ADHD’s Genetic Link

What causes attention-deficit hyperactivity disorder – ADHD? Research in the English medical journal, The Lancet, says it’s not too much sugar, bad diet, or poor parenting. Professor Anita Thapar, lead author of the study, says it’s likely genetic.

Thapar and her group of scientists at Cardiff University in Wales compared 366 children with ADHD to 1,047 kids without ADHD. In particular, the researchers examined differences in the children’s DNA. They found that kids with ADHD were more likely to have small segments of DNA that were duplicates or missing (copy number variants or CNVs — either a deletion or duplication of genetic material).

“We hope that these findings will help overcome the stigma associated with ADHD,” Professor Anita Thapar, the study’s lead author, said in a written statement. “Too often, people dismiss ADHD as being down to bad parenting or poor diet. As a clinician, it was clear to me that this was unlikely to be the case. Now we can say with confidence that ADHD is a genetic disease and that the brains of children with this condition develop differently to those of other children.”

While being media friendly, Thapar’s last statement is a stretch in relation to her research. People and the media love statements that provide seemingly conclusive answers.

Let’s go beyond the media hype that says this research concludes there is a definite genetic link. The researchers really only say there seems to be a possible “genetic link.”  However, their research did not conclude that it is purely or even primarily genetic. What they truly are saying is that this study is evidence that ADHD is not purely social.

The authors conclude:

“Our findings provide genetic evidence of an increased rate of large CNVs in individuals with ADHD and suggest that ADHD is not purely a social construct.”

This is logical because only 15% of the research subjects with ADHD demonstrated increased CNVs. So is it safe to conclude that genetic makeup may contribute, at least in some particular cases, to ADHD? Yes, but to be clear,  this research did not conclude that it is entirely genetically based and was only partially genetically based in a small segment of their study population. This is very similar to other genetic research.

Why is it, if ADHD is genetically based, at least in part, that 30% don’t have it as adults when diagnosed as a child? What happened? Where did it go? This is what is most  important to parents and professionals.

Epigenetic theory, now being widely embraced by the scientific community, maintains that human development  includes both genetic origins of behavior and the direct influence that environmental forces have on the expression of those genes (nature/nurture). Epigenetic theory regards human development as a dynamic interaction between these two influences.

Simply put, how our genes express themselves is greatly impacted by environment. This is likely why, over time, 30% of children don’t display symptoms as adults. The brain changes, rewires, or (a radical version of epigenetic theory) their genes change.

Do tools exist to do this? Yes. See www.playattention.com.

If I may quote Dr. Theodore Dalrymple, “What seems to have happened is that parents have lost the awareness that they had for decades – if not for centuries – that concentration and self-discipline do not come naturally to children, and have to be taught (as well, sometimes, as enforced).”

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.

Meditation & ADHD

Sunset & Sky 098 Researchers, Dr. Zylowska, et al from the University of California-Los Angeles conducted a feasibility study of an 8-week mindfulness training program for adults and adolescents with ADHD. Their report was published in The Journal of Attention Disorders (2008 May;11(6):737-46. Epub 2007 Nov 19).

The researchers sought to inquire whether mindfulness meditation could improve attention, reduce stress, and improve mood. The researchers recruited 34 adults and 8 adolescents. Study participants were given a weekly training session. They were also required to practice daily starting with 5 minutes of meditation per day and gradually increasing to 15 minutes per day.

The majority of participants (after dropouts) reported improvements in self-reported ADHD symptoms. Independent tests on tasks measuring attention and cognitive inhibition also indicated improved symptom outcomes. Improvements in anxiety and depressive symptoms were also observed.

In yet another pilot study conducted by Sarina J. Grosswald, Ed.D., a George Washington University-trained cognitive learning specialist, a group of middle school students with ADHD were required to meditate twice a day in school. After three months, researchers found over 50 percent reduction in stress and anxiety and improvements in ADHD symptoms.

