Concerta Placed on FDA’s Watch List

Concerta Placed on FDA’s Watch List
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Medscape reports that on April 21, 2014 the US Food and Drug Administration (FDA) has placed a generic drug that treats attention-deficit/hyperactivity disorder (ADHD) on its latest quarterly list of products to monitor because of potential health risks, the agency announced today.

In the case of the ADHD drug — certain generic versions of methylphenidate hydrochloride (Concerta, Janssen Pharmaceuticals) — the issue is a possible lack of therapeutic effect, which may be linked to product quality issues, according to the FDA.

A drug’s appearance on the list, which grows quarter by quarter, does not mean the FDA has concluded that the drug actually poses the health risk reported through FAERS. Instead, the agency is studying whether there is indeed a causal link. If it establishes one, the FDA then would consider a regulatory response such as gathering more information to better describe the risk, changing the drug’s label, or mandating a risk evaluation and mitigation strategy.

The FDA also emphasizes that it is not suggesting that clinicians should stop prescribing watch list drugs or that patients should stop taking them while the jury is out.

More Drugs Added to FDA Watch List
Members of a certain class of cancer drugs, as well as a drug treating ADHD, made the list on the basis of potential signals of health risks.

Misdiagnosing ADHD

According to a study released by the University of Michigan, nearly 1 million children in the United States are potentially misdiagnosed with ADHD.

The research was conducted, not by a medical group, but by economist Todd Elder  in the Journal of Health Economics (Elder et al. The importance of relative standards in ADHD diagnoses: Evidence based on exact birth dates. Journal of Health Economics, 2010; DOI: 10.1016/j.jhealeco.2010.06.003).

Elder found that the youngest or often the most immature children are misdiagnosed with the ADHD label simply because of their age and exhibited maturity. Elder also found that these children are significantly more likely than their older classmates to be prescribed medications like Ritalin to control their behavior. Using a sample of 12,000 children, Elder examined the difference in ADHD diagnosis and medication rates between the youngest and oldest children in a grade. He found that the youngest kindergartners were 60 percent more likely to be diagnosed with ADHD than the oldest kindergarten children. Elder followed that group of children and found that they were more than twice as likely to be prescribed stimulant medication by the time they reached the fifth and eighth grades.

Currently, about  4.5 million children are diagnosed with ADHD. Elder concludes that about 20 percent  or about 900,000 children have likely been misdiagnosed.

In a press release from the University of Michigan, Elder said that such inappropriate treatment is particularly worrisome because of the unknown impacts of long-term stimulant use on children’s health. Elder is also concerned that misdiagnosis wastes an estimated $320 million-$500 million a year on unnecessary medication. He estimates that between $80 million-$90 million of it is paid by Medicaid.

"If a child is behaving poorly, if he’s inattentive, if he can’t sit still, it may simply be because he’s 5 and the other kids are 6," said Elder. "There’s a big difference between a 5-year-old and a 6-year-old, and teachers and medical practitioners need to take that into account when evaluating whether children have ADHD."

ADHD has no pathology, no biological marker in the brain that clearly demonstrates its existence. Thus, its diagnosis is always subjective. While teachers are not permitted to make this diagnosis, their perceptions and opinions serve as the initial step to a diagnosis made by a doctor.

"Many ADHD diagnoses may be driven by teachers’ perceptions of poor behavior among the youngest children in a kindergarten classroom," he said. "But these ‘symptoms’ may merely reflect emotional or intellectual immaturity among the youngest students."

According to Science Daily, Elder’s paper will be published in the Journal of Health Economics in conjunction with a related paper by researchers at North Carolina State University, Notre Dame and the University of Minnesota that arrives at similar conclusions as the result of a separate study.

Is ADHD all in your head?

A study published in the June 14 edition of the Journal of Developmental and Behavioral Pediatrics has sparked controversy regarding ADHD medication and the brain’s power to regulate itself.

