A team from Harvard Medical School and Massachusetts General Hospital conducted a six-week open-label trial of liquid-formulation extended-release methylphenidate (MPH-ER) to treat ADHD in adults with high-functioning autism spectrum disorder (HF-ASD). ASD is a lifelong disorder with deficits in social communication and interaction and restricted, repetitive behaviors. Roughly half of those diagnosed with ASD also are diagnosed with ADHD.

This was the first stimulant trial in adults with both ASD and ADHD. There were twelve male and three female participants, all with moderate to severe ADHD, and in their twenties, with IQ scores of at least 85.

Use of a liquid formulation enabled doses to be raised very gradually, starting with a daily dose of 5mg (1mL) and titrating up to 60mg over the first three weeks, then maintaining that level through the sixth week. Participants were reevaluated for ADHD symptoms every week during the six-week trial. Severity of ASD was assessed at the start, midpoint, and conclusion of the trial, as were other psychiatric symptoms.

Prior to the trial, researchers agreed on a combination of targets on two clinician-rated scoring systems that would have to be reached for treatment to be considered successful. One is a score of 2 or less on the CGI-S, a measure of illness severity, with scores ranging from 1 (normal, not at all ill) to 7 (most extremely ill). The other, a reduction of at least 30 percent in the AISRS score, which combines each of 18 symptoms of ADHD on a severity grid (0=not present; 3=severe; overall minimum score: 0; overall maximum score: 54).
At the conclusion of the trial, twelve of the fifteen patients (80 percent) met the preset conditions for success. Fully fourteen (93 percent) saw a ≥ 30 percent reduction in their AISRS score, while twelve scored ≤ 2 on illness severity.

However, when using the patient-rated ASRS scoring system, only five (33 percent) saw a ≥ 30 percent reduction in ADHD severity.

Thirteen participants (87 percent) reported at least one adverse event, and nine (60 percent) reported two or more. One reported a serious adverse event (attempted suicide) in a patient with multiple prior attempts. Because the attempt was not deemed due to medication they continued in and completed the trial. Seven participants experienced titration-limiting adverse events (headaches, palpitations, jaw pain, and insomnia). Headache was most frequent (53%), followed by insomnia and anxiety (33% each), and decreased appetite (27%).

During the trial, weight significantly decreased, while pulse significantly increased. There were no significant differences in other vital and cardiovascular measurements.

The authors concluded, “this OLT of short-term MPH-ER therapy documents that acute treatment with MPH-ER in young adults with ASD was associated with significant improvement in ADHD symptoms, mirroring the typically-expected magnitude of response observed in adults with only ADHD. Treatment with MPH-ER was well-tolerated, though associated with a higher than expected frequency of adverse events.”

They also cautioned, “The results of this study need to be considered in light of some methodological limitations. This was an open-label study; therefore, assessments were not blind to treatment. We did not employ a placebo control group and, therefore, cannot separate the effects of treatment from time or placebo effects. … firmer conclusions regarding the safety and efficacy of MPH-ER for the treatment of ADHD in HF-ASD populations await results from larger, randomized, placebo-controlled clinical trials.”

REFERENCES:
Gagan Joshi, Maura DiSalvo, Janet Wozniak, T. Atilla Ceranoglu, Amy Yule, Craig Surman, Ronna Fried, Maribel Galdo, Barbora Hoskova, Abigail Belser & Joseph Biederman, “A Prospective Open-Label Trial of Long-Acting Liquid Methylphenidate for the Treatment of Attention Deficit/Hyperactivity Disorder in Intellectually Capable Adults with Autism Spectrum Disorder,” The World Journal of Biological Psychiatry (2019) DOI: 10.1080/15622975.2019.1679392.

To gauge the extent of stigma towards persons with ADHD, a European research team hired a company specialized in market and social research to conduct a poll of some five thousand randomly selected Germans. Just over a thousand completed the interview, representing a response rate of only one in five. The team acknowledged, “Although non-responder bias has to be considered to be important, ethical considerations prohibited the collection of any detailed information on non-respondents.” The sample had slightly more women and elderly persons, and a higher average level of educational attainment relative to the German population as a whole. Sampling weights were used to compensate for these discrepancies.

The poll relied on computer-assisted telephone interviews. Interviews began with prerecorded vignettes of either a 12-year-old child or 35-year-old adult exhibiting core symptoms of ADHD (such as “careless mistakes in schoolwork,” “does not follow through on instructions,” “easily distracted by extraneous stimuli”, “loses things”, “leaves his place in the classroom or when sitting at the dining table”). Half those interviewed were presented with child vignettes and half with adult vignettes. The gender of the person described varied randomly.

On a scale of one to five, respondents were asked to indicate levels of agreement with two statements: 1. ‘‘Basically, we are all sometimes like this person. It’s just a question of how pronounced this state is.’’ 2. “All in all the problems of Robert / Anne are abnormal.” For both child and adult vignettes, two out of three respondents agreed that “we are all sometimes like this person.” One in three respondents considered the problems depicted in the child vignettes as abnormal. That dropped to one in four in the adult vignettes.

