Attention Deficit/Hyperactivity Disorder · (e.g., schizophrenia, psychotic disorder,mooddisorder,anxiety disorder, or personality disorder) should be ruled out. Attention deficit

Attention Deficit/Hyperactivity Disorder - Medical Clinical Policy Bulletins | Aetna

(https://www.aetna.com/)

Attention Deficit/HyperactivityDisorder

Number: 0426 Policy *Please see amendment for Pennsylvania Medicaid

at the end of this CPB.

I. Aetna considers certain services medically necessary for the

assessment of attention deficit hyperactivity disorder (ADHD):

Complete psychiatric e valuation (adults)

Electroencephalography (EEG) or neurological consult when the

presence of focal signs or clinical findings are suggestive of a

seizure disorder or a degenerative neurological condition

Laboratory evaluation (complete blood count [CBC], liver

function tests [LFT]) and a cardiac evaluation and screening

incorporating an electrocardiogram (ECG) if indicated, prior to

beginning stimulant medication therapy

Measurement of blood lead level for individuals with risk

factors

Medical evaluation (complete medical history and physical

examination)

Parent/child interview, or if adult, patient interview which may

include obtaining information about the individual’s daycare,

school or work functioning utilizing the criteria listed in the

DSM-5. May also include an evaluation of comorbid psychiatric

disorders and review of the individual’s family and social

history.

L ast Review

04/23/2020

Effective: 09/11/2000

Next Review: 04/22/2021

Review History

Definitions

Addit ional Information

C linical Policy Bulletin

Notes

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https://www.aetna.com/


Thyroid hormone levels if individual exhibits clinical

manifestations of hyperthyroidism (e.g., modest acceleration of

linear growth and epiphyseal maturation, weight loss or failure

to gain weight, excessive retraction of the eyelids causing lid lag

and stare, diffuse goiter, tachycardia and increased cardiac

output, increased gastrointestinal motility, tremor,

hyperreflexia)

Notes:

Neuropsychological testing is not considered medically necessary

for the clinical evaluation of persons with uncomplicated cases of

ADHD. Psychological testing is not considered medically necessary

for evaluation of children with uncomplicated cases of ADHD. In

addition, neuropsychological or psychological testing performed

solely for educational reasons may be excluded from coverage, as

many Aetna benefit plans exclude coverage of educational testing;

please check benefit plan descriptions. Neuropsychological testing

may be medically necessary in neurologically complicated cases of

ADHD (e.g., post head trauma, seizures). (See

CPB 0158 - Neuropsychological and Psychological Testing

(../100_199/0158.html)

Referral to an outpatient mental health or chemical dependency

provider may be medically necessary for the evaluation and

comprehensive bio-psychosocial treatment for these disorders in

collaboration with primary care physicians and other specialists.

II. Aetna considers pharmacotherapy and behavioral modification

medically necessary for treatment of ADHD* .

III. Aetna considers the following experimental and investigational for

the assessment and treatment of ADHD because the peer-

reviewed medical literature does not support the use of these

procedures/services for this indication.

A. Assessm ent

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4/24/2020 Attention Deficit/Hyperactivity Disorder - Medical Clinical Policy Bulletins | Aetna

Actometer/Actigraph (see

CPB 0710 - Actigraphy and Accelerometry

(../700_799/0710.html)

AFF2 gene testing

Computerized EEG (brain mapping or neurometrics (see C

PB 0221 - Quantitative EEG (Brain Mapping)

(../200_299/0221.html)

Computerized tests of attention and vigilance (continuous

performance tests) (eg, G ordon Diagnostic System)

Education and achievement testing*

EEG theta/beta power ratio for the diagnosis of attention

deficit hyperactivity disorder

Electronystagmography (in the absence of symptoms of

vertigo or balance dysfunction)

Evaluation of iron status (e.g., measurement of serum iron

and ferritin levels)

Event-related potentials (see

CPB 0181 - Evoked Potential Studies (../100_199/0181.html))

Functional near-infrared spectroscopy (fNIRS)

Hair analysis (see

CPB 0300 - Hair Analysis (../300_399/0300.html))

IgG blood tests (for prescription of diet)

Measurement of blood and hair magnesium levels

Measurements of peripheral brain-derived neurotrophic

factor

Measurements of serum lipid patterns

Measurement of zinc

Neuroimaging (e.g., CT, CAT, MRI [including diffusion tensor

imaging], magnetic resonance spectroscopy (MRS), PET and

SPECT)

Neuropsychiatric EEG-based assessment aid (NEBA) System

Otoacoustic emissions (in the absence of signs of hearing

loss)