The study was funded by the National Institutes of Health and conducted by Dr. Adrian Sandler, a developmental-behavioral pediatrician and medical director of the Olson Huff Center for Child Development at Mission Children’s Hospital in Asheville, North Carolina.  The research was performed over the course of eight years using 99 patients from Western North Carolina.

Sandler found that children with ADHD can do just as well on half their medication when the medication is combined with a placebo. They performed as well even when parents and children had full knowledge they were taking a placebo.

[Placebo –  A substance containing no medication and prescribed or given to reinforce a patient’s expectation to get well. The placebo in this research was akin to a harmless inert pill].

Previous studies have shown that common stimulant medication causes side-effects like tics, weight loss, stunted growth, and even heart complications in some instances. This often causes trepidation in parents afraid of the possible side-effects on their children.

Sandler compared fully medicated children, children on reduced medication, and children on reduced medication with a known placebo. The results were quite intriguing.  Both the fully medicated and reduced medication groups had increased side-effects while the reduced medication with placebo demonstrated decreased side-effects. Furthermore, the reduced medication group reported decreased control of their ADHD symptoms. However, the control of ADHD symptoms was no different in the reduced medication with placebo group than in the full dose group, i.e. the reduced medication with placebo performed as well as the fully medicated group with less side-effects as well.

“I’ve been getting a lot of calls and e-mails,” said Sandler,, who conducted the research with James Bodfish, a professor in the departments of psychiatry and pediatrics at UNC Chapel Hill School of Medicine, and study coordinator Corrine Glesne.

“Medications work,” Bodfish said in a statement. “The question is whether we always need to use them at the highest dose. Many parents are concerned about placing their child on medication. Some choose not to treat their child because of concerns about side effects.”

While the research doesn’t address it, the obvious question is, Why? Parents and children in this study knew they were taking a placebo. Why then did they perform as well as their peers without the side-effects — at essentially half the dose as their peers? While the placebo effect has been studied widely, the exact mechanisms are unknown. We do know that the mechanism is governed by the brain. This clearly tells us that having ADHD or not, our brain is still a powerful weapon in our arsenal.

We also cannot exclude the influence of the parents during this research. Did they expect their child to do better? The authors suggest that this was so. This dynamic cannot be overlooked in your family either.

The bottom line is that we likely have far more control over our behaviors and cognitive processes than we are given credit for. Modern medicine, as this research suggests, is just beginning to understand the brain’s role in shaping our lives. We’ve known this for years at Play Attention. Cognitive training. Memory training. Motor skills. Attention training. Behavioral shaping. It’s time to take control over our lives. We’ve all got the power to do it. It lies right behind our eyes.

The ADHD link to social dynamics

If I told you that women who received only basic education were 130 % more likely to have a child on ADHD medication than women with university degrees, you’d see a link, wouldn’t you? 

Well, that’s what a  study published this month in Acta Paediatrica found.  That implies that nearly half of the serious cases of ADHD  in children are closely tied to social factors. The study reveals that factors like single parenting and poor maternal education were directly tied to ADHD medication use.

While we know that a genetic propensity likely exists, the human brain develops based on a complex interplay between nature and nurture; between genetic endowment (nature) and environment/social factors (nurture). Epigenetic theory tries to explain this relationship.

Curiously, few large-scale studies have tried to determine the impact of social and family influences on ADHD. Researchers at the Karolinska Institute in Stockholm, Sweden assessed data on 1.16 million school children and examined the health histories of nearly 8,000 Swedish-born kids, aged six to 19, who had taken ADHD medication.

"We tracked their record through other registers … to determine a number of other factors," said lead author Anders Hjern.

Here’s what the researchers found:

  • Living in a single parent family increased the chances of being on ADHD medication by more than 50 percent.
  • A family on welfare upped the odds of medication use by 135%.
  • Boys were three times more likely to be on medication than girls.
  • Social dynamics affected both sexes equally.