Next, respondents were asked whether they ever had a problem like this and whether someone among their family or close friends ever had to deal with such a problem. For both vignettes, one in four acknowledged having had a problem like this, and half said a close friend or family member had such a problem.

On the assumption that “negative emotional reactions are an important consequence of negative stereotypes, leading to separation, discrimination and status loss,” respondents were probed for the specific emotional reactions. “I feel annoyed,” “I react angrily,” and “provokes my incomprehension” were interpreted as indicating varying levels of anger. “Provokes fear” and “Makes me feel insecure” were seen as indicating fear. “I feel uncomfortable” was viewed as indicating somewhere between fear and anger. On the other hand, “I feel the need to help,” “I feel pity,” and “I feel sympathy” were interpreted as “pro-social” responses.

Pro-social reactions were by far the most common. Over two-thirds felt a need to help a child, and over half to help an adult, in such a situation. In both instances, almost half felt sympathy, and half or more felt pity. On the other hand, a quarter of respondents in each case felt annoyed, and just under one in five felt uncomfortable. Almost one in seven reacted angrily to the child vignette and almost one in six to the adult vignette. Fear was the least frequent emotional reaction.

In the case of adults, respondents were also asked about their willingness to accept the person described in the vignette in seven social situations:

  • Working together
  • As a neighbor
  • Marrying into the family
  • Introducing to a friend
  • Renting a room
  • Recommending for a job
  • Taking care of children

While three out of four respondents were willing to accept such persons as co-workers, only one in three would recommend them for a job. Two out of three would accept such persons as neighbors, and almost as many to marry into the family. Three out of five would very willingly introduce such persons to friends. Slightly over half would rent a room to them. But less than one in three would be willing to have such individuals take care of their own children.

Older respondents were more likely to see the problems as “abnormal” and to seek greater social distance. Women and respondents with higher levels of education were less likely to see the problems as abnormal and more likely to respond in pro-social ways.

Though showing most Germans to be accepting of persons with ADHD, these findings still indicate a significant degree of stigma, though less than for other psychiatric conditions such as depression, schizophrenia, or alcohol dependence.

REFERENCES:
Sven Speerforck, Susanne Stolzenburg, Johannes Hertel, Hans J. Grabe, Maria Strauß, Mauro G. Carta, Matthias C. Angermeyer, Georg Schomerus, “ADHD, stigma and continuum beliefs: A population survey on public attitudes towards children and adults with attention deficit hyperactivity disorder,” Psychiatry Research (2019) DOI: https://doi.org/10.1016/j.psychres.2019.112570.

Stephen V. Faraone, PhDMethylphenidate (MPH) is one of the most widely-prescribed medications for children. Given that ADHD frequently persists over a large part of an individual’s lifespan, any side effects of medication initiated during childhood may well be compounded over time. With funding from the European Union, a recently released review of the evidence looked for possible adverse neurological and psychiatric outcomes.

From the outset, the international team recognized a challenge: “ADHD severity may be an important potential confounder as it may be associated with both the need for long-term MPH therapy and high levels of underlying neuropsychiatric comorbidity.” Their searches found a highly heterogeneous evidence base, which made meta-analysis inadvisable. For example, only 25 of 39 group studies reported the presence or absence of comorbid psychiatric conditions, and even among those, only one excluded participants with comorbidities. Moreover, in only 24 of 67 studies was the type of MPH used (immediate or extended-release) specified. The team, therefore, focused on laying out an “evidence map” to help determine priorities for further research.

The team found the following breakdown for specific types of adverse events:

  • Low mood/depression. All three noncomparative studies found MPH safe. Two large cohort studies, one with over 2,300 participants, the other with 142,000, favored MPH over the non-stimulant atomoxetine. But many other studies, including a randomized controlled trial (RCT), had unclear results. Conclusion: “the evidence base regarding mood outcomes from long-term MPH treatment is relatively strong, includes two well-powered comparative studies, and tends to favor MPH.”
  • Anxiety. Here again, all three noncomparative studies found MPH safe. But only two of seven comparative studies favored MPH, with the other five having unclear results. Conclusion: “while the evidence with regard to anxiety as an outcome of long-term MPH treatment tends to favor MPH, the evidence base is relatively weak.”
  • Irritability/emotional reactivity. A large cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: “the evidence base … is limited, although it includes one well-powered study that found in favor of MPH over atomoxetine.”
    Suicidal behavior/ideation. There were no noncomparative studies, but all five comparative studies favored MPH. That included three large cohort studies, with a combined total of over a hundred thousand participants, that favored MPH over atomoxetine. Conclusion: “the evidence base … is relatively strong, and tends to favor MPH.”
  • Bipolar disorder. A very large cohort study, with well over a quarter-million participants, favored MPH over atomoxetine. A much smaller cohort study comparing MPH with atomoxetine, with less than a tenth the number of participants, pointed toward caution. Conclusion: “the evidence base … is limited and unclear, although it includes two well-powered studies.”
  • Psychosis/psychotic-like symptoms. By far the largest study, with over 145,000 participants, compared MPH with no treatment and pointed toward caution. A cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: “These findings indicate that more research is needed into the relationship between ADHD and psychosis, and into whether MPH moderates that risk, as well as research into individual risk-factors for MPH-related psychosis in young people with ADHD.”
  • Substance use disorders. A cohort study with over 20,000 participants favored MPH over anti-depressants, anti-psychotics, and no medication. Other studies looking at dosages and durations of treatment, age at treatment initiation, or comparing with no treatment or “alternative” treatment, all favored MPH with the exception of a single study with unclear results. Conclusion: “the evidence base … is relatively strong, includes one well-powered study that compared MPH with antipsychotic and antidepressant treatment, and tends to favor MPH.”
  • Tics and other dyskinesias. Of four noncomparative studies, three favored MPH, the other, with the smallest sample size, urged caution. In studies comparing with dexamphetamine, pemoline, Adderall, or no active treatment, three had unclear results and two pointed towards caution. Conclusion: “more research is needed regarding the safety and management of long-term MPH in those with comorbid tics or tic disorder.”
  • Seizures or EEG abnormalities. With one exception, the studies had small sample sizes. The largest, with over 2,300 participants, compared MPH with atomoxetine, with inconclusive results. Two small studies found MPH safe, one had unclear results, and two others pointed towards caution. Conclusion: “While the evidence is limited and unclear, the studies do not indicate evidence for seizures as an AE of MPH treatment in children with no prior history … more research is needed into the safety of long-term MPH in children and young people at risk of seizures.”
  • Sleep Disorders. All three noncomparative studies found MPH safe, but the largest cohort study, with over 2,300 participants, clearly favored atomoxetine. Conclusion: “more research is needed into the relationship between ADHD, sleep, and long-term MPH treatment.”
  • Other notable psychiatric outcomes. Two noncomparative studies, with 118 and 289 participants, found MPH safe. A cohort study with over 700 participants compared with atomoxetine, with inconclusive results. Conclusion: “there is limited evidence regarding long-term MPH treatment and other neuropsychiatric outcomes and that further research may be needed into the relationship between long-term MPH treatment and aggression/hostility.”

Although this landmark review points to several gaps in the evidence base, it mainly supports prior conclusions of the US Food and Drug Administration (FDA) and other regulatory agencies (based on short-term randomized controlled trials) that MPH is safe for the treatment of ADHD in children and adults. Give that MPH has been used for ADHD for over fifty years and that FDA monitors the emergence of rare adverse events, patients, parents, and prescribers can feel confident that the medication is safe when used as prescribed.

REFERENCES:
Helga Krinzinger, Charlotte L Hall, Madeleine J Groom, Mohammed T Ansari, Tobias Banaschewski, Jan K Buitelaar, Sara Carucci, David Coghill, Marina Danckaerts, Ralf W Dittmann, Bruno Falissard, Peter Garas, Sarah K Inglis, Hanna Kovshoff, Puja Kochhar, Suzanne McCarthy, Peter Nagy, Antje Neubert, Samantha Roberts, Kapil Sayal, Edmund Sonuga-Barke , Ian C K Wong , Jun Xia, Alexander Zuddas, Chris Hollis, Kerstin Konrad, Elizabeth B Liddle and the ADDUCE Consortium, “Neurological and psychiatric adverse effects of long-term methylphenidate treatment in ADHD: A map of the current evidence,” Neuroscience and Biobehavioral Reviews (2019) DOI: https://doi.org/10.1016/j.neubiorev.2019.09.023

A Dutch and German team compared the performance of 45 adults with ADHD and 51 normally developing controls on a battery of standardized tests and questionnaires designed to assess competence in financial decision-making (FDM). These were supplemented with neuropsychological tests, as well as evaluations of each participant’s personal financial situation.

The two groups had roughly comparable demographic characteristics. There were no significant differences in age, gender balance, years of education, or work status. Students were excluded from both groups because they tend to be financially dependent and to have little or no income.

The ADHD group scored more than three times higher on self-report questionnaires for both the retrospective assessment of childhood symptoms (Wender Utah Rating Scale—Childhood) and for evaluating current symptoms of ADHD (ADHD self-report scale). Researchers did not perform clinical evaluations of ADHD.

To determine their personal financial situation, participants were asked about their income range as well as, “Do you have debts other than mortgage or study loans?”; “Do you receive social security?”; “Do you have a savings account?”; “Do you save actively, that is, do you put money on your savings account on a regular basis?”; “Do you save for retirement?”; and “Do you own a house?” They were also asked how much they set aside in monthly savings, and, where applicable, how much they receive in social security.

