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A recent finding that ADHD can begin in adulthood has surprised researchers. Here are reasons why it may be wrong.

Discovery of Adult-Onset ADHD Raises Questions

Diagnostic and Statistical Manual of Mental Disorders

, 5th edition (DSM-5) classifies attention-deficit/hyperactivity disorder (ADHD) as a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.

 There is growing evidence that symptoms of ADHD can persist into adulthood and can cause significant impairments in social, academic, and occupational functioning. In addition, there is emerging evidence for the existence of a different variant of adult ADHD (aADHD) where ADHD symptoms emerge for the first time in young adulthood without any symptoms being 

 In this article we review various aspects of adult ADHD (aADHD) and suggest possible treatments.

The prevalence of ADHD in childhood is between 

 Emerging evidence indicates that ADHD symptoms may persist into adulthood in approximately 

 to suggest that adult ADHD (aADHD) is not just a continuation of childhood onset ADHD (cADHD), as many individuals do not have a history of this 

 It is postulated that there may be 2 distinct subtypes of aADHD: the first with childhood onset and the other with onset exclusively in adulthood. A meta-analysis evaluating the risk markers that predicted the persistence of ADHD from childhood into adulthood found that the severity of ADHD (odds ratio (OR) = 2.33, 

 < 0.001), treatment for ADHD (OR = 2.09, 

 = 0.037), comorbid conduct disorder (OR = 1.85, 

 = 0.030), and comorbid major depressive disorder (OR = 1.8, 

 = 0.019) emerged as predictors for childhood ADHD persisting into adulthood.

A meta-analysis by Simon et al, found the conservative pooled prevalence rate for adult ADHD (aADHD) to be 

 This study also found that the proportion of individuals with ADHD decreases with age, and the prevalence rates were equal among men and women. This data is in contrast to cADHD, where boys had 3 to 10 times greater prevalence rates when compared to girls. The authors also opined that the true prevalence rate of adult ADHD may be an underestimate, as some children with ADHD do not outgrow the disorder but outgrow the current diagnostic criteria (

Adult ADHD results in significant impairments in the individual’s personal, social, and professional life.

 Individuals with aADHD tend to have poor self-esteem and reduced quality of interpersonal and professional relationships. These individuals are twice as likely to be divorced, when compared to age-matched controls. They also have significant educational difficulties with lower grades, greater rates of academic suspension and dropout rates, and are less likely to graduate than students without ADHD. Individuals with aADHD have greater rates of traffic violations and motor vehicle accidents, and higher rates of emergency room visits and hospital admissions. They also have lower life expectancies and higher risk for death, including accidental deaths. Individuals with aADHD are more likely to be unemployed and have a greater likelihood of being involved in criminal behaviors. The overall national annual incremental costs of ADHD ranges from $143 to $266 billion.

 Most of these costs were incurred by adults ($105 billion to $194 billion) compared to children ($38 to $72 billion), and the largest cost category in this group was productivity and income losses of $87 billion to $138 billion. 

Approximately 80% of aADHD cases present with at least 1 lifetime psychiatric comorbidity.

 The National Comorbidity Survey found that aADHD was significantly comorbid with mood disorders (OR = 2.7 to 7.5), anxiety disorders (OR = 1.5 to 5.5), substance use disorders (SUDs, OR = 1.5 to 7.9), and intermittent explosive disorder (OR = 3.7).

 aADHD was also associated with greater disability in both basic functioning (self-care, mobility, and cognition) and instrumental functioning (days out of role), productive role functioning and also on social role functioning). Only 10.9% of these individuals with aADHD received treatment for ADHD in the preceding 12 months.

Available evidence from family, twin, and adoption studies indicates that ADHD tends to run in families, with a high heritability rate of 74%.

 In addition, a third of ADHD’s heritability is due to a polygenic component, indicating many common variants with each having small effects. The heritability of aADHD and cADHD appear to be very similar, although family studies indicate that there may be an increased familial liability for aADHD when compared with cADHD.

 Twin studies that are based on self-rated symptoms among a sample of adult population show a moderate heritability rate at 30% to 40%.

Current evidence indicates that some of the same genes that may be involved in cADHD may also be involved in aADHD.

 Linkage studies have identified LPHN3 and CDH13 as novel genes associated with ADHD across the lifespan. In a systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed among individuals with aADHD found an association between aADHD and the gene brain-specific angiogenesis inhibitor 1-associated protein 2.

