Should Glaxo Test Paxil On Children?
23 CommentsBy Ed Silverman // May 24th, 2010 // 11:37 am
Six years ago, Paxil was one of several antidepressants that had a Black Box warning slapped on its labeling over links to suicidal thought and behavior in youngsters. Since then, there has been nothing but controversy over the extent to which this move did more than harm than good, with some doctors arguing that the negative publicity and regulatory restrictions were scaring some physicians and patients who might otherwise benefit from a helpful treatment (see this, this and this).
And so on this basis, GlaxoSmithKline is now conducting a pediatric study in Japan. The randomized, double-blind, placebo-controlled trial seeks to compare Paxil over an eight-week period in 130 children and adolescents age seven to 17 suffering from major depressive disorder. “There remains a substantial unmet clinical need for the treatment of pediatric major depressive disorder in Japan, and it is hoped that the data will ultimately help healthcare providers in Japan make treatment decisions in this often difficult to treat group,” a Glaxo spokeswoman writes us.
This raises a thorny issue. The drugmaker is entitled to conduct such a study, but are patients unnecessarily at risk? Art Caplan, who heads the Center for Bioethics at the University of Pennsylvania, notes that the Glaxo has a long list of reasons to exclude certain children from its trial, including prior suicidal ideation or behavior (see the posting on ClinicalTrials.gov) and that eight weeks may be sufficientally minimal exposure. But there may still be issues. One, he says, is cultural.
“On the other hand, when you’re in Japan, you have to be careful dealing with parents who sign their kids up. There’s a tremendous amount of paternalisitc practice in Japan with patients yielding to what they think doctors want,” he explains. “There’s going to be a lot of parents who will be told they want to put their kids a in study and doctors will say yes and that will be that.”
And while Glaxo maintains MDD is a problem among Japanese youngsters, he says “they had better be darn sure the depression is so bad that it’s worth doing in the face of all these red flags. It’s not an impossible bar to jump over, but its a really high one. Unless these kids are really unable to go to school or get out of bed - they’re severely hobbled by their depression - taking them into a non-indicated drug would be tough to justify, presuming there’s no other drug that could help.”
There is one other point. The trial will only enroll patients who, in the opinion of the chief investigator running the trial, are judged as not being appropriate. “This is leaning toward a selection that might give a favorable result,” Caplan adds. “You don’t usually see something that vague.” Glaxo, which last year saw Paxil global sales remain relatively flat, maintains it will act property and responsbily, and post and report all results. What do you think?
Should Glaxo Conduct Such A Clinical Trial?
- No (74%, 75 Votes)
- Yes (27%, 27 Votes)
Total Voters: 101
Loading ...UPDATE: On June 1, Glaxo wrote us to say that it “does not have any plans to compensate the study investigators beyond payment of research expenses to the study site. Research expenses were agreed upon between Glaxo and the study sites in advance and were calculated based on the study protocol.”
SteveM
Cymbalata is an absolutely toxic brain bomb, with a boatload of side effects. Discontinuation symptoms can be brutal. Lilly has not developed a clinical proven protocol for discontinuation management.
Of course Eli-Lilly is running a US based pediatric trial right now with FDA approval:
http://clinicaltrials.gov/ct2/show/NCT00849693?term=duloxetine&age=0&rank=2
Sick…
BTW, discontinuation effects is not a Secondary Outcome Measure. The parents will not be properly informed prior to consenting. Those poor kids are hosed.
MsPiggy
This is absolutely absurd, a drug proven dangerous in Western Markets, and GSK just goes East with their dangerous marketing game.
Just another example of why Big Pharma never learns from fines, signing CIA’s, criminal penalties, court actions, and civil litigation. It all about profit, and same old dirty business as usual is more profitable than conducting an ethical business.
Fid has been writing about GSK and their despicable practices for years now.
http://fiddaman.blogspot.com/2010/05/email-to-japanese-drug-regulator-re.html
Tom
I know my experience is only anecdoctal, but I have seen firsthand life-changing positive effects of antidepressant therapy in a small child, my own child.
My daughter seemed a prefectly normal little girl at home, then she went to preschool. We were told soon after that in school she never spoke nor did she interact with teachers or children. In play time, she chose to sit and watch. We could hardly believe it- at home she would chat about learning things at school, even recite the lessons, but in school she was paralyzed by fear/social anxiety.
