Children + Pharmaceutical Industry
Antidepressants Cause Abnormalities in Newborns’ Developing Brains
According to a new study antidepressants change the electrical brain activity of newborns exposed during pregnancy to Serotonin Reuptake Inhibitors (SRIs). The fact that antidepressants can cause brain abnormalities in newborns is in addition to the 18 drug regulatory warnings on antidepressants causing birth defects, including heart and lung malfunctions, pulmonary hypertension, preterm births, respiratory difficulties, seizures, feeding problems, vomiting, low blood sugar, floppiness, stiffness and shaking.
The new study, from Helsinki University Hospital’s Children’s Hospital and published last month in Cerebral Cortex, is the first to examine the effects of SRI exposure directly on the brain activity of newborns. The study authors found that the changes that occur in newborns’ brains, due to the mother’s SRI use, are, among other things, associated with less organized communication between the baby’s brain hemispheres. In other words, the antidepressants taken by mothers during pregnancy (compared to those who had not taken antidepressants) caused subtle abnormalities in the newborns’ brains.
According to Dr. Mari Videman, a senior consultant in child neurology and one of the study’s principal investigators, “The most interesting aspect in our observations is that comparable effects were recently found in animal experiments after fetal SRI exposure.” Yes, there can be no argument that an abundance of proof of the dangerous effects of antidepressants on a child’s developing brain is rapidly increasing.
Still, despite the known adverse effects of antidepressants on infants, according to the Centers for Disease Control and Prevention (CDC) pregnant and non-pregnant women 18-44 years old (from 2005-2009) with depression received treatment with prescription medication as the most common form of treatment. And, in a study of pregnancies between 1998 and 2005, 4.5% of women reported using an antidepressant 3 months before becoming pregnant or during pregnancy. 
Moreover, children remain a robust target of the psycho/pharmaceutical industry. IMS Health Vector One National database reported that in 2013 more than two million children in the U.S. between the ages of 0-17 had been prescribed antidepressants. And unbelievably, of those, 26,406 were 0-1 year olds.
For all age groups, there are 134 drug regulatory agency warnings on antidepressants from eleven countries (U.S., United Kingdom, Canada, Japan, Australia, New Zealand, Ireland, Russia, Italy, Denmark and Germany) and the European Union citing the following adverse reactions; suicide/risk/attempts, cardiac problems, hostility/violence/aggression, self-harm, anxiety, mania or psychosis, hallucinations or delusional thinking, depression, involuntary movements, sexual dysfunction and even homicidal ideation.
It is because of the self-harm associated with antidepressant use that more than a decade ago, the Food and Drug Administration (FDA) mandated that all antidepressants carry the agency’s most serious “Black box” warning for suicidality. Eleven years after the FDA’s warning for suicidality associated with antidepressant use, a Dutch study (the largest-ever statistical analysis of 70 antidepressant clinical trials) concluded that antidepressants double the risk of aggression and suicide in children and teens.
The harmful and violent side effects associated with antidepressant use is further supported by a study published in PLOS Medicine which found young adults between the ages of 15 and 24 were nearly fifty percent more likely to be convicted of a homicide, assault, robbery, arson, kidnapping, sexual offense or other violent crimes when taking antidepressants than when they were not taking the psychiatric drugs.
In fact, according to a study conducted by the Institute for Safe Medication Practices and published in the journal PLoS One and data collected by the FDA’s Adverse Event Reporting System, 25 of the 31 top drugs associated with violent behavior are psychiatric drugs, including the antidepressants Pristiq, Effexor, Luvox, Strattera, Paxil, Prozac, Zoloft, Lexapro, Celexa, Wellbutrin, Remeron and Cymbalta.
Apparently the results of the recent study were so conclusive that the study’s psychiatric consultant, Adjunct Professor Outi Mantere of McGill University in Canada recommends, “If the mother using an SRI plans a pregnancy, it would be advisable to consider a close follow-up or a therapeutic intervention without SRI medication.”
Sounds like appropriate advice. But one cannot help but wonder: If antidepressants alter the brain functions of infants through the mother’s intake during pregnancy, how can the scientific community fail to acknowledge that this may also be occurring through the direct intake of antidepressants on the still developing brains of the more than 2 million 0-17 year olds and, especially, the 26 thousand 0-1 year olds on psychiatric drugs?
The question, of course, is no longer whether antidepressants are harmful but, rather, how much more damning research will be necessary before regulators take action to remove them from the market.
Source : CCHR Intl (June 2016)
GlaxoSmithKline to face class action over anti-depressant used on children
A Sydney law firm has launched a class action on behalf of people who as children and adolescents were prescribed the anti-depressant drug Paroxetine.
Drayton Sher Lawyers has called for expressions of interest from people who were prescribed the drug, commonly known as Aropax in Australia, when they were 18 or younger.
Solicitor Tony Nikolic said hundreds of people had indicated they would join the class action, which he expects to file in the Federal Court at the end of May.
Paroxetine was a commonly-prescribed anti-depressant more than a decade ago and for a time was the most commonly used antidepressant in Australia.
In 2001, GlaxoSmithKline (then SmithKline Beecham) funded a randomised trial of the drug that showed Paroxetine was safe for use in adolescents.
But concerns about its use persisted. In 2004 the Therapeutic Goods Administration's Adverse Drug Reactions Advisory Committee said there was international concern about the risk of increased suicidal ideation and self-harm among children and adolescents using Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants.
"It should be noted that none of the SSRIs is approved for the treatment of MDD [major depressive disorder] in children or adolescents in Australia, but these drugs are being used for this purpose."
A team led by the University of Adelaide's Professor Jon Jureidini re-examined the GlaxoSmithKline research last year and found there were "quite striking" rises in the suicidal thoughts experienced by those taking the drug compared with those taking a placebo.
The review team found that 11 people who took the drug in 2001 experienced experienced suicidal thoughts or behaviours, compared with one person who took the placebo.
Mr Nikolic said one person joining the class action had been prescribed Paroxetine as a six-year-old, and soon began having suicidal thoughts.
"Now, if someone is assisted by this, fine. But they know that these things have suicidal thoughts or ideations attached to them."
Mr Nikolic is calling for anyone who was, as a minor, prescribed Paroxetine - which also traded under a number of generic names including Chemmart Paroxetine, Extine, GenRx Paroxetine, Paroxetine Actavis and Terry White Chemists Paroxetine - to come forward if they experienced side effects.
These side effects could include suicidal feelings, attempted suicide, and causing others an injury.
Fairfax contacted GlaxoSmithKline for comment.
Source LaLeva (March 2016)
Toddlers Dosed With Speed? How Big Pharma Hooks America's Kids on Dangerous Meds
Children with ADHD are easy targets because they will be lifelong patients and repeat customers.
A report from the Centers for Disease Control and Prevention last week confirmed what many have suspected: more than 10,000 2- and 3-year-olds in the U.S. are being dosed with drugs like Ritalin and Adderall for "attention deficit hyperactivity disorder." You read that right.
There is no medical basis to the dosing. American Academy of Pediatrics' guidelines for ADHD "do not even address the diagnosis in children 3 and younger—let alone the use of such stimulant medications," reported the New York Times, especially because "hyperactivity and impulsivity are developmentally appropriate for toddlers."
Toddlers on Medicaid are especially targeted for ADHD meds, commensurate with Big Pharma's heisting of government funds as its main source of revenue, a marketing plan also seen with Medicare, TRICARE and the VA prescriptions. Why does the richest nation in the world have so many children afflicted with ADHD, conduct disorders, depression, "spectrum" disorders, oppositional defiant disorder, mixed manias, social phobia and bipolar disorder?
Because children are good customers.
"Children are known to be compliant patients and that makes them a highly desirable market for drugs,” says former Pharma rep Gwen Olsen, author of Confessions of an Rx Drug Pusher. "Children are forced by school personnel to take their drugs, they are forced by their parents to take their drugs, and they are forced by their doctors to take their drugs. So, children are the ideal patient-type because they represent refilled prescription compliance and 'longevity.' In other words, they will be lifelong patients and repeat customers for Pharma."
Pathologizing kids for money is so insidious, psychiatrist Phillip Sinaikin recounts reading a scientific article in which it was debated whether a 3-year-old girl who ran out in traffic had oppositional defiant disorder or bipolar disorder! The latter is marked by the "grandiose delusions" that she was special and cars could not harm her, said the article.