On five out of nine criteria, significant differences emerged between the two groups. Whereas healthy controls had median incomes in the range of €35,000 to €45,000, for those with ADHD it was dramatically lower, between €15,000 and €25,000. Healthy controls also had twice as much disposable income. Whereas almost half of adults with ADHD reported debts other than a mortgage or educational loans, only a third as many healthy adults had such debt. And whereas only slightly over half of those with ADHD reported having savings accounts, among healthy adults, it was more than six out of seven. Finally, healthy controls were four times as likely to own a home.

Participants were then given standardized tests to evaluate financial competence, financial decision-making capacity, financial decision styles, the ability to make financial decisions using decision rules, the capacity to make decisions with implications for the future, impulsive buying tendencies, and a gambling task as a measure of emotional decision-making.

Adults with ADHD scored significantly lower than healthy adults on the financial competence test, and in particular, on financial abilities, financial judgment, financial management, and financial support resources. Similar outcomes emerged from the financial decision-making capacity test, especially when it came to identifying and understanding relevant information. Adults with ADHD were also significantly more likely to use avoidant and spontaneous decision styles. They also showed significantly more temporal discounting, meaning they tended to prefer immediate gratification over long-term financial security. That translated into significantly higher propensities to buy on impulse. In all cases, these differences had large effect sizes.

Finally, participants were tested on nine cognitive functions: information processing speed, vigilance and selective attention, inhibition, interference, figural fluency, cognitive flexibility, task switching, verbal working memory, and numeracy.

Those with ADHD performed significantly worse, with medium effect sizes, on three cognitive measures: vigilance, interference, and numeracy. There were no significant differences on the other six measures.

The authors concluded, “The results show that the personal financial situation of adults with ADHD was less optimal than the financial situation of healthy controls. Furthermore, adults with ADHD showed significantly decreased performances compared with healthy controls in five out of seven tasks measuring FDM and on measures of vigilance, interference, and numeracy. However, mediation analyses indicated that differences in cognitive functioning cannot fully explain the differences with regard to FDM between adults with ADHD and healthy controls.”

They also pointed to the limitations of the study. One is that 19 of the 45 adults with ADHD had comorbid disorders, of which three were substance dependencies. However, removing them had little effect on the outcome. Another limitation was that adults with ADHD were off medication during the testing, so it is unclear how stimulants would affect the test outcomes. The authors state, “The influence of treatment use should, therefore, be explored in future research on FDM and adults with ADHD.”

REFERENCES:
Dorien F. Bangma, et al., “Financial Decision-Making in Adults With ADHD,” Neuropsychology (2019), http://dx.doi.org/10.1037/neu0000571.

Drivers with ADHD are far more likely to be involved in crashes, to be at fault in crashes, to be in severe crashes, and to be killed in crashes. The more severe the ADHD symptoms, the higher the risk. Moreover, ADHD is often accompanied by comorbid conditions such as oppositional-defiant disorder, depression, and anxiety that further increase the risk.
What can be done to reduce this risk? A group of experts has offered the following consensus recommendations:

  • Use stimulant medications. While there is no reliable evidence on whether non-stimulant medications are of any benefit for driving, there is solid evidence that stimulant medications are effective in reducing risk. But there is also a “rebound effect” in many individuals after the medication wears off, in which performance actually becomes worse than if had been prior to medication. It is therefore important to time the taking of medication so that its period of effectiveness corresponds with driving times. If one has to drive right after waking up, it makes sense to take a rapid-acting form. The same holds for late-night driving that may require a quick boost.
  • Use a stick shift vehicle wherever possible. Stick shifts make drivers pay closer attention than automatic transmissions. The benefits in alertness are most notable in city traffic. But using a stick shift is far less beneficial in highway driving, where shifting is less frequent.
  • Avoid cruise control. Highways can be monotonous, making drivers more prone to boredom and distraction. That is even more true for those with ADHD, so it is best to keep cruise control turned off.
  • Avoid alcohol. Drinking and driving is a bad idea for everyone, but, once again, it’s even worse for those with ADHD. Parents should consider a no-questions-asked policy of either picking up their teenager anytime and anywhere or setting up an account with a ride-sharing service.
  • Place the smartphone out of reach and hearing. Cell phone use is as about as likely to impair as alcohol. Hands-free devices only reduce this risk moderately, because they continue to distract. Texting can be deadly. Sending a short text or emoticon can be the equivalent of driving 100 yards with one’s eyes closed. Either turn on Do Not Disturb mode, or, for even greater effectiveness, place the smartphone in the trunk.
  • Make use of automotive performance monitors. These can keep track of maximum speeds and sudden acceleration and braking, to verify that a teenager is not engaging in risky behaviors.
  • Take advantage of “graduated driver’s licensing laws” wherever available. These laws forbid the presence of peers in the vehicle for the first several (for example, six) months of driving. Parents can extend that period for teenagers with ADHD, or set it as a condition in states that lack such laws.
  • Encourage practicing after obtaining a learner’s permit. Teenagers with ADHD generally require more practice than those without. A “pre-drive checklist” can be a good place to start. For example: check the gas, check the mirrors, make sure the view through the windows is unobstructed, put cell phone in Do Not Disturb mode and place it out of reach, put on a seatbelt, scan for obstacles.
    Consider outsourcing. Look for a driving school with a professional to teach good driving skills and habits.