 They also found lower serum docosahexaenoic acid (DHA) levels among aADHD individuals.

There is evidence from neuroimaging studies that among individuals with ADHD there is a dysfunction of dopamine pathways that are involved in attention, executive function, and motivation and reward.

 Additionally, dysfunctions are also noted in noradrenergic pathways, especially those projecting into the prefrontal cortex, the central region for executive function.

A simultaneous electroencephalography and functional magnetic resonance imaging (fMRI) study found that aADHD individuals had increased medial/lateral frontal and parietal activity during the voluntary selection task on fMRI.

 A meta-analysis found that right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in cADHD.

 Additionally, these changes and alterations in limbic regions like anterior cingulate cortex and amygdala were more pronounced among non-treated individuals and these appeared to diminish over time from childhood to adulthood.

In a study that sought to delineate the neural correlates of component-specific inhibitory deficits in aADHD using fMRI, brain activation was assessed during 3 stages of behavioral inhibition, ie interference inhibition (Simon task), action withholding (Go/no-go task), and action cancelation (Stop-signal task).

 Individuals with ADHD were impaired in all tasks. It was noted that impaired interference inhibition was associated with hypoactivation in parietal and medial frontal regions. During action withholding and cancelation, individuals with ADHD displayed hypoactivation in a fronto-striatal network. These findings indicate that at least 2 disturbed neural circuits in aADHD differentially associated with deficits in separate inhibitory subcomponents. Frontal brain responses were reduced among individuals with aADHD when compared to controls during free responses, whereas parietal brain functions seemed to be unaffected. These results appear to indicate that selection processes are related to dysfunctions, predominantly in frontal brain regions among individuals with ADHD. 

A study that investigated neural and behavioral correlates of visual encoding during a working memory (WM) task among young adults with aADHD found that there was ineffective allocation of attentional resources involved in encoding of information in WM.

 It has been noted that individuals with aADHD have significantly lower sensory gating than controls, suggesting an impaired ability to filter incoming information.

 Additionally, increased connectivity between the default mode network and a region within left lateral prefrontal cortex (PFC) has been noted. Furthermore, greater levels of resting state activity within that area of PFC was noted to be associated with reduced performance on attentional tasks.

 A common reason for this under-diagnosis is the nature of the illness, as it shares many clinical characteristics with common psychiatric disorders. These disorders include major depression, bipolar disorder, anxiety disorders, SUDs, and personality disorders. Given this overlap in symptomatology, it is recommended that aADHD should be evaluated using a dimensional rather than a categorical approach.

 Katzman et al recommend asking about long-standing and consistent problems with attention and distractibility. Additionally, inquire about complaints from the last 10 to 20 years, conceptualizing how the individual would have been as a child in a classroom. Early diagnosis and treatment of comorbid disorders appear to improve the outcomes among individuals with aADHD. 

It is also recommended that the focus of the evaluation in an adult presenting with symptoms of ADHD should be on the individual’s mental state, as it adds immediate and greater clinical value than the use of cognitive or neuroimaging information.

 Additionally, certain symptoms like physically restless, emotional dysregulation, excessive mental wandering, and sleep-onset insomnia may suggest a diagnosis of aADHD. It is also prudent to exercise caution when evaluating individuals with aADHD, as some individuals may feign ADHD symptoms in order to obtain stimulant medications for diversion to non-medical use.

To meet the DSM-5 diagnostic criteria for ADHD among adults, the individual needs to have 5 or more of the 9 symptoms of inattention and/or of hyperactivity and impulsivity.

 These symptoms need to also have persisted for at least 6 months. In addition, several inattentive or hyperactive–impulsive symptoms should have been present prior to the age of 12 years. These symptoms should be present in 2 or more settings, including home, school, or work; with friends or relatives; in other activities. Furthermore, there should be clear impairment with/or reduced quality of social, academic, or occupational functioning. These symptoms should not occur due to another psychiatric disorder, especially due to psychotic, mood, or anxiety disorders; or due to substance intoxication or withdrawal. The DSM-5 also defines 3 clinical presentations of ADHD based on symptom profile: predominantly inattentive, predominantly hyperactive/impulsive, and a combined (inattentive and hyperactive and impulsive) presentation. The DSM-5 recommends that collateral information should be obtained, as adult recall of childhood symptoms tend to be unreliable.