Pharmacogenetic testing of drug response

Quotient ADHD system/test

SNAP25 gene polymorphisms testing

Testing of serotonin receptor family genetic variations

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Transcranial magnetic s timulation-evoked measures (e.g.,

short interval cortical inhibition in motor cortex) as a marker

of ADHD symptoms

Tympanometry (in the absence of hearing loss)

B. T re a tment

Acupuncture

Anti-candida albicans medication

Anti-fungal medications

Anti-motion-sickness medication

Applied kinesiology

Brain integration therapy

Chelation

Chiropractic manipulation

Cognitive behavior modification (cognitive rehabilitation)

Computerized training on working memory (e.g., Cogmed

and RoboMemo)*

Deep pressure sensory vest

Dietary counseling and treatments (ie Feingold diet)

Dore program/dyslexia-dyspraxia attention treatment

(DDAT)

Educational intervention (e.g., classroom environmental

manipulation, academic skills training, and parental training)

EEG biofeedback, also known as neurofeedback (see C

PB 0132 - Biofeedback (../100_199/0132.html))

External trigeminal nerve stimulation

Herbal remedies (e.g., Bach flower)

Homeopathy

Intensive behavioral intervention programs (e.g., applied

behavior analysis [ABA], early intensive behavior

intervention [EIBI], intensive behavior intervention [IBI], and

Lovaas therapy)

Megavitamin therapy (see

CPB 0388 - Complementary and Alternative Medicine

(../300_399/0388.html)

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Metronome training (see

CPB 0325 - Physical Therapy Services (../300_399/0325.html))

Mineral supplementation (e.g., iron, magnesium and zinc)

Music therapy (see


(../300_399/0388.html)

Neurofeedback (EEG biofeedback)

Occupational therapy

Optometric vision training/Irlen lenses

Physical therapy

Psychopharmaceuticals: lithium, benzodiazepines, and

selective serotonin re-uptake inhibitorsFootnotes*

Reboxetine

Sensory (auditory) integration therapy (see

CPB 0256 - Sensory and Auditory Integration Therapy

(../200_299/0256.html)

Speech therapy

Syntonic phototherapy

The Good Vibrations device*

The Neuro-Emotional Technique

Therapeutic eurythmy (movement therapy)

Transcranial magnetic stimulation/cranial electrical

stimulation (see

C PB 0469 - Transcranial Magnetic Stimulation and Cranial

Electrical Stimulation (0469.html)

Vayarin (phosphatidylserine-containing omega3 long-chain

polyunsaturated fatty acids)

Vision therapy

Yoga (see


(../300_399/0388.html)

* Notes:

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Coverage of pharmacotherapies is subject to the member's specific

benefits for drug coverage. Please check benefit plan descriptions for

details.

Many Aetna plans exclude coverage of educational interventions.

Please check benefit plan descriptions for details.

Psychotherapy is covered under Aetna mental health benefits if the

member also exhibits anxiety and/or depression.

Attention deficit/hyperactivity disorder (ADHD) is a common condition

among children and adolescents, and has been diagnosed with increased

frequency in adults. It is characterized by symptoms of inattention and/or

hyperactivity/impulsivity that have persisted for at least 6 months to a

degree that is maladaptive and inconsistent with developmental level.

Usually, some symptoms that caused impairment were present before the

age of 7 years. Some impairment from the symptoms is present in 2 or

more settings (e.g., at home and at school). Other causes of symptoms

(e.g., schizophrenia, psychotic disorder, mood disorder, anxiety disorder,

or personality disorder) should be ruled out.

Attention deficit hyperactivity disorder (ADHD) is one of the most common

neuro-behavioral disorders of childhood. Approximately eight to ten

percent of school age children are diagnosed with ADHD, with males

predominantly more affected than females. Often, individuals with ADHD

are affected by comorbidities, which are other conditions that exist

simultaneously with and independent of ADHD. Examples include, but

may not be limited to, anxiety disorder, conduct disorder, depression,

oppositional defiant disorder and learning disabilities. Although ADHD is

usually diagnosed in childhood, it may last into adulthood.

The behavior of individuals with ADHD may generally be classified into

three subtypes; predominantly inattentive, predominately hyperactive-

impulsive or a combination of the two.

ADHD is characterized by a pattern of behavior, present in multiple

settings (eg, school and home), that can result in performance issues in

social, educational or work settings. There is no single test to diagnose

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ADHD. Typically, a diagnosis is made by a comprehensive exam that

assesses the onset and course of symptoms consistent with ADHD. A

functional assessment, if conducted, evaluates both the severity of

impairment and the pervasiveness of symptoms occurring in different

environments.

