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Meta-analysis Finds Strong Link Between Parental and Offspring ADHD

A large international research team has just released a detailed analysis of studies looking at the connection between parents' mental health conditions and their children's mental health, particularly focusing on ADHD (Attention Deficit Hyperactivity Disorder). This analysis, called a meta-analysis, involved carefully examining previous studies on the subject. By September 2022, they had found 211 studies, involving more than 23 million people, that could be combined for their analysis.

Most of the studies focused on mental disorders other than ADHD. However, when they specifically looked at ADHD, they found five studies with over 6.7 million participants. These studies showed that children of parents with ADHD were more than eight times as likely to have ADHD compared to children whose parents did not have ADHD. The likelihood of this result happening by chance was extremely low, meaning the connection between parental ADHD and child ADHD is strong.

Understanding the Numbers: How Likely Is It for a Child to Have ADHD?

The researchers wanted to figure out how common ADHD is among children of parents both with and without ADHD. To do this, they first analyzed 65 studies with about 2.9 million participants, focusing on children whose parents did not have ADHD. They found that around 3% of these children had ADHD.

Next, they analyzed five studies with over 44,000 cases where the parents did have ADHD. In this group, they found that 32% of the children also had ADHD, meaning about one in three. This is a significant difference—children of parents with ADHD are about ten times more likely to have the condition than children whose parents who do not have ADHD.

How Does This Compare to Other Mental Disorders in Parents?

The researchers also wanted to see if other mental health issues in parents, besides ADHD, were linked to ADHD in their children. They analyzed four studies involving 1.5 million participants and found that if a parent had any mental health disorder (like anxiety, depression, or substance use issues), the child’s chances of having ADHD increased by 80%. However, this is far less than the 840% increase seen in children whose parents specifically had ADHD. In other words, ADHD is much more likely to be passed down in families compared to other mental disorders.

Strengths and Weaknesses of the Research

The study had a lot of strengths, mainly due to the large number of participants involved, which helps make the findings more reliable. However, there were also some limitations:

  • The researchers did not look into "publication bias," which means they didn’t check whether only certain types of studies were included (those showing stronger results, for example), which could make the findings seem more extreme.
  • The team reported that differences between the studies were measured, but they didn’t explain clearly how these differences affected the results.
  • Most concerning, the researchers admitted that 96% of the studies they included had a "high risk of bias," meaning that many of the studies might not have been entirely reliable.

Conclusion

Despite these limitations, the research team concluded that their analysis provides strong evidence that children of parents with ADHD or other serious mental health disorders are at a higher risk of developing mental disorders themselves. While more research is needed to fill in the gaps, the findings suggest that it would be wise to carefully monitor the mental health of children whose parents have these conditions to provide support and early intervention if needed

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More Data About Gifted People with ADHD

More Data About Gifted People with ADHD

I recently came across a paper from Tom Brown that adds to the growing scientific literature about smart people with ADHD. Dr. Brown's study measured executive functions in 157 ADHD adults with an intelligence quotient (IQ) in the top 9 percent of the population. The executive functions of the brain regulate cognitive processes in a manner that allows for the effective planning and execution of behaviors.

We know from many studies that both children and ADHD have deficits in executive functions, which impair their ability to manage time and keep themselves organized. Dr. Brown extends that literature by showing that three out of four ADHD adults with high IQ scores were significantly impaired on tests of executive functioning. They had problems in many areas: working memory, processing speed, and auditory-verbal working memory relative.

The lesson from this literature is clear. Smart people can have ADHD. Their high IQs will help them do better than the average person with ADHD, but they may not achieve their potential without appropriate diagnosis and treatment.

For more evidence-based info about adult ADHD, go to www.adhdinadults.com.

May 9, 2021
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Does ADHD Medication Improve the Parenting Skills of Adults with ADHD?

Does ADHD Medication Improve the Parenting Skills of Adults with ADHD?

Raising children is not easy. I should know.

As a clinical psychologist, I've helped parents learn the skills they need to be better parents. And my experience raising three children confirmed my clinical experience.

Parenting is a tough job under the best of circumstances, but it is even harder if the parent has ADHD.

For example, an effective parent establishes rules and enforces them systematically. This requires attention to detail, self-control, and good organizational skills. Given these requirements, it is easy to see how ADHD symptoms interfere with parenting. These observations have led some of my colleagues to test the theory that treating ADHD adults with medication would improve their parenting skills. I know about two studies that tested this idea.