As there is significant co-occurrence of many common psychiatric disorders with aADHD, these disorders should ideally be diagnosed and treated first.

 This will ensure that the best treatment can be chosen for the core aADHD symptoms. If that is not possible, co-treating these disorders may also be beneficial among individuals with aADHD.

Pharmacological agents are considered first line interventions for the treatment of aADHD.

 The medications that are approved for the treatment of adult ADHD include stimulants, such as amphetamines (amphetamine, dextroamphetamine, and lisdexamfetamine) and methylphenidate (methylphenidate and dexmethylphenidate); and non-stimulants (atomoxetine).

 Other medications that are used off-label include modafinil, guanfacine, venlafaxine, bupropion, and desipramine.

Both amphetamines and methylphenidate are available as immediate release preparations requiring multiple dosing each day and sustained release preparations for once or twice daily dosing.

 The amphetamines and methylphenidate have been found equally efficacious in the treatment of aADHD, with approximately 70% of individuals reporting immediate improvement in core symptoms within 1 hour after administration of the drug. The common adverse effects of these drugs include insomnia, dry mouth, decreased appetite, weight loss, headaches, depression, and anxiety. They are contraindicated among individuals with hypertension, psychosis, or tics, as the medications may worsen these conditions. These medications need to be used with caution among individuals with serious heart disease. Stimulant medications are classified by the Drug Enforcement Agency as Schedule II substances, as they have a potential for abuse especially among individuals with SUDs.

The only non-stimulant medication that is approved for the treatment of aADHD is atomoxetine.

 It appears to have lower potential for abuse than stimulant medications. It is also preferred for use among individuals with ADHD and comorbid substance use disorders, tics, anxiety, or psychosis. However, atomoxetine appears to be less effective than stimulant drugs in reducing core ADHD symptoms and requires 1 to 2 weeks of treatment to achieve full benefit.

Additionally, there is no convincing evidence that atomoxetineis safer than stimulants, and it needs to be used cautiously among individuals with cardiovascular and cerebrovascular disease. The common side effects of atomoxetine include dry mouth, insomnia, nausea, decreased appetite, constipation, decreased libido, dizziness, and sweating.

 Other non-stimulant medications that can be used off-label among individuals with aADHD include modafinil, guanfacine, venlafaxine, bupropion, and desipramine, but the evidence for their use is limited to a few small controlled studies of short duration.

In a meta-analysis that included data from 19 trials and studied 13 different drugs, the investigators found that although both stimulant and non-stimulant medications are effective treatments for aADHD, stimulant medications show greater efficacy for the short durations of treatment when compared to placebo.

 However, there were no significant differences noted between short- and long-acting stimulant medications.

A systematic review of 18 published studies found that that cognitive behavioral therapy (CBT) was the most effective psychological treatment for aADHD and the comorbid symptoms of anxiety and depression.

The National Institute for Health and Care Excellence recommends prescribing medications to adults with ADHD if their ADHD symptoms are causing a significant impairment in at least 1 

, after environmental modifications have been implemented.

 The guideline recommends using lisdexamfetamine or methylphenidate as first-line pharmacological agents for the management of aADHD.

Another recommendation is switching between the 2 medications for adults who have had a 6‑week trial of 1 medication at an adequate dose without significant benefit. Atomoxetine was recommended if the individual cannot tolerate lisdexamfetamine or methylphenidate or their symptoms have not responded to separate 6‑week trials with either medication. The guideline recommends using non-pharmacological treatments among individuals with aADHD who have made a choice not to use medications, had difficulty adhering to medications, or found medications to be ineffective or intolerable. The guideline also recommended considering non-pharmacological treatment in combination with medication for individuals with aADHD who have benefited from medications, but whose symptoms are still causing a significant impairment in at least 1 domain. The recommendation involves elements of or a full course of CBT.

In a meta-analysis that evaluated psychostimulants (methylphenidate, dexamphetamine, mixed amphetamine salts, and lisdexamfetamine) and non-psychostimulants (such as atomoxetine) for the treatment of aADHD, the investigators found that pharmacological treatments were significantly more efficacious than placebo (standardized mean difference = 0.45) but less well accepted (odds ratio (OR) = 1.18) and tolerated (OR = 2.29).

 The effects of pharmacological treatments for individuals with co-occurring ADHD and substance use disorder remains uncertain. The evidence for the effectiveness of non-pharmacological treatments for aADHD as well as the combination of pharmacological and non-pharmacological strategies was found to be preliminary.

