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April 23, 2025

Study Finds LSD Microdosing No More Effective Than Placebo For ADHD

Double-blind Randomized Clinical Trial Finds LSD Microdosing No More Effective Than Placebo in Treating ADHD Symptoms

Background:

Stimulants, such as methylphenidate and amphetamines, are currently considered effective medications for treating ADHD. However, approximately one-third of patients do not have an adequate response to these treatments. Additionally, long-term adherence is relatively low, with only about half of the patients still using methylphenidate after six years. 

Recently, there has been increasing attention to the concept of microdosing with psychedelic drugs such as psilocybin and LSD. A microdose typically ranges from one-tenth to one-twentieth of a recreational dose and does not produce noticeable perceptual effects or interfere with daily activities.  

The Study:

A European research team recently published the findings of the first double-blind, placebo-controlled randomized clinical trial examining the safety and efficacy of repeated low doses of LSD in adults diagnosed with ADHD. 

The six-week trial took place at University Hospital in Basel, Switzerland, and Maastricht University, Netherlands. Participants, aged 18 to 65, had clinical diagnoses of ADHD with moderate to severe symptoms.  

The team excluded persons with a past or present diagnosis of psychotic disorders, substance use disorders, or other psychiatric or somatic disorders likely to require hospitalization or treatments. 

Participants were randomly assigned in a 1:1 ratio to receive either LSD or placebo. Neither study staff nor participants were aware of the assignments until the conclusion of the trial. 

During the six-week trial, participants received twice-weekly doses on-site, amounting to a total of 12 doses. Following the first and final doses, participants were asked to determine whether they had been administered LSD or a placebo in order to assess blinding. Four weeks after the conclusion of the microdosing period, participants returned for an evaluation of the treatment's safety and efficacy. 

Twenty-seven of the 53 participants were randomized to receive the LSD microdosing treatment in a liquid solution, and 26 to receive placebo. Placebo consisted of the same drinking solution, minus the microdose of LSD. 

The average age was 37, and 42% of participants were female. Forty-six of the 53 participants completed the study. 

Out of 29 participants, 21 from the LSD group and eight from the placebo group correctly guessed their allocation, totaling 63% overall.  

As assessed through the Adult ADHD Investigator Symptom Rating Scale, ADHD symptoms improved by 7.1 points in the LSD group and 8.9 points in the placebo group, with no significant difference between them. 

Regarding safety, the LSD group experienced nearly double the adverse events compared to the placebo group. None of the events in either group were classified as serious. The five most frequent adverse events were headache, nausea, fatigue, insomnia, and visual alterations, occurring around three times more frequently in the LSD group than in the placebo group. 

The team concluded, “although repeated low-dose LSD administration was safe in an outpatient setting, it failed to demonstrate efficacy compared with placebo in improving ADHD symptoms among adults.” 

Conclusion: Microdosing with LSD did not offer significant advantages over placebo in treating ADHD symptoms, despite being physically safe and well tolerated in the trial setting. This suggests that further research is needed to explore alternative treatments for ADHD.

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Link Found Between ADHD Risk Genes and Reduced Estimated Life Expectancy

Association found between ADHD risk genes involved in dopamine signaling and reduced estimated life expectancy

Behavioral disinhibition is a trait associated with both ADHD and several genes that affect dopamine signaling. Anew study by three American medical researchers set out to examine how threaded risk genes – DRD4 (dopamine 4 receptor density), DAT1 (dopamine 1transporter), and DBH (dopamine beta-hydroxylase) – affect estimated life expectancy in young adulthood.

The method used was a longitudinal study of 131 hyperactive children and 71 matched controls through early adulthood. The original evaluations were done in 1979-1980, when both groups were children in the 4 to 12 age range. They were reevaluated in1987-1988 as adolescents aged 12 to 20. The next follow-up was in 1992-1996 in early adulthood, aged 19 to 25. The final follow-up was in 1998-2004, as adults aged 24 to 32. All agreed to physical examinations that formed the basis for calculating estimated life expectancy using actuarial tables that factor in the effects of smoking, body mass index, alcohol, and other risk factors on expected longevity. Participants also provided blood samples that enabled gene typing.

For the DAT1gene, participants who had the homozygous nine-repeat allele (9/9) had an a five-year reduction in estimated life expectancy relative to those with the ten-repeat allele (10/10). Those with the intermediate (9/10) configuration had a three-year reduction in estimated life expectancy.

