Court Documents Show Celexa in Bad Light for Kids

The above meme is applicable to doctors and patients alike. The 'open your mouth' line fits perfectly for both. Doctors should know all the facts before they recommend a treatment to a patient, a patient should know all the facts about the said treatment before they open their mouths to ingest it.

Which brings me nicely to a study recently published regarding a clinical trial involving a widely prescribed antidepressant. Citalopram, known better by its brand names of Celexa in the US and Cipramil in the UK.

Citalopram was tested in kids between 1999 and 2002 and was known as CIT-MD-18 pediatric depression trial. The results and subsequent publication of those results were, as we've come to expect, ghostwritten by PR company Weber Shandwick, more specifically it was ghostwritten by Natasha Mitchner at Weber Shandwick Communications, under instruction from Jeffrey Lawrence (Product Manager Forest Marketing)

For those who don't know, Forest Labs are the American pharmaceutical company that market Celexa. Forest Labs are a subsidiary of Forest Pharmaceuticals.

“A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents,” was published in the American Journal of Psychiatry in June 2004. However, its lead author wasn't neither Mitchner or Lawrence.

Some 10 years after publication a lawsuit against Forest was, in part, settled. The lawsuit, Celexa and Lexapro Marketing and Sales Practices Litigation, had during its intensive investigation, found the confidential documents relating to CIT-MD-18, 750 of which, have now been made public on the on the Drug Industry Document Archive (DIDA) website. In all, over 63,000 documents were handed over to plaintiff lawyers who were suing Forest Labs for the safety and efficacy of Celexa and Lexapro (US trade names for citalopram and escitalopram respectively) in marketing the drugs “off-label” for pediatric use.

The 750 public documents have been desconstructed by Jon N. Jureidini, Jay D. Amsterdam, and Leemon B. McHenry and the results are startling, to say the least.

"The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance" shows, amongst other things, that;

CIT-MD-18...

• Contained efficacy and safety data inconsistent with the protocol criteria.
• Procedural deviations went unreported.
• Negative secondary outcomes were not reported.
• Adverse events were misleadingly analysed.
• Manuscript drafts were prepared by company employees and outside ghostwriters with academic researchers solicited as ‘authors’.
• Authors failed to mention that the five citalopram-treated subjects discontinuing treatment did so due to one case of hypomania, two of agitation, and one of akathisia, none of these conditions were found in the placebo group.

The deconstruction of the 750 documents also showed the authors that protocol-specified outcome measures showed no statistically significant difference between citalopram and placebo. In other words, children taking citalopram found it as effective as taking a sugar-coated pill.

This is contrary to the 2004 study published in the American Journal of Psychiatry in June 2004 where it was stated that, "In this population of children and adolescents, treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated."

Fig 1

The 2004 study shows that its lead author was Karen Dineen Wagner (Fig 1) but as the deconstruction study shows Wagner merely added her name to the study (as lead author) that was penned by Natasha Mitchner at Weber Shandwick Communications.

Wagner is no stranger to controversy, she'd previously added her name to the Paxil 329 ghostwritten paper without actually looking at the raw data [which showed an increased rate of suicidal thoughts in kids taking Paxil]. It's also been learned through various litigation in the US that Wagner was paid to deliver lectures promoting the use of Paxil for depressed kids and teens to both GSK’s sales reps and doctors, this despite ever taking a look at the raw data of 329. Maybe she had faith in the ghostwriter of Paxil 329, Sally K. Laden, just as she did with the Celexa ghostwriter Natasha Mitchner ~ Who knows what makes Wagner tick?

In the complaint filed against Forest Labs it was alleged that the American pharmaceutical company arranged for Karen Wagner to give promotional presentations on the pediatric use of Celexa and to serve as the chair of a seven-city Continuing Medical Education ("CME") program on treating pediatric depression... even though the CIT-MD-18 trial was a failure.

So, to recap...