Emerging evidence indicates that there may be 2 distinct subtypes of aADHD: the first that arises in childhood and persists into adulthood and the other that occurs only in adulthood. Individuals with aADHD have significant educational, social, and occupational impairments in addition to greater rates of morbidity and mortality. There also appears to be a genetic preponderance for aADHD with moderate heritability. Available evidence indicates both neurochemical and neurofunctional impairments among individuals with aADHD involving the dopaminergic and noradrenergic systems and the frontal and parietal cortices. Unfortunately, aADHD is often underdiagnosed as this condition shares many clinical characteristics with common psychiatric illnesses including mood and anxiety disorders. Stimulant medications are the treatment of choice among individuals with aADHD with similar efficacy noted for the amphetamine and methylphenidate group of drugs. Atomoxetine is the only non-stimulant medication that is approved for the treatment of aADHD. CBT has the best evidence among non-pharmacological treatments and is beneficial for those individuals who decline pharmacotherapy, are intolerant to medications, or have residual symptoms despite adequate pharmacotherapeutic trials.

is chairman, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, OH; chief, Section for Geriatric Psychiatry, Cleveland Clinic, Cleveland, OH; and professor of medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH. 

co-founder and managing principal, Behavioral Health Advisory Group, Princeton, NJ

is program director, Psychiatry Residency Program, Cleveland Clinic Akron General, Akron, OH; clinical professor of psychiatry at Northeast Ohio Medical University, Rootstown, OH.

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Desk Reference To The Diagnostic Criteria From Diagnostic and Statistical Manual of Mental Disorders

. 5th ed. American Psychiatric Association; 2013.

2. Mahadevan J, Kandasamy A, Benegal V. Situating adult attention-deficit/hyperactivity disorder in the externalizing spectrum: Etiological, diagnostic, and treatment considerations. 

3. Spencer TJ, Biederman J, Mick E. Attention-deficit/hyperactivity disorder: diagnosis, lifespan, comorbidities, and neurobiology. 

4. Faraone SV, Biederman J, Mick E. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. 

5. Caye A, Rocha TB, Anselmi L, et al. Attention-deficit/hyperactivity disorder trajectories from childhood to young adulthood: evidence from a birth cohort supporting a late-onset syndrome. 

6. Agnew-Blais JC, Polanczyk GV, Danese A, et al. Evaluation of the persistence, remission, and emergence of attention-deficit/hyperactivity disorder in young adulthood. 

7. Simon V, Czobor P, Bálint S, et al. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. 

8. Katzman MA, Bilkey TS, Chokka PR, et al. Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. 

9. Doshi JA, Hodgkins P, Kahle J, et al. Economic impact of childhood and adult attention-deficit/hyperactivity disorder in the United States. 

10. Klassen LJ, Katzman MA, Chokka P. Adult ADHD and its comorbidities, with a focus on bipolar disorder. 

11. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. 

12. Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. 

13. Franke B, Faraone SV, Asherson P, et al. The genetics of attention deficit/hyperactivity disorder in adults, a review. 

14. Bonvicini C, Faraone SV, Scassellati C. Attention-deficit hyperactivity disorder in adults: a systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies. 

15. Volkow ND, Swanson JM. Clinical practice: Adult attention deficit-hyperactivity disorder. 

16. Karch S, Thalmeier T, Lutz J, et al. Neural correlates (ERP/fMRI) of voluntary selection in adult ADHD patients. 

17. Frodl T, Skokauskas N. Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects. 

18. Sebastian A, Gerdes B, Feige B, et al. Neural correlates of interference inhibition, action withholding and action cancelation in adult ADHD. 

19. Kim S, Liu Z, Glizer D, et al. Adult ADHD and working memory: neural evidence of impaired encoding. 

20. Jadidian A, Hurley RA, Taber KH. Neurobiology of adult ADHD: emerging evidence for network dysfunctions. 

21. Asherson P, Buitelaar J, Faraone SV, Rohde LA. Adult attention-deficit hyperactivity disorder: key conceptual issues. 

22. Katzman MA, Bilkey TS, Chokka PR, et al. Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. 

23. National Institute for Health and Care Excellence. Attention deficit hyperactivity disorder: diagnosis and management NICE guidelines [NG87]. 2019. Accessed November 24, 2020.