Experts do not agree on whether to delay licensing for those with ADHD. On the one hand, teenagers with ADHD are 3-4 years behind in the development of brain areas responsible for executive functions that help control impulses and better guide behavior. Delaying licensing can reduce risk by about 20 percent. On the other hand, teens with ADHD are more likely to drive without a license, and no one wants to encourage that, however inadvertently. Moreover, graduated driver’s licensing laws only have legal effect on teens who get their licenses at the customary age.

REFERENCES:
Paula A. Aduen, Daniel J. Cox, Gregory A. Fabiano, Annie A. Garner, Michael J. Kofler, “Expert Recommendations for Improving Driving Safety for Teens and Adult Drivers with ADHD,” ADHD Rep. (2019) 27(4): 8–14. doi:10.1521/adhd.2019.27.4.8.

The Nordic countries maintain detailed registers of their inhabitants. This enables researchers to examine patterns over entire nations. An international research team used the Swedish national registers for a prospective cohort study of 2,675,615 persons in the Medical Birth Register born in Sweden over a 27-year period from January 1, 1983 through December 31, 2009. Follow-up was completed in December 2013, with the oldest cohort member aged 31. The mean age at study entry was 6, and the mean at follow-up was 11.

Using personal identification numbers, researchers were able to cross-reference with the National Patient Register and the National Drug Register. From this they determined that 86,670 members of the cohort (3.2 percent) had ADHD, based either on records of clinical diagnosis or of prescription of ADHD drugs. Psychiatric comorbidities were likewise identified in the National Patient Register.

These comorbidities were significantly more prevalent in the ADHD population than in the rest of the cohort. For example, whereas only 2.2% of the non-ADHD group was diagnosed with substance use disorder (SUD), 13.3% of the ADHD group also had SUD, a six-fold difference. For depression it was a seven-fold difference, for schizophrenia a nine-fold difference.

The ADHD group had a significantly higher risk of premature death from all causes than the non-ADHD group, with an adjusted hazard ratio (HR) of 3.94 (95% CI 3.51-4.43). Unintentional injury (36%) and suicide (31%) were the leading causes of death in the ADHD group. Those with ADHD were more than eight times more likely to die by suicide than non-ADHD individuals, and roughly four times more likely to die from unintentional injury.

The vast majority of the increased risk appears to be associated with comorbid psychiatric conditions. Those with ADHD but no diagnosed comorbidities had an adjusted HR of 1.41 (95% CI 1.01-1.97). With a single comorbidity, the HR more than doubled to 3.71 (95% CI 2.88-4.78). With four or more comorbidities, it rose to a staggering 25.22 (95% CI 19.6-32.46).

The comorbid condition with the greatest impact was SUD, which increased the risk eight-fold by comparison with those with only ADHD (HR = 8.01, 95% CI 6.16-10.41). Anxiety disorder, schizophrenia, and personality disorder increased the risk about fourfold. Bipolar disorder, depression, and eating disorder increased risk roughly two and a half times.

Covariate analysis helped tease out what portion of the risk was associated with ADHD alone versus comorbid conditions. Adjusting for year of birth, sex, birth weight, maternal age at birth, parental educational level, and parental employment status, those with ADHD (including comorbid conditions) were 2.7 times more likely to prematurely die of natural causes than those without. Adjusting for comorbid psychiatric conditions completely eliminated the risk from ADHD alone (HR = 1.01, 95% CI .72-1.42).

Likewise, those with ADHD (including comorbid conditions) were six times as likely to die of unnatural causes. Adjusting for early-onset comorbid disorders (such as conduct disorders, autism spectrum disorder, and intellectual disability) only modestly reduced the HR to 5.3, but further adjusting for later-onset comorbid disorders (including substance use disorder, depressive disorder, bipolar disorder, anxiety disorder, schizophrenia, personality disorder, and eating disorders) reduced the HR to 1.57 (95% CI 1.35-1.83), and reduced it to insignificance in the case of suicide (HR = 1.13, 95% CI .88-1.45).

Summing up, the lion’s share of the greater risk of premature death in persons with ADHD is attributable to psychiatric comorbidities. Nevertheless, those with ADHD alone still face a 40 percent greater risk than those without ADHD.

The study did not examine effects of ADHD medication, which the authors state “should be analyzed because of documented potential benefits on ADHD symptoms and comorbid disorders.”