Stimulants for ADHD are not innocuous. They produce sleep, growth and appetite problems in children, hallucinations and other mental problems and set them up for life-long drug use. There is another class of drugs Big Pharma has convinced doctors to prescribe to large swathes of kids, especially Medicaid kids—atypical antipsychotics like Risperal and Zyprexa. Big Pharma even schmoozed doctors on the golf course to get kids hooked on the dubious drugs. Court documents unsealed in South Carolina in 2009 show that Lilly sales reps used golf bets to push Zyprexa, one doctor agreeing to start new patients on Zyprexa "each time a sales representative parred." Nice.
Texas' Medicaid program spent $557,256 for just two months' worth of pediatric Geodon, another atypical antipsychotic, in 2005, according to court documents, and Geodon was not even approved for children at the time.
A National Institute of Mental Health study of children ages 8 to 19 with psychotic symptoms found Risperdal and Zyprexa were no more effective than the older antipsychotic, Moban, but caused such obesity a safety panel ordered the children off the drugs. In just eight weeks, children on Zyprexa gained 13 pounds and kids on Risperdal gained 9 pounds. Kids taking the older drug, Moban, gained less than a pound.
"Kids at school were making fun of me," said study participant Brandon Constantineau, who put on 35 pounds while taking Risperdal. In fact, the atypical antipyschotics cause so much weight gain and diabetes, Alaska won a $15 million settlement from Eli Lilly in a suit to recoup medical costs generated by Medicaid patients who developed diabetes while taking Zyprexa.
(The government also bought a lot of Risperdal for adults. The Department of Veterans Affairs spent $717 million on Risperdal for Afghanistan and Iraq war troops's PTSD over a period of nine years only to discover, after a large-scale study, the drug worked no better than placebo. Oops. VA doctors wrote more than 5 million prescriptions for risperidone/Risperdal from 2000 through June 2010 apparently for naught.)
Pharma ads to get children on the drugs are also unconscionable. The London-based ad agency, Junction 11 (GSW Worldwide) hired noted Welsh oil painter, Mark Moran, to create the award-winning Risperdal "Living Nightmares" campaign. The paintings were designed to "capture physicians' attention and communicate patients' agony and need for treatment" said its originators while helping Janssen to "own the relapse/prevention space." The paintings were called, among other things, "Dog-Woman," "Witches," "Rotting Flesh" and " Boiling Rain."
Another Risperdal campaign, called "Prescribe Early," uses a macabre abandoned wallet, teddy bear and keys on a barren street, "to reposition a drug that was being used too late to achieve its maximum benefits," said its ad agency, Torre Lazur McCann. Get it? You should have prescribed the drug earlier. Brand managers for the atypical antipsychotic Seroquel also chased children, even considering creating Winnie the Pooh characters like Tigger (bipolar) and Eeyore (depressed) according to published reports, at an AstraZeneca sales meeting. A mother I interviewed said she saw toys emblazened with Seroquel logos in a healthcare setting.
"Disney-fying" psychoactive drugs for children is not just a U.S. phenomenon. A lime-green kids' brochure for Zyprexa, published by Britain's National Health Service shows cartoons of happy children skating, roller blading and playing soccer while telling kids, "Many children, teenagers and young people need to take medicines prescribed by doctors to help them stay well and healthy." Similar NHS brochures exist for Risperdal and Strattera, an ADHD drug.
Pyschoactives are not the only drugs pushed on kids and often prescribed early, as one cynical doctor put it, "before the symptoms go away." Singulair is heavily marketed to kids for allergies and asthma, and even comes in a cherry-flavored chewable formulation. "When your child breathes in an asthma trigger, such as pollen from trees or weeds, the body releases leukotrienes (loo-ko-TRY-eens)" and Singulair blocks the loo-ko-TRY-eens, said marketing materials jointly produced and distributed by Merck and the publisher Scholastic.
Many were offended by the partnership. Marketing included an endorsement from Olympic gold-medalist swimmer Peter Vanderkaay, a basketball "skills challenge" for kids 9 to 14 and materials distributed through the American Academy of Pediatrics, said published reports. The Scholastic sales pieces assure parents that Singulair is "steroid-free" but kids may experience, "hallucinations (seeing things that are not there), irritability, restlessness, sleepwalking, suicidal thoughts and actions (including suicide), trembling, and trouble sleeping." But hey, they won't have sniffles.
One mother I interviewed gave her son Singulair for "hayfever" and he took his own life days later. Soon after, warnings about suicide appeared on the label. In 2010, television news reports investigated Singulair's links to ADHD-like, out-of-control behaviors. Parents on the website askapatient.com recount chilling stories of how Singulair turned their children into people they "didn't even know" and many say the drug should be banned. Many parents were urged by doctors to treat their toddlers' sniffles, asthma or allergy symptoms "early."
Believe it or not, Pharma has even reclassified babies spitting up as "GERD" to make money off kids. Prescriptions for GERD for babies have quadrupled in recent years. Even though babies spit up approximately 70 times a day, it's normal and does not damage the esophagus like reflux disease, writes pediatrician Darshak Sanghavi, author of A Map of the Child. Prescriptions for GERD meds, on the other hand (proton pump inhibitor drugs or PPIs) are damaging, says Sanghavi, and "may increase brain bleeds and gut damage in preterm infants as well as the risk of food allergies in older infants."
The use of GERD meds is up by 147 percent in children and other non-psychiatric meds are also ballooning in use. Since 2001, high blood pressure meds for kids have risen 17 percent, respiratory meds 42 percent and diabetes meds by 150 percent. And 50 percent of pediatricians also prescribe kids insomnia drugs, according to an article in the journal Pediatrics. Clearly, treating kids for ADHD is only one of Pharma's revenue streams.
Source : Alternet (May 2014)
A Call for Safer Drugs for Kids
Many of the medicines children take have never been proved safe and effective for them. A new law will help change that
Parents assume that when a pediatrician prescribes a drug for their child, that drug has been tested and proven safe and effective. If only it were so. Only half of the medicines doctors prescribe to patients 18 and younger have been through the same rigorous trials as those drugs prescribed to adults. The other half are given off-label—that is, in circumstances for which they were never properly vetted, putting children at risk for overdoses, side effects and long-term health problems. For newborns, that fraction rises to 90 percent. In July the U.S. Congress gave the Food and Drug Administration new authority to compel companies to test their products for kids. The law should improve the situation, but it has worrying gaps.
As biologists have come to appreciate, drug metabolism is one of the many ways in which kids are not just small adults. When doctors downsize an adult dosage to suit a child's weight or body surface area, a drug can prove ineffective or harmful. Infants have immature livers and kidneys, so even a seemingly small dose of medicine can build up quickly in their bodies. As children mature, their organs can develop faster than their body size, so they need to take disproportionately more of the drug. For example, some recent pediatric clinical trials have found that the asthma medication albuterol does not work for children younger than four when taken through an inhaler. The seizure drug gabapentin (Neurontin) requires higher-than-expected doses for children under five.
The reason that drug companies neglect their youngest customers is simple. Children make up a small fraction of the world's drug recipients, so developing and testing new medicines for them is rarely worthwhile from a business perspective. Pediatric trials are especially expensive and complex, in part because of the difficulty of finding enough patients to enroll in them.
Congress began to address the issue in 1997, and its latest legislation, known as the FDA Safety and Innovation Act, strengthens those earlier efforts. The law requires pediatric studies for certain drugs and provides incentives to test others, such as a six-month patent extension. In addition, the law requires better advance planning of pediatric studies, improves the transparency of data and makes special provisions for newborns. The American Academy of Pediatrics praised the law: “The bill ensures that children will have a permanent seat at the table for drug research and development.”
Still, the law leaves many children vulnerable. It does little for youngsters with cancer, who rely disproportionately on undocumented drugs. Earlier this year Genentech won FDA approval for the skin cancer drug vismodegib, which intervenes in the same molecular process thought to be involved in a childhood brain tumor, yet the company was under no obligation to test the drug in younger patients. Congress needs to close this loophole, and in the meantime the FDA should continue to work closely with pharmaceutical companies and pediatric oncologists to find new ways of identifying and testing promising cancer medicines in children.