"The effect was much greater than we expected," said Sarina J. Grosswald, Ed.D., a George Washington University-trained cognitive learning specialist and lead researcher on the study. "The children also showed improvements in attention, working memory, organization, and behavior regulation."

Due to the neuroplasticity of the brain, better attention can be attained through meditation. Buddhist monks have been doing it for centuries. This seems to be true of ADHD persons as well. However, it is quite apparent that attention difficulties are just the tip of the ADHD iceberg. Other skills including organization, filtering out distractions, memory, time on-task, motor skills, visual tracking, etc, are typically diminished in ADHD persons. A complete program like Play Attention is required to teach these skills.

As for meditation, it is likely a good supplement to training in the aforementioned skill areas, but given the nature of the cited studies, a controlled clinical study is warranted.

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.

Adult ADHD and Job Performance

As I reported earlier (Do ADHD Adults Really Lose 3 Weeks of Work Each Year?), a study published in the journal Occupational and Environmental Medicine, found that ADHD adults worked 22.1 days less than other workers each year. Furthermore, the study found that they were unable to carry out normal work activities an average of 8.4 days per year, 21.7 days of reduced work quantity and 13.6 days of reduced work quality.

However the study actually begs the question of what is adult ADHD. If you’ve found that it’s difficult to concentrate because you may be hyperactive, have trouble remembering appointments or finishing a project once the challenge is gone, are easily distracted, or avoid tasks that require concentration the World Health Organization (“WHO”) says that you may have adult ADHD! The WHO also thinks that many adults do not know they have the condition.

Who (no pun) hasn’t felt easily distracted or avoids boring tasks? I wonder if the shaky diagnosis of adult ADHD – which by the way, is totally subjective – is being exaggerated so that more people can be ‘treated’ i.e. prescribed medication.

The researchers (World Health Organization (“WHO”) research consortium at Harvard Medical School in Boston Medicine) formed their conclusions by evaluating data from 7,075 adult workers in several countries. The workers ranged in ages from 18 to 44 and were screened for ADHD as part of the World Health Organization World Mental Health Survey Initiative. The researchers surveyed the workers about their performance at work in the last month.

Both the media and the pharmaceutical industries have helped spur the diagnosis of ADHD by clinicians. However it will remain a controversial diagnosis shrouded by concerns about context; we are now required to sit and perform focused and organizational tasks more now than ever before in history. This has changed greatly from work at standard manual labor and assembly lines of the past. Is it natural for us to become distracted at tedious or boring jobs? Do we need medication to improve our work? For whose benefit? Furthermore, an ADHD diagnosis can be symptomatic of personal learning problems or family dysfunction among many other scenarios that comprise the human situation.

Adult ADHD is caught in the midst of a tug-of-war between pharmaceutical marketing, changes in the workplace, and a very loose, subjective diagnosis. Buyer beware.

Women with ADHD affected more?

In most clinical settings, boys are treated for ADHD at least 4 to 1 over girls. Boys, it is thought, tend to present symptoms outwardly more than girls resulting in physical behaviors that are easily noticeable (hyperactivity).

In an article reported in the Journal of Clinical Psychiatry, February 2008, author of the University of Utah in Salt Lake City and his colleagues find that the roles are reversed in adults; females seem to be more impacted than men.

“We found that adult women with ADHD frequently have high levels of emotional symptoms as well as the cognitive problems found in ADHD,” Dr. Frederick W. Reimherr told Reuters Health.

Reimherr’s conclusions were drawn from analysis of data from two clinical trials of Strattera. Strattera is a non-stimulant medication for ADHD produced by Eli Lilly, a pharmaceutical giant.

ADHD symptom data were collected ADHD on 515 individuals. Approximately one third of this population were women. Seventy-five percent of the women in this population had a combined-type ADHD as opposed to only 62% of the male population represented in this study.

Women also presented more problems with sleep than did males in the study. Women had higher scores measuring both anxiety and depression than did their male counterparts.

Women presented poor temper control, mood volatility, and emotional over-reactivity than did their male counterparts (37 % in women as opposed to 29 % of males).