24. Wilens TE, Morrison NR, Prince J. An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in adults. 

25. Faraone SV, Glatt SJ. A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes. 

26. Vidal-Estrada R, Bosch-Munso R, Nogueira-Morais M, et al. Psychological treatment of attention deficit hyperactivity disorder in adults: a systematic review. 

27. De Crescenzo F, Cortese S, Adamo N, Janiri L. Pharmacological and non-pharmacological treatment of adults with ADHD: a meta-review. 

Although normally associated with children, attention-deficit/hyperactivity disorder can also persist in adulthood, presenting challenges to both patients and clinicians. 

Adult Attention-deficit/Hyperactivity Disorder (aADHD)

Academy of Pediatrics Clinical Practice Guidelines

Screening for ADHD and Comorbidities

Collaborative Management: Pediatricians and Psychiatrists

Managing ADHD During the COVID-19 Pandemic

The Impact of COVID-19 Pandemic on Pediatrics 

Practical Advice for Caregivers During COVID-19 Pandemic 

Medicine Management During COVID-19 Pandemic

Unmet Needs in Pediatric ADHD Management

Stimulant Abuse in Pediatric ADHD Populations

The Future of the ADHD Treatment Landscape

A discussion on the multidisciplinary management of ADHD, challenges in treatment during COVID-19, and the impact of human abuse potential of ADHD medications. 

ADHD: Strategies for Developing a Further Dialogue

Supernus Pharmaceuticals, Inc recently announced regulatory updates on their drugs, SPN-812 for the treatment of attention-deficit/hyperactivity disorder. The United States Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) stating SPN-812 is not ready for approval in its present form.

“On SPN-812, we look forward to collaborating with the FDA to clarify and resolve the facility matter and put SPN-812 back on track to help the millions of children and adolescents in the US with ADHD,” Jack Khattar, President and CEO of Supernus, said to the press.

SPN-812, or viloxazine hydrochloride, is a novel non-stimulant intended for the treatment of ADHD in pediatric patients aged 6 to 17. The application for SPN-812 included data from 4 Phase III clinical trials, in which the serotonin norepinephrine modulating agent of SPN-812 caused improvements in both the hyperactivity/impulsivity and inattention subscales of the ADHD Rating Scale V.

Supernus plans to discuss and clarify the CRL for SPN-812 with the FDA. The main issue cited in the letter is Supernus’ in-house analytical testing laboratory, which has recently move to a new location. The application does not solely rely on this facility for product release, which is hoped to be brought up in discussions, along with the resubmission of the NDA for SPN-812.

Supernus plans to provide further updates on the expected launch timing for SPN-812 after their discussion with the FDA.

1. Supernus Pharmaceuticals. Supernus Provides Regulatory Updates for SPN-812 and SPN-830. News release. 

https://www.globenewswire.com/news-release/2020/11/09/2123296/0/en/Supernus-Provides-Regulatory-Updates-for-SPN-812-and-SPN-830.html

2. Bratulic A. FDA rebuffs Supernus filings for ADHD, Parkinson’s disease treatments. 

https://beta.firstwordpharma.com/story/5148683

A potential treatment for attention-deficit/hyperactivity disorder goes back to the drawing board. 

Proposed Treatment for ADHD Suffers Setback

, despite significant decline in antipsychotic use in privately insured children since 2009, doctors continue to prescribe antipsychotic medication off-label for conditions not approved by the US Food and Drug Administration. These conditions include conduct disorder, attention-deficit/hyperactivity disorder, anxiety, and depression.

“We lack information on the effectiveness and safety of antipsychotics for treating those conditions in young children,” lead author Greta Bushnell, PhD, MSPH, a member of the Rutgers Institute for Health, Health Care Policy and Aging Research and an assistant professor at Rutgers School of Public Health, said to the press. “Guidelines recommend that psychosocial services are used before antipsychotic treatment and that children are carefully assessed before initiating antipsychotics. However, fewer than half of the children receiving antipsychotic treatment in our study had a visit with a psychiatrist or a psychotherapy claim.”

Journal of the American Academy of Child & Adolescent Psychiatry

, the study examined more than 300,00 antipsychotic prescriptions for privately insured children in the United States aged 2 to 7. The study also found antipsychotics were more often prescribed to boys aged 6 or 7.