Another problem is that doctors are worryingly in the dark about the long-term health effects of pediatric drugs. Young people take medications for asthma, diabetes, arthritis and many other chronic conditions, yet rarely are side effects recorded and followed up on. In its February report “Safe and Effective Medicines for Children,” the Institute of Medicine recommended that the FDA make greater use of its authority to require long-term safety studies when it approves a product for pediatric use.
That said, the FDA Safety and Innovation Act is an important achievement. Children's medications are safer now than at any time in history, and many doctors and children's health advocates are so elated by the act's passage that they are reluctant to talk about what still needs to be done. But now is not the time to let up on our drive to make drugs safe for all our citizens. We hope this legislative victory will breed even more success.
Source : Scientific American
Psychiatric adverse drug reactions reported during a 10-year period in the Swedish pediatric population
Maria Bygdell, Gertrud Brunlöf, Susanna M. Wallerstedt and Jenny M. Kindblom*
Clinical Pharmacology, Institute of Medicine, the Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden
Purpose Psychiatric Adverse Drug Reactions (ADRs) are frequent in the pediatric population. The aim of the present study was to analyze spontaneously reported psychiatric ADRs in children during a 10-year period.
Methods All spontaneously reported Individual Case Safety Reports (ICSRs) concerning children (<18 years old) and psychiatric adverse reactions assessed as at least possible, registered in the Swedish Drug Information System (SWEDIS) during the period 2001–2010, were extracted and characterized. Age and sex distribution and labeling/registration status were studied.
A total of 600 ICSRs concerning 744 psychiatric adverse reactions were identified and included in the analysis. Boys were overrepresented among included ICSRs (60.3% vs. 39.7%; p < .001). After exclusion of vaccines, the three most frequently suspected drugs were montelukast, centrally working sympathomimetic drugs, and inhaled glucocorticoids. Serious adverse reactions were reported more frequently for drugs used off-label than for drugs used according to the Swedish Physician’s Desk Reference. Aggressiveness was reported more frequently for boys than for girls as were suicidal conditions.
Psychiatric ADRs in the pediatric population have been reported for a wide range of reactions and drugs and display age and sex differences including a higher number of suicidal reactions in boys. An association was seen between serious reactions and off-label drug use. Further studies are needed to elucidate safety aspects of unlicensed drugs and drugs used off-label and whether there are differences in
children’s susceptibility to develop ADRs.
Source : pharmacoepidemiology and drug safety 2012; 21: 79–86
Link to Full Article
Antidepressants for Children - Prozac – how could it be approved for children in
In December 2003, the British MHRA (Medicines and Healthcare products Regulatory Agency) banned the use of all antidepressants for children and adolescents under 18 years [1,2].There were no proven benefits with the drugs but evidence that they resulted in increased suicidal behaviour. The only antidepressants that MHRA specifically excluded from the ban was Prozac, earlier the same year approved by FDA [3, 4], based on two short studies (more about them later ) .
On 25 April 2005 the European Medicines Agency, EMEA, published warnings for all antidepressants - including Prozac. They should not be given to children and adolescents diagnosed with depression , they increased the risk for suicidal behaviour and hostility. The British Medical Journal (BMJ) wrote: “The European Medicines Agency has ruled that selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) [newer classes of antidepressants] should not be prescribed for
children and adolescents under the age of 18 [for depression]…” . This created a very special situation. FDA had approved Prozac for children, the British MHRA had not wanted to offend FDA and leading psychiatrists and exempted Prozac from their ban of antidepressants, but now the EMEA issued warnings for all antidepressants –
including Prozac – and “said “should not be given to children and adolescents “ . MHRA's angry reaction to the decision of EMEA told some of the pressure exerted on the agency. A spokeswoman for the agency said:
“There is still time to influence it [the decision]. We back what Emea’s scientific panel is saying but the key difference is that Prozac is the one drug for which there is clinical-trial evidence that it is effective. The profession know they are going to have to prescribe something and it is important they know what the dangers are and the best way of prescribing it. We think it is safe to use so long as it is monitored carefully.”  [Italics here.] There was a strong pressure from the “profession” [psychiatry], which“have to prescribe
something”, and when it was not possible to prescribe Prozac, it became a big problem. The directive from EMEA about Prozac to children went straight against the approval that FDA made in early 2003, in that a majority of experts from European agency now found that Prozac should not be given to children and adolescents. And here is where this story starts. We did not know anything about the game behind
the scenes – we did not know how it could be that the same authority – the European Medicines Agency, EMEA – one year later 6 June 2006 approved Prozac for children. The British Medical Journal then wrote: “The European Medicines Agency has approved the use of fluoxetine (Prozac) for children aged 8 years or more and teenagers who have moderate to severe depression…”  How did the turnaround happen? What new information had emerged in one year? What forces pushed through the change of the decision? None of this has been answered in the past for the simple reason that the records from the medical agencies telling the story have not seen the light.
To get an application approved of course first requires an application. And a newspaper article from June 2004  revealed: MHRA had in order to deal with the pressure asked the pharmaceutical company Eli Lilly to submit an application for approval of Prozac in the UK and Europe. A representative of a patient association, who quit the UK expert committee because of lack of transparency, was very upset that MHRA, who should
oversee the pharmaceutical companies, contacted one of them and asked them to apply for an approval. He said: “This raises real issues about their impartiality. They are saying they want an SSRI [this type of antidepressants] to be given to children. It is not their job to decide such a thing. If they are going to do deals with the drug companies, where does it stop?” Well, we already know that it stopped with Prozac being approved for children in Europe two years later. But it can already now be said that Sweden had at least as much to do with the approval decision being pushed through. UK and Sweden – and the psychiatric consultants
that these countries made use of – pushed it through while several other countries strongly argued for not approving Prozac. At the same time as EMEA (25 April 2005) issued warnings on all antidepressants and wrote
“should not be used to treat depression in children and adolescents”, the Swedish Medical Products Agency, MPA, (29 April) submitted it comments to the evaluation done by France and UK about the application submitted by Lilly for the approval of Prozac (France opposed the approval). The Swedish Medical Products Agency (MPA) gave the following amazing assessment  (p. 1): “…the MPA currently supports the overall view of the UK, i.e. that approval may be recommended provided commitments of further studies and appropriate wording of the SPC [Summary of Product Characteristics].” In other words, the Swedish MPA and the UK MHRA at this time supported the approval of Prozac for children. The arguments for giving approval were strange, to say the least, they had little to do with any good scientific evidence that this was an effective and safe medicine for children. This is what the MPA had to say (p. 1): “It is a fact that SSRIs, including fluoxetine [Prozac], are used ’off label’ [without being approved for what it is prescribed for] in children and adolescents, and approving use of fluoxetine allows for providing treatment recommendations, better post marketing surveillance in these populations and possibilities to request further studies.” MHRA had used the absurd argument ”the profession [psychiatry] know they are going to have to prescribe something”, and the reasons given by the MPA were of the same low class. The Swedish agency responsible for making sure that people got safe and effective medicines said they wanted to accept a psychiatric drug for children because doctors already prescribed it! The agency further stated that if Prozac is approved for children now they can later require
further studies about the harmful effects. With this logic one could easily approve all antidepressants to children – not to mention even more toxic psychiatric drugs, as psychiatrists already prescribe also these for children, despite all evidence of harmful effects. Strangely enough the Swedish Medical Products Agency, eight days after EMEA issued directives about all antidepressants, convened its own expert meeting. Among the participants were the officials who signed the above assessment , as well as prominent consultants as
Psychiatry Professor Anne-Liis von Knorring, scientific advisor to the Agency, and Psychiatry Professor Bruno Hägglöf. The result of this meeting was treatment recommendations for antidepressants for children – ”an update of the state of knowledge” . In those it was written that no antidepressants are approved for children, but that “it is well known that pharmacological treatment of children is sometimes deemed necessary and that antidepressants are used” (the same kind of argument that was used in the assessment above). About Prozac it is written: “Among antidepressant drugs fluoxetine has the most convincing clinical documentation ... ” [Italics here.] The risk of suicidal behaviour is mentioned, the risk that together with the absence of positive effect, got EMEA to eight days earlier, for all antidepressants announce: “should not be given to children and adolescents”. The experts in the MPA-meeting however go far to ignore the proven risk of increased
suicidal behaviour (i.e. “not significant increase in risk compared to placebo” ). What is really strange is that the MPA opposes the just issued European warnings and that the Agency issues the positive statements about Prozac (“the most convincing clinical documentation”) when they know that several other medical agencies in Europe have another view on this. In addition, the MPA at this point knows that the investigation of Prozac is
continuing at European level, that a variety of questions about the clinical trials of Prozac and the safety risks of the drug have been submitted to the manufacturer Eli Lilly, and that the answers from the company, when eventually received, will form the basis for a reassessment of the drug. The continued handling of the case at European level was referred to Holland, who, in the role of “Rapporteur ”, should request further answers from the pharmaceutical company Eli Lilly and submit a new evaluation. On 31 October 2005 the evaluation from the Dutch Medicines Evaluation Board (CBG) was issued: Prozac (fluoxetine) - Paediatric Indication, Rapporteurs' Assessment Report. It is an incredible report. It begins with the words: “It is not recommended to grant an indication to fluoxetine for the treatment of depression in children and adolescents because the benefit/risk balance in the claimed indication is deemed negative.” In other words, Prozac should not be approved for depressed children and adolescents; the dangers of the drug are greater than any benefit. Note that this evaluation is made about 10 years after the prescription of Prozac for children in the United States began to rise heavily (although the drug was not approved for children), and nearly three years after FDA (January 2003) approved Prozac for children. Please note that the evaluation is made after the Dutch Medicines Evaluation Board asked for and received answers to a number of follow-up questions from the company Eli Lilly.