In an interview with Reuter’s Health correspondents, Reimherr cites that, “these symptoms – depression, temper control problems, feelings of tension, and over-reacting to life stresses – might cause a doctor to miss the diagnosis of ADHD … We feel that this will lead to problems in treatment for such women.”

Such studies are limited to the initial data collected by the original researchers at Lilly. Therefore, one is not able to draw positive conclusions regarding the origins of the differences cited by Reimherr. For example, do hormones, age differences, economic statuses, education, or marital statuses, affect the data? We cannot know due to the limitations of the data in this study.

Can ADHD be identified in blood?

Researchers Sharon A. Murphy, MD, and Douglas Woodruff, MD, psychiatrists in private practice in Baltimore, Maryland presented their findings at the 160th annual meeting of the American Psychiatric Association (APA). Their work is based a particular technique called cell membrane potential. They propose that use of this technique may help medical professionals clearly identify attention deficit hyperactivity disorder (ADHD), bipolar disorder, and possibly major depressive disorder.

According to investigators, this physiologic property of cells differs among these disorders and is also differentiated from that seen in healthy controls. This is an interesting theory which has some credibility from years of previous research on manic and depressed persons. To extrapolate this theory to ADHD persons is intriguing.

The theory is a little complex, so I’ll attempt to simplify it. Cells contain energy. In that regard, they are like little batteries. If you attach a voltmeter to two terminals of a battery, a voltage difference will be measured across the two terminals. If you have a battery tester that lights up, you’re actually testing the voltage difference between the positive and negative ends of the battery. Since a cell is like a battery, if you attach a voltmeter to measure voltage across the cell membrane (outside of a cell) you’ll find that the inside of the cell has a negative voltage (measured in millivolts; mV) with respect to the outside of the cell (which is referenced as 0 mV).

If the cell is at rest, it is termed the resting membrane potential. By convention, the potential outside the cell is arbitrarily defined as zero. There exists an excess of negative charges inside the membrane because it is filled with many potassium (K+) and organic ions. Thus, the potential difference across the membrane is expressed as a negative value. The resting membrane potential is disrupted when net flux of ions (charged particles) moves into or out of the cell. Ions flow through various channels constructed of proteins to traverse the cell membrane. These are called, ion channels. Sodium and potassium are known as electrolytes – substances that conduct electrical activity that play a vital role in the normal functioning of the nervous system. There is a higher concentration of sodium outside the nerve cell and a higher concentration of potassium inside. The sodium pump is a process that maintains the normal distribution of sodium and potassium.

The researchers maintain that when cells are placed in a potassium-free buffer, the assay used in their test, cells are stressed. Abnormal regulation of ion distribution and variability in the functioning of the sodium-potassium pump within cells is known to be associated with bipolar I disorder and may also be a hallmark of ADHD, according to Drs. Murphy and Woodruff. I had heard of malfunctioning neuronal sodium-potassium pumps being associated with bipolar I disorder or ADHD, but not blood cells, so this intrigued me.

“While using the membrane potential assay to identify bipolar I disorder, we were intrigued by data that suggested this membrane potential test is also sensitive to presumed malfunctioning of the sodium-potassium pump in ADHD,” the authors reported.

Here’s the theory upon which the researchers are presumably basing their work: Any factor that alters the sodium or potassium pump in a neuron likely alters the neuron’s capacity to respond to stimuli basically affecting the functioning of the neurons. This may then affect the central nervous system and human behavior. Various studies over many years have demonstrated that depressed and manic patients may exhibit disturbances in the distribution of sodium and potassium (pump problems). Some research indicates patients with psychotic depression and mania had higher levels of intracellular sodium. The hypothesis is that manic and depressed people may have a highly excitable (hyperexcitable) central nervous system due to the excess sodium levels. They are treated successfully with lithium salts which greatly reduce intracellular sodium and so may reduce central nervous system hyperexcitability.