For the DBHTaq1 gene, those with a heterozygous (A1/A2) combination had almost a three-year reduction in estimated life expectancy relative to those with homozygous (A1/A1 or A2/A2) configurations.

For DRD4, on the other hand, no significant differences were found for estimated life expectancy.

In a related study, several background traits were found to be significantly predictive of variance in estimated life expectancy. The largest of these was behavioral disinhibition, followed by verbal IQ, self-rated hostility, and a nonverbal fluency test. But no significant differences were found between any of the gene polymorphisms on any of these four measures, indicating that the present gene associations were independent of the background traits.

The researchers next sought to determine which variables used in the estimated life expectancy calculations were associated with the two significant genes. For DBH, one variable stood out. Those with the A1/A2 heterozygous pairings had almost twice the alcohol consumption of those with homozygous pairings (p = 0.023).

For DAT1, two variables stood out. Overall, the 9/9 pairings smoked two and a half times as much as the 10/10 pairings, with the 9/10 pairings midway between the extremes(p = 0.036). They were also 73 percent more likely to be smokers relative to the 10/10 pairings, and 61 percent more likely relative to the 9/10 pairings. They also had significantly less education than the 10/10 pairings, with the 9/10pairings again being intermediate (p = 0.027).

An obvious limitation of the study was its small sample size. The authors cautioned, “our findings should be considered quite preliminary and in need of much greater research before being given much weight in the literature or in public policy.

“With these limitations in mind,” they concluded, “the present study demonstrated that two ADHD risk genes (DBH and DAT1) independently contributed to a reduction in ELE [estimated life expectancy] beyond the second order variables of behavioral disinhibition, IQ, hostility, and nonverbal fluency that contributed in the related study to variation in ELE. The gene polymorphisms seemed to be influencing ELE through their affiliation with first-order or more proximal factors related to ELE such as education, smoking, alcohol use, and possibly exercise.”

February 28, 2021
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Evaluating Financial Decision-Making in Adults With ADHD

Evaluating Financial Decision-Making in Adults With ADHD

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 in 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 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 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.”

February 26, 2021
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Driving, Safety, and ADHD

How to Improve Driving Safety for Teens and Adults With ADHD

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 smart phone 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 seat belt, 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.

February 22, 2021
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How extensive is perceived discrimination among adults with ADHD?

How extensive is perceived discrimination among adults with ADHD?

How Extensive Is Perceived Discrimination Among Adults With ADHD?

An international team of mental health professionals used a nationally representative sample of English adults over age 16 to explore this question. Of 13,671 households selected, 7,461 (a little more than half) participated.

Participants used the Adult ADHD Self-Report Scale (ASRS) Screener to assess symptoms of ADHD on a scale ranging from 0 to 24. Those scoring ≥ 14 were considered as having high levels of ADHD symptoms. They also responded to a computer-assisted self-interview that asked, “Have you been unfairly treated in the last 12 months … because of your mental health,” requiring a yes or no answer.

The raw data showed an exponential relationship between levels of ADHD symptoms and mental health discrimination. Respondents scoring 0-9 on the ASRS reported negligible discrimination (prevalence of 0.3%). Among those scoring 10-13, the prevalence was 2.3%, rising to 5.5% of those with scores in the 14-17 range, and 18.8% among those in the 18-24 range.

After adjusting for sociodemographic variables (sex, age, ethnicity, marital status, educational attainment, and income), those with high levels of ADHD symptoms were nearly 10 times more likely to have experienced discrimination than others.  After adjusting for other psychopathology and stressful life events, this increased risk fell to 2.8.

The authors concluded, “This is an important finding given that mental health discrimination has been associated with detrimental consequences in individuals with mental health disorders and therefore might also be a factor in the negative outcomes that have been noted in adults with ADHD/ADHD symptomatology. As ADHD continues to be underdiagnosed and untreated in adults, the results of this study highlight the importance of identifying and treating these individuals and suggest that interventions to inform the public about ADHD may be important for reducing the stigma and discrimination associated with this condition.”

February 20, 2021
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Can College Students Trying to Fake ADHD be Detected

Can College Students Trying to Fake ADHD be Detected?

