The Journal of Attention Disorders has published two papers about a new formulation of mixed amphetamine salts that uses a triple bead technology (MAS-TB). This technology allows for a delayed release of the medication and enables a duration of effect up to sixteen hours.

This 16-hour effect is significantly higher than existing stimulant medications which on average last for 8-10 hours. This new formulation is based on patient desire to experience beneficial medication effects from morning through evening.

Previously, Spencer et al. ( reported a 7-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, dose-optimization study of 272 adults with ADHD.   They found that MAS-TB significantly reduced ADHD symptoms, behavioral measures of executive dysfunction and increased quality of life ratings. (Other studies have confirmed the benefit of select medications not only for ADHD symptoms, but for executive dysfunctions as well, although no ADHD medications treat executive dysfunction as well as they treat ADHD.)

An assessment of ADHD symptoms 13 to 16 hours post-dose confirmed the duration of action. The first new paper by Frick et al. ( reported a 6 week, randomized controlled study comparing MAS-TB with placebo.   As with the prior study, MAS-TB significantly reduced ADHD symptoms. Mean ± SD pulse and systolic blood pressure increases at end of study were 3.5 ± 10.33 bpm and 0.3 ± 10.48 mmHg, which are medically non-consequential.  

In the second new study, Adler et al. ( reported a long-term, open-label, safety study of MAS-TB in adults with ADHD. Of 505 enrolled participants, 266 completed the study.   Study discontinuation was more likely for patients taking higher (37.5-75 mg) vs. lower doses (12.5 and 25 mg). Blood pressure and pulse increases were observed at end-of-study. ADHD symptoms decreased modestly during the follow-up period.

The most frequently reported treatment emergent adverse events in both studies were insomnia, decreased appetite, and dry mouth. These observed side effects are similar to those seen for other stimulant medications, and are typically well managed by physicians when they occur by adjusting the dose or changing medications.


I have too often seen on the Internet or media the statement that ADHD is a recent invention of psychiatrists and/or pharmaceutical companies.  Such statements ignore the long history of ADHD that my colleague and I reviewed in our “Primer” about ADHD,   As you can see from The Figure, ADHD has a long history.  The first ADHD syndrome was described in a German medical textbook by Weikard in 1775.  That’s not a typo.  The ADHD syndrome had been identified before the birth of the USA.   Dr. Weikard did not use the term ADD or ADHD, yet he described a syndrome of hyperactivity and inattention that corresponds to what we call ADHD today.  As you can see from the Figure, ADHD-like syndromes were described in Scotland in 1798 and in France in the late 19th century.  The first description of an ADHD-like syndrome in a medical journal was by Dr. George Still in 1901 who described what he called a ‘defect of moral control” in The Lancet.  The discovery that stimulant drugs are effective in treating ADHD occurred in 1937 when Dr. Charles Bradley discovered that Benzedrine (an amphetamine compound) improved the behavior of children diagnosed with behavioral disorders.  In subsequent years, several terms were used to describe children with ADHD symptoms.  Examples are Kramer-Pollnow syndrome, minimal brain damage, minimal brain dysfunction and hyperkinetic reaction.  It was not until the 1980s that the term Attention Deficit Disorder (ADD) came into widespread use with the publication of the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM).   During the ensuing decades, several changes were made to the diagnostic criteria and the term ADD was replaced with ADHD so as not to overemphasize either inattention of hyperactivity when diagnosing the disorder.  And, as the graphic below describes, these new and better diagnostic criteria led to many breakthroughs in our understanding of the nature of the disorder and the efficacy of treatments.   So, if you think that ADHD is an invention of contemporary society, think again.  It has been with us for quite some time.


Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20 ;