The parameters for diagnosing ADHD are found in the Fifth Edition of the

Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published

by the American Psychiatric Association (APA). The DSM-5 includes a set

of diagnostic criteria that indicate the symptoms that must be present to

establish the diagnosis of ADHD.

There are several types of specialists qualified to diagnose and treat

ADHD. Examples include, but may not be limited to, child psychiatrists,

family physicians, pediatricians, psychiatrists or neurologists. The

treatments for ADHD may involve pharmacotherapy and

nonpharmacologic therapy, including such interventions as individual

and/or family psychotherapy.

There is no specific test for ADHD; its diagnosis is a clinical one. A

parent/child interview is the cornerstone in the assessment of ADHD in

children and adolescents. It is used to rule out other psychiatric or

environmental causes of symptoms. A medical evaluation with a

complete medical history and a physical examination is necessary.

According to the American Academy of Child and Adolescent Psychiatry

(AACAP)’s Practice Parameter for the Assessment and Treatment of

Children and Adolescents with Attention-Deficit/Hyperactivity Disorder,

neuropsychological testing of children for the purpose of diagnosing

ADHD is not considered necessary, unless there is strong evidence of a

possible neurological disorder. There are few medical conditions which

present with ADHD-like symptoms and most patients with ADHD have

unremarkable medical histories. Neuropsychological assessment may be

useful in neurologically-complicated cases of ADHD; however, such

testing does not confirm the diagnosis of ADHD.

In general, attention-deficit disorders are best diagnosed through a careful

history and the use of structured clinical interviews and dimensionally-

based rating scales. Most psychologists obtain behavior ratings at home

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from the parents and at school from the teacher. Examples of the rating

scales commonly used by psychologists are the Achenbach Child

Behavior Checklist, Conners Rating Scales, and ADHD Symptoms Rating

Scale.

Measurement of blood level of lead is appropriate only if clinical or

environmental risk factors are present. An electroencephalogram

(EEG) provides a graphic record of the electrical activity of the brain.

Electroencephalography or neurological consult is indicated only in the

presence of focal signs or clinical suggestions of seizure disorder or

degenerative condition.

Brain mapping is the computerized conversion of data from brain

electrical potentials into colored topographical maps of the brain.

Quantitative electroencephalograph (QEEG) involvesdigital technology

and computerized EEG. There are insufficient data to support the

usefulness of computerized EEG (brain mapping or neurometrics)

There are insufficientdata to support event-related potentials,

neuroimaging, computerized tests of attention and vigilance, or

neuropsychological tests (e.g., Test of Variables of Attention, the

Continuous Performance Task, the Wisconsin Card-Sorting Test, the

matching Familiar figures Test, and the Wechsler Intelligence Scale for

Children-Revised). However, neuropsychological testing may be required

in neurologically complicated cases of ADHD (e.g., post head trauma,

seizures). There are no data to support the use of hair analysis or

measurement of zinc.

Medical management of ADHD entails the use of stimulants --

methylphenidate (Ritalin), dextroamphetamine (Dexedrine),

methamphetamine (Desoxyn), as well as an amphetamine-

dextroamphetamine combination (Adderall). Pemoline (Cylert) is

restricted to secondary use because of hepatic dysfunction associated

with its use. Tricyclic anti-depressants are used for patients who do not

respond to stimulants listed above, or for those who develop significant

depression or other side effects on stimulants, or for the treatment of

ADHD symptoms in patients with tics or Tourette's disorder.

Psychotherapy is appropriate patients also exhibit anxiety and/or

depression.

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In a Cochrane review on the use of amphetamine for ADHD in people with

intellectual disabilities (ID), Thomson et al (2009a) concluded that there is

very little evidence for the effectiveness of amphetamine for ADHD in

people with ID. The use of amphetamine in this population is based on

extrapolation of research in people without ID. The authors stated that

more research into effectiveness and tolerability is urgentlu needed.

Furthermore another Cochrane review discussed the use of risperidone

for ADHD in people with ID (Thomson et al, 2009b). The authors

concluded that there is no evidence from randomized controlled trials that

risperidone is effective for the treatment of ADHD in people with ID. The

use of risperidone in this population is based on open-label studies or

extrapolation from research in people with autism and disruptive

behavioral disorders; however these studies have not investigated people

with ID separately so there are reservations regarding the applicability of

these findings. Research into effectiveness and tolerability is urgently

needed.