“The low rate of use of safer first-line psychosocial treatments, such as parent-child interaction therapy or cognitive-behavioral therapy, potentially puts children at unnecessary risks associated with antipsychotic treatment,” Bushnell said to the press.

Risks associated with antipsychotic medication for children include weight gain, sedation, diabetes, high cholesterol, cardiovascular disease, and unexpected death.

The challenge for the future, the researchers concluded, will be improving antipsychotic prescriptions in young children.

1. Bushnell GA, Crystal S, Olfson M. Trends in Antipsychotic Medication Use in Young Privately Insured Children. 

https://www.jaacap.org/article/S0890-8567(20)31987-0/fulltext

2. Rutgers University. Prescriptions of Antipsychotic Medications in Young Children is Declining. News release. November 8, 2020. 

https://www.newswise.com/articles/prescriptions-of-antipsychotic-medications-in-young-children-is-declining?sc=dwhr&xy=5013482

Antipsychotic medications for young children are not being prescribed appropriately, according to a recent study. 

The Decline of Child Antipsychotic Medications

 found that children diagnosed with attention deficit/hyperactivity disorder (ADHD) had a 10-fold increase in the incidence of later development of bipolar disorder compared with matched children without ADHD.

, has a more severe course than either diagnosis alone, and is associated with greater risk of suicide attempts.

 Clinicians will have trouble determining which diagnosis best fits the patient, and it actually could be that the patient has both. Often the patient (and/or prescriber) prefers the ADHD diagnosis and the stimulant medications used to treat it. They hope to avoid the diagnosis of bipolar disorder and medications used to treat it, because of the perceived stigma and complexity of treatment. The differential diagnosis is made by recognizing that bipolar (hypo)manias occur in discreet episodes of at least 4 to 7 days, whereas the hyperactivity and associated symptoms of ADHD are more or less constantly present as features of the individual’s temperament.

The comorbidity of ADHD and bipolar may involve overlapping genetics. In Sweden, 13,532 twin pairs (aged 9 to 12 years) were evaluated using parent-rated instruments for 

 Overlapping symptoms were removed to aid in the analysis. The twin pairs were reassessed at age 15 and again (n=3013) at age 18. They found that genetic factors associated with hypomania explained 25% to 42% of likelihood of having ADHD’s hyperactive/impulsive symptoms. There was less effect on the inattentive symptoms of ADHD. Monozygotic twins had a stronger association of the 2 conditions than the dizygotic twins. The rest of the variance was presumed to be associated with causes of ADHD that do not contribute to causing hypomania.

The bottom line of these data is that it is important to take the time to diagnose bipolar accurately in patients with a history of ADHD or presenting with current ADHD. Mood stabilizing medications such as lithium will usually be indicated for the bipolar condition.

Stimulant treatment of ADHD when there is comorbid bipolar has been controversial. However, 

 was published in 2016 by Viktorin and colleagues

 that may influence practice. This large observational study found that if patients are treated with methylphenidate for ADHD, and their bipolar disorder is not being treated with a mood stabilizer, the likelihood of manic switch over 3 to 6 months is increased by nearly 7-fold, compared with patients with bipolar disorder not treated with methylphenidate. However, if patients are on a bipolar mood stabilizer, the addition of methylphenidate was associated with 

 odds of becoming manic, compared with the control patients with bipolar disorder not given a stimulant, with a hazard ratio of 0.6 (ie, a 40% reduction). Thus, it seemed that methylphenidate can be safe and effective for ADHD symptoms if the patient is on a mood stabilizer to manage the bipolar disorder. Note that amphetamine products were not evaluated in this Scandinavian study: many European countries have not approved them.

In summary, it is critically important to carefully evaluate whether patients with ADHD also have bipolar disorder. If you miss the bipolar diagnosis and treat the ADHD with a stimulant, the potential for harm (induction of mania) is considerable. However, if the bipolar disorder is under control with a mood stabilizer, the use of a stimulant (at least methylphenidate) need not be avoided. Indeed, it may be quite helpful.

is associate professor of psychiatry, Harvard Medical School, and co-lead psychiatrist, US Department of Veterans Affairs, National Telemental Health Center, Bipolar Disorders Telehealth Program, Brockton, MA. He is a member of 

Editorial Board. The author reports no conflicts of interest concerning the subject matter of this article.

1. Meier SM, Pavlova B, Dalsgaard S, et al. Attention-deficit hyperactivity disorder and anxiety disorders as precursors of bipolar disorder onset in adulthood. 