Screen Shot 2017-03-12 at 8 Ralh0G




Eight Pictures Describe Brain Mechanisms in ADHD

When my colleagues and I wrote our “Primer” about ADHD,, the topic of brain mechanisms was a top priority.   Because so much has been written about the ADHD brain, it is difficult to summarize.   Yet we did it with the eight pictures reproduce here in one Figure.   A quick overview of this Figure shows you the complexity of ADHD’s pathophysiology.  There is no single brain region or neural circuit that is affected.   Figures (a) and (b) show you the main regions implicated by structural and functional neuroimaging studies.  As (c) shows, these regions are united by neural networks rich in noradrenalin (aka, norepinephrine) and dopamine, two neurotransmitters whose activity is regulated by medications that treat ADHD.  Figure (d) describes two functional networks.   The Executive Control network is, perhaps, the best described network in ADHD.  This network regulates behavior by linking dorsal striatum with the dorsolateral prefrontal cortex.  This network is essential for inhibitory control, self-regulation, working memory and attention.  The Corticocerebellar network is a well-known regulator of complex motor skills.  Data also suggest it play a role in the regulation of cognitive functions.   Figure (d) describes the Reward Networks of the brain that link ventral striatum with prefrontal cortex.   This network regulates how we experience and value rewards and punishments.   In addition to its involvement in ADHD, this network has also been implicated in substance use disorders, for which ADHD persons are at high risk. Figures (f) (g) and (h) complete the puzzle with additional regions implicated in ADHD whose role is less well understood.  One role for these regions is in the regulation of the Default Mode Network, which controls what the brain does when it is not focused on any specific task (e.g., daydreaming, mind wandering).  People differ in the degree to which they shift between the default mode network and networks like Reward or Executive Control, which are active when we engage the world.  Recent data suggest that the brains of ADHD people may be in ‘default mode’ when they ought to be engaged in the world.    


Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20 ;

Faraone 8 Brain Images the growth of the Internet, we are flooded with information about attention deficit hyperactivity disorder from many sources, most of which aim to provide useful and compelling “facts” about the disorder. But, for the cautious reader, separating fact from opinion can be difficult when writers have not spelled out how they have come to decide that the information they present is factual.

My blogs several guidelines to reassure readers that the information they read about ADHD is up-to-date and dependable. They are as follows:
Nearly all the information presented is based on peer-reviewed publications in the scientific literature about ADHD. “Peer-reviewed” means that other scientists read the article and made suggestions for changes and approved that it was of sufficient quality for publication. I say “nearly all” because in some cases I’ve used books or other information published by colleagues who have a reputation for high quality science.

When expressing certainty about putative facts, I am guided by the principles of evidenced based medicine, which recognizes that the degree to which we can be certain about the truth of scientific statements depends on several features of the scientific papers used to justify the statements such as the number of studies available and the quality of the individual studies. For example, compare these two types of studies. One study gives drug X to 10 ADHD patients and reports that 7 improved. Another gave drug Y to 100 patients and a placebo to 100 other patients and used statistics to show that the rate of improvement was significantly greater in the drug treated group. The second study is much better and much larger, so we should be more confident in its conclusions. The rules of evidence are fairly complex and can be viewed at the Oxford Center for Evidenced Based Medicine (OCEBM;

The evidenced-based approach incorporates two types of information: a) the quality of the evidence and b) the magnitude of the treatment effect. The OCEBM levels of evidence quality are defined as follows (higher numbers are better:

  1. Mechanism based reasoning.   For example, some data suggest that oxidative stress leads to ADHD and we know that omega-3 fatty acids reduce oxidative stress.  So there is a reasonable mechanism whereby omega-3 therapy might help ADHD people.
  2. Studies of one or a few people without a control group or studies that compare treated patients to those that were not treated in the past.
  3. Non-randomized, controlled studies.    In these studies the treatment group is compared to a group that receives a placebo treatment, which is a fake treatment not expected to work.   Non-randomized means that the comparison might be confounded by having placed different types of patients in the treatment and control groups.
  4. Single randomized trial.   This type of study is not confounded.
  5. Systematic review and meta-analysis of randomized trials.  This means that many randomized trials have been completed and someone has combined them to reach a more accurate conclusion.