In 2008, Dr. Chronis-Toscano and colleagues published a study using a sustained-release form of methylphenidate for mothers with ADHD. As expected, the medication decreased their symptoms of inattention and hyperactivity/impulsivity. The medication also reduced the mother's use of inconsistent discipline and corporal punishment and improved their monitoring and supervision of their children.

In a 2014 study, Waxmonsky and colleagues observed ADHD adults and their children in a laboratory setting once when the adults were off medication and once when they were on medication. They used the same sustained-release form of amphetamine for all the patients. As expected, the medications reduced ADHD symptoms in the parents. This laboratory study is especially informative because the researchers made objective ratings of parent-child interactions, rather than relying on the parents' reports of those interactions. Twenty parents completed the study. The medication led to less negative talk and commands and more praise by parents. It also reduced negative and inappropriate behaviors in their children.

Both studies suggest that treating ADHD adults with medication will improve their parenting skills. That is good news. But they also found that not all parenting behaviors improved. That makes sense. Parenting is a skill that must be learned. Because ADHD interferes with learning, parents with the disorder need time to learn these skills. Medication can eliminate some of the worst behaviors, but doctors should also provide adjunct behavioral or cognitive-behavioral therapies that could help ADHD parents learn parenting skills and achieve their full potential as parents.

May 7, 2021
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Love, Sex and ADHD

Love, Sex and ADHD

As a researcher who has devoted most of the past three decades to studying ADHD, I am surprised (and somewhat embarrassed) to see how little research has focused on how ADHD affects the romantic side of life. There are over 25,000 articles about ADHD listed onwww.PubMed.gov, but only a few have provided data about love, sex, and ADHD. Brunner and colleagues studied ADHD symptoms and romantic relationship quality in 189 college students. Those students who had high levels of both hyperactivity-impulsivity and inattentiveness reported that the quality of their romantic relationships was relatively low compared with students who had low levels of ADHD symptoms. Another study of 497 college students found that ADHD symptoms predicted greater use of maladaptive coping strategies in romantic relationships and less romantic satisfaction. A study of young adults compared conflict resolution and problem-solving in romantic couples. It found that ADHD symptoms were associated with greater negativity and less positivity during a conflict resolution task, and that higher symptoms predicted less relational satisfaction. But this was not true, as the ADHD member of the couple only had inattentive symptoms, which suggests that the severity of ADHD symptoms might drive relationship problems. Unlike the studies of adults, the romantic relationships of adolescents with and without ADHD did not differ in levels of aggression or relationship quality, although only one study addressed this issue.
What about sex? 
The study of adolescents found that irrespective of gender, adolescents with ADHD had nearly double the number of lifetime sexual partners. That finding is consistent with Barkley's follow-up study of ADHD children. He and his colleagues found that ADHD predicted early sexual activity and early parenthood. Similar findings were reported by Flory and colleagues in a retrospective study of young adults. Childhood ADHD predicted earlier initiation of sexual activity and intercourse, more sexual partners, more casual sex, and more partner pregnancies. When my colleagues and I studied 1001 adults in the community, we found that adults with ADHD endorsed less stability in their love relationships, felt less able to provide emotional support to their loved ones, experienced more sexual dysfunction, and had higher divorce rates. The research literature about love, sex, and ADHD is small, but it is consistent.

May 5, 2021
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Is ADHD a Serious Condition?

Is ADHD a Serious Condition?