Murphy and Woodruff recruited 273 subjects, of whom 123 were controls. Within that group, 55 were identified by the blood work assay as having bipolar I disorder, and 95 were identified as having ADHD. The assay consists of fluorescence intensity of the membrane potential dye in patients’ blood cells. I would truly enjoy seeing fluorescence intensity of membrane potential dye. Fluorescence intensity is widely used in the manner in which the researchers used it. However, fluorescence intensity is a relative measurement which depends on instrument characteristics. This means that different fluorescence measuring instruments or even the same fluorescence instrument produce different data at different times. Additionally, turbidity (similar to muddy water) or the presence of colored compounds in the sample further complicate the interpretation of the measurements.

After all was said and done, the researchers used clinical response to medication to see if their diagnoses were correct. If the patients responded well, then the researchers concluded they were right! I’ve seen many medical practitioners perform this reverse diagnosis; concluding a child has ADHD if he responds well to ADHD medication.

Seems rather ridiculous. Both their methodology and their conclusions seem quite a stretch given the technology they’re working with.

Murphy and Woodruff claim that their test gives “a very clear and distinct difference among the controls, people with ADHD, and people with bipolar I disorder.” The average membrane potential ratio was 0.8, and the average ratio for ADHD was 1.1; the mean ratio in controls was 0.9

Essentially, I have five primary arguments against this type of test presenting any conclusive evidence:

  • It is curious that the researchers used blood cells rather than neurons as previous research upon which their theory is based was produced from neural cell examination.
  • Fluorescence is a relative measurement that varies with each measuring instrument and is highly susceptible to the most minor variations in the substance being measured.
  • Using a reverse diagnosis to verify one’s test data is suspect.
  • Their data don’t seem statistically significant, but since they didn’t provide their standard deviation, one cannot determine significance.
  • Extrapolation to ADHD from bipolar I is quite a stretch.

Again, the Holy Grail of ADHD is to find that true biological marker that absolutely defines the disorder. We haven’t been able to find it for mania, depression, etc. for the past 50 years. I doubt we’ll find one for ADHD for a variety of reasons, but that’s another chapter unto itself.

ADHD and Social Distancing

As I’ve discussed in previous blogs, ADHD children and adults have difficulty recognizing social cues or regulating impulse control and therefore frequently cannot maintain friendships or adapt well socially.

A recent study published in the Journal of Health and Social Behavior, (48, 50-67) examines the other side of this issue; it examines the attitudes of adults toward persons with depression or AD/HD. The study indicates that many adults would personally prefer not to interact or have their child not interact (social distancing) with an AD/HD child. The study also reveals factors that contribute to the desire for social distancing. Participants in the study consisted of 1393 adults from across the US.

Participants were read a randomly selected vignette that provided a brief behavioral description of 1 of 4 different children. While no diagnoses were provided, the vignettes depicted behaviors characteristic of a child with a medical condition (asthma), a child with depression, a child with ADHD, and a child that presented what the authors described as “normal troubles.”

After listening to the vignette, researchers asked a series of questions to learn about the participants’ thoughts and emotions regarding the child depicted in the vignette. To more deeply delve into the reasoning behind social distancing, the researchers also examined participants’ beliefs about the suspected causes of behavior displayed by the child in the vignette. These included whether the participants believed the child had a mental illness, “bad character”, or “chemical imbalance in the brain.” Participants were also queried whether they believed the child depicted was a danger to self or others.

CONCLUSIONS

Interestingly, percentages of adults who were more likely to not engage with a child or child’s family, if that family was described as having symptoms characteristic of AD/HD or depression, were 2-3 times higher than when a child with “normal troubles” or asthma was depicted.

Some clear trends were also established: male participants were more likely to desire distance than females and older children desired distancing more frequently than younger (8 yrs.) children.

Furthermore, preference for distance increased if participants believed that the depicted child’s problems were caused by poor parental discipline.

When participants believed the depicted child’s problems were caused naturally, e.g. from food allergies or “normal ups and downs” their preference for distance decreased.