It is possible to have high quality evidence proving that a treatment ‘works’ but the treatment might not work very well.  So it is important to consider the magnitude of the treatment effect, also called the “effect size” by statisticians.  For ADHD, it is easiest to think about ranking treatments on a ten point scale.   The stimulant medications have a quality rating of 5 and also have the strongest magnitude of effect, about 9 or 10.  Omega-3 fatty acid supplementation ‘works’ with a quality rating of 5, but the score for magnitude of effect is only 2 so it doesn’t work very well.  We have to take into account patient or parent preferences, comorbid conditions, prior response to treatment and other issues when choosing a treatment for a specific patient, but we can only use an evidenced-based approach when deciding which treatments are well supported as helpful for a disorder. ADHD is an American disorder.
Those who claim ADHD is an American disorder believe that ADHD is due to the pressures of living in a fast paced, competitive American society. Some argue that if we lived in a simpler world, ADHD would not exist.
Fact: ADHD occurs throughout the world.
Wherever scientists have searched for ADHD, they have found it. They have done this by going to different countries, speaking to people in the community to diagnose them with or without ADHD. These studies show that ADHD occurs throughout the world and that the percent of people having ADHD does not differ between the United States and the rest of the world. Examples of where ADHD has been found include: Australia, Brazil, Canada, China, Colombia, Finland, Germany, Iceland, Israel, Italy, Japan, New Zealand, Spain, Sweden, Taiwan, The Netherlands, and Ukraine. ADHD is not an American disorder.

Myth: A child who sits still to watch TV or play video games cannot have ADHD.
Many parents are puzzled that their child can sit still to watch TV or to play video games for hours but that same child cannot sit still for dinner or stay at their desk for long to do homework. Are these children faking ADHD symptoms to get out of homework?
Fact: ADHD does not necessarily interfere with playing video games or watching TV.
Because children cannot turn their ADHD on and off to suit their needs, it does seem odd that a child who is typically hyperactive and inattentive can sit for hours playing a video game. But this ability of ADHD children fits in very well with scientific facts about ADHD. First, you probably understand the effects of rewards and punishment on behavior. If your behavior is rewarded, you are likely to do it again. If it is punished, you will avoid that behavior in the future. Rewards that have the strongest effect on our behavior are large and will occur soon. For example, consider these two choices:
-if you listen to a boring one hour lecture, I will pay you $100 immediately after the lecture
-if you listen to a boring one hour lecture, I will pay you $110 one year after the lecture
Choice (a) is more appealing that choice (b). Most people will not think it is worthwhile to wait one year for $10. We say they have ‘discounted’ the $10 to 0$.
Now consider the choices:
-if you listen to a boring one hour lecture, I will pay you $100 immediately after the lecture
-if you listen to a boring one hour lecture, I will pay you $2,000 one year after the lecture
Choice (d) is more appealing that choice (c). Most people will wait one year for $2,000. It is obvious here is that if I want the best chance of having you watch a lecture, I should offer you a large sum of money immediately after the lecture. What is not so obvious is that people vary a great deal in the degree to which they are affected by rewards that are either small or distant in the future. For some people, getting $2,000 in one year is almost like getting nothing at all. We say that such people are not sensitive to distant rewards.
What does this have to do with ADHD and video games? Well people with ADHD are usually not very sensitive to weak or distant rewards. To affect the behavior on a person with ADHD, the reward needs to be immediate and fairly large. When a child with ADHD sits down to do homework, the potential reward is getting a good grade on their report card, but they won’t receive that grade for weeks or months, so it is very distant. Thus, it is not surprising that the possibility of that reward cannot control the child’s behavior. In contrast, video games are created so that players are rewarded very frequently by winning points or completing one of the many levels one must pass to finally complete the game. Because playing well is also rewarded by friends, the video game rewards are strong and immediate, which makes it easy for people with ADHD to sit still and play for long periods of time.

Myth: ADHD disappears in adulthood.
Until the 1990s, it was commonly believed that children grew out of ADHD. The reason for this is not clear. Some theories about ADHD suggested that ADHD children had a lag in brain development and that they would make up that lag during adolescence. So ADHD was seen as a delay in brain development that could be overcome. In fact, the idea that children routinely recovered from ADHD was so strong that many insurance companies would not pay for the ADHD treatment of adults.
Fact: In the majority of cases, ADHD persists into adulthood.
This myth about ADHD has been proven wrong by studies that diagnosed ADHD in children and then examined them many years later as adults. These studies showed that, although there was some recovery from ADHD, about two-thirds of cases persisted into adulthood. The studies also taught us that ADHD symptoms tend to change with age. The extreme and disruptive hyperactivity of many ADHD children gets somewhat better by adulthood as do some symptoms of impulsivity. In contrast, inattentive symptoms do not decrease much with age.