The ”unresolved issues” around Prozac, the reasons why different medical agencies in Europe in the end of April 2005 rejected Lilly's application for approval was taken up by the Dutch medical agency: “Overall there were unresolved objections and concerns with respect to the following issues:
- Representativeness of the included patient population.
- The lack of information regarding optimal dose.
- The limited information regarding long-term efficacy.
Safety from clinical studies:
- Higher rates of suicidal related events in the fluoxetine compared to placebo treated patients.
- Concerns about reduced height and weight gain.
- Lack of data concerning effects on maturation, cognition and behavioural development.
- Limited long-term safety data.
- Effects on bone development.
- Effects on sexual development.
- Irreversible testicular toxicity.
- Effects on emotional development.”
It was these questions and others that the Dutch Medicines Evaluation Board (as “Rapporteur”) should give further consideration and on which the agency requested additional information from Eli Lilly.
So what was the reason that the “Rapporteur” in October 2005, after having received the
replies from Eli Lilly, stated that Prozac could not get an approval in Europe? The Board referred to what was already known and said that the answers from Lilly had not diminished worries of damage. They wrote:
“Concerns about safety issues were not resolved, specifically concerns about suicide related behaviours, including suicide attempt and suicidal ideation, and, from non-clinical data, about the effect on growth, sexual maturation, cognitive and emotional development. The limited evidence concerning long-term safety
is a concern as well, especially given these safety signals.” The Board further questioned whether the descriptions of positive effects in the studies submitted had anything to do with the actual effect in clinical activities (more about that later):
“Moderate effects, though somewhat inconsistent across trials, were seen, but there are doubts about the external validity of these results due to the stringent selection procedure.”
The Board further wrote: “In addition to objections that were raised in response to the request, during
the course of this procedure new information concerning safety have become available from preclinical as well as clinical studies. Animal studies have raised concerns with respect to effects of early exposure on growth and sexual maturation. A non-company sponsored clinical study (the Treatment of Adolescents with Depression Study (TADS)) demonstrated that fluoxetine, in common with other SSRls, is associated with increased risk of suicidal behaviours in young persons.”
Comments about the “efficiacy” of Prozac In the report the Dutch agency then assesses the clinical trials that were part of the application, which should show that Prozac was “effective” for children and adolescents, one
of the requirements for the approval of the drug. The Board writes (p. 9) that the evidence of efficiacy is “mixed – a modest effect that reached significance only in some trials…”. But, as they write, “more important is the fact that the patients population that was included in the trials is a highly selected group that is not likely
to be representative of the total depressed patient population”. The Board explains in detail how the various studies of Prozac were done, and compare them with other studies of antidepressants in children. It is explained that Eli Lilly and the researchers who conducted the trials of Prozac had used another method than what had been used in the trials of other antidepressants. For example, all children who would participate in
the Prozac studies, had to undergo “an extensive screening and evaluation procedure” before
they became included in the actual studies, with the result that many were excluded from the
studies. Part of this extensive procedure was (in two of the studies ) that all children before the actual study were given a placebo (sugar pill) for a week. The children who showed improvement when they received placebo were excluded from the study. We know from other trials of antidepressants that a high proportion of those receiving placebo improved just as much as those receiving antidepressants. In other words, when comparing the groups one gets no positive effect of the antidepressant drug, compared to placebo, which in itself shows that the drug does not work, it does not have a positive chemical effect (placebo works just as
well). So the reason they gave all children placebo for a week before they began the actual study
was to be able to exclude children who got better on placebo, and thus it was expected that a
smaller proportion of children who received placebo in the actual study would get a positive
result. The researchers wanted to increase the chance of obtaining a difference between the
active drug (Prozac) and placebo, increasing the chance of obtaining “evidence” that Prozac
It was this approach that the Medicines Evaluation Board was referring to when they wrote
about “a highly selected group ”. The Board also made the comparison to what happened
when researchers in other studies of antidepressants did not from the beginning exclude
children that could worsen the results of the drug versus placebo. A comparison is made with
the studies of paroxetine (Seroxat/Paxil) where a ”lower percentage of patients were excluded”. The Board said: “Comparison of the results indicate that the percent responders in the active arms are similar in the paroxetine and the f1uoxetine trials … while the percent responders to placebo are generally higher in the paroxetine trials.” [Emphasis added.] In studies with paroxetine, the proportion of ”placebo responders” was 55%, 58%, 46%, whereas in studies with fluoxetine it was 32%, 53%, 35%. Exclusion of children in the Prozac studies strongly diminished the proportion who received a positive result on placebo – thus creating a
”positive” difference between the antidepressant and placebo; with this approach Eli Lilly
could argue that Prozac was ”effective” – which the Dutch Medicines Evaluation Board did not agree to.
Conclusions on the “safety” of Prozac The Dutch Medicines Evaluation Board summarizes the safety risks :
“In the face of the limited efficacy results, safety concerns are all the more salient. Increased risk for suicide related behaviours emerged as the most concerning safety finding from the clinical trials. Other safety concerns include effects on growth and sexual maturation including effects on fertility, and effects on cognitive and emotional development.” They note again that Prozac can not be approved (the benefit is not greater than the risk) and write:
“The company should be encouraged to conduct further trials, concerning the dose, the efficacy in a more general population and concerning long-term safety.”
And so Prozac got approved
The above means that in the end of 2005, the medical agency in Europe that had been responsible (as “Rapporeur”) to investigate the matter, considered that Prozac was not acceptable for children. It had raised a number of issues for the pharmaceutical company, but found that the answers the company provided did not change anything in the assessment. Prozac was not approved.
In the additional documents in the case it can be seen in the summary report from 6 February
2006 (Joint Assessment Report)  that several countries (France, Ireland and Denmark) supported Holland's assessment that Prozac cannot be approved for children and adolescents.
The updated assessments from the “Rapporteur”, the Dutch medical agency, shows that at crucial points it is written ”Issue not resolved”, while estimates from the Swedish Medical Products Agency (“Co-Rapporteur”) of these points are ”Issue solved” or ”Issue to be discussed with the company ”.
The Dutch agency expresses its deep disappointment with the pharmaceutical company Eli Lilly and writes (p. 6):
“The responses of the company at this time ... indicates that the company is not intending to carry out any more studies to address the unresolved safety concerns.”
The Board also states:
“The lack of willingness on the part of the company to carry out additional studies that would elucidate safety concerns is disappointing, as the MAH [Marketing Authorization Holder] has a clear responsibility for evaluation of safety in this population.”
And based on this information the European Medicines Agency (EMEA) the 25-27 April 2006, is conducting hearings in London with Eli Lilly. Now they agree, and now it goes fast. On 6 June, an approval is granted for Prozac! It is associated with ”requirements” for a number of follow-up studies – on the very safety issues that should have been resolved before an approval was granted.
The Swedish Medical Products Agency tells on its website : “Fontex/Prozac (fluoxetine)
is approved for treating depression in children and adolescents ”, and says that ”EMEA decided to recommend that Prozac is approved for treating depression in children and adolescents over eight years of age”. It further says: “The Scientific Committee, the CHMP [Committee for Human Medicinal Products, experts in EMEA from the various countries], states that studies in children and adolescents demonstrated that fluoxetine is effective against moderately severe and severe depression.”