Many college students truly have ADHD and deserve to be treated but some attempt to fake ADHD symptoms with the goal of getting stimulant medications for non-medical uses such as studying and getting high.  Some students who fake ADHD also seek to gain accommodations that would give them additional time to complete exams. To address this issue, two psychologists examined data from 514 university students being assessed for ADHD to evaluate the ability of assessment tools to detect students who fake ADHD symptoms.

All participants had asked to be assessed to determine whether they could qualify for disability services. This was therefore by no means a random sample of university students, and could be expected to include some non-ADHD individuals seeking the benefits of an ADHD diagnosis.; however, this offered a good opportunity to explore which combination of tools would yield the best accuracy, and be best at excluding malingerers.

That was achieved by using both multiple informants and multiple assessment tools, and comparing results. Self-assessment was supplemented by assessment by other informants (e.g. parent, partner, friend, or other relative). These were supplemented with symptom validity tests to check for telltale highly inconsistent symptom reporting, or symptom exaggeration, which could signal false positives.

On the other hand, some individuals with ADHD have executive functioning problems that may make it difficult for them to reliably appraise their own symptoms on self-assessment tests, which can lead to false negatives. Performance validity tests were therefore also administered, in order to detect poor effort during evaluation, which could lead to false negatives.

Observer reporting was found to be more reliable than self-reporting, with significantly lower inconsistency scores (p< .001), and significantly higher exaggeration scores (p < .001). More than twice as many self-reports showed evidence of symptom exaggeration as did observer reports. This probably understates the problem when one considers that the observer reports were performed not by clinicians but by parents and partners who may themselves have had reasons to game the tests in favor of an ADHD diagnosis.

Even so, the authors noted, “External incentives such as procurement of a desired controlled substance or eligibility for a desired disability accommodation are likely to be of more perceived value to those who directly obtain them.” They suggested compensating for this by making ADHD diagnoses only on the basis of positive observer tests in addition to self-reports: “Applying an ‘and’ rule—one where both self- and observer reports were required to meet the diagnostic threshold— generally cut the proportions meeting various thresholds at least in half and washed out the differences between the adequate and inadequate symptom validity groups.”

They also recommended including formal tests of response validity, using both symptom validity tests and performance validity tests. Overall, they found that just over half the subsample of 410 students administered performance validity tests demonstrated either inadequate symptom or performance validity.

Finally, they recommended “that clinicians give considerable weight to direct, objective evidence of functional impairment when making decisions about the presence of ADHD in adults. The degree to which symptoms cause significant difficulty functioning in day-to-day life is a core element of the ADHD diagnostic criteria (American Psychiatric Association,2013), and it cannot be assumed that significant symptoms cause such difficulty, as symptoms are only moderately associated with functional impairment. we urge clinicians to procure objective records (e.g., grade transcripts, work performance evaluations, disciplinary and legal records) to aid in determining functional impairment in adults assessed for ADHD.”

February 18, 2021
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Variations in Diagnosis

Variations in Diagnosis

A cohort study looked at over five million adults, and over 850,000 children between the ages of five and eleven, who received care at Kaiser Permanente Northern California during the ten-year period from the beginning of 2007 through the end of 2016. At any given time, KPNC serves roughly four million persons. It is representative of the population of the region, except for the highest and lowest income strata.

Among adults rates of ADHD diagnosis rose from 0.43% to 0.96%. Among children the diagnosis rates rose from 2.96% to 3.74%, ending up almost four times as high as for adults.

Non-Hispanic whites had the highest adult rates throughout, increasing from 0.67% in 2007 to 1.42% in 2016. American Indian or Alaska Native (AIAN) had the second highest rates, rising from 0.56% to 1.14%. Blacks and Hispanics had roughly comparable rates of diagnosis, the former rising from 0.22% to 0.69%, the latter from 0.25% to 0.65%. The lowest rates were among Asians (rising from 0.11% to 0.35%) and Native Hawaiian or other Pacific Islanders (increasing from 0.11% to 0.39%).

Odds of diagnosis dropped steeply with age among adults. Relative to 18-24-year-olds, 25-34-year-olds were 1/6th less likely to be diagnosed with ADHD, 35-44-year-olds 1/3rd less likely, 45-54-year-olds less than half as likely, 55-64-year-olds less than a quarter as likely, and those over 65 about a twentieth as likely. This is consistent with other studies reporting and age dependent decline in the diagnosis.

Adults with the highest levels of education were twice as likely to be diagnosed as those with the lowest levels. But variations in median household income had almost no effect. Women were marginally less likely to be diagnosed than men.