Myth: People with ADHD cannot do well in school or succeed in life.
This myth is based on several facts: 1) ADHD affects many aspects of life; 2) ADHD impairs thinking and behavior and 3) for most people, ADHD is a lifelong disorder. Altogether, doesn’t this mean that people with ADHD won’t succeed in life?
Fact: People with ADHD can succeed and live productive lives.
There are two reasons why people with ADHD can succeed in life. The first is obvious. Although treatments for ADHD are not perfect, they can eliminate many of the obstacles that would otherwise make it difficult for ADHD patients to do well in school or on the job. But, more importantly, having ADHD is only one of many facts about a person’s life. Some ADHD people have other skills or traits that help them compensate for their ADHD. For example, if you have a high level of intelligence, an engaging personality or excellent athletic skills, you can do well despite having ADHD. Consider Michael Phelps, who broke so many Olympic swimming records. He was diagnosed with ADHD at age 9 and took Ritalin to help his hyperactivity. James Carville has ADHD, but he completed law school and helped Bill Clinton become president of the United States. Cammi Granato’s ADHD did not stop her from becoming captain of the United States Olympic ice hockey team and Ty Pennington’s ADHD did not stop him from becoming a star on TV.

Myth: ADHD does not affect highly intelligent people
The mistake behind this myth is that it assumes that being very intelligent protects people from having ADHD. It’s true that if you are highly intelligent, you can use that intelligence to compensate for some of ADHD’s effects, but does high intelligence completely protect a person from ADHD?
Fact: People with ADHD can succeed and live productive lives.
When my colleagues and I studied this question, we found clear evidence that high intelligence does not completely protect people from ADHD. Like people who don’t have ADHD, having high intelligence will help ADHD people do better than ADHD people who are not a smart. But when we compared highly intelligent ADHD people with highly intelligent non-ADHD people we found that the highly intelligent ADHD people had many of the impairing problems that are know to be associate with ADHD. For details about these problems, see Complications of ADHD. In another study, we compared ADHD adults who had received straight A grades in high school, with non-ADHD people who had achieved the same grades. Despite their good grades, these ADHD adults were not doing as well in their jobs and not earning as much income as the non-ADHD adults. And ADHD also has an impact at every level of education. As you can see from the figure, even for people with college degrees, having ADHD lowers your chances for being employed.

Faraone, S. V., Sergeant, J., Gillberg, C. & Biederman, J. (2003). The Worldwide Prevalence of ADHD: Is it an American Condition? World Psychiatry 2, 104-113.

Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J. & Rohde, L. A. (2007). The Worldwide Prevalence of ADHD: A Systematic Review and Metaregression Analysis. Am J Psychiatry 164, 942-8.

Scheres, A., Lee, A. & Sumiya, M. (2008). Temporal reward discounting and ADHD: task and symptom specific effects. J Neural Transm 115, 221-6.

Faraone, S., Biederman, J. & Mick, E. (2006). The Age Dependent Decline Of Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis Of Follow-Up Studies. Psychological Medicine 36, 159-165. is a serious disorder that requires treatment to prevent many adverse outcomes. But, because the diagnosis of ADHD is based on how the patient responds to questions, it is possible for people to pretend that they have ADHD, when they do not. In fact, if you Google “fake ADHD” you’ll get many pages of links including a Psychology Today article on the topic and bloggers describing how they were able to fool doctors into giving them ADHD medications. Is fake ADHD a serious problem? Not really.

The Internet, it seems, is faking an epidemic of fake ADHD. I say that because we have decades of research that show many objective measures of abnormality and impairment in people who say they have ADHD. These include traffic accidents, abnormalities on brain imaging and molecular genetic differences. Some studies even suggest that ADHD adults downplay their ADHD symptoms. For example, one study diagnosed ADHD in children and then contacted them many years later when they were young adults. When they were interviewed as young adults, their responses to questions about ADHD suggested that they did not have the disorder. But when the same questions about the patient were asked to someone who lived with the patient as a young adult, it was clear that they still had ADHD. So rather than faking ADHD, many ADHD adults do not recognize that they have symptoms of the disorder.

That said, we also know from research studies that, when asked to pretend that they have ADHD, adults can fake the disorder. That means that they can learn about the symptoms of the disorder and make up examples of how they have had them, when they have not. This research suggests that this is not common, but we do know that some people have motives for faking ADHD. For example, some college students seek special accommodations for taking tests; others may want stimulants for abuse, misuse or diversion.

