Natural Remedies for ADHD: Are they Effective?

Stephen V. Faraone, PhD on September 2, 2021

Are Nonpharmacologic Treatments for ADHD Useful?

There are several very effective ADHD medications, and treatment guidelines from professional organizations view these drugs as the first line of treatment for people with ADHD symptoms.  (The only exception is for preschool children where medication is only the first line treatment for severe ADHD; the guidelines recommend that other preschoolers with ADHD be treated with non-pharmacologic treatments, when available.)

Despite these guidelines, some parents and patients have been persuaded by the media or the Internet that ADHD drugs are dangerous and that non-drug alternatives are as good or even better. Parents and patients may also be influenced by media reports that doctors overprescribe ADHD drugs or that these drugs have serious side effects. Such reports typically simplify and/or exaggerate results from the scientific literature.  Thus, many patients and parents of ADHD children are seeking “natural remedies for ADHD.” 

What are these non-pharmacologic treatments and do they work?  

My upcoming series of blogs will discuss each of these treatments in detail.  Here I’ll give an overview of my evidenced-based taxonomy of nonpharmacologic treatments for ADHD described in more detail in a book I recently edited (Faraone, S. V. & Antshel, K. M. (2014). “ADHD: Non-Pharmacologic Interventions.” Child Adolesc Psychiatr Clin N Am 23, xiii-xiv.).  I use the term “evidenced-based” in the strict sense applied by the Oxford Center for Evidenced Based Medicine (OCEBM; http://www.cebm.net/). 

Most of the non-drug treatments for ADHD fall into three categories: behavioral, dietary, and neurocognitive.

Behavioral interventions include training parents to optimize methods of reward and punishment for their ADHD child, teaching ADHD children social skills and helping teachers apply principles of behavior management in their classrooms.  Cognitive behavior therapy (CBT) is a method that teaches behavioral and cognitive skills to adolescent and adult ADHD patients.

Dietary interventions include special diets that exclude food colorings or eliminate foods believed to cause ADHD symptoms.  Other dietary interventions provide supplements such as iron, zinc or omega-3 fatty acids.

Neurocognitive interventions typically use a computer based learning setup to teach ADHD patients cognitive skills that will help reduce ADHD symptoms.

There are two metrics to consider when thinking about the evidence-base for these methods.  The first is the quality of the evidence.   For example, a study of 10 patients with no control group would be a low quality study, but a study of 100 patients randomized to either a treatment or control group would be of high quality, and the quality would be even higher if the people rating patient outcomes did not know who was in each group. 

The second metric is the magnitude of the treatment effect.  Does the treatment dramatically reduce ADHD symptoms or does it have only a small effect?  This metric is only available for high quality studies that compare people treated with the method and people treated with a ‘control’ method that is not expected to affect ADHD.

I used a statistical metric to quantify the magnitude of effect. Zero means no effect and larger numbers indicate better effects on treating ADHD symptoms.  For comparison, the effect of is about 0.9, which is derived from a very strong evidence base.     The effects of dietary treatments on symptoms of adult ADHD are smaller, about 0.4 to 0.5, but because the quality of the evidence is not strong, these results are not certain and the studies of food color exclusions apply primarily to children who have high intakes of such colorants.

In contrast to the dietary studies, the evidence base for behavioral treatments is excellent but the effects of these treatments of ADHD symptoms is very small, less than 0.1.    Supplementation with omega-3 fatty acids also has a strong evidence base but the magnitude of effect is also small (0.1 to 0.2).    The neurocognitive treatments have modest effects on ADHD symptoms (0.2 to 0.4) but their evidence base is weak.

This review of non-drug treatments explains why ADHD drug treatments are usually used first.  Their evidence base is stronger and they are more effective in reducing ADHD symptoms.  There is, however, a role for some non-drug treatments. I’ll be discussing that in subsequent blog posts.

If you are health professional, you can learn more about screening, diagnosing and treating ADHD with the latest evidence-based medicine.  Earn FREE CME on Adult ADHD.

If you are a member of the public, you can download a FREE SCREENER and take it to your healthcare professional for a discussion.  If you provider does not know about ADHD, and many don’t, them please send him or her to ADHD in Adults.com

References :

Faraone, S. V. & Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child Adolesc Psychiatr Clin N Am 23, xiii-xiv.

Faraone, S. V. & Antshel, K. M. (2014). Towards an evidence-based taxonomy of nonpharmacologic treatments for ADHD. Child Adolesc Psychiatr Clin N Am 23, 965-72.

What’s the Relationship Between Daytime Sleepiness and Cognitive Functioning in Adults with ADHD?

Stephen V. Faraone, PhD on March 16, 2020

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.”