"Almost half of the cases could be explained by the socioeconomic factors included in our analysis, clearly demonstrating that these are potent predictors of ADHD-medication in Swedish school children," Hjern said.

It’s clear that this study found a link between socioeconomic factors and ADHD medication use/diagnosis. Other US studies have found that minority children and children of low socioeconomic status were more likely to receive ADHD medication.

Factors like low income and diminished quality time are more common in single-parent families. These typically lead to stressors like family conflict and a lack of social support, Hjern said.

While more research must be done, one has to ask, is medication the answer to social stressors like lack of time and money? Sounds too silly to ask, but it seems that our answer, ridiculously, is a resounding, YES!

We are the masters of our lives. We can make significant personal changes, but we must have the tools to do so. That’s why I began Play Attention ( years ago.

Immediate rewards and the ADHD brain

A Nottingham University research team in the United Kingdom found that the brains of children with ADHD appear to respond to immediate rewards in the same way as they do to medication. Their research was published in the journal Biological Psychiatry.

“Our study suggests that both types of intervention [medicine and immediate reward/reinforcement] may have much in common in terms of their effect on the brain,” said Professor Chris Hollis, the lead investigator of  the study.

The research team used an EEG (electroencephalograph) to measure the brain activity of children as they played a computer game that provided extra points for less impulsive behavior.

The researchers devised a computer space game which rewarded the ADHD children when they caught aliens of specific colors  while avoiding aliens of designated colors. The game design actually tested the children’s ability to resist the impulse to grab the wrong colored aliens.

To test whether immediate reward/reinforcement made a difference, one iteration of the game rewarded the children fivefold for catching the right alien and penalized them fivefold for catching the wrong one.  All of this was done while activity in different parts of their brains was monitored with an EEG.

Hollis found that the immediate rewards helped the children perform better at the game. This was verified by the EEG which  revealed that both medication and immediate reward/reinforcement were "normalizing" brain activity in the same regions.

Many parents of ADHD children are aware that giving a reward to an ADHD child a week after their good behavior is insignificant to that child. ADHD children respond better to immediate reward, not delayed reward.

"Although medication and behavior therapy appear to be two very different approaches of treating ADHD, our study suggests that both types of intervention may have much in common in terms of their effect on the brain. Both help normalize similar components of brain function and improve performance,"  said Hollis.

"We know that children with ADHD respond disproportionately less well to delayed rewards – this could mean that in the ‘real world’ of the classroom or home, the neural effects of behavioral approaches using reinforcement and rewards may be less effective."

It’s obvious that providing immediate rewards/reinforcement 24 hours a day and 7 days a week would be impractical and impossible. But what does this research tell us? It tells us that if we are to train an ADHD student, feedback, reward, and reinforcement need to be immediate if we are to get their brain to rewire.

We at Play Attention have known this for many years. This is why we integrated immediate feedback/reinforcement for attention training, cognitive training, memory training, and behavioral shaping by using feedback technology. We patented this method years ago because of its inherent strength. While we knew this was the best way to achieve success, we feel research like this rather reinforces our approach. It’s about time the world caught up!

Dopamine & ADHD

thinkingm4  The Journal of the American Medical Association (JAMA. 2009;302(10):1084-1091) recently published work by Dr. Nora D. Volkow, MD, et al regarding evaluation of the biological bases that may reveal a reward/motivational deficit present in the brains of persons with ADHD.

Volkow and her colleagues theorized that ADHD may be connected to reward-motivation deficits. Volkow investigated whether lack of motivation and its relationship to reward could be traced to depression of dopamine in various areas of the brain.

To determine whether dopamine was depressed in ADHD persons, the researchers used positron emission tomography (PET scans) to measure dopamine levels in 53 nonmedicated ADHD adults and 44 healthy non ADHD adults between 2001-2009.