Fortunately, doctors can detect fake ADHD in several ways. If an adult is self-referred for ADHD and asks specifically for stimulant medication, that raises the possibility of fake ADHD and drug seeking. Because the issue of stimulant misuse has been mostly a concern on college campuses, many doctors treating college students will require independent verification of the patients ADHD symptoms by speaking with a parent, even over the phone if an in-person visit is not possible. Using ADHD rating scales will not detect fake ADHD and it is easy to fake poor performance on tests of reading or math ability. Neuropsychological tests can sometimes be used to detect malingering but require referral to a specialist. Researchers are developing methods to detect faking of ADHD symptoms. These have shown some utility in studies of young adults but are not ready for clinical practice.

So, currently, doctors concerned about fake ADHD should look for objective indicators of impairment (e.g., documented traffic accidents; academic performance below expectation) and speak to a parent of the patient to document that impairing symptoms of the disorder were present before the age of twelve. Because the issue of fake ADHD is of most concern on college campuses, it can also be helpful to speak with a teacher who has had frequent contact with the patient. In an era of large lecture halls and broadcast lectures, that may be difficult. And don’t be fooled by the Internet. We don’t want to deny treatment to ADHD patients out of undocumented reports of an epidemic of fake ADHD.
The best way for health professionals to determine if someone has ADHD by the way, is by performing a complete diagnosis. We teach that in our FREE online CME courses on ADHD in Adults.

Harrison, A. G., Edwards, M. J. & Parker, K. C. (2007). Identifying students faking ADHD: Preliminary findings and strategies for detection. Arch Clin Neuropsychol 22, 577-88.
Sansone, R. A. & Sansone, L. A. (2011). Faking attention deficit hyperactivity disorder. Innov Clin Neurosci 8, 10-3.
Loughan, A., Perna, R., Le, J. & Hertza, J. (2014). C-88Abbreviating the Test of Memory Malingering: TOMM Trial 1 in Children with ADHD. Arch Clin Neuropsychol 29, 605-6.
Loughan, A. R. & Perna, R. (2014). Performance and specificity rates in the Test of Memory Malingering: an investigation into pediatric clinical populations. Appl Neuropsychol Child 3, 26-30.
Quinn, C. A. (2003). Detection of malingering in assessment of adult ADHD. Arch Clin Neuropsychol 18, 379-95.
Suhr, J., Hammers, D., Dobbins-Buckland, K., Zimak, E. & Hughes, C. (2008). The relationship of malingering test failure to self-reported symptoms and neuropsychological findings in adults referred for ADHD evaluation. Arch Clin Neuropsychol 23, 521-30.
Greve, K. W. & Bianchini, K. J. (2002). Using the Wisconsin card sorting test to detect malingering: an analysis of the specificity of two methods in nonmalingering normal and patient samples. J Clin Exp Neuropsychol 24, 48-54.
Killgore, W. D. & DellaPietra, L. (2000). Using the WMS-III to detect malingering: empirical validation of the rarely missed index (RMI). J Clin Exp Neuropsychol 22, 761-71.
Ord, J. S., Greve, K. W. & Bianchini, K. J. (2008). Using the Wechsler Memory Scale-III to detect malingering in mild traumatic brain injury. Clin Neuropsychol 22, 689-704.
Wisdom, N. M., Callahan, J. L. & Shaw, T. G. (2010). Diagnostic utility of the structured inventory of malingered symptomatology to detect malingering in a forensic sample. Arch Clin Neuropsychol 25, 118-25. myths have been manufactured about attention deficit hyperactivity disorder (ADHD).  Facts that are clear and compelling to most scientists and doctors have been distorted or discarded from popular media discussions of the disorder.   Sometimes, the popular media seems motivated by the maxim “Never let the facts get in the way of a good story.”  That’s fine for storytellers, but it is not acceptable for serious and useful discussions about ADHD.

Myths about ADHD are easy to find.  These myths have confused patients and parents and undermined the ability for professionals to appropriately treat the disorder.   When patients or parents get the idea that the diagnosis of ADHD is a subjective invention of doctors, or that ADHD medications cause drug abuse, that makes it less likely they will seek treatment and will increase their chances of having adverse outcomes.