ADHD is associated with some other psychiatric disorders. Compared with normally developing adults, and adjusted for confounders, those with ADHD were five times as likely to have an eating disorder, over four times as likely to be diagnosed with bipolar disorder or depression, more than twice as likely to suffer from anxiety, but only slightly more likely to abuse drugs or alcohol.

The authors speculate that rising rates of diagnosis could reflect increasing recognition of ADHD in adults by physicians and other clinicians as well as growing public awareness of ADHD during the decade under study. Turning to the strong differences among ethnicities, they note, Racial/ethnic differences could also reflect differential rates of treatment seeking or access to care. Racial/ethnic background is known to play an important role in opinions on mental health services, health care utilization, and physician preferences. In addition, rates of diagnosis- seeking to obtain stimulant medication for nonmedical use may be more common among white vs nonwhite patients. They conclude, greater consideration must be placed on cultural influences on health care seeking and delivery, along with an increased understanding of the various social, psychological, and biological differences among races/ethnicities as well as culturally sensitive approaches to identify and treat ADHD in the total population.

But the main take home message of this work is that most cases of ADHD in adults are not being diagnosed by clinicians. We know from population studies, worldwide, that about three percent of adults suffer from the disorder. This study found that less than 1 percent are diagnosed by their doctors. Clearly, more education is needed to teach clinicians how to identify, diagnose and treat ADHD in adults.

December 18, 2023
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Sleep and ADHD?

Sleep and ADHD?

Sleep disorders are one of the most commonly self-reported comorbidities of adults with ADHD, affecting 50 to 70 percent of them. A team of British researchers set out to see whether this association could be further confirmed with objective sleep measures, using cognitive function tests and electroencephalography (EEG).

Measured as theta/beta ratio, EEG slowing is a widely used indicator in ADHD research. While it occurs normally in non-ADHD adults at the conclusion of a day, during the day it signals excessive sleepiness, whether from obstructive sleep apnea or from neurodegenerative and neurodevelopmental disorders. Coffee reverses EEG slowing, as do ADHD stimulant medications.

Study participants were either on stable treatment with ADHD medication (stimulant or non-stimulant medication), or on no medication. Participants had to refrain from taking any stimulant medications for at least 48 hours prior to taking the tests. Persons with IQ below 80 or with recurrent depression or undergoing a depressive episode were excluded.

The team administered a cognitive function test, The Sustained Attention to Response Task (SART). Observers rated on-task sleepiness using videos from the cognitive testing sessions. They wired participants for EEG monitoring.

Observer-rated sleepiness was found to be moderately higher in the ADHD group than in controls. Although sleep quality was slightly lower in the sleepy group than in the ADHD group, and symptom severity slightly greater in the ADHD group than the sleepy group, neither difference was statistically significant, indicating extensive overlap.

Omission errors in the SART were strongly correlated with sleepiness level, and the strength of this correlation was independent of ADHD symptom severity. EEG slowing in all regions of the brain was more than 50 percent higher in the ADHD group than in the control group and was highest in the frontal cortex.

Treating the sleepy group as a third group, EEG slowing was highest for the ADHD group, followed closely by the sleepy group, and more distantly by the neurotypical group. The gaps between the ADHD and sleepy groups on the one hand, and the neurotypical group on the other, were both large and statistically significant, whereas the gap between the ADHD and sleepy groups was not. EEG slowing was both a significant predictor of ADHD and of ADHD symptom severity.

The authors concluded, These findings indicate that the cognitive performance deficits routinely attributed to ADHD  are largely due to on-task sleepiness and not exclusively due to ADHD symptom severity. We would like to propose a simple working hypothesis that daytime sleepiness plays a major role in cognitive functioning of adults with ADHD. As adults with ADHD are more severely sleep deprived compared to neurotypical control subjects and are more vulnerable to sleep deprivation, in various neurocognitive tasks they should manifest larger sleepiness-related reductions in cognitive performance. One clear testable prediction of the working hypothesis would be that carefully controlling for sleepiness, time of day and/or individual circadian rhythms, would result in substantial reduction in the neurocognitive deficits in replications of classic ADHD studies.