Since the biological mechanisms of ADHD are unknown, studies of this type have become the holy grails of research. While Volkow’s credentials are quite impressive (NIH, NIDA, etc.) this research is not new or conclusive. The theory that dopamine dysfunction/depression may be involved with ADHD symptoms has been researched for many years.

Furthermore, Volkow’s  small sample size consisted only of adults and therefore should not be extrapolated to include the child population. The small sample size alone should prevent it from being generalized to the entire adult ADHD population. One has a problem of antecedence here; is ADHD caused by dopamine depression in the brain? Or is the dopamine depression the result of ADHD that was acquired by other biological means? This research cannot answer that question.

What does the research tell us? It tells us that for some adults, dopamine may play a role in ADHD. For those adults, taking a stimulant medication may increase dopaminergic activity thus increasing reward/motivation responses and thus increasing attention to task. That might be a stretch.

On the downside, persons with depressed dopamine levels would probably greatly enjoy using stimulants. Study participants reported this. This may contribute to the frequent incidences of substance abuse among ADHD persons.

The authors write,"Despite decades of research, the specific neurobiological mechanisms underlying this disorder still remain unclear. Genetic, clinical and imaging studies point to a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs (methylphenidate hydrochloride and amphetamine), which increase extracellular dopamine in the brain."

Unfortunately, the study leaves us with more questions than answers. Does it tell us what happens long term? Does it tell us of side effects?  Does it tell us if this actually applies to children? Can we conclusively determine a causal relationship between reward/motivation and ADHD? Does it solve the problem of antecedence? Do we know anything conclusively about all ADHD adults. No. There’s still a long road ahead.

Omega 3 Fatty Acids (Fish Oils) and ADHD

While the topic of nutrition & ADHD is contentious, omega 3s have gained ground in the relief of ADHD symptoms.  

Respectable studies from Goteborg University in Sweden, University of South Australia, and Oxford University in the United Kingdom have shown that omega 3 fatty acids have reduced symptoms by as much as 50%. A more recent Norwegian study produced similar results. 

In the study performed at the University of South Australia, children were divided randomly into three groups for the first 15 weeks of the study. One group was given a fish oil & primrose oil combination; the second took the same combination plus a multivitamin/mineral supplement, and the third group took a placebo. During the second 15 weeks, the kids on the placebo were given the fish oil & primrose oil combination plus the multivitamin/mineral as well.

While the studies received little press, the results were quite good for the two 30-week fish-oil groups. They demonstrated 40%- 50% improvement in behavior while the 15-week group showed a 30% – 40% percent improvement.  

Ritalin and Concerta are the drugs most often prescribed for ADHD. The results actually were far better for fish oil when compared with results of studies of Ritalin and Concerta. Fish oils were more effective.

Let me make it clear that fish oil will not cure ADHD. Could it possibly mitigate symptoms for you? Possibly. According to Dr. Andrew Weil  “Levels of omega-3s in the plasma and red blood cells of children with ADHD are lower than in kids who don’t have the disorder.”

As attention issues are only the tip of the ADHD iceberg, it’s not a good idea to use fish oils as your only intervention. I strongly recommend using Play Attention; a cognitive program to improve attention, memory, visual tracking, time on-task, motor skills, and discriminatory processing.

ADHD Medications: Mayo Clinic Study Contradicts MTA Study

As I wrote earlier, the longest study actually performed while following live children was the MTA and its 3-Year Follow-up of the NIMH MTA (multi-modal treatment) recently published in the journal of the American Academy of Child and Adolescent Psychiatry.

Co-author, Professor William Pelham, of the University at Buffalo, says: “The children had a substantial decrease in their rate of growth so they weren’t growing as much as other kids both in terms of their height and in terms of their weight. And the second was that there were no beneficial effects – none.”

Pelham adds, “In the short run [medication] will help the child behave better, in the long run it won’t. And that information should be made very clear to parents.”