• Forest conduct clinical trials then write up the results of that trial via a ghostwriter.
• Once the study result are written, Forest hire well known pediatric psychiatrists to claim the the ghostwritten work is theirs.
• Despite Celexa showing no efficacy over placebo, the study (now allegedly written by Karen D. Wagner) shows that it "reduced depressive symptoms to a significantly greater extent than placebo."
• Forest Labs are denied a licence to sell Celexa for child depression but, none the less, send out reps to promote it's safety to prescribing physicians, who were often "dined and dashed" in efforts to get them to prescribe Celexa, the drug that was shown not to work in kids, to kids.

Oh, I forgot to mention, the kids targeted by Forest, Wagner et al were age 7 to 17.

Jon N. Jureidini, Jay D. Amsterdam, and Leemon B. McHenry conclude their findings with...

"It is important to make these articles transparent to correct the scientific record. It is furthermore imperative to inform the medical community of mischaracterized data that could lead to potential harm to children and adolescents who are vulnerable to the effects of medication on the growing brain and may increase suicidal thinking and behaviour."

I couldn't agree more.

Jureidini, Amsterdam, and McHenry ~ take a bow. I salute you all.

Drs. Amsterdam and Jureidini were engaged by Baum, Hedlund, Aristei & Goldman as experts in the Celexa and Lexapro Marketing and Sales Practices Litigation. 

Dr. McHenry was also engaged as a research consultant in the case. Dr. McHenry is a research consultant for Baum, Hedlund, Aristei & Goldman.

"The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance" appears in the International Journal of Risk & Safety in Medicine, vol. 28, no. 1, pp. 33-43, 2016

Fiddy Rant.

So, here we see yet another pharmaceutical company hiring the ghost writing services of a PR firm. Yet another pharmaceutical company who make claims that a drug is safe and effective when it isn't. Once again we see prominent psychiatrists adding their names to published papers when their input to these published papers is minimal to say the least. Furthermore, and yet again, we see a pharmaceutical company promote the use of a non-efficacious drug by wining and dining health care professionals.

Citalopram is from a group of medicines known as Selective Serotonin Reuptake Inhibitors (SSRIS). It has been well documented that Citalopram can induce thoughts of suicide and homicide in many numbers of people that take it. Why then, did Forest Labs spin the data on the CIT-MD-18 pediatric depression trial? Why did Karen Wagner et al claim to have written the study when court documents show that it was written by someone else?

Moreover, what is it with pharmaceutical companies and top paediatric psychiatrists and their apparent lack of care for the safety of 7-to 17 year-olds?

Criminal charges need to be brought against those who played a part in the manipulation of this study. That goes for the top executives at Forest Labs, the reps who promoted its use in kids and the top psychiatrists who put their names to support the data (without actually looking at the data). Charges too should be brought against any doctor who received a bribe from Forest Lab reps, be that a free dinner of tickets to the baseball game.

Off-label prescribing of antidepressants to kids is wrong. I know there are some that disagree with me but look at the facts now. Study 329 (Paxil didn't work in kids) - CIT-MD-18 (Celexa didn't work in kids) ~ So, why prescribe something that doesn't work? 

The side effects of Celexa are pretty horrific for adults let alone children ~ don't even get me started on they harm the can cause to fetuses!

The evidence in these two recent cases now show that neither Paxil or Celexa is beneficial to children yet in 2016 both drugs are still prescribed to children. The heavy illegal promotion undertaken by GlaxoSmithKline and Forest Labs reps still works to this day.

Shit doesn't just stink, it sticks.

Over to you, DOJ.

Bob Fiddaman.

Related

The jewel in the crown ~ Mikey Nardo

The Shane Clancy Case: Celexa Induced Homicide/Suicide

Citalopram Birth Defects (Guest Post)

Karen Wagner on Treating Kids With Antidepressants

Dr Karen Wagner, "no financial relationships with pharmaceutical companies"

You'd have to be from the planet Zog if you didn't know who Karen Wagner was.