November 1, 2023
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ADHD in College Students

ADHD in College Students

ADHD continues to be a significant and difficult challenge in the collegiate world. The symptoms of the disorder directly impact a person's ability to manage the demands of college. Matriculating students are expected to rapidly obtain and deploy many self-management skills. Increased academic expectations demand a greater capacity for sustained attention. And the evolving social milieu can tax the emotional regulation and social cognition of those with ADHD.

Having seen our patients struggle, the Association for Collegiate Psychiatry decided to submit a workshop for presentation at the 2019 APA meeting in San Francisco. While developing the presentation we discovered a wealth of recent young adult follow-up data from longitudinal studies.1 Without exception, the study's findings reflected a significant decrease in functional outcomes across multiple domains of adult life. Further, we discovered that the new work coming from the TRAC observational study of college students has found troublesome rates of psychiatric comorbidity after the first year.

This epidemiologic evidence supports devoting resources to the care of this cohort. But it appears that this has not penetrated the world of campus mental health treatment. At present, most post-secondary schools (to our knowledge, data is quite limited) lean toward policies that make it difficult for students with ADHD to be diagnosed or treated on campus. One obstacle is requiring evidence of a childhood diagnosis, which many children with high-IQ compensated ADHD may not have received. Another can be the demand for expensive and comprehensive neuropsychological testing even though the diagnostic value of that testing remains unclear.3 Some student health centers ask students to obtain prescriptions from the treaters they saw prior to coming to campus, even if those prescribers are out of state. Though these policies may be deployed in an effort to decrease the diversion of stimulant medication, such hurdles may be difficult for the 18-year-old ADHD student to navigate. The result is that many students with this predictably destructive condition go untreated.

The good news is this subject interests the collegiate community. Among other things, our APA workshop was selected to be the APA's Member's Course of the Month for January 2020.

Much work remains in developing and deploying diagnostic policies and treatment strategies that colleges and universities feel comfortable supporting. We mentioned the APSARD community during the workshop as a resource for professionals interested in ADHD. And we hope the wider ADHD research and treatment communities will join us in focusing our energy on this underserved and sometimes maligned group of students who need our help.

February 10, 2021
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Liquid Medication Options for ADHD Adults with Autism Spectrum Disorder

Long-Acting Liquid Methylphenidate for Treating ADHD in Intellectually Capable Adults with Autism Spectrum Disorder

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.”

February 8, 2021
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How to Identify ADHD in Adults With Alcohol Use Disorder (AUD)

How to identify ADHD in adults with alcohol use disorder (AUD)

ADHD is far more prevalent among persons with AUD (roughly 20 percent) than it is in the general population. The most accurate way of identifying ADHD is through structured clinical interviews. Given that this is not feasible in routine clinical settings, ADHD self-report scales offer a less reliable but much less resource-intensive alternative. Could the latter be calibrated in a way that would yield diagnoses that better correspond with the former?

A German team compared the outcomes of both methods on 404 adults undergoing residential treatment for AUD. All were abstinent while undergoing evaluations. First, to obtain reliable ADHD diagnoses, each underwent the Diagnostic Interview for ADHD in Adults, DIVA. If DIVA indicated probable ADHD, two expert clinicians conducted successive follow-up interviews. ADHD was only diagnosed when both experts concurred with the DIVA outcome.

Participants were then asked to use two adult ADHD self-report scales, the six-item Adult ADHD Self Report Scale v1.1 (ASRS) and the 30-item Conners’ Adult ADHD Rating Scale (CAARS-S-SR). The outcomes were then compared with the expert interview diagnoses.

Using established cut-off values for the ASRS, less than two-thirds of patients known to have ADHD were scored as having ADHD by the test. In other words, there was a very high rate of false negatives. Lowering the cut-off to a sum score ≥ 11 resulted in a correct diagnosis of more than seven out of eight. But the rate of false positives soared to almost two in five.  Similarly, the CAARS-S-SR had its greatest sensitivity (ability to accurately identify those with ADHD) at the lowest threshold of ≥ 60, but at a similarly high cost in false positives (more than a third).

The authors found it was impossible to come anywhere near the precision of the expert clinical interviews. Nevertheless, they judged the best compromise to be to use the lowest thresholds on both tests and then require positive determinations from both. That led to successfully diagnosing more than three out of four individuals known to have ADHD, with a false positive rate of just over one in five.

Using this combination of the two self-reporting questionnaires with lower thresholds, they suggest, could substantially reduce the under-diagnosis of ADHD in alcohol-dependent patients.

February 6, 2021
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