Fortunately, as John Adams famously said of the Boston Massacre, “Facts are stubborn things.”  And science is a stubborn enterprise; it does not tolerate shoddy research or opinions not supported by fact.   ADHD scientists have addressed many of the myths about the disorder in the International Consensus Statement on ADHD, a published summary of scientific facts about ADHD endorsed by a of 75 international ADHD scientists in 2002.  The statement describes evidence for the validity of ADHD, the existence of genetic and neurobiologic causes for the disorder and the range and severity of impairments caused by the disorder.The

Statement makes several key points:

  • The U.S. Surgeon General, the American Medical Association, the American Psychiatric Association, the American Academy of Child and Adolescent Psychiatry, the American Psychological Association, and the American Academy of Pediatrics recognize ADHD as a valid disorder.
  • ADHD involves a serious deficiency in a set of psychological abilities and that these deficiencies pose serious harm to most individuals possessing the disorder.
  • Many studies show that the psychological deficits in people with ADHD are associated with abnormalities in several specific brain regions.
  • The genetic contribution to ADHD is routinely found to be among the highest for any psychiatric disorders.
  • ADHD is not a benign disorder. For those it afflicts, it can cause devastating problems.

The facts about ADHD will prevail if you take the time to learn about them.   This can be difficult when faced with a media blitz of information and misinformation about the disorder.  In future blogs, I’ll separate the fact from the fiction by addressing several popular myths about ADHD. Behavioral Therapy (CBT) is a one to one therapy, for adolescents or adults, where a therapist teaches an ADHD patient how thoughts, feelings, and behaviors are all interrelated and how each of these elements affects the others. CBT emphasizes cognition, or thinking, because a major goal of this therapy is to help patients identifying thinking patterns that lead to problem behaviors. For example, the therapist might discover that the patient frequently has negative automatic thoughts such as “I’m stupid” in challenging situations. We call the though ‘automatic’ because it invades the patients consciousness without any effort. Thinking “I’m stupid” can cause anxiety and depression which leads to failure. Thus, stopping the automatic thought will modify this chain of events and, hopefully, improve the outcome from failure to success.

CBT also educates patients about their ADHD and how it affects them in important daily activities. For example, most ADHD patients need help with activity scheduling, socializing, organizing their workspace and controlling their distractibility. By teaching specific cognitive and behavioral skills, the therapist helps the patient deal with their ADHD symptoms in a productive manner. For example, some ADHD patients are very impulsive when conversing with others. They don’t wait their turn during conversations and may blurt out irrelevant idea. This can be annoying to others, especially in the context of school or business relationships. The CBT therapist helps the patient identify these behaviors and creates strategies for avoiding them.

So, does CBT work for ADHD? The evidence base is small, but when CBT has been used for adult ADHD, it has produced positive results in well-designed studies. These studies typically compare patients taking ADHD medications with those taking ADHD medications and receiving CBT. So for now, it is best to consider CBT as an adjunct to rather than a replacement for medication. There are even fewer studies of CBT for adolescents for ADHD. These initial studies also suggest that CBT will be useful for adolescents with ADHD who are also taking ADHD medications. Some data suggest that CBT can be successfully applied in the classroom environment but, again, the evidence base is very small.

How can this information be used by doctors and patients for treatment planning? Current treatment guidelines suggest starting with an ADHD medication. After a suitable medication and dose is found, the patient and doctor should determine if any problems remain. If so, than CBT should be considered as an adjunct to ADHD medications.