In the popular media, ADHD has sometimes been portrayed as a minor condition or not a disorder at all. It is easy to find websites claiming that ADHD is an invention of the medical profession and that the symptoms used to diagnose the disorder are simply normal behaviors that have been "medicalized". These claims are wrong. They miss the main point of any psychiatric diagnostic process, which is to identify people who experience distress or disability due to a set of well-defined symptoms. So, does ADHD cause serious distress and disability? It is a serious psychiatric condition? To illustrate the strong evidence base for the "Yes" answer to that question, my colleagues and I constructed this infographic for our "Primer" about ADHD,http://rdcu.be/gYyV.It describes the many ways in which the symptoms of ADHD impact and impair the lives of children, adolescents, and adults with the disorder. We divided these 'impacts' into four categories: other disorders (both psychiatric and medical), psychological dysfunction, academic and occupational failure, social disability, and risky behaviors. Let's start with other health problems. We know from many studies that have followed ADHD children into adolescence and adulthood that having the disorder puts patients at risk for several psychiatric disorders, addictions, criminality, learning disabilities, and speech/language disorders. ADHD even increases the risk for-psychiatric diseases such as obesity, hypertension, and diabetes. Perhaps most worrisome is that people with ADHD have a small increased risk for premature death. This increased risk is due in part to their having other psychiatric and medical conditions and also to their risky behaviors which, as research documents, lead to accidents and traumatic brain injuries. In the category of psychological dysfunction,' we highlighted emotional dysregulation, which makes ADHD people quick to anger or fail to tame extreme emotions. Other serious psychological issues are low self-esteem and increased thoughts of suicide, which lead to more suicide attempts than for people without ADHD. This increased risk for suicide is small, but it is real. A more prevalent impact of ADHD is the broad category of social disability, which includes marital discord, poor parenting, legal problems, arrests, and incarceration. This typically starts in youth with poor social adjustment and conflict with parents, siblings, and friends. Another common impact of ADHD is on academic and vocational pursuits. ADHD youth are at risk for underachievement in school, repeating grades, and dropping out. As adults, they are more likely to be unemployed or underemployed, which leads to them having lower incomes than expected for their level of school achievement. So, don't believe anyone who claims that ADHD is not a disorder or is only a mild one. To be sure, there is a wide range of impairments among people with ADHD but, in the absence of treatment, they are at risk for adverse outcomes. Fortunately, the medications that treat ADHD have been documented to reduce this risk, which is why they are typically the first-line treatment for most people with ADHD.

May 3, 2021
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Is ADHD A Serious Conidtion?

How Serious is ADHD?

The US Center for Disease Control's (CDC)review of ADHD starts with the statement: "Attention-deficit/hyperactivity disorder (ADHD) is a serious public health problem affecting many children and adults" (http://www.cdc.gov/ncbddd/adhd/research.html). My colleagues and I recently reviewed the ADHD literature. That let us describe ADHD as "... a seriously impairing, often persistent neurobiological disorder of high prevalence..." (Faraone et al., 2015). The figure 1, which comes from that paper, provides an overview of the lifetime trajectory of ADHD-associated morbidity.

Especially compelling data about ADHD and injuries comes from a recent paper, in Lancet Psychiatry, which used the Danish national registers to follow a cohort of 710,120 children (Dalsgaard et al., 2015a).   Compared with children not having ADHD, those with ADHD were 30% more likely to sustain injuries than other children.  Pharmacotherapy for ADHD reduced the risk for injuries by 32% from 5 to 10 years of age. Pharmacotherapy for ADHD reduced emergency room visits by 28.2% at age 10and 45.7% at age 12.    

These results are shown in Figure 2, taken from the publication.

Especially compelling data about ADHD and injuries comes from a recent paper, in Lancet Psychiatry, which used the Danish national registers to follow a cohort of 710,120 children (Dalsgaard et al., 2015a).   Compared with children not having ADHD, those with ADHD were 30% more likely to sustain injuries than other children.  Pharmacotherapy for ADHD reduced the risk for injuries by 32% from 5 to 10 years of age. Pharmacotherapy for ADHD reduced emergency room visits by 28.2%at age 10and 45.7% at age 12.    

These results are shown in Figure2, taken from the publication.  The Figure compares the prevalence of injuries among three groups.  ADHD children treated with medication, ADHD children not treated with medication, and children without ADHD.  The Figure shows how ADHD risk for injuries occurs for all age groups. It also shows how the risk for injuries drops with treatment so that by age 12, the prevalence of injuries among treated ADHD children is the same as the prevalence of injuries for children without ADHD.

Documented examples of ADHD-associated injuries which impact day-to-day functioning include severe burns (Fritz and Butz, 2007), dental injuries (Sabuncuoglu, 2007), penetrating eye injuries (Bayar et al., 2015), the hospital treated injuries (Hurtig et al., 2013), and head injuries (DiScala et al., 1998).  In one study (DiScala et al., 1998), when compared to other children admitted to the hospital for injuries, ADHD children were more likely to sustain injuries in multiple body regions (57.1% vs 43%), sustain head injuries (53% vs 41%), and to be severely injured as measured by the Injury Severity Score (12.5% vs5.4%) and the Glasgow Coma Scale (7.5% vs 3.4%).