2. Lan WH, Bai YM, Hsu JW, et al. Comorbidity of ADHD and suicide attempts among adolescents and young adults with bipolar disorder: a nationwide longitudinal study. 

3. Hosang GM, Lichtenstein P, Ronald A, et al. Association of genetic and environmental risks for attention-deficit/hyperactivity disorder with hypomanic symptoms in youths. 

4. Viktorin A, Rydén E, Thase ME, et al. The risk of treatment-emergent mania with methylphenidate in bipolar disorder. 

Although clinicians and patients may wish otherwise, the comorbidity of ADHD and bipolar disorder needs to be considered.  

ADHD in Bipolar Patients: Genetics, Diagnosis, and Treatment

Akili announced new data on its therapeutic EndeavorRx, an FDA-cleared digital treatment for children diagnosed with attention-deficit/hyperactivity disorder (ADHD). The data, which highlights real-world improvements and benefits, includes results from the STARS-Adjunct trial, a multi-site open-label study created to examine the impact of EndeavorRx on impairments in daily life scenarios for children with ADHD. The initial presentation of data occurred this week at the American Academy of Child and Adolescent Psychiatry (AACAP) 2020 Virtual Annual Meeting.

“The STARS-Adjunct study provides further evidence for physicians on the use of EndeavorRx in clinical practice, including duration of treatment and use alongside traditional ADHD medications,” said Anil Jina, MD, chief medical officer of Akili, to press. “Building on the improvements in objective measures of attention demonstrated in our prior clinical studies of EndeavorRx, these data help show the benefits of treatment seen by parents assessing their child’s ADHD-related impairments in everyday life.”

The study included 206 pediatric participants aged 8-14 years with a diagnosis of ADHD, across 2 cohorts: children who were taking ADHD stimulant medications and children who were not taking ADHD medications for the duration of the study. Children completed 1 month of treatment with EndeavorRx, followed by a 1 month pause and then another 1-month treatment with EndeavoRx.

Administered as a video game experience, EndeavorRx is shown to improve attention function as ascertained by computer-based testing in children aged 8-12 with primarily inattentive or combined-type ADHD. It is not intended to be used as a sole treatment and is not an adequate replacement for a child’s medication.

Several key results about EndeavorRx were revealed in the presentations. First, both children taking stimulants and those not taking any ADHD medication demonstrated similar and statistically significant improvements on the ADHD Impairment Rating Scale (IRS) compared to baseline.

Second, observations from parents showed half of children responded to the treatment following 1 month of usage. Improvements remained stable for 1 month following treatment.

Third, 34.5% of children no longer showed attention impairment on at least 1 aspect of objective attention post-treatment.

Lastly, early evidence suggests children who improved in attention functioning following treatment also improved their math and reading skills, as demonstrated by their performance on the Test of Silent Reading Efficiency and Comprehension (TOSREC) and the Mathematics Fluency and Calculation Tests (MFaCTS).

1. Researchers Present New Outcome Data for Akili Digital Therapeutic EndeavorRx™ in Pediatric ADHD. News release. 

https://www.businesswire.com/news/home/20201021005068/en/Researchers-Present-New-Outcome-Data-for-Akili-Digital-Therapeutic-EndeavorRx™-in-Pediatric-A DHD

Akili announces new data on treatment EndeavorRx that reports real-world improvement for children with ADHD. 

New Data Supports Use of Digital Treatment for ADHD 

The year 2020 has proven to be a year of challenges and uncertainties thanks to 

 (COVID-19). We started the year relatively unaware of the virus, and now it impacts every aspect of our lives. Although the initial concern was aimed at the oldest and most frail segments of the population, we must not forget our younger patients and the unique psychological challenges that children face during this pandemic.

The reopening debate: in-person versus online learning

One of the most contested issues in the country revolves around the reopening of schools. On the one hand, there are concerns over the social and learning needs of children; on the other are the health risks facing students, teachers, other school personnel, and their respective families.

for in-person school and learning, since schools provide academic, social, and emotional skills and support that are hard to replicate at home.