The authors concluded, “Among adults, early-onset psychiatric comorbidity contributed substantially to the premature mortality risks due to natural causes. On the other hand, later-onset psychiatric comorbidity, especially SUD, explained a substantial part of the risk for unnatural deaths, including all the risk of suicide deaths and most of the deaths due to unintentional injuries. These results suggest that overall health conditions and risk of psychiatric comorbidity should be evaluated clinically to identify high-risk groups among individuals with ADHD.”

REFERENCES:
Shihua Sun, MD; Ralf Kuja-Halkola, PhD; Stephen V. Faraone, PhD; Brian M. D’Onofrio, PhD; Søren Dalsgaard, PhD; Zheng Chang, PhD; Henrik Larsson, PhD, “Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder,” JAMA Psychiatry doi:10.1001/jamapsychiatry.2019.1944 Published online August 7, 2019.

ADHD, especially when untreated impairs patients and creates difficulties in families. Although these are the proximal targets of treatment, ADHD also burdens society due, for example, to underemployment and use of health resources. A recent study assessed economic burden using the Danish population registries, researchers, which link medical information with employment, education, crime, and social care registers while maintaining confidentiality. They identified 5,269 adults with adult ADHD who had not been diagnosed with ADHD in childhood and, we can assume, were probably not treated for the disorder. They excluded patients with other psychiatric diagnoses, and cases without a same sex sibling free of any diagnosed psychiatric diagnoses. That left 460 pairs of same-sex siblings, one with adult ADHD and the other with no psychiatric diagnosis. They selected the non-ADHD sibling closest in age to the ADHD sibling. Using siblings mitigated effects of genetics and upbringing between the ADHD group and normally developing controls.

Looking at personal income (combining work income and public transfers), adults with ADHD on average brought home about 12,000 Euros less – almost a third less – than their sibling counterparts. They also paid 40% less tax. Balancing that out, their after-tax income was roughly 7,500 Euros less than their siblings. With the additional personal cost of prescribed medication (prescriptions are relatively inexpensive in Denmark, and copayments even more so) the net personal cost to adults with ADHD was 7,700 Euros.

The net public costs were considerably greater. That was primarily due to the reduction in taxes paid (about 4,500 Euros) and increase in income replacement transfers (just over 5,500 Euros). The cost of additional crimes committed by adults with ADHD added another 1,000 Euros. Additional primary and secondary health care costs contributed another 1,000 Euros. Subsidies for prescribed medicines added 661 Euros, but that was partly counterbalanced by a reduction of 344 Euros in education costs. There were no significant differences in costs from traffic accidents or adult continuation of foster care. Overall, the net per capita public cost of adults with ADHD was just over 12,400 Euros each year.

Combining public and private costs, the per capita economic burden of adult ADHD was just over 20,000 Euros each year.

The study could not evaluate the extent to which ADHD treatment may reduce economic burden but given many studies that show treatment for ADHD reduces impairments, we would expect treatment to have a positive impact on economic burden. These results are extremely important for policy makers and for those who control the allocation of treatment in health care systems. Although treating ADHD incurs costs, not treating in incurs even greater costs in the long run

REFERENCES
D. Daley, R.H. Jacobsen, A.-M. Lange, A. Sørensen, J. Walldorf, “The economic burden of adult attention deficit hyperactivity disorder: A sibling comparison cost analysis,” European Psychiatry 61 (2019) 41–48.

A newly published meta-analysis of 57 studies encompassing almost a third of a million participants has uncovered a very strong association between ADHD and suicide, a strong association with suicidal ideation, and a small-to-medium association with suicide attempts.

The population examined included children, adolescents, and adults. Only persons formally diagnosed were considered to have ADHD. Studies that included self-injuries without suicidal intent were excluded. Most of the studies focused on European and American populations, with one in six from other locations, mostly Asian.

The most striking result was for actual suicides. The odds ratio (OR) for four datasets encompassing roughly one hundred forty thousand participants was 6.69 (95% CI 3.24 to 17.39, p < .0001). As a frame of reference, an OR of 1.5 is a small effect size, 2.5 a medium one, and 4.3 a large one. That means the effect size in this case is very large.

For suicidal ideation, 23 datasets with a combined total of just over 73,000 participants produced a medium-to-large OR of 3.5 (95% CI 2.94 to 4.25, p < .0001). In three datasets with more than nine thousand participants that adjusted for confounders, the adjusted OR was 4.5 (95% CI 1.72 to 11.63, p < .0001), indicating a large effect size.

For suicide attempts, 44 datasets encompassing over 228,000 participants produced an OR of 2.4 (95% CI 1.64 to 3.43, p < .0001). In six datasets with over 65,000 participants that adjusted for confounders, the adjusted OR dropped to 2.1 (95% CI 1.27 to 3.47, p = .005).

There was no evidence of publication bias for studies on suicides or suicidal ideation, but significant evidence of bias for studies on suicide attempts (Egger’s p = .03). This means that studies with positive findings were more likely to be published than negative studies.