REFERENCES:
Bartosz Helfer, Natali Bozhilova, Ruth E. Cooper, Joanna Ismene Douzenis, Stefanos Maltezos, Philip Asherson, “The Key Role of Daytime Sleepiness in Cognitive Functioning of Adults with ADHD,” European Psychiatry (2020), https://doi.org/10.1192/j.eurpsy.2020.28.

ADHD in College Students

Stephen V. Faraone, PhD on January 13, 2020

This article was selected by the APA as January’s ‘Member Course of the Month.’

Authors:
Aaron E. Winkler, MD. University of Maryland / Sheppard Pratt Psychiatry Residency Program. David W. Goodman, MD, FAPA. Assistant Professor of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine; Director of the Adult Attention Deficit Disorder Center of Maryland

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 emotion-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.2

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 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 2020.4

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.

REFERENCES:

1) Gordon CT, Fabiano GA. The Transition of Youth with ADHD into the Workforce: Review and Future Directions. Clinical child and family psychology review. 2019 Feb 6:1-32.

2) Anastopoulos AD, DuPaul GJ, Weyandt LL, Morrissey-Kane E, Sommer JL, Rhoads LH, Murphy KR, Gormley MJ, Gudmundsdottir BG. Rates and patterns of comorbidity among first-year college students with ADHD. Journal of Clinical Child & Adolescent Psychology. 2018 Mar 4;47(2):236-47.

3) Antshel, K. Role of Neuropsychological Assessment in ADHD. APSARD blog post Jan 2, 2020. Accessed Jan 17, 2020. https://apsard.org/role-of-neuropsychological-assessment-in-adhd-2/

4) https://www.psychiatry.org/psychiatrists/education/apa-learning-center/members-course-of-the-month

ADHD is Underdiagnosed, to Varying Degrees, Among Adults of Different Ethnicities, Ages, and Education Levels in the U.S.

Stephen V. Faraone, PhD on January 3, 2020

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.

REFERENCES:

Winston Chung, MD, MS; Sheng-Fang Jiang, MS; Diana Paksarian, MPH, PhD; Aki Nikolaidis, PhD; F. Xavier Castellanos, MD; Kathleen R. Merikangas, PhD; Michael P. Milham, MD, PhD, “Trends in the Prevalence and Incidence of Attention-Deficit/Hyperactivity Disorder Among Adults and Children of Different Racial and Ethnic Groups,” JAMA Network Open (2019) 2(11): e1914344. DOI:10.1521/adhd.2019.27.4.8.

How effective are ADHD medications in adults with Autism Spectrum Disorder (ASD)?

Stephen V. Faraone, PhD on December 26, 2019

Autism spectrum disorder (ASD) is frequently comorbid with ADHD. Among adults with ADHD, as many as half are reported to also have ASD.

A Dutch team set out to answer two questions:

  1. Do adults with ADHD and comorbid ASD experience less effectiveness of pharmacological treatment for ADHD than adults with only ADHD?
  2. Do adults with ADHD and comorbid ASD experience different or more severe side effects of pharmacological treatment for ADHD than adults with only ADHD, as measured in side-effect scores, blood pressure, heart rate, and weight?

This was a retrospective study, using well-documented medical records, of the effects of drug treatment with methylphenidate (MPH), dexamphetamine (DEX), atomoxetine (ATX), bupropion, or modafinil.

The researchers compared 60 adults with comorbid ASD and ADHD to 226 adults with only ADHD. ADHD symptoms were scored using the Conners’ ADHD Rating Scale: Self Report–Short Version (CAARS: S-S). Side effects of ADHD medication were measured using either a 13-item or 20-item checklist with 4-point scales for item response. Researchers also tracked changes in body weight, blood pressure, and heart rate.

Following treatment, ADHD symptoms among the comorbid group declined by a quarter, and among the ADHD-only group by almost a third. There was no significant difference between men and women. Controlling for age, gender, and ADHD subtype, a comorbid diagnosis of ASD also did not significantly affect ADHD symptom reduction.

Turning to side effects, in the ADHD+ASD group, there were significant increases in decreased appetite and weight loss, and decreases in agitation, anxiety, and sadness/unhappiness. In the ADHD-only group, there were significant increases in decreased appetite, weight loss, and dry mouth, and decreases in sleeping disorder, nervousness, agitation, anxiety, and sadness / unhappiness. Yet there were no significant differences between the two groups. Side effects increased and decreased similarly in both. Likewise, there were no significant differences between the groups in changes in heart rate and blood pressure. The only significant difference in medication dosage was for bupropion, which was higher in the ADHD+ASD group, though without any sign of difference in side effects.

The authors concluded that this retrospective study “showed pharmacological treatment of adults with diagnoses of ADHD and ASD to be just as successful as the pharmacological treatment of adults with only ADHD,” but cautioned that “a randomized controlled trial should be conducted to evaluate the effectiveness and possible side effects of pharmacological treatment for ADHD in patients with ASD more reliably.”