The MPA of course says nothing about the story above. There is nothing in the MPA statement about the previously used “scientific arguments” that ”The profession know they are going to have to prescribe something... ” (MHRA)  and that Prozac should be approved because it is already used for children [MPA] .
In its assessment from April 2005  the MPA also told that one of the good grounds on which it would approve Prozac for children was that one then – after the approval – got good chances for “better post marketing surveillance in these populations and possibilities to request further studies”. What happened with this may require a separate article. The wise reader can guess: Did Eli Lilly really in an effective way conduct the required studies, that they previously did not want to do, now when Prozac had been approved? Did the MHRA, MPA and Eli Lilly after the approval start with new effective follow-up actions for the children who received Prozac?
Reporter – investigating psychiatry
Here you can read the full report from Holland: CBG, The Dutch Medical Evaluation
Board, Prozac (fluoxetine) - Paediatric Indication, Rapporteurs' Assessment Report, 31
October 2005, http://jannel.se/Prozac-HollandAR.pdf
 The Independent, Threat of suicide leads to ban of major antidepressants for children,10 December 2003,
 Medical News Today,UK - Major antidepressants banned - Suicide Threat,13 December 2003,
 M2 Press Wire,FDA Approve Prozac for Pediatric use, 6 January 2003,
 FDA, Approval of Prozac for Pediatric Use, FDA Patient Safety News, 14 April 2003,
 EMEA press release,The European Medicines Agency finalis review of antidepressants in children and
adolescents, 25 April 2005 http://www.ema.europa.eu/pdfs/human/press/pr/12891805en.pdf
 BMJ, Regulator restricts use of SSRIs in children, 30 April 2005,
 The Independent, Britain set for clash with Europe over ban on Prozac for under - 18s, 26 April 2005,
 BMJ, European agency approves use of fluoxetine for children and teens, 17 June 2006,
 The Guardian, Safety alert on adult use of antidepressants,14 June 2004,
 MPA, Comments From The Medical Products Agency, On The Final Variation Assessment Reports
(FVARS); 29 April 2005, (Lena Björk, Hans Melander, Ulla Liminga, Eva Gil Berglund ) .
 MPA, Pharmacological treatment of depression in children and adolescents - an update of the state of
knowledge - Treatment Recommendation, May 2005 ; http://www .lakemedelsverket.se / upload / health -
medical care / reading / depressionbarn.pdf
 CBG, The Dutch Medical Evaluation Board, Prozac (fluoxetine) - Paediatric Indication, Rapporteurs'
Assessment Report, 31 October 2005, http://jannel.se/Prozac-HollandAR.pdf
 CBG, The Dutch Medical Evaluation Board, Joint Assessment Report, 6 February 2006.
 MPA, [Swedish] Fontex/Prozac (fluoxetin) godkänns för behandling av depression hos barn och ungdomar,
6 June 2006, http://www.lakemedelsverket.se/Alla-nyheter/NYHETER-2006/FontexProzac-fluoxetin-godkannsfor-behandling-av-depression-hos-barn-och-ungdomar/
LINK TO SOURCE
Antidepressants for Children - Part II
Prozac for children - what happened with the follow-up?
By Janne Larsson
Reporter - investigating psychiatry
September 21, 2010
Prozac was approved for children in Europe in 2006. [1, 2] Several countries were strongly opposed, but the UK and Swedish medical agencies pushed to get the drug approved. They thought it was a good idea to first approve Prozac and afterwards do the needed safety studies.
So what happened to the needed studies and the careful monitoring which were a requirement - a condition - for the approval of Prozac for children in Europe?
The Dutch Medicines Evaluation Board (CBG) was in 2005 responsible for the assessment of whether or not Prozac could be approved for children in Europe. The Agency found that Prozac could not be approved and wrote about the effects and harmful effects of the drug:
"In the face of the limited efficacy results, safety concerns are all the more salient. Increased risk for suicide related behaviours emerged as the most concerning safety finding from the clinical trials. Other safety concerns include effects on growth and sexual maturation including effects on fertility, and effects on cognitive and emotional development." 
The Dutch agency expressed its deep disappointment with the pharmaceutical company Eli Lilly and wrote (p. 6):
"The responses of the company at this time... indicates that the company is not intending to carry out any more studies to address the unresolved safety concerns."
The Agency also stated:
"The lack of willingness on the part of the company to carry out additional studies that would elucidate safety concerns is disappointing, as the MAH [Marketing Authorization Holder] has a clear responsibility for evaluation of safety in this population." 
In Part I of this article I let the wise reader guess: Did Eli Lilly really in an effective way conduct the required studies, that they previously did not want to do, now when Prozac had been approved? Did the UK MHRA, the Swedish MPA and Eli Lilly after the approval start with new effective follow-up actions for the children who received Prozac?
The Swedish Medical Products Agency (MPA) had already in the early negotiations about the approval of Prozac for children pushed for such authorization. The Agency was aware of the serious signs of damage that had been presented in the case files, but said that safety issues could be investigated after the pharmaceutical company had got its positive decision:
The Agency wrote:
"...the MPA currently supports the overall view of the UK, i.e. that approval may be recommended provided commitments of further studies and appropriate wording of the SPC [Summary of Product Characteristics]." [Emphasis here.]
"It is a fact that SSRIs, including fluoxetine [Prozac], are used 'off label' [without being approved for what it is prescribed for] in children and adolescents, and approving use of fluoxetine allows for providing treatment recommendations, better post marketing surveillance in these populations and possibilities to request further studies." [Emphasis here.] 
And the English and Swedish Agencies pushed through the approval with these "scientific arguments". Prozac was approved in June 2006 and the pharmaceutical company Eli Lilly agreed to do the studies that had not been made prior to approval, and to ensure that children who received Prozac were closely monitored for effects and harmful effects.
Eli Lilly undertook at the time of approval  to do several things, which included the following:
1. Investigate the effect of Prozac on sexual maturation in children 8-12 years. This would be done in an American study ("TADSjr") under the National Institute of Mental Health (NIMH).
2. Examine if different registers in Europe could be used to obtain data on how Prozac affects the sexual maturation of children.
The company should also in Prozac studies with rats investigate the following:
4. "neurohormonal investigation of sexual maturation".
5. "characterization of testicular pathogenesis".
6. "characterization of effects on specified emotional behavior".
The Company should among other things examine what the Dutch Medicines Board had taken up about Prozac's "effects on growth and sexual maturation including effects on fertility, and effects on cognitive and emotional development".
We take a big step forward to 2010 and look at what happened to the proud commitments - the requirements, the conditions, for the approval of Prozac for children in Europe.
And we can in the UK electronic Medicines Compendium read:
"In addition, only limited evidence is available concerning long-term effect on safety in children and adolescents, including effects on growth, sexual maturation and cognitive, emotional and behavioural developments." 
More than four years after the requirements to closely examine these long-term effects there is still "limited data" available.
So what did Eli Lilly do, and what did the regulatory agencies, who should ensure that Eli Lilly complied to the requriements, do?
Eli Lilly should first investigate the effect of Prozac on sexual maturation in children 8-12 years. This would be done in collaboration with the researchers who had conducted the TADS study, Treatment for Adolescents with Depression Study, the main study that Eli Lilly used to push through the approval of Prozac for children (see Part I).
The researchers who conducted TADS would with funding from the National Institute of Mental Health (NIMH) conduct a follow-up study of children 8-12 years ("TADSjr"). Eli Lilly would "catch on" and as part of this study examine the effects of Prozac on sexual maturation.
In September 2006, Lilly submitted a proposal on how to conduct the study. 
The Assessor at the UK MHRA was not satisfied and wanted several questions answered. On November 16, Lilly responsed. The Assessor from MHRA, who apparently had decided to do a thorough job, was not at all satisfied. In the response to Lilly, on December 12, the often used phrase was "Issue not resolved" and the Assessor concluded by writing that almost none of the questions had received satisfactory answers.  On December 19, other Assessors in Europe commented on the report and a summary assessment report was issued.  On January 31, 2007, Eli Lilly replied to the Evaluators' comments and questions.  On March 1, MHRA answered on Lilly's report.  On March 12, MHRA sent a letter to Lilly to explain what was now required for this study.  And Lilly replied on April 12.  MHRA sent a report to other European regulatory agencies for comments on April 23.  Only Italy responded, and MHRA May 2, sent a new letter to Lilly and requested information.  On May 21, Lilly submitted the information.  After a few short communications Eli Lilly, July 6, submitted the revised design of the study. 