Here’s the most telling observation of the study: “I think that we exaggerated the beneficial impact of medication in the first study. We had thought that children medicated longer would have better outcomes. That didn’t happen to be the case. There’s no indication that medication’s better than nothing in the long run.”

It’s obvious that this information was not good for the pharmaceutical industry. As is now common practice, a study will be launched to counter this kind of negative press. So, it was no surprise that the respected Mayo Clinic released a study two months later that “…reveals that compared to children without AD/HD, children with ADHD are at risk for poor long-term school outcomes such as low achievement in reading, absenteeism, repeating a grade, and dropping out of school. Both studies appear in the current edition of the Journal of Development & Behavioral Pediatrics, (”

“In this study, treatment with stimulant medication during childhood was associated with more favorable long-term school outcomes,” explains William Barbaresi, M.D., Mayo Clinic pediatrician and lead author of the reports.

The MTA study focused on real families in real-time. The researchers were able to observe family dynamics, environment, pharmacological interventions and their relationships to academic and behavioral outcomes. This, of course, takes a significant amount of time and field researchers.

According to the Mayo Clinic Press Release, “The two Mayo Clinic studies are the first population-based, long-term studies to investigate links between ADHD, school performance and factors that modify long-term school performance of children with ADHD.”

Here’s how research like this works: researchers are given access to school files and medical records. They select and review data from files to draw their conclusions. This is becoming more popular than live research because it is less expensive, doesn’t require a significant number of field researchers, and can be done in less time. Unlike real-time research like the MTA, the Mayo study’s limitations are significant; it doesn’t allow real-time access to families or teachers to gain information regarding environment, family issues, etc; to interpret information; or to clarify written information. So the researchers are fairly limited to test scores and medical records. While this makes it easy to prepare and select data, it falls far short the information gather by a real-time study.

The Mayo study press release summarizes the research:

Dr. Barbaresi believes that both studies provide the first solid evidence of the long-term negative academic performance associated with untreated ADHD – as well as evidence for the best way to manage this problem. Dr. Barbaresi says, “The finding that treatment with stimulant medications is associated with long-term improvement in school outcomes is significant. Previously, there was evidence that treatment with stimulant medications improved short-term academic performance, but there was no good evidence that long-term outcomes are better with stimulant treatment. Our data can guide clinicians in their efforts to help children with ADHD succeed in school.”

Note that no mention is made of height and weight loss of children in the Mayo Clinic study as was found by the MTA. Furthermore it also directly contradicts information released by the MTA. Here’s the rub, funding for the Mayo study was contributed by grants from the U.S. Public Health Service; National Institutes of Health; Mayo Clinic Foundation for Biomedical Research; and McNeil Consumer and Specialty Pharmaceuticals.

Obviously the one extraordinary contributor was McNeil Consumer and Specialty Pharmaceuticals. McNeil is the producer of Concerta, a stimulant medication for ADHD. Is it likely that McNeil would contribute to a study that would indicate weight loss and stunted growth from use of its product? Not likely.

Would McNeil contribute to a study whose researchers said, “I think that we exaggerated the beneficial impact of medication in the first study. We had thought that children medicated longer would have better outcomes. That didn’t happen to be the case. There’s no indication that medication’s better than nothing in the long run.” Not likely.

It is a direct conflict of interest for a pharmaceutical company to participate in research with universities, hospitals, or other entities. I’ve never seen negative information released from a study performed by a pharmaceutical company on their own drug. Strange, isn’t it?

Medication, ADHD and Heart Complications

Long-Term Safety Questioned of Ritalin

In research published in Pediatrics, [December 2007; vol 120: pp 1494-1501], lead author, Almut G. Winterstein, PhD, assistant professor of pharmacy health care administration, University of Florida College of Pharmacy, Jacksonville, found that common stimulants used to treat attention deficit hyperactivity disorder (ADHD) don’t often cause serious heart complications in children. However, she warns that their safety is undetermined for prolonged use.