A change in preschool didn’t help. Many psychologists, psychiatrists, behaviorists we visited all came up with nothing. Extensive literature work helped me turn up a doctor with a theory that selective mutism in kids may be treated with SSRIs. My daughter took low-dose Prozac syrup and after a few weeks it was like somebody flipped a switch- at school she was talkative and social. After 6 months we tapered off the Prozac dose to nothing, with no ill-effects.
Thereafter she had no social anxiety issues. Now 10 years later she is an active engaging middle school straight A student, having never taken any drugs other than 6 months of Prozac at age 4. The drug transformed her brain in a remarkably positive way. It hit home to me that not all drugs used on childen are for made-up issues.
It has to be don with care, but never discount that there may be a need.
M. Black
NO, NO, NO effing way. NO SSRI’s should be ingested by children. In my opinion, NO SSRI’s on teens either. Unless that teen really knows what the implications are for either 1) taking an SSRI forever (as in, forever) OR the scrumptiodness spectrum of withrawl symptoms that they will face when they
stop using it.
MB
Fid
The trial has been set up in such a way so it cannot fail Ed.
“Patients in the opinion of the chief investigator (sub-investigator) judged as not eligible for the study”.
In other words, they are loading a study with children who they think will do well.
I’ve wrote to the Japanese health Minister about this - no answer - http://fiddaman.blogspot.com/2009/04/email-to-ministry-of-health-japan.html
I also wrote to both GlaxoSmithKline [1] and the Japanes drug regulator [2] - as yet, no answer.
Interestingly, only about 1% of the Japanese population are considered poor metabolizers (PM) of 2D6 – but about 60% are considered to be of the intermediate metabolizer type (IM). (Bernard 2006). IMs are slower than the (normal) extensive metabolizer (EM) type and can also suffer severe adverse reactions at lower doses. I wouldn’t put it past GlaxoSmithKline to secretly run 2D6 genotyping and exclude the PM and IM types. After all, the last exclusion criteria (above) seems to be intentionally written vaguely enough to allow them to exclude based on genotype without disclosing that they had performed the test.
[1] http://fiddaman.blogspot.com/2010/05/email-to-glaxosmithkline-re-paxil-study.html
[2]] http://fiddaman.blogspot.com/2010/05/email-to-japanese-drug-regulator-re.html
Fid
Author of Seroxat Sufferers
Tony Miller
Hmmm…even though the FDA said ‘do not give to children under 18″in a black box warning and despite the majority of credible studies showing SSRI’s to be no more effective than a sugar pill(placebo)….these quack doctors thumb their nose at them and prescribe away. They make a killing on the placebo effect and anecdoctal letters. Big pharma loves psychiatry and rewards them generously. Politicians love big pharma for all the bribes that help them get elected and lastly the news media treats them with kids gloves so as not to lose the millions in ad revenue.
Psychiatrists are the covert terrorists in America if body count is considered.
Tom
I am a skeptic, a Ph.D. chemist and a Univerity Professor, and generally I am cautious when it comes to medicating anyone. My experience with my daughter made me realize that anxiety disorders are real and reversible, in our case with SSRIs, after 2 years of trying other courses of action did nothing. Thank goodness we found a Boston doctor willing to try this “off label” as a part of her therapy.
Google “selective mutism” and SSRIs for info about some of the published studies done, admittedly on small groups of patients and generally not double-blinded. Care is needed in designing these studies and what patients to target, but there is worthwhile science there.
Stephany
Interesting thing is, that Bob Fiddaman has been writing about this for over a year…and trying to contact the GSK sponsored health minister in Japan regarding the study.
They ARE trialing the drug in 7-17 year olds, whether we vote yes or no here, it’s already happening.
The children under age 12 do not sign informed consent their parents do….7 year olds being trialed with a drug already holding a black box warning for use in kids and teens, by GSK, is unacceptable, and they are getting away with it because they are using Japan which obviously must not have anything in place to protect kids this way…??
Why won’t they reply to Bob Fiddaman’s questions?
M. Black
Probably because their heads are up their @$$es.
Tom McCollum
Ed,
How is this study going to be recruited? When you compare this post to your post about the Australian families “pimping” their kids for a flu vaccine, how much will they have to pay for patients that “will only enroll patients who, in the opinion of the chief investigator running the trial, are judged as not being appropriate.”
Where are the watchdog comments NOW about pediatric safety?
Tom
There is always careful patient selection criteria for ANY clinical trial, particularly in phase II studies. Patients are chosen with a more homogeneous profile with few or no other meds. That’s the way trials have always been designed What is unusual is the language admitting this, upfront, in layman’s terms.