Attributing the child’s problems to a mental illness increased the preference for distance. Related to this, believing that the child posed a danger to himself or to others increased the preference for distance.

SUMMARY

The researchers cite that “… a substantial minority of American adults are reluctant to interact, or to have their children interact, with children described in ways consistent with ADHD and depression. Specifically, about 1 in 5 adults was unwilling to have these children living next door, in his or her child’s class, or as his or her child’s friend.”

It is a myth that poor parenting causes AD/HD. However it is evident that social distancing is desired if parents deem the offending child’s behavior to be caused by poor parenting.

By middle school, I would suggest a majority of AD/HD children feel socially outcast. Social acceptance of AD/HD children by their peers may be influenced by the parental attitudes either explicitly conveyed or indirectly communicated. Regardless, it’s evident that despite continued public education, barriers toward social acceptance exist albeit on a minor scale as about 4 out of 5 adults did not report these biases.

I think the greatly varying attitudes toward AD/HD reflect a general confusion regarding the subject. It’s regarded a brain disorder, not as a learning disability which is where I would prefer to see it. The brain disorder lends a certain stigma to AD/HD which is unfortunate. If it were considered a simple lack of certain skills (which is what it actually is) then not only could it be better understood by the general populace, but it would force the medical community to broaden their utterly narrow perspective on treatment benefiting all concerned.

Kids with mental illness often rejected socially

March 19, 2007

NEW YORK (Reuters Health) – Research suggests that a “substantial minority” of American adults are reluctant to let their children interact with children who suffer from depression or attention deficit hyperactivity disorder.

About one out of five parents would not want these children as neighbors, in their child’s classroom, or as their child’s friend, report Jack K. Martin and colleagues from Indiana University in the Journal of Health and Social Behavior.

Older children and boys with mental conditions are most likely to be rejected.

This troubling pattern, the investigators report, appears to result from perceptions that a mentally ill child may be “dangerous.”

“If, as it seems, the ‘mental illness’ of either children or adults signals danger to the public, this barrier must be addressed by future political, legal, and research agendas,” according to Martin and colleagues.

The research stems from interviews with more than 1,100 adults as part of the General Social Survey administered by the National Opinion Research Center. The interviewees were given descriptions of children of various ages with asthma, attention deficit hyperactivity disorder, depression or “normal” ups and downs of childhood.

Levels of rejection for children with depression and ADHD were two to three times higher than those reported for children with asthma or “normal” childhood troubles.

The results showed that almost 30 percent of parents said they would not like their child to become friends with a child who was depressed and more than 18 percent wouldn’t want to live next door to a family with a depressed child.

Roughly 23 percent of parents said they preferred that their child not make friends with a child with behaviors consistent with ADHD and 22 percent wouldn’t want to live next door to a family with a child with ADHD.

“In line with the 1999 Surgeon General’s report on mental illness, our analyses point to continuing barriers to public acceptance,” note the report’s authors. “While not as significant an obstacle as the rejection of adults, social distance does reflect stigma surrounding children’s mental health problems.”

They hope a greater understanding of the roots of this stigma will lead to effective efforts to confront the persistent lack of social acceptance of the mentally ill.

SOURCE: Journal of Health and Social Behavior, March 2007.

Brain Volume and ADHD

I’ve briefly mentioned research studies in the past that find ADHD children have decreased brain volumes (essentially smaller brains) than their peers. Recently, another of these studies was published in the American Journal of Psychiatry (April 2007). Using MRI, the study followed 36 children over two years. How research like this gets published is beyond speculation, but in the publish or perish world of academia, it’s fairly standard trash.

The journal reports that the researchers (a group of MDs and PhDs) “…compared the volumes of each lobe of the cerebellar hemispheres and vermis in children with ADHD and comparison subjects and used a new regional cerebellar volume measurement to characterize the developmental trajectory of these differences.”

Just an anatomical note, the cerebellar vermis is a part of the structure of animal brains. It’s a thin wormlike structure between the hemispheres of the cerebellum. It would take far too long to fully detail the brain structures the researchers have noted as being reduced in volume, but the anatomy is easily available for review on the web.