Antshel, K. M. & Olszewski, A. K. (2014). Cognitive Behavioral Therapy for Adolescents with ADHD. Child Adolesc Psychiatr Clin N Am 23, 825-842.
Safren, S. A., Sprich, S., Mimiaga, M. J., Surman, C., Knouse, L., Groves, M. & Otto, M. W. (2010). Cognitive behavioral therapy vs relaxation with educational support for medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. JAMA 304, 875-80.
Solanto, M. V., Marks, D. J., Wasserstein, J., Mitchell, K., Abikoff, H., Alvir, J. M. & Kofman, M. D. (2010). Efficacy of meta-cognitive therapy for adult ADHD. Am J Psychiatry 167, 958-68. stimulants methylphenidate and amphetamine are well known for their efficacy in treating symptoms of ADHD in both youth and adults. Although these medications have been used for several decade, relatively little is known about the mechanisms of action that lead to their therapeutic effect. New data about mechanism comes from a meta-analysis by Katya Rubia and colleagues. They analyzed 14 functional magnetic resonance imaging (fMRI) data sets comprising 212 youth with ADHD. Each of these data sets assessed the short term effects of stimulants on fMRI assessed brain activations. In the fMRI paradigm, ADHD and control participants are asked to do a neurocognitive task while the activity of their brains is being measured. Dr. Rubia and colleagues analyzed data from fMRI assessments of time discrimination, inhibition and working memory, each of which are known to be deficient in ADHD patients. The meta-analysis found that the most consistent brain activations were seen in a region comprising the right inferior frontal cortex (IFC) and insula, even when the analysis was limited to previously medication naïve patients. The implicated region of the brain is known to mediate cognitive control, time estimation and attention. Dr. Rubia also notes that other studies show that the IFC/Insula is needed for updating information and allocating attention to relevant stimuli. Another region implicate by the meta-analysis was the right putamen, a region that is rich in dopamine transporters. This finding is consistent with the fact that the dopamine transporter is the main target of stimulant medications. What are the potential clinical implication of these findings? As Dr. Rubia and colleagues note, it is possible that the fMRI anomalies they identified could be used as a biomarker for ADHD or a biomarker to select patients who should respond optimally to stimulant medication. Although fMRI cannot be used as a clinical tool at this time, research of this sort is opening up new horizons for how we understand the etiology of ADHD and the mechanisms whereby medications exert their effects.

Rubia, K., Alegria, A. A., Cubillo, A. I., Smith, A. B., Brammer, M. J. & Radua, J. (2014). Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Biol Psychiatry 76, 616-28. recent paper by Margaret Sibley and colleagues addresses a key issue in the diagnosis of adult ADHD. Is it sufficient to only collect data from the patient being diagnosed or are informants useful or, perhaps, essential, for diagnosing ADHD in adults. Dr. Sibley presented as systematic review of twelve studies that prospectively followed ADHD children into adulthood. Each of these studies asked a simple question: What faction of ADHD youth continued to have ADHD in adulthood. Surprisingly, the estimates of ADHD’s persistence ranged from a low of 4% to a high of 77%. They found two study features that accounted for much of this wide range. The first was the nature of the informant; did the study rely only on the patient’s report or were other informants consulted. The second was the use of a strict diagnostic threshold of six symptoms. When they limited the analysis to studies that used informant and eliminated the six symptom threshold, the range of estimates was much narrower, 40% to 77%. From studies that computed multiple measures of persistence using different criteria, the authors concluded: “(1) requiring impairment to be present for diagnosis reduced persistence rates; (2) a norm-based symptom threshold led to higher persistence than a strict six-symptom DSM-based symptom count criterion; and (3) informant reports tended to show a higher number of symptoms than self-reports.” These data have clear implications for what clinicians can do to avoid false positive and false negative diagnoses when diagnosing adult ADHD. It is reassuring that the self-reports of ADHD patients tend to underestimate the number and severity of ADHD symptoms. This means that your patients are not typically exaggerating their symptoms. Put differently, self-reports will not lead you to over-diagnose adult ADHD. Instead, reliance on self-reports can lead to false negative diagnoses, i.e., concluding that someone does not have ADHD when, in fact, they do. You can avoid false negatives by doing a thorough assessment, which is facilitated by some tools available at and described in CME videos there. If you think a patient might have ADHD but are not certain, it would be helpful to collect data from an informant, i.e., someone who knows the patient well such as a spouse, partner, roommate or parent. You can collect such data by sending home a rating scale or by having the patient bring an informant to a subsequent visit. Dr. Sibley’s paper also shows that you can avoid false negative diagnoses by using a lower symptom threshold than what is required in the diagnostic manual. In fact, the new DSM 5 lowered the symptom threshold for adults from six to five. Can you go lower? Yes, but it is essential to show that these symptoms lead to clear impairments in living. Importantly, this symptom threshold refers to the number of symptoms documented in adulthood, not to the number of symptoms retrospectively reported in childhood. To be diagnosed with ADHD in adulthood, one must document that the patient had at least six impairing symptoms of ADHD prior to the age of 12.

Sibley, M. H., Mitchell, J. T. & Becker, S. P. (2016). Method of adult diagnosis influences estimated persistence of childhood ADHD: a systematic review of longitudinal studies. Lancet Psychiatry 3, 1157-1165.