Ed Silverman
Hi Tom McCollum,
Thanks for the note. And that’s a good question. I don’t know the answer. I did ask Glaxo if investigators are being paid for patient recruitment, but never received a reply to that question, perhaps, in part, because it was a follow up to my initial inquiry. In any event, I will pass along further information if and when I receive any.
Regards
ed
patrons99
@ Fid -
Related to your comment above, is the following:
“Paroxetine is a strong inhibitor of CYP450 2D6 and it inhibits it irreversibly, inhibits its own metabolism and turns even extensive metabolisers into Poor metabolisers in time, I bet they eliminate poor metabolisers and they do not tell the prescribing community that have done that.”
“…east Asians have a high rate (50% of a diminished metabolism allele 2D6*10 and 35% of another diminished metabolism allele 2C19*2. This makes them highly at risk for all CYP metabolised drugs.”
- Yolande Lucire, PhD MBBS DPM FRANZCP (a medical anthropologist and a forensic psychiatrist in private practice).
Lisa Van Syckel
whose idea was it to interview Art Caplan? This so called expert, was on many networks, supporting a mandatory H1N1 vaccine for nurses. He can do the public a favor by staying behind closed doors!!!!!!!!!!!!!!!!
Fid
@Patrons99
Thanks for the info. I am familiar with Yolande’s work.
Fid
Paddy
As was the case in the now infamous Paxl study 329 - adolescents identified with any prior alcohol or substance use/ dependence issues are excluded from this trial. So the combined effects of Paxil and alcohol for example, in the teen population have not been studied. The alcohol warning in the GSK product monograph is very weak at best( ie limit alcohol to 1 or 2 drinks per day). The problem here is that in real life prescibing. physicians may not be properly screening teens who are binge drinking & using other party drugs (cannabis, ecstasy etc)on weekends. Throwing Paxil (another psychotropic)into the mix could be disaterous for some. And I don’t think it is realistic to simply tell a teen not to drink and or toke.I think the alcohol warning is made intentionally weak less they sacre away teens from Paxil, who like to party with friends on weekends.
toshiko kobayashi
Dr. Ed Silverman, please provide me with the research source in Japan. If you could email me at brrhtkk@omh.state.ny.us, I really appreciate it.
toshiko kobayashi, ATR-BC, LCAT
carin
We no longer regularly prescribe paxil to adults due the it being so difficult to stop due to serotonin withdrawal syndrome. So, now they want to try it on kids?!
carin, nurse practitioner.
jeff winter
My 22 year old daughter Beth commited suicide after 9 days on Paxil . Beth had a problem sleeping so a doctor precribed Paxil even though it lists insomnia as a side effect. Beth was happy just could not sleep , on the paxil she changed ,said she felt strange , wierd in her skin before we knew it was the paxil Beth killed herself. So the answer is NO , NO test on any body period. I pray these companys stop marketing too the masses as if we are all potential profits .
patrons99
@ Fid -
“The trial has been set up in such a way so it cannot fail Ed.”
Isn’t this the problem with nearly ALL pharma-sponsored clinical research? How often will pharma sponsor research which stands a 50:50 chance of an unfavorable result?
Study design bias and publication bias are ENORMOUS. This is why most of the published medical literature over the last 20 years cannot be trusted.
Fid
@patrons99
Absolutely.
James Love
Will GSK obtain a six month extended US exclusivity by doing the pediatric trials?
truthman30
I have been very busy of late and i am just catching up on seroxat-paxil related news. I, like fid, have been covering mental health issues, particularly in relation to seroxat, on my blog for some years now. It looks like i’m gonna have a blogging-busy summer ahead now that i have some time. One question I would like to ask is- how are GSK allowed to test paxil on children again considering it has already been proven not to work? Also, i might add, it has been banned in that age group in the uk, not just because it is ineffective, but also because it has a propensity to make children want to kill themselves (and sometimes other people). Should we maybe do some clinical trials again with thalidomide on expectant mothers? Or maybe we should crash cars into kids at 90mph and see does it damage their bodies.. Because basically, what GSK are doing here is a similar thing. I have a feeling though that GSK have other motives with this trial, motives that go beyond the treatment of depression in japanese kids. There were reports a while back about increased suicide rates for paxil in japan, also there is an article on my blog, that i posted about GSK’s creation and marketing of a depression epidemic in Japan to coincide with their introduction of Paxil into the consumer market there. Is it no wonder that some people call them ‘ global serial killers’ ? ..