Category — ADHD: Concerta

  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.

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.

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, (http://www.jrnldbp.com).”

“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?

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.

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

From CNN.com

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.