 However, the AAP also affirmed “science should drive decision-making on safely reopening schools,” and noted “a one-size-fits-all approach is not appropriate for return to school decisions.” The AAP added:

“Reopening schools in a way that maximizes safety, learning, and the well-being of children, teachers, and staff will clearly require substantial new investments in our schools and campuses. We call on Congress and the administration to provide the federal resources needed to ensure that inadequate funding does not stand in the way of safely educating and caring for children in our schools. Withholding funding from schools that do not open in person full-time would be a misguided approach, putting already financially strapped schools in an impossible position that would threaten the health of students and teachers.”

American Academy of Child & Adolescent Psychiatry 

 similarly stated, “In these uncertain times, making educational decisions based on science and community circumstances ensures the mental health needs of our children and adolescents are being addressed, allowing them to feel engaged, safe, secure, supported, and loved.”

 They also acknowledged that “education, including school attendance, is an essential component of successful and healthy development for all children and adolescents” and offered guidelines for reopening. They mentioned ensuring the well-being and educational needs of vulnerable populations like “children with emotional, learning, and physical disabilities as well as those in foster care, poverty, and for whom English is a second language, to mention but a few.”

What is “safe”? Lessons from around the world

The push to open schools in-person was originally based on the theory that children were largely not affected by COVID-19 and that transmission from asymptomatic children was uncommon. However, this assumption came after the strict physical distancing measures and school closures, and the story appears to have changed. The appearance of multisystem inflammatory syndrome, which causes serious, even life-threatening illness in previously healthy children and adolescents, served as a rude wake-up call.

 By August 6, 2020, the Centers for Disease Control received reports of 570 cases and 10 deaths across 40 jurisdictions (

 The affected children were aged 1 to 14 years; their average age was 8 years. Almost all children (96%) with the syndrome tested positive for SARS CoV-2, the virus responsible for COVID-19; the others had been in the vicinity of someone infected with the virus.

New data also show that children are not invulnerable to COVID-19. In the United States, the number of cases in children rose 44% between July 9 and July 23, according to a report which also found that children accounted for 8.4% of US cases.

 With 20 states reporting, researchers found between 0.6% and 9.0% of all juvenile COVID-19 cases resulted in hospitalization, confirming that severe illness was possible in children, albeit rarer than in adults. Similarly, in 8 days in July, Florida saw a 34% increase in new cases and a 23% increase in hospitalizations among children; the test positivity rate among children also increased.

 Recent news reports also tell of thousands of students and teachers quarantined as the number of COVID-19 infections rip through schools in several states after re-opening in person.

Some proponents of a wider in-person school opening have noted that children are less likely to spread the virus, but a new report in 

 The authors found that replication of SARS-CoV-2 in older children resulted in similar levels of viral nucleic acid as in adults, but found significantly greater amounts of viral nucleic acid in children younger than 5 years. Considering behavior and hygiene issues in younger children, the authors said, “Young children can potentially be important drivers of SARS-CoV-2 spread in the general population.”

Lessons can also be learned by looking abroad. Two weeks after reopening schools, Israel saw a spike in COVID-19 cases, with more than 200 cases among students, and 130 cases at a single school.

 Countries including Singapore and South Korea also experienced spikes in cases when schools were reopened.

Guiding parents and supporting young patients

This is new territory for everyone, and young patients and their parents are likely to experience stress and anxiety as the school year begins. There are several ways parents can prepare themselves and their children for a relatively smooth transition.

First and foremost, clinicians should counsel parents to consider their individual family needs and issues, then develop a clear plan in terms of social distancing.

 Families with at-risk individuals may prefer more stringent rules, while others may err on the side of socialization. Once parents have determined what works best for their family, they should make the socialization rules very clear to their children, discussing realistic and practical strategies to mitigate the chances of infection.

 The approach and discussion should be tailored to the age and maturity of the child.

Children need a sense of safety and stability, so navigating these waters can be tricky. Parents should explain that although schools are reopening, socialization will be a step-by-step process. Regroup as needed with children and adolescents to provide updates, share reminders, and allow for questions.

Children in upper elementary and middle school grades are prone to receiving misinformation, either via friends or social media. Parents should facilitate family conversations, listening carefully to their children’s concerns and helping them separate fact from fiction.

Finally, role play may assist children and adolescents as they negotiate this new school year. It can be difficult even for adults to request that someone maintain their distance or ensure that their mask is properly covering their mouth and nose. Share ways to make the conversations easier. For younger children, you can even make it a game. Act out correct and incorrect behaviors, and see if they can pick out the mistakes.

Younger patients are facing unique psychological challenges during this pandemic.

ADHD