Her name is synonymous with antidepressant pediatric studies. She added her name to the Paxil 329 ghostwritten paper without actually looking at the raw data [which showed an increased rate of suicidal thoughts in kids taking Paxil] - The result of that piece of Pharmafia fraud told millions of prescribing physicians that Paxil was safe to use in children and adolescents...when in actual fact it wasn't.

Wagner has been relentless to disprove those who believe antidepressant use in kids is wrong. She sees no problem with it...despite overwhelming evidence that shows just how dangerous antidepressant use in kids can be.

An article published in Clinical Psychiatry News a couple of days ago shows Wagner, once again, promoting the use of SSRi medication in children and adolescents.

Wagner was present at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry where she claimed that "...60% of youngsters will respond favorably to their first antidepressant medication – generally a selective serotonin reuptake inhibitor (SSRI)"

Wagner also went on to claim that Switching to a different antidepressant will help about 50% of those who don’t respond. But adding psychotherapy will grab about 10% more – bringing the total response rate up to around 70%". She was referring to a 2008 study, TORDIA (Treatment of Resistant Depression in Adolescents)

So, Wagner hits the stage at these types of events, she's a key opinion leader, in other words, those employed in the same field as her look up to her, respect her, hang on to her every word. She is the Geldof of the pop world, pushing her message at every given opportunity. Quite why she sticks her middle finger up at evidence that shows kids kill themselves whilst on these drugs kind of alarms me.

So, is Wagner on a mission to help depressed children and teens, does she genuinely care about this population or are there more sinister undertones?

It would help if she and the article published in Clinical Psychiatry News was actually more transparent about her relationship and financial ties to the pharmaceutical industry [Pharmafia].

Upon reading the article I had to do a double take at the end... "Dr. Wagner has no financial relationships with pharmaceutical companies."

Um, excuse me?

Was this a line Wagner told the writer of the article, Michele Sullivan, or has Sullivan just not done her homework?

The content of the article doesn't interest me. Anything that comes out of the mouth of Karen Wagner should be carefully scrutinised given her links to the Paxil 329 study...and other studies for that matter.

What interests me is the startling revelation that Wagner has "no financial relationships with pharmaceutical companies."

Let's just dispel this shoddy piece of journalism.

An article from Alicia Mundy in 2009 [Wall Street Journal] shows that Wagner didn't report some $150,000 in funds such as speakers fees received from GlaxoSmithKline, she also failed to report a trip to Paris.

In fact the then Iowa Republican, Senator Charles Grassley, claimed that the amount Wagner didn't report may have been as high as $230,000.

Wagner, who at the time was working out of the University of Texas, had the backing of her peers who told Grassley they were never aware of any discrepancies regarding Dr. Wagner’s reporting of income from GSK.

Wait a minute... Let's just go back to the recent article in the Clinical Psychiatry News. "Dr. Wagner has no financial relationships with pharmaceutical companies."

Maybe someone should inform Michele Sullivan that she has dropped a clanger in her article.

Sullivan should have also noted that Wagner, according to documents disclosed by GSK under court order, was paid to deliver lectures promoting the use of Paxil for depressed kids and teens to both GSK’s sales reps and doctors.

At a training session for the sales reps, Wagner told the sales force that depression in adolescents was a lethal disorder that, if untreated, could lead to suicide and linger into adulthood. Wagner told the sales reps that the study in question demonstrated that Paxil was both safe and effective treatment for adolescent depression, and that they could expect the positive results for the first of the Paxil studies to be published in early 2000. [Complaint, United States v. GlaxoSmithKline, et al. (“GSK Complaint”), para 52, and Ex. 3 thereto]

Wagner also appeared at no less than 5 “Paxil forum” meetings, which were resort holidays sponsored by GSK for high-prescribing psychiatrists. In these meetings, Wagner falsely claimed that adolescent patients who received Paxil in GSK’s study “showed significantly greater improvement.”