One year had now passed since Prozac was approved for children and the discussions were still about the design of the study that would provide answers to how Prozac affected different important aspects of children's life, including sexual maturation.
On July 19, MHRA issued a new assessment report to the European regulatory authorities. It was now agreed how the study should be done.  What remained was to actually conduct the study for which the design had been discussed over a year.
And this takes us forward to September 9, 2009. Now, MHRA publishes a summary of what has happened with the study that Lilly would conduct.
The Agency writes (p. 3):
"Now the TADS Jr study will not be conducted because of lack of funding by the NIMH, and consequently the exploration of possible effects of fluoxetine [Prozac] treatment on sexual maturation as part of this study will not be feasible."
One of the requirements for the approval of Prozac, in June 2006, was that this study must be conducted. The design of the study was then discussed for a year. And now, three years afterwards, it is said that the study was not even begun - and will not be done!
So how do MHRA and the other regulatory agencies handle this situation?
The MHRA writes:
"The MAH [the manufacturer, Eli Lilly] therefore requests [as this study would not be conducted] that the post-authorisation commitment [the requirements that should be fulfilled after approval of the drug] to clinically evaluate the effect of fluoxetine on sexual maturation be considered fulfilled." 
In other words, Eli Lilly requests that the requirement in this area should be considered fulfilled - even if the company has done nothing. The major concern about the effects of Prozac on children, that got the Dutch Medicines Evaluation Board (CBG) not to grant approval for Prozac, is existing just as much as four years earlier. Despite that Eli Lilly wants to skip all studies of long-term effects of Prozac in this area.
And what does MHRA say about this?
"The RMS [Reference Member State] [in this case UK] agrees that any clinical study to investigate the effects of fluoxetine on sexual maturation would be forbiddingly hard to conduct and difficult to interpret. The RMS therefore recommended accepting the Company's request that the FUM [Follow-Up Measure] to clinically evaluate the effect of fluoxetine on sexual maturation be considered fulfilled."
Abracadabra, the requirement was conjured away. The Swedish MPA, who wanted to approve Prozac for children on the basis that there would be extensive post-marketing studies, has no real objections to the magic trick of MHRA.
And therefore, now and forever, the following will be the words in the product description for Prozac:
"In addition, only limited evidence is available concerning long-term effect on safety in children and adolescents, including effects on growth, sexual maturation and cognitive, emotional and behavioural developments." 
No long-term studies will be conducted for the simple reason that the "responsible" medical agencies fail to request such studies.
What happened with the requirement to examine if different registers in Europe could be used to obtain data on how Prozac affects the sexual maturation of children?
No, it did not work either. According to Lilly no such suitable records were available. MHRA also accepted the Company's evaluation on this point. The Swedish Medical Products Agency did at least find something to say about it, and sent the following lame comment to MHRA and other regulatory agencies:
"We acknowledge these problems, however, we do to some extent question the unfeasibility of the company setting up a registry/observational study themselves."  The Agency also says "that the non-clinical FUMs [Follow-Up Measure] should be finally assessed before it is finally decided whether further clinical work is necessary." [They use "further" even if nothing is done.]
Then there is the non-clinical studies in rats that Eli Lilly should conduct ("neurohormonal investigation of sexual maturation", "characterization of testicular pathogenesis", "characterization of effects on specified emotional behavior").
Well, MHRA takes up data from these studies in its final report. The Agency writes that data from these studies have not been made available as part of the assessment procedure, but says also:
"The MAH [the manufacturer, Eli Lilly] has conducted the required pre-clinical studies, confirming a delay in sexual maturation in rodents but apparently failing to elucidate a causal mechanism for this effect." 
In other words, Eli Lilly had got proof that Prozac gives a delay in sexual maturation, but has "apparently" failed to clarify the causal mechanism.
In conclusion we can say that Eli Lilly got Prozac approved in Europe, even if different countries felt that the drug should not be approved for children. MHRA did not want to offend FDA (who approved Prozac for children in 2003) and wanted to save the only tool available for biological psychiatry (when all other antidepressants had been banned for children); the Agency wrote that "the profession" [psychiatry] "must be able to prescribe something". The Swedish MPA wanted to approve Prozac so that good follow-up studies on the safety risks could be conducted afterwards.
As we have seen above, the follow-up studies came to nothing and the careful monitoring of children receiving Prozac (through different registers) did not happen. Eli Lilly got away with doing nothing all.
The only results of all follow-up requirements are that we, more than 20 years after Prozac was approved in the U.S. and 4 years after the drug was approved for children in Europe, can say that new rat studies have demonstrated a delay in sexual maturation, and that Eli Lilly conjured away the possible causal mechanisms in the new studies.
Can the medical agencies' betrayal of the children get much worse ?
Reporter - investigating psychiatry
 MPA, Prozac / Prozac ( fluoxetine ) is approved for treating depression in children and adolescents, 6 June 2006, http://www.lakemedelsverket.se/Alla-nyheter/NYHETER-2006/FontexProzac-fluoxetin-godkanns-for-behandling-av-depression-hos-barn-och-ungdomar/
 Today's Medicine, Prozac may be used to treat depression in children, 6 June 2006, http://www.dagensmedicin.se/nyheter/2006/06/06/fontex-far-anvandas-vid-dep/index.xml
 The Dutch Medicines Evaluation Board (CBG), Prozac (fluoxetine) - Paediatric Indication, Rapporteurs' Assessment Report, 31 October 2005, http://jannel.se/ProzacDutchAsessement31October2005.pdf
 The Dutch Medicines Evaluation Board (CBG), Joint Assessment Report, 6 February 2006, http://jannel.se/Prozac-JointAssessmentReport6February2006.pdf
 MPA, Comments From The Medical Products Agency on the Final Variation Assessment Report (FVARS); 29 April 2005 (Lena Björk, Hans Melander, Ulla Liminga, Eva Gil Berglund), http://jannel.se/Prozac-MPA-29April2005.pdf
 Eli Lilly, Letter of Undertaking, 31 May 2006. See Attachmen 5.1, http://jannel.se/Prozac-Lilly-RegulatoryResponsetoMHRA-sexual-maturation31Jan2007.pdf
 UK electronic Medicines Compendium (eMC), SPC Prozac, visited September 19, 2010, http://www.medicines.org.uk/EMC/medicine/504/SPC/Prozac+20mg+hard+capsules%2c+and+20mg+per+5ml+oral+liquid/
 Eli Lilly, Draft Protocol, TADSjr, September 29, 2006, http://jannel.se/Prozac.Lilly_DraftProtocol_TADSjr-sexmaturation29Sept2006.pdf
 Eli Lilly, Response to Qs on TADS, November 16, 2006, http://jannel.se/Prozac-Lilly-ResponseQs-TADSjr16nov2006.pdf
 MHRA, Response Assessment Report, December 12, 2006,
http://jannel.se/Prozac-MHRA-ResponseToLillyon % 20SexualMaturation12Dec2006.pdf
 MHRA, Revised Response Assessment Report, December 19, 2006,
 Eli Lilly, Response to MHRA, 31 January 2007;
 MHRA, Response Assessment Report 2, 1 March 2007; http://jannel.se/Prozac-MHRA-assessment%20of%20responses2 - sexmaturation1March2007.pdf
 MHRA, Request for Information, 12 March 2007 http://jannel.se/Prozac-MHRA-RequestInformation12March2007.pdf
 Eli Lilly, Response to MHRA, April 12, 2007, http://jannel.se/Prozac-LillyRegulatoryResponeMHRA-12April2007.pdf
 MHRA, Assessment Report, April 23, 2007, http://jannel.se/Prozac-MHRA-AssessmentofResponses3-23April2007.pdf
 MHRA, Request for Information, 2 May 2007 http://jannel.se/Prozac-MHRA-ResquestForFurtherInformation-2May2007.pdf
 Eli Lilly, Response to MHRA, 21 May 2007, http://jannel.se/Prozac-Lilly-RegulatoryResponseMHRA21May2007.pdf
 Eli Lilly, Revised Draft Protocol, TADSjr, 6 July 2007; http://jannel.se/Prozac-LillyProtocolTADSjr-SexMat6July2007.pdf
 MHRA, Final Assessment Report, 19 July 2007; http://jannel.se/Prozac-MHRA-FINAL-AssessmentofResponses19July2007.pdf
 MHRA, Assessment Report, September 9, 2009, http://jannel.se/Prozac-MHRA.AssessmentReport9Sept2009.pdf
 MPA, Dear Colleague, September 21, 2009, http://jannel.se/Prozac-LV-FollowUp21Sept2009.pdf
SOURCE: LaLeva.org Sept 2010
LINK TO SOURCE
Children Are Being Exploited to Extend Pharmaceutical Patents
Want to protect your kids from high cholesterol? Just give ’em drugs—like the new, chewable form of Lipitor. Yes, chewable. Like candy. A new Action Alert asks Congress to repeal a really rotten law that encourages this. Lipitor, the world’s top-selling drug—made by Pfizer, the world’s largest pharmaceutical company—has just been approved for use with children in the European Union. It is already approved for children in the US. The motivation is obvious: Lipitor’s 2009 sales were about $13 billion, but its US patent expires at the end of November 2011. This means Pfizer will quickly lose much of its Lipitor revenue once the generic competition hits the market. The company is desperately trying to boost its sales everywhere it can before then.