Injuries are a substantial cause of ADHD-associated premature death.  This assertion comes from the work of Dalsgaard et al. (2015b)based on the same Danish registry discussed above.   In this second study, ADHD was associated with an increased risk for premature death and 53% of those deaths were due to injuries.  They reported the risk for premature death in three age groups: 1-5, 6-17, and >17.  For all three age groups, they found a greater risk for death in the ADHD group. For ages 6 to 17 and greater than 17. The ADHD-associated risk for mortality remained significant after excluding individuals with antisocial or substance use disorders.

There are currently no data about the effect of ADHD treatment on ADHD-associated premature death.  We do, however, know from the data reviewed above that ADHD treatment reduces injuries and that half the deaths in the ADHD group were due to injuries.  From this, we infer that ADHD treatments could reduce the risk of ADHD-associated premature death.

Two other ADHD-associated mobilities, obesity and cigarette smoking, have clear medical consequences.  In a meta-analysis of 42 cross-sectional studies comprising 48,161 people with ADHD and 679,975 controls, my colleagues and I reported that the pooled prevalence of obesity was increased by about 40% in ADHD children compared with non-ADHD children and by about 70% in ADHD adults compared with non-ADHD adults(Cortese et al.,2015). The association between ADHD and obesity was significant for ADHD medication-naïve subjects but not for those medicated for ADHD, which suggests that medication reduces the risk for obesity.  

Likewise, a meta-analysis of 27 longitudinal studies assessed the risk for several addictive disorders with sample sizes ranging from 4142 to 4175 for ADHD and 6835 to 6880 for non-ADHD controls (Lee et al., 2011).  Children with ADHD were at higher risk for disorders of abuse or dependence on nicotine, alcohol, marijuana, cocaine, and other unspecified substances.  Another meta-analysis (42 studies totaling, 2360 participants) showed that medications for ADHD reduced the ADHD-associated risk for smoking (Schoenfelder et al., 2014).   The authors concluded that, for ADHD patients, "Consistent stimulant treatment for ADHD may reduce the risk of smoking". This finding is especially notable given that, for ADHD youth, cigarette smoking is a gateway drug to more serious addictions (Biederman et al., 2006).

 Yes, ADHD is a serious disorder.  Although most ADHD people will be spared the worst of these outcomes, they must be considered by parents and patients when weighing the pros and cons of treatment options.

November 16, 2023
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How to Avoid False Positives and False Negatives when Diagnosing Adult ADHD

How to Avoid False Positives and False Negatives when Diagnosing Adult ADHD?

A 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 a systematic review of twelve studies that prospectively followed ADHD children into adulthood. Each of these studies asked a simple question: What fraction of ADHD youth continued to have ADHD in adulthood. Surprisingly, the estimates of ADHD's persistence ranged from a low of4% 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 informants 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 www. ADHD in adults. Command 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. 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 before the age of 12.

April 29, 2021
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What Can Doctors Do About Those Faking ADHD?

What can Doctors do about Fake ADHD?

ADHD 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, people can pretend that they have ADHD when they do not. 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 Internetseems to be 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 in 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 makeup examples of how they have had them when they have not. The research discussed above 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 itself-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 patient's 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 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.

April 27, 2021
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Attention Deficit Hyperactivity Disorder: Fact vs. Fiction

Attention Deficit Hyperactivity Disorder: Fact vs. Fiction

Many 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 of 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 75 international ADHD scientists in2002.  The statement describes evidence for the validity of ADHD, the existence of genetic and neurobiological 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 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 disorder.
  • 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.

April 25, 2021
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What is Evidenced-Based Medicine?

What is Evidenced-Based Medicine?

With 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 blog has 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 evidence-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 reported 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;http://www.cebm.net/).


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.

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.  

  1. Non-randomized means that the comparison might be confounded by having placed different types of patients in the treatment and control groups.
  2. A single randomized trial.  This type of study is not confounded.
  3. 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 the magnitude of the 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 evidence-based approach when deciding which treatments are well-supported as helpful for a disorder.

April 23, 2021
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How do Stimulants Modulate the Brain to Improve ADHD Symptoms?

How do Stimulants Modulate the Brain to Improve ADHD Symptoms?

The 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 decades, relatively little is known about the mechanisms of action that lead to their therapeutic effect.    

New data about the 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 is 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 is 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.

April 21, 2021
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