She was also persuasive: according to internal memos, to psychiatrists attending the meetings who reported feeling more comfortable prescribing Paxil to young patients. Paxil revenues went up at least $900,000 from these doctors in 2000 alone. [GSK Complaint, para. 72-76]

Wagner has also been named in a complaint against Forest Labs. In a nutshell the complaint alleges that Forest promoted its antidepressants for pediatric use without FDA approval, and paid kickbacks to doctors to encourage prescriptions. The complaint also alleges that  Forest Labs arranged for Karen Wagner to give promotional presentations on the pediatric use of Celexa and to serve as the chair of a seven-city Continuing Medical Education ("CME") program on treating pediatric depression.

Are we expected to believe that Wagner received no payment for this and she just attended the promotional presentations out of the goodness of her heart?

As, I said earlier, the content of Sullivan's article in the Clinical Psychiatry News is irrelevant. It should, however, be scrutinised given what we know about Wagner's links to the Pharmafia dollar. If the author of the article cannot even get one simple fact correct, a very important fact, then the content, in my opinion, is highly questionable.

I'll leave it to Michele Sullivan to rectify.

Forest Pharmaceuticals and Forest Labs are on the verge of getting a severe spanking after a lawsuit filed by two mothers from Missouri has alleged that Forest Pharmaceuticals and Forest Labs “misrepresented and concealed” information concerning the effectiveness of two company drugs for the treatment of depression in pediatric patients. It will be interesting to see if Wagner is brought to task over her dealings with Forest in this particular case. The suit was filed on behalf of the two Missouri mothers by Baum, Hedlund, Aristei & Goldman, PC and Pendley, Baudin & Coffin LLP.



Bob Fiddaman

Update: Dr. Vernon L. Kliewer and the 3 year-old

3 year-old Destiny Hager was prescribed Seroquel and Geodon after being diagnosed with bi-polar by pediatric psychiatrist Dr. Vernon L. Kliewer of Kansas.

Following on from my previous post about 3 year-old Destiny Hager. [Pictured]

Destiny was prescribed Seroquel and Geodon after being diagnosed with bi-polar by pediatric psychiatrist Dr. Vernon L. Kliewer of Kansas.

Destiny died of fecal impaction and had “antipsychotic drugs present in concentrations considered therapeutic in adults.” The dosage of Seroquel was ramped up to 600 milligrams per day by Kliewer.

Kliewer subsequently entered into an agreement with the Kansas State Board of Healing Arts that would restrict his license to practice medicine and surgery by placing that licence on probation.

Kliewer voluntary excluded treating children under the age of six and was ordered to pay costs to the Kansas State Board of Healing Arts of $13,079, about £8,000. [Back Story]

Both Seroquel and Geodon were prescribed off-label in this particular case.

Seroquel is sold and marked in the United States by AstraZeneca.

Geodon is sold and marked in the United States by Pfizer.

Dine and Dash

The drug industry last updated its marketing code in 2002, when it banned “dine and dash” events in which drug makers provided free dinners to doctors who agreed to listen to brief sales pitches.

On the scale of things Kliewer hasn't really received much from the drug industry but he certainly has been entertained by both makers of Seroquel and Geodon.

Statistics, from 2010 to 2012 show that Kliewer was taken for three meals by Geodon reps [Pfizer] and was given a gift or item to the value of $99.

The same statistics show that Kliewer was taken for two meals by Seroquel reps [AstraZeneca].

Here's the list [taken from ProPublica Dollars For Docs Database]

Pfizer - 2010 - Meals - $6
Pfizer - 2010 - Items, Gifts - $99
Pfizer - 2011 - Meals - $85
Pfizer - 2012 - Meals - $99
AstraZeneca - 2011 - Meals - $36
AstraZeneca - 2012 - Meals - $276

Unfortunately the database only starts from 2010. 3 year-old Desting Hager died in 2006. Is it safe to assume that Kliewer had already been targeted by both Pfizer and AstraZeneca reps?

The money isn't really an issue here, it's more of the motive.

Why would Pfizer and AstraZeneca reps entertain a pediatric psychiatrist?


Answers on a postcard please to:

Off-Label Promotional Tactics
A.N.Y Pharmaceutical Company
PO Box 666


Bob Fiddaman

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. ClinicalTrials.gov 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