REFERENCES
J. J. Muit, N. Bothof, and C. C. Kan, “Pharmacotherapy of ADHD in Adults With Autism Spectrum Disorder: Effectiveness and Side Effects,” Journal of Attention Disorders (2019) DOI: 10.1177/1087054719866255.

Addressing the Challenge of Under-Diagnosed Adult ADHD

Stephen V. Faraone, PhD on November 26, 2019

There is a well-documented gap between the known prevalence of adult ADHD and rates of diagnosis and treatment. In Germany, epidemiological studies of nationally representative community samples have found prevalence rates ranging from 3.1% to 4.7%. Yet studies of publicly insured individuals age 18 to 69 years old report rates of diagnosed ADHD between 0.04% and 0.4%. So, even in a country with universal health insurance more than nine out of ten adults with ADHD go undiagnosed.

Many factors contribute to underdiagnosis: stigma, culturally influenced perceptions, and lack of motivation by those affected. Another crucial factor is the lack of recognition of ADHD symptoms by clinicians.

A research team surveyed 144 psychologists, 32 physicians, and two occupational therapists. Almost three in five participants were psychotherapists, a quarter were neuropsychologists, and one in seven were psychiatrists.

Four out of five clinicians stated they had received only “a few hours” of ADHD-specific training. One in four stated they had not examined guidelines for diagnosing ADHD. A lack of formal training among the vast majority and unfamiliarity with current diagnostic guidelines in a significant minority were surprising findings among clinicians who regularly work with adults with ADHD.

Many clinicians had difficulty identifying core features of adult ADHD as defined by the DSM-5 and International Classification of Diseases, Tenth Revision (ICD-10). Roughly one in five stated that hyperactivity had little relevance to adult ADHD. The only core feature correctly identified by more than half the respondents was having “difficulties concentrating.” Impairments in social behavior or aggression and memory impairment were not identified as being clearly “relevant” or “irrelevant” to adult ADHD.

The authors concluded, “these findings appear to indicate some uncertainty or at least a lack of consensus among clinicians about what symptoms are relevant to ADHD in adulthood and it is likely that this uncertainty contributes to diagnostic inaccuracy.”

Most respondents reported using self-report scales of ADHD symptoms and using unstructured interviews. While slightly more than half agreed that collateral reports are important to diagnosis, only about a third reported regularly using them. This is a problem given the limited accuracy of self-reported childhood symptoms for documenting the childhood-onset of the disorder. Semi-structured interviews are also known to improve the accuracy of diagnosis but are rarely used in clinical practice.

Over half of psychologists and a quarter of physicians reported using cognitive or neuropsychological testing, even though this is at variance with German (and other) guidelines, which specify that such testing is suitable for clarifying strengths and weaknesses, but not for ruling out or confirming a diagnosis of ADHD. The European Consensus Statement also states that cognitive/neuropsychological testing should only be used as a secondary or supplementary assessment tool.

While three out of four clinicians recommended stimulant drug treatment, psychologists tended to be more hesitant to do so. This is likely because German psychologists receive little training in pharmacotherapy, and do not have prescription privileges. Given the demonstrated efficacy of stimulant treatment, this points to a need to better educate psychologists in this regard.

Almost three in four respondents cited “lack of clinician knowledge and experience” as a barrier to ADHD diagnosis. Most clinicians also stated they were either “uncertain” or only “somewhat certain” of their ability to diagnose ADHD. That suggests that more extensive ADHD-specific training is needed.

A limitation of the survey was the relatively low participation by physicians. It is also likely that the findings are not reflective of practices in ADHD specialty clinics.

The authors concluded, “Further training is needed to improve clinicians’ understanding of ADHD in adulthood and to align diagnostic practices with guideline recommendations. Whereas discrepancies between respondents regarding the relative importance of peripheral symptoms (e.g., memory problems) were most common, a lack of consensus was found even for core symptoms listed by diagnostic criteria. Particularly among psychologists, improved awareness regarding the benefits of stimulant medications is needed to bring their treatment recommendations in line with evidence-based guidelines.”

REFERENCES:
Brooke C. Schneider, Daniel Schöttle, Birgit Hottenrott, Jürgen Gallinat, and Steffen Moritz, “Assessment of Adult ADHD in Clinical Practice: Four Letters—40 Opinions,” Journal of Attention Disorders (2019) DOI: 10.1177/1087054719879498.

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

Stephen V. Faraone, PhD on November 20, 2019

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.

Are There Adverse Effects to Long-Term Treatment of ADHD with Methylphenidate?

Stephen V. Faraone, PhD on October 17, 2019

Methylphenidate (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

Stigma: Public Attitudes Towards Children and Adults with ADHD

Stephen V. Faraone, PhD on October 17, 2019

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.

Evaluating Financial Decision-Making in Adults With ADHD

Stephen V. Faraone, PhD on August 20, 2019

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.