According to the researchers, the “36 children with ADHD were divided into a group of 18 with better outcomes and a group of 18 with worse outcomes and were compared with 36 matched healthy comparison subjects. The volumes of six cerebellar hemispheric lobes, the central white matter, and three vermal subdivisions were determined from MR images acquired at baseline and two or more follow-up scans conducted at 2-year intervals.”

I’m not bothered by the low number of children in the study. However, we cannot forget that ADHD is a subjective diagnosis. This study, like many others before it, seeks to find some biological marker that might reveal the nature of ADHD. Unfortunately, we have several problems: one, go to any search engine you wish, type in ADHD and then any structure in the brain that you wish, e.g. cerebellum, frontal cortex, basal ganglia, putamen, etc. You’ll find a controlled study indicating that that structure of the brain is diminished in volume, not functioning normally, etc. Apparently, if one takes these studies seriously, the brains of ADHD persons are extraordinarily damaged. Not likely.

The Holy Grail of ADHD is to find a correlation between brain structure and specific dysfunction which would cause ADHD. This is a foolhardy endeavor. Since ADHD is diagnosed through a checklist of symptoms presented over time, it is very likely it is caused by a variety of factors including environment, heredity, etc.

Furthermore, brain structures that are smaller in volume (if this rot could be proven), or function differently, may be related to the manner in which they ADHD person engages with his environment, i.e. the different structures may not have been congenital, but are the direct effect the person’s interaction with their environment. This is a problem of antecedence (chicken and egg). Secondly, until we study several million brains to find out what the ‘normal’ brain looks like among the full spectrum of human traits and personality characteristics, studies of the sort mentioned are simply a house of cards ready to fall.

Are ADHD drugs safe? Report finds little proof

M. ALEXANDER OTTO;
The News Tribune
September 13th, 2005

At a time when millions of children and adults are taking drugs for Attention Deficit Hyperactivity Disorder, the most comprehensive scientific analysis of the drugs to date has found little evidence that they are safe, that one drug is more effective than another or that they help school performance.

The 27 drugs studied included Adderall, Concerta, Strattera, Ritalin, Focalin, Cylert, Provigil, and others that, in some households, are well-known for their sometimes calming affects.

The 731-page report was done by the Drug Effectiveness Review Project, based at Oregon State University. The group analyzed 2,287 studies – virtually every investigation ever done on ADHD drugs anywhere in the world – to reach its conclusions

They found:

• “No evidence on long-term safety of drugs used to treat ADHD in young children” or adolescents.

• “Good quality evidence … is lacking” that ADHD drugs improve “global academic performance, consequences of risky behaviors, social achievements” and other measures.

• Safety evidence is of “poor quality,” including research into the possibility that some ADHD drugs could stunt growth, one of the greatest concerns of parents.

• Evidence that ADHD drugs help adults “is not compelling,” nor is evidence that one drug “is more tolerable than another.”

• The way the drugs work is, in most cases, not well understood.

The findings do not mean ADHD drugs are unsafe or unhelpful, just that sound scientific proof is lacking.

The Pharmaceutical Research and Manufacturers of America, the Washington, D.C.-based drug industry lobby group, had no comment on the report, but its senior vice president, Ken Johnson, said the benefits of most drugs “clearly outweigh the risks.”

ADHD is suspected when people have a harder time than others their ages paying attention, sitting still or controlling impulses. To be diagnosed, those tendencies must interfere with work, school or other activities.

Nationally, about 4.4 million kids between 4 and 17 fit the bill. Of those, more than 2.5 million take ADHD drugs. Up to 8 percent of kids in Washington state have been diagnosed with the condition.

The Drug Effectiveness Review Project was formed in 2003 to give consumers and state insurance plans trustworthy information about pharmaceuticals.

Industry studies, which researchers have shown sometimes are rigged for favorable outcomes, don’t give the confidence “many of us would like to decide whether or not we should be using a given medication,” said the project’s deputy director, Mark Gibson.