Winterstein found that stimulants such as Ritalin, Adderall, and Concerta frequently raise blood pressure and heart rate. The researchers analyzed health records from 55,000 children and teens newly diagnosed with ADHD from 1994 to 2004 with two significant findings:

  1. Children who used stimulant medication had a 20% increase in visits to hospital ERs or doctors’ offices for heart palpitations and racing heartbeat, compared with children who didn’t use stimulant medication.
  2. Stimulant medications did not appear to be associated with an increase in hospitalizations or deaths due to cardiac causes.

Last year the FDA took a special interest in the matter of heart safety when it announced a special Black Box advisory to be placed on stimulant medication. This was in part due to reports of the sudden deaths of 12 children who used ADHD Drug, Adderall.

The Canadian government quickly suspended sales of Adderall XR in Canada, but later permitted sales after further investigation.

Winterstein, PhD, in an interview with WebMD, notes:

… that because serious cardiac events are so rare among children and teens, a much larger study is needed to confirm the safety of these drugs.

“We can’t really say that there is no increase in risk (for serious cardiac events) among children who take these drugs,” she says. “What we can say is that if there is an increase in risk, it will not affect a large number of children.”

ADHD Drugs and Heart Risk

The CDC estimates that 4.4 million children between the ages of 4 and 17 have been diagnosed with ADHD, and as of 2003, 2.5 million were taking medication for it.

Children are increasingly taking the drugs for longer and longer periods, but little is known about their long-term cardiovascular impact, Winterstein says.

“The average exposure in our study was two years, but we see children who are on these drugs for five years, 10 years, and even longer,” she says.

She adds that it is also not clear if the drugs are safe for children with existing heart problems or with risk factors for heart disease.

A Probe into the Side Effects of ADHD Drugs

The FDA probes side effects of ADHD drugs Government plans to strengthen label warnings.


Thursday, June 30, 2005; Posted: 11:27 a.m. EDT (15:27 GMT)

WASHINGTON (AP) – The government is planning to strengthen warnings about possible psychiatric side effects from Concerta and related treatments for attention deficit hyperactivity, and is probing whether other ADHD drugs need updating, too.

Concerta is a long-acting form of methylphenidate, sold generically and under the brand name Ritalin. For years, those drugs’ labels have listed possible psychiatric side effects, such as agitation, psychosis or transient depression.

But a routine Food and Drug Administration review of Concerta’s use in children turned up more reports of psychiatric reactions than anticipated, including some that aren’t explicitly labeled, such as suicidal thoughts, hallucinations and violent behavior. A subsequent review of all methylphenidate products found similar reports.

The FDA can’t say if the drugs actually causes those side effects – the reports are from a database of reactions reported by medication users that make such determinations very difficult.

But, in a statement posted on its Web site, the agency said it does intend to strengthen the labeled warnings for all methylphenidate products.

Currently, the drugs’ labels may downplay the seriousness of psychiatric side effects, and suggest they’re only a risk in people who’ve already experienced psychiatric disorders, wrote FDA drug safety evaluator Kathleen Phelan.

Indeed, stimulant drugs “may exacerbate symptoms and reveal them for the first time” in children with previously unrecognized psychiatric illnesses, she wrote.

But, among 36 cases of psychiatric side effects in child Concerta users, six report histories of psychiatric illness, three deny such histories and there’s no information on the rest, Phelan wrote. Further investigation is needed to determine if such side effects may also occur in people without underlying illness, she added.

FDA said it doesn’t intend to change the drugs’ labels right away. It is investigating whether similar behaviors are seen with additional ADHD treatments, such as Adderall and Strattera – to avoid people switching drugs over the concern “based on incomplete safety assessments,” said an FDA document prepared for a meeting of the agency’s scientific advisers on Thursday.

That probe should be finished early next year.