There was, however, strong statistical evidence for differences between studies in the size of their ORs. This indicates that the pooled OR cannot summarize results from all datasets and more work is needed to clarify why the ORs differ among studies.

The authors appropriately caution that their meta-analysis is “not informative on cause-effect relationships,” but offer as a hypothesis that ADHD contributes to suicidal spectrum behaviors (SSBs) through “Impulsivity, a core symptom of ADHD, along with impaired decision-making and risk taking, that characterize a number of individuals with ADHD … Additionally, a sizeable portion of individuals with ADHD present with deficits in executive functions. As executive functions are implicated in the regulation of impulse control and emotions, executive dysfunctions may contribute to SSBs.”

In view of the large to very large effect sizes for suicide and suicidal ideation, the authors advise: “Awareness of this association should prompt practitioners to systematically screen for SSBs in patients with ADHD at the first assessment and at each follow-up, which in turns should contribute to decrease the risk of SSBs. This is particularly noteworthy considering that questionnaires/scales commonly used to screen/assess ADHD symptoms generally do not include suicide related items.”

REFERENCES
Septier M, Stordeur C, Zhang J, Delorme R, Cortese S, Association between suicidal spectrum behaviors and Attention-Deficit/Hyperactivity Disorder: A systematic review and meta-analysis, Neuroscience and Biobehavioral Reviews (2019), https://doi.org/10.1016/j.neubiorev.2019.05.022.

A Canadian team has published a systematic review examining the effectiveness of Mindfulness-Based Interventions (MBIs) for treating adults with ADHD. MBIs usually involve three forms of meditation – body scan, sitting meditation, and mindful yoga – that are intended to cultivate nonjudgmental awareness of present-moment experience. The team reviewed thirteen studies.

Three were single-group studies with no control group. One used dialectical behavior therapy (DBT). It reported mild to moderate improvements in ADHD symptoms, and substantial improvements in neurocognitive function (with standardized mean difference effect sizes from .99 to 2.22). A second enrolled both adults and adolescents in a mindful awareness program (MAP) which included a psychoeducational component. It found improvements in self-reported ADHD symptoms with standardized mean difference (SMD) effect sizes running from .50 to.93. Following training, it also reported improvement in attentional conflict (.93) set-shifting (.43). The third study also used DBT, focused on acceptance, mindfulness, functional behavioral analysis, and psychoeducation. ADHD symptoms showed mild improvement (.22), and functional impairment was slightly reduced (.15) and remained stable at 3-month follow-up.

The other ten studies used control groups. One used MAP and carefully stratified participants based on their ADHD medication status, then randomly assigned them to mindfulness treatment or waitlist. It reported large effect sizes in improvement of self-reported and clinician ratings of ADHD symptoms (1.35 to 3.14), executive functioning (1.45 to 2.67), and self-reported emotion regulation (1.27 to 1.63). Another study nonrandomly assigned adults to either mindfulness-based training (MBT) or skills training. Effect sizes were small to medium (.06 to .49), with 31% of MBT participants showing some improvement, versus only 11% of skills training participants.

Another study involved a controlled trial of college students with ADHD, randomized to receive either MBT or skills treatments. Treatment response rates were higher for MBT (59-65%, vs. 19-25%). At follow-up, the effect size for MBT on ADHD symptoms was large (.84), and similarly large on executive functioning (.81).

Another study tried a year’s worth of mindfulness training on poor responders to medication. Participants who received the treatment were compared to others who were waitlisted. The study reported a medium effect size (.63) in reducing the severity of ADHD.
Another looked at the impact of MAP on affective problems and impaired attention. It compared adults with ADHD and healthy controls who participated in MAP sessions with similar patients and controls who did not. The authors reported that MAP improved sustained attention and mood with medium to large effect sizes (.50 to .80).

A recent study explored the impact of MAP on neurocognitive performance with a randomized controlled trial. Following an 8-week mindfulness training, researchers “found a significant decrease in ADHD symptoms and significant improvement in task performance in both the MAP and the psychoeducation comparison group post- versus preintervention but did not find evidence for a significant main effect of treatment or a significant interaction effect on any ADHD symptoms (self- and observer-rated) nor on task performance (WM).”

Another study randomly assigned adults with ADHD either to a waitlist or to mindfulness-based cognitive therapy (MBCT). It found that MBCT led to a medium-to-large reduction in self-reported ADHD symptoms (.64) and a large reduction in investigator-reported symptoms (.78). It also found large (.93) improvements in executive functioning.

An 11th study looked at the effects of MBCT on neurophysiological correlates (event-related potentials (ERPs)) of performance monitoring in adults with ADHD. Half the patients were randomly assigned to MBCT, the other half to waitlist. MBCT produced reduced inattention, hyperactivity/impulsivity, and global ADHD index symptoms with medium to large effect sizes (.49 to .93).