Pfizer also plans to apply for a six-month extension of its patent in European countries. As is the case in the United States, the EU allows drug makers to seek an additional six months of patent protection for medications if they test them in children, who generally are excluded from the drug studies done before a new medication is approved. The company has already received the extension in the US. And those extra six months could put several billion extra dollars in Pfizer’s pockets.
Lipitor has been available in the US for children since 2002. But it’s rarely prescribed, and it’s not (yet) the EU-approved chewable type. The fact that kids can be used by pharmaceutical corporations to extend their patents is nothing short of outrageous. This law provides huge incentives to drug companies to sell drugs to children—whether they’re good for kids or not. Case in point: the FDA has approved another statin drug, Prevachol, for 8-year-olds, despite the weighty risks for a growing child.
Duane Graveline, MD, former NASA astronaut and scientist, demonstrated the link between statin drugs and muscle and neurological problems, including memory loss and Lou Gehrig’s Disease, in his book Statin Drug Side Effects. Other documented side effects include nerve damage, muscle damage (don’t forget that the heart is a muscle too), liver enzyme derangement, and in some cases even kidney failure. Dr. Joseph Mercola notes a number of other side effects of statins, which he calls “some of the most dangerous drugs on the market”: blood glucose elevation, tendon problems, anemia, acidosis, cataracts, and sexual dysfunction.
Meanwhile, Harvard researchers have found that 85% of heart disease can be prevented by lifestyle changes alone—the correct diet, plenty of exercise, and extra nutrients such as fish oil, l-carnitine, coenzyme Q10, d-ribose, and others.
Many doctors are now calling for universal school screening of children for high cholesterol. This invasion of the home and of parents’ rights would lead to more and more statins being given at a younger and younger age.
And it’s not just cholesterol drugs they’re giving to kids. The journal Pediatrics found that medications are being prescribed for children in the US at a dramaticly increasing rate—for diabetes, hypertension, obesity, asthma, ADHD, and depression. Using a database of prescription claims from children with private health insurance, they were able to find prescriptions for almost 4 million children. In addition to calls for universal school screening for cholesterol, there are also plans to screen kids for mental health issues, which will lead to more mental health medications being used on children. We are creating a generation of drugged kids.
Some of the price to be paid for this is already visible. Pediatrics also found ADHD drugs causing hallucinations and other psychotic symptoms (in addition to growth stunting, reported elsewhere). Half a million children are being treated annually for drug side effects.
Pfizer has worked hard to protect Lipitor, its cash cow. In 2003, it funded the National Lipid Education Council (NLEC), a promotional tool for Pfizer which was thinly disguised as a continuing medical education group whose job was to educate doctors on cholesterol issues. Half the members of the US government’s National Institute of Health’s National Cholesterol Education Program were also members of the NLEC. That same year, a whistleblower from Pfizer alleged that the pharma giant marketed Lipitor for patients with moderately high cholesterol when the FDA approval was only for high cholesterol patients. Of course Pfizer has also worked to redefine what is considered “high.”
Doctors who were selected by Pfizer as investigators on the NLEC received multimillion dollar research grants, an honorarium, speaker fees, travel, entertainment, and the opportunity to attend meetings and network with luminaries in the cardiovascular disease world.
ANH-USA has been dedicated to children’s health issues since its founding—including the rising concern of environmental toxins—but nothing makes us more upset than the outright exploitation of kids so the richest corporations in the world can extend their patents and become just a little richer.
This six-month extension on drug patents so they can test them on children is reprehensible, but it’s a law like any other law, and it can be changed. Please contact your senators and your representatives, and ask them to get this law changed for the sake of all our children. Please TAKE ACTION now.
Source : Alliance for Natural Health
LINK TO SOURCE
Nigerian's Can Proceed With Their Pfizer Lawsuits
The US Supreme Court has rejected an appeal by Pfizer to overturn a ruling that reinstated lawsuits filed by Nigerian families, who say the drugmaker tested an experimental antibiotic on their children without getting adequate consent. Earlier this month, the US Solicitor General filed a brief arguing the Supreme Court should not bother to hear the case. At issue was the Alien Tort Statute, which has been relied upon to claim US companies committed eggregious behavior overseas, and was cited by several Nigerian families who accuse Pfizer of international humans rights law in connection with the 1996 Trovan study. The trial was conducted on about 200 children during a meningitis epidemic that killed 12,000 children.
Pfizer was accused of failing to obtain proper regulatory approval and misleading parents. The study allegedly left 11 children dead and the others were deformed. Pfizer denied the charges and settled the bulk of litigation this summer by agreeing to pay $75 million to settle civil and criminal charges brought by the Kano State government in Nigeria.
The appeal was closely watched, in part, because it raised points that are important to multi-national corporations - whether such a company can be sued under the Alien Tort Statute and whether violations of this statute encompass activities conducted overseas. A federal judge had dismissed the case and ruled the lawsuits should be heard in Nigeria, before an appeals court overturned that ruling.
UPDATE: Pfizer writes to say the drugmaker is “disappointed with the Supreme Court’s order. Today’s decision, however, is not a determination on the merits of these cases, but rather a procedural ruling. The Supreme Court order returns the cases for further consideration to the District Court, where the company has reserved its right to again move to dismiss the cases on various grounds, including the fact that Nigeria is the appropriate forum for the cases to be heard.
“Pfizer continues to believe that the Court of Appeals’ decision represents an unprecedented expansion of international law by allowing non-U.S. citizens to bring a wide range of lawsuits in U.S. courts that have not been recognized before. The company looks forward to presenting its defenses in court and remains confident it will ultimately prevail in these cases.
“Pfizer stands by its 1996 Trovan clinical study, which the company has said all along was conducted with the approval of the Nigerian government, the consent of the participants’ parents or guardians, and was consistent with Nigerian laws.”
LINK TO SOURCE
Pharma Targets Children-- Fastest Growing Market for Rx Drugs
Thursday, 20 May 2010
One-in-four American children are being prescribed adult drugs for chronic adult diseases.MEDCO Drug Trend report (2010): children who are covered by health insurance are the drug industry's fastest growing market.
In 2009, prescription drug use for U.S. children increased by 5%, while prescription drug spending for children increased 10.8%
According to MEDCO, the growth in prescription drug use among American children was nearly four times higher than the rise seen in the overall population.
"While H1N1 caused a spike in antiviral use among children last year, the far more alarming trend since the beginning of the decade is the increasing use of medications taken by children on a regular basis and in some cases, for conditions that we don't often associate with youth, such as type 2 diabetes," said Dr. Robert S. Epstein, Medco's chief medical officer and president of the Medco Research Institute."
In 2009, the FDA facilitated the expanded use of adult drugs for children when it expanded the labels for pediatric use of drugs for the indications for cholesterol control Welchol® (colesevalm HCl) and Crestor® (rosuvastatin); for hypertension Atacand® (candesartan cilexetil); for migraines Axert®; for heartburn Protonix® (pantoprazole); and, worst of all, atypical antipsychotic medications Abilify® (aripriprazole), Seroquel® (quetieapine fumarate) and Zyprexa® (olanzapine).