Complicating efforts to get reliable information, the U.S. Food and Drug Administration doesn’t require companies to compare new drugs to ones on the market. Most times, firms instead compare their wares to sugar pills because it is easier to show benefit and get approved for sale.

The problems leave insurers and patients in the lurch when they need to know what drugs work best. That’s where the Drug Effectiveness Review Project comes in. Its physicians and pharmacists analyze virtually every study on a given class of pharmaceuticals to find the best drugs.

The American Association of Retired Persons and Consumers Union, the publisher of Consumer Reports, use the project’s findings to tell people what drugs give the most for the money. Fourteen states, including Washington, also use its services to decide what drugs to cover for beneficiaries. Those states are the project’s chief funders.

For ADHD, the project analyzed published studies as well as unpublished data from the six leading makers of ADHD drugs. The group rejected 2,107 investigations as unreliable, and reviewed the remaining 180 to find superior drugs.

Instead, it found that evidence to choose one drug over another for safety or effectiveness is “severely limited” by a lack of studies measuring “functional or long-term outcomes.”

The project could not find a “good quality” study that tested the drugs against each other. It also could not find comparative evidence to determine which ADHD drugs are less likely to cause tics, seizures and heart and liver problems.

That evidence is needed. Canadian authorities have recently warned against using Adderall Extended Release in patients with heart problems. Cylert and Strattera have been linked to liver damage, the report said.

Until better research is done, the findings mean that choosing the right ADHD drug is largely a matter of trial and error. They also suggest some people might do as well or better on cheap generic Ritalin, sold by its scientific name methylphenidate, instead of far more expensive, newer options such as Concerta and Adderall.

In fact, in the few instances where the Oregon group could draw conclusions, it found Concerta “did not show overall difference in outcomes” compared to generic Ritalin, and proof that Adderall is better “lacking.” What little evidence there is comparing another newer expensive drug, Strattera, to generic Ritalin “suggests a lack of difference in efficacy.”

Gibson cautioned that his project’s latest report is still open for public comment and possible fine-tuning. But the overall results did not surprise Libby Munn, a nurse practitioner at Greater Lakes Mental Healthcare in Lakewood.

“I’ve never been aware of any evidence of any one being better than another,” said Munn, who treats patients for ADHD and other conditions. “That’s true of antidepressants and antipsychotics, too. Once you compare meds for a given disorder, there are often no proven differences.”

Tacoma psychiatrist Dr. Fletcher Taylor, an expert in adult ADHD at Rainier Associates, works with drug companies to develop new products. He said he stands by the effectiveness and safety of the drugs.

Still, he said, Adderall and Concerta are largely equal in their effect, though some people do better on one than another. Their greatest advantage over generic Ritalin is that people take fewer pills during the day.

ADHD DRUG COSTS*

• Methylphenidate (generic Ritalin) $15.69

• Ritalin (brand name): $27.79

• Amphetamine/dextroamphetamine (generic Adderall): $47.09

• Adderall (brand name): $94.49

• Concerta: $103.99

• Strattera: $123.99

• Focalin: $25.99

*Comparisons based on the lowest dose for 30 days.

Source: Walgreens Pharmacy

FIND THE RIGHT DRUG

These Web sites offer help comparing drugs to find what works best:

• The American Association of Retired Persons lets you compare drugs at www.aarp.org/health/comparedrugs/

• Consumers Union, the publishers of Consumer Reports, gives tips on the best drug buys for safety and effect at www.crbestbuydrugs.org/

• The consumer-advocacy group Public Citizen has a solid record of spotting problem drugs, calling, for instance, for the removal of Vioxx in 2001, when few knew there were problems. The group is now worried about the cholesterol pill Crestor. Public Citizen’s drug information site is www.worstpills.org/

• The Oregon State University Drug Effectiveness Review Project is online at www.ohsu.edu/drugeffectiveness/

M. Alexander Otto: 253-597-8616 alex.otto@thenewstribune.com