A 12th study randomly assigned college students to MBCT or waitlist. At follow-up, participants who had received MBCT exhibited large (1.26) reductions in ADHD symptoms as well as greater treatment response rates (57%-71% vs. 23%-31%) versus waitlist. They also registered greater improvement on most neuropsychological performance and attentional scores.

Finally, another study compared the efficacy of MBCT plus treatment as usual (TAU) versus TAU only in reducing core symptoms in adults with ADHD. Participants were randomly assigned to an 8-weekly group therapy including meditation exercises, psychoeducation, and group discussions, or to TAU only, including pharmacotherapy and/or psychoeducation. At 6-month follow-up, MBCT+TAU patients reported large (SMD = .79) improvements in ADHD symptoms relative to TAU patients.

Overall, these are promising results for mindfulness-based interventions, and all the more so for those who do not respond well to drug therapy. Nevertheless, they must be seen as tentative. The sum total of participants over all thirteen studies was just 753, or an average of only 58 per study. There was too much variation in the studies to perform a meta-analysis. Only one of the studies included a healthy (non-ADHD) control group. And only one study received a perfect score by Cochrane Collaboration standards. Most studies did not use a suitable control group, i.e., in which there was an expectation of benefit from participating. As the authors noted, “Attrition bias was found to have high or unclear risk in more than a half of the studies. The reason for dropout of participants was not always clearly specified in those studies, so it is difficult to decide if it might be related to adverse effects or to some discomfort with treatment or instead to some incidental reasons.”

REFERENCES
Hélène Poissant, Adrianna Mendrek, Nadine Talbot, Bassam Khoury, and Jennifer Nolan, “Behavioral and Cognitive Impacts of Mindfulness-Based Interventions on Adults with Attention-Deficit Hyperactivity Disorder: A Systematic Review,” Behavioural Neurology, Vol. 2019, Article ID 5682050, 16 pages, https://doi.org/10.1155/2019/5682050.

The study team began with a representative sample of 69,972 U.S. adults aged 18 years or older who completed the 2012 and 2013 U.S. National Health and Wellness Survey. These adults were invited to complete the Validate Attitudes and Lifestyle Issues in Depression, ADHD and Troubles with Eating (VALIDATE) study, which included 1) a customized questionnaire designed to collect data on sociodemographic and clinical characteristics and lifestyle, and 2) several validated work productivity, daily functioning, self-esteem, and health-related quality of life (HRQoL) questionnaires. Of the 22,937 respondents, 444 had been previously diagnosed with ADHD, and 1,055 reported ADHD-like symptoms but had no previous clinical diagnosis.

There were no significant differences between the two groups in terms of age, education, income, health insurance, and most comorbid disorders. But those who had not been previously diagnosed were significantly more likely to be first-generation Americans (p<.001), nonwhite (p<.001), unemployed (p=.024), or suffer from depression, insomnia, or hypertension.

After matching the two groups for sociodemographic characteristics and comorbid conditions, covariate comparisons were made between 436 respondents diagnosed with ADHD and 867 previously undiagnosed respondents. Among respondents who were employed, diagnosed individuals registered a mean work productivity loss of 29% as opposed to 49% for the previously undiagnosed (p<.001). They also registered a 37% level of activity impairment versus a 53% level among the undiagnosed (p<.001). On the Sheehan Disability Scale, which ranges from 0 (no impairment) to 30 (highly impaired), the diagnosed group had a mean of 10, as opposed to a mean of 15 for the undiagnosed (p<.001). Diagnosed respondents also significantly outperformed undiagnosed ones on the Rosenberg Self-Esteem Scale (19 versus 15, on a scale of 0 to 30, p<.001), and on two quality-of-life scales (p<.001).

Applying a linear regression mixed model to the matched sets, the diagnosed still scored 16 points better than the undiagnosed on the WPAI:GH Productivity Loss scale (p<.001), 14 points better on the WPAI:GH Activity Impairment scale (p<.001), 4.5 points better on the Sheehan Disability Scale (p<.001), almost 4 points on the Rosenberg Self-Esteem Scale (p<.0001), with comparable gains on the two quality-of-life scales (p<.001 and p<.0001).

The authors concluded, “This comparison revealed that individuals who had been diagnosed with ADHD were more likely to experience better functioning, HRQoL [health related quality-of-life], and self-esteem than those with symptomatic ADHD. This result appears to be robust, withstanding several levels of increasingly rigorous statistical adjustment.” That points to substantial benefits from the treatment that follows diagnosis of adult ADHD.

REFERENCES
Manjiri Pawaskar, Moshe Fridman, Regina Grebla, and Manisha Madhoo, “Comparison of Quality of Life, Productivity, Functioning and Self-Esteem in Adults Diagnosed With ADHD and With Symptomatic ADH,” Journal of Attention Disorders, Published online May 2, 2019 https://doi.org/10.1177/1087054719841129.