At no other time in history have doctors become partners of drug manufacturers prescribing dangerous drugs with serious medical side effects for vast numbers of children.
Doctors who prescribe such drugs are disregarding the documented risks of harm for children. Clearly children's vulnerability is being exploited: they are being exposed to adult prescription drugs for chronic adult diseases to meet industry marketing goals.
At no other time in history has the US government--i.e., the FDA--lent its seal of approval to the dubious use of such adult drugs for children.
Vera Hassner Sharav
New research: Kids' consumption of chronic medications on the rise
-- Single year prescription utilization growth hits five percent for children largest jump among all age groups -- More than one-in-four children take medications to treat ongoing health conditions
ORLANDO, Fla., May 19, 2010 – In growing numbers, children across America are adding a dose of medicine to their daily routine. In 2009, drug trend for children - a measure of prescription spending growth - increased 10.8 percent, driven by a 5 percent increase in drug utilization and higher medication costs, according to the Medco 2010 Drug Trend Report. The growth in prescription drug use among children was nearly four times higher than the rise seen in the overall population.
A corresponding analysis of pediatric medication use found that in 2009, more than one in four insured children in the U.S. and nearly 30 percent of adolescents (10-19 year olds) took at least one prescription medication to treat a chronic condition; the most substantial increases were seen in the use of antipsychotic, diabetes and asthma drugs over the past nine years.
"While H1N1 caused a spike in antiviral use among children last year, the far more alarming trend since the beginning of the decade is the increasing use of medications taken by children on a regular basis and in some cases, for conditions that we don't often associate with youth, such as type 2 diabetes," said Dr. Robert S. Epstein, Medco's chief medical officer and president of the Medco Research Institute. "The fact that one-in-three adolescents are being treated for a chronic condition points to the need for additional health education and lifestyle changes that can address the obesity issue that is likely a driving force behind such conditions as type 2 diabetes and even asthma."
Type 2 Diabetes continues climbing in kids
Type 2 diabetes medication use by juveniles increased 5.3 percent in 2009, the largest increase across all age groups, and higher than overall utilization growth of 2.3 percent. Since 2001, the number of children ages 19 and younger using these medications has risen more than 150 percent, with girls between 10 and 19 showing the greatest jump at nearly 200 percent. While growth in use of these treatments is substantial, the actual number of children using these drugs is still far less than is seen in adults.
The obesity epidemic may also be responsible for a higher prevalence of hypertension and gastroesophageal reflux disease (GERD) in youngsters. From 2001 to 2009, there was a 17 percent increase in the use of antihypertensives in children, with the greatest growth (29 percent) seen in boys ages 10-19. The number of children on proton pump inhibitors, used to treat heartburn and GERD, and in some cases prescribed for colic in infants, increased by 147 percent from 2001 to 2009. Last week, The Archives of Internal Medicine published a study showing that daily use of these drugs increases the risk of infection by Clostridium difficile, a harmful intestinal bacteria.
Utilization and costs of behavioral drug treatments continue to rise in children. In 2009, 13.2 percent of the prescription drug benefit dollars spent on children went to ADHD treatments. However, the greatest spike in utilization growth last year was not seen in the youngest demographic but rather in adults aged 20-34 where use of these drugs rose 21.2 percent.
Among the drugs that have experienced substantial gains in the pediatric population are atypical antipsychotics; traditionally used to treat schizophrenia, these drugs have more recently been prescribed for a variety of psychiatric disorders. The nine-year analysis revealed that the use of these treatments in children has doubled over that time period. While atypicals are still more prevalent among boys, the rate of growth (130 percent) was greatest in girls ages 10-19.
"Atypical antipsychotics are extremely powerful drugs that are being used far too commonly - especially in children - given their safety issues and side effects," said Dr. David Muzina, a specialist in mood disorders and national practice leader of the Medco Therapeutic Resource Center for Neuroscience.
"We're seeing them prescribed for a number of different conditions including depression and anxiety for which there is not good evidence that they are an effective treatment and yet we're exposing children to the possibility of extreme weight gain that could lead to a host of health problems including diabetes."
Questions of safety did have a major impact on curbing antidepressant use in young people, dropping about 23 percent since 2004 when the FDA issued its strongest safety warnings on the risk of suicidality in children using these medications.
Respiratory drug use grew 5.0 percent for children in 2009 and was up 42 percent since 2001. Rising asthma rates accounted for much of the increase, as well as greater awareness of the disease and the importance of early intervention in controlling disease progression. This class of drugs was responsible for the highest proportion of net costs of medications among children.
The H1N1 factor
Children saw a 46 percent spike in the use of antiviral drugs, by far the largest increase of all age groups and driven by the high incidence of H1N1 in the young. Children's usage was primarily responsible for the 9.0 percent rise in utilization for the overall population.
Additional pediatric drug developments
In 2009, the FDA expanded to pediatric patients the indications for cholesterol drugs, Welchol® (colesevalm HCl) and Crestor® (rosuvastatin); Atacand® (candesartan cilexetil) for hypertension; Axert® for migraines; heartburn treatment Protonix® (pantoprazole); and atypical antipsychotic medications Abilify® (aripriprazole), Seroquel® (quetieapine fumarate) and Zyprexa® (olanzapine).
Copies of the Medco 2010 Drug Trend Report can be downloaded from www.drugtrend.com.
Big Pharma Makes More Money On Kids , Use Of Medications Among The Young Rises
May 19, 2010
The pharmaceutical industry has found a growing source of sales–the prescription of medicines, primarily used by adults in the past, to children. A portion of the sharp increase in drugs used by children last year was due to H1N1 doses. But, the majority of the “improvement” in sales was because children are being treated for a rising number of chronic illnesses.According to an annual study done by Medco Health Solutions, Inc. (NYSE: MHS):
An analysis of pediatric medication use found that in 2009, more than one in four insured children in the U.S. and nearly 30 percent of adolescents (10-19 year olds) took at least one prescription medication to treat a chronic condition; the most substantial increases were seen in the use of antipsychotic, diabetes and asthma drugs over the past nine years.
The data showed that Type 2 diabetes medication use by juveniles increased 5.3% in 2009. There was a 17% increase in the use of antihypertensives in children. Both of these trends are almost certainly due to the rise in childhood obesity. The underlying cause of the illness and the need for treatment will almost certainly continue into adulthood and overweight children remain overweight as they age.
The growing use of asthma treatments was also significant. Respiratory drug use moved higher by 5% for children in 2009 and was higher 42%t since 2001.
For psychiatric disorders, the largest spending on drugs for children was treatments for ADHD. During 2009, 13.2% of the prescription drug benefit dollars spent on children were for ADHD medications.
But the real growth in the psychiatric pharma area was a rise in the prescriptions for severe mental disorders–atypical antipsychotics. Since 2001, the use of these drugs in children has doubled. The medical community is ambivalent about the trend. “Atypical antipsychotics are extremely powerful drugs that are being used far too commonly – especially in children – given their safety issues and side effects,” said Dr. David Muzina, a specialist in mood disorders and national practice leader of the Medco Therapeutic Resource Center for Neuroscience.”
Several large drug companies benefited as the FDA gave them permission to offer treatments formerly for adults for pediatric use as well. These include cholesterol drugs Welchol made by Daiichi Sankyo, Inc. and Crestor made by AstraZeneca PLC (NYSE: AZN) ; Atacand for hypertension also made by AstraZeneca; Axert for migraines made by Ortho-McNeil-Janssen Pharmaceuticals; heartburn treatment Protonix made by Pfizer Inc (NYSE: PFE); and atypical antipsychotic medications Abilify made by Bristol-Myers Squibb Company (NYSE: BMY), Seroquel made by AstraZeneca and Zyprexa made by Eli Lilly and Company (NYSE: LLY)
The big pharma industry is under siege as many of its drugs go off patent and their sales are largely replaced by less expensive generics. Drug companies are finding that their costs of R&D to find “blockbuster” treatments remains high but they are simultaneously faced with growing competition from biopharmaceutical companies.
It appears that much of the growth in sales for major drug companies during the decade will be for treating children who are overweight, unable to breathe, or mentally unsettled.
Douglas A. McIntyre
Source: Alliance for Human Research Protection
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