miss him every single day ( he died at the age of 39 from profound hyperglycemia from Zyprexa) , I know that he would have wanted me to go on with life and make it as happy a one as possible under the circumstances.
Seeking justice for their having been innocent victims is another kettle of fish – the corporate executives at Eli Lilly who sat around the conference table time and again figuring out how to combat the bad press Zyprexa was getting deserve to be in prison. But they are not – one of them is now the President of Perdue University, having previously been the Governor of Indiana and, before that, President of Northern American Operations for Lilly during the roll-out of Zyprexa.
I have to work to not focus on this – to not get sucked into the anger and rage that simmer beneath the surface – so as to have some quality of life.
I doubt that “justice” – in the sense of any of them being behind bars – will happen in my lifetime. But if enough people, such as those commenting here, work at it, the tide may turn around. Thank you for all that you are doing.
I saw with my own eyes what antidepressants did to my 20 year old sons mental state. The thought of kids as young as 7 taking this drug just literally breaks my heart.
Seriously I can’t stop thinking about it. Its an absolute disgrace.
These poor children will probably be left with damage from this drug that they will have to carry round for life.
What a terrible thing to do to kids.
You and me both Lisa, you and me both. Watching young men suffering was bad enough, but seven year olds? – wow, I can hardly comprehend it.Had to re-read the facts here, couldn’t digest what I had read – and the doses that they were given! I wonder how many of these poor children are now on a cocktail of other drugs, trying to correct the damage caused, and being labelled with allsorts of other mental health conditions?
There is only one word to describe this treatment of young lives “Barbaric!”.
http://prescribeddrug.org/new-bma-report-calls-for-concerted-action-to-tackle-dependence-caused-by-prescribed-drugs/
starting with a government-funded national telephone helpline.”
And then what……….?
A call centre approach with a slightly sympathetic air about them.
Come on….
http://www.madinamerica.com/2015/10/report-calls-for-policy-changes-in-response-to-dependence-and-withdrawal-from-prescribed-drugs/
Come on….
Doctors are not doing what weak advisors tell them to do and in so doing put us all in jeopardy…..
http://hitchensblog.mailonsunday.co.uk/2015/01/a-wholly-inadequate-response-from-ben-goldacre-and-my-reply.html
40 mg of Paxil for a seven year old…
horrifying…
Truly horrifying.
“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.”
This was exactly my thoughts even before i got down to reading this. I can tell you as an adult a CT is hell.
“Could their suicidal ideation have been caused by the withdrawal effects of the medication they were taking prior to the Japanese study? ” Of course !!!
What i dont understand is how can a child, 7 yrs old say, be diagnosed with depression.
That is sooo wrong, Children are the most resilient humans there are. Just read
Parvana’s Journey ‘ by D Ellis. Its a high school reading text. Google it.
Simply provide them with a toy and some gum and they are away laughing. But drug them ??? that is just obscene.
Where is seal team 6 when we really need them ?
Can you imagine a 18 month child on risperidone?
If it is approved, it is safe, right?
I know that vitamins don’t have as big profit margins as certain drugs. But they are safer. Why not just give vitamins to everyone first, and see if anything changes? If there is any problem in the brain, then it does seem more likely that things like micronutrients (magnesium, choline, pantothenate, folate, ascorbate) can restore “balance” in the brain, rather than substances like paroxetine and fluoxetine. I would require psychiatrists to prove that there is no nutritional deficiency in a person before resorting to psychiatric drugs. At the very least, they should check with a blood test.
When all these deaths of children and adults happen on an unprecedented occurrence, and, the media are alive with the sounds of it, still, and we happened to have swallowed, Seroxat, and maybe lived to tell the tale, and, a lawyer screwed up his opportunity, with GlaxoSmithKline, and, all we do is read this stuff……
http://www.bbc.co.uk/news/uk-scotland-34517223
http://www.heraldscotland.com/news/health/13844131._quot_More_than_one_in_seven_people_quot__in_Scotland_prescribed_antidepressants/?ref=fb#comments
http://www.cbc.ca/m/news/health/health-canada-drug-confidentiality-data-1.3269107
http://healthaffairs.org/blog/2015/10/14/the-fda-could-earn-over-60-million-a-day-from-enforcing-the-law/
UCLA/ISEPP
The Mental Illness Ghetto
Better to die on your feet than live on your knees….keep shouting..he said..
http://www.transformingmadscience.com/david-healy/
Work in Progress…
Talking about Scotland – Dr Peter Gordon, psychiatrist from Bridge of Allan, has a fascinating blog which covers much of Scottish culture, and he has petitioned the Scottish Government for a Sunshine Act. His requests for transparency within medical care in Scotland have resulted in the NHS Director General’s office as suggesting that he is ‘unwell’.
Very worrying, not least for Peter – shades of the Soviet gulag’s response to anyone questioning the ‘establishment’. Let us not suffer this kind of intimidation – please have a look at Peter’s blog:
https://holeousia.wordpress.com/2015/10/17/i-no-longer-feel-safe/
And if you feel sufficiently motivated, write a letter to his employer about bullying in the workplace. So few doctors are willing to make a stand over these issues, we cannot afford for someone like Peter to be silenced.
Walter K.