There is a lack of scientific evidence to support the use of megavitamin

therapy, herbal remedies, cognitive behavior modification,anti-motion-

sickness medication, anti-candida-albicans medication,

psychopharmaceuticals such as lithium,benzodiazepines, and selective

serotonin re-uptake inhibitors, biofeedback, sensory (auditory) integration

therapy, optometric vision training/Irlen lenses, chiropractic manipulation,

or dietary interventions for the treatment of ADHD.

Konofal et al (2008) studied the effects of iron supplementation on ADHD

in children. A total of 23 non-anemic children (aged 5 to 8 years) with

serum ferritin levels less than 30 ng/ml who met DSM-IV criteria for ADHD

were randomized (3:1 ratio) to either oral iron (ferrous sulfate, 80 mg/day,

n = 18) or placebo (n = 5) for 12 weeks. There was a progressive

significant decrease in the ADHD Rating Scale after 12 weeks on iron

(-11.0 +/- 13.9; p < 0.008), but not on placebo (3.0 +/- 5.7; p = 0.308).

Improvement on Conners' Parent Rating Scale (p = 0.055) and Conners'

Teacher Rating Scale (p = 0.076) with iron supplementation therapy failed

to reach significance. The mean Clinical Global Impression-Severity

significantly decreased at 12 weeks (p < 0.01) with iron, without change in

the placebo group. The authors concluded that iron supplementation

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appeared to improve ADHD symptoms in children with low serum ferritin

levels suggesting a need for future investigations with larger controlled

trials.

The American Academy of Pediatrics (2000) has the following statements

regarding the diagnosis and evaluation of patients with ADHD:

Available evidence does not support routine screening of thyroid

function as part of the effort to diagnose ADHD.

Current data do not support the use of any available continuous

performance tests in the diagnosis of ADHD

Current literature does not support the routine use of EEG in the

diagnosis of ADHD.

Neuroimaging studies should not be used as a screening or diagnostic

tool f or children with ADHD bec ause they are associated with high

rates of false-positives and false-negatives.

Regular screening of children for high lead levels does not aid in the

diagnosis of ADHD.

Continuous performance tests are computer-based tests designed to

measure inattention and impulsivity.

Neuropsychological and psychological testing for purely educational

reasons are not generally considered medically necessary. This testing is

usually provided by school systems under applicable state and federal

rules. Neuropsychological testing may be medically necessary in

neurologically complicated cases of ADHD (e.g., post head trauma,

seizures). Children with uncomplicated ADHD do not require

neuropsychological or psychological testing.

Feifel (1996) stated that ADHD may affect up to 3 % of the adult

population. Attention deficit hyperactivity disorder is not an acquired

disorder of adulthood. Adults who were never diagnosed as having

ADHD in childhood may present with many of the symptoms of the

disorder. Inattention and distractibility, impulsivity, as well as hyperactivity

are the classic hallmarks of ADHD, but adult patients often lack the full

symptom complex, especially hyperactivity. Mood-associated symptoms

(e.g., low frustration tolerance, irritability) are often present. In this

regard, adults with ADHD usually have a difficult time with activities that

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require passive waiting. Adults with ADHD can be evaluated and

successfully treated. Since the diagnosis is a clinical one, a

comprehensive interview is the most important diagnostic procedure. A

complete psychiatric evaluation with particular attention to the core

symptoms of ADHD is essential for assessing ADHD in adults. Childhood

history is also extremely important (Wender, 1998).

Wender developed ADHD criteria, known as the Utah criteria, which

reflect the distinct features of the disorder in adults (Wender, 1998). The

diagnosis of ADHD in an adult requires a longstanding history of ADHD

symptoms, dating back to at least age 7. In the absence of treatment,

such symptoms should have been consistently present without

remission. In addition, hyperactivity and poor concentration should be

present in adulthood, along with 2 of the 5 additional symptoms: affective

lability; hot temper; inability to complete tasks and disorganization; stress

intolerance; and impulsivity.

The same medications used for children with ADHD are effective in adult

patients. In a randomized controlled study (n = 146), Spencer et al (2005)

concluded that robust doses of methylphenidate (average of 1.1mg/kg

body weight/day) are effective in the treatment of adult ADHD. This is in

agreement with the findings from a meta-analysis (Faraone et al, 2004)

that the degree of efficacy of methylphenidate in treating ADHD adults is

similar to what has been reported from meta-analyses of the child and

adolescent literature. However, it should be noted that there is limited

information regarding the long-term use of stimulants in adults (Kooij et al,

2004).

Kates (2005) noted that pharmacotherapies for patients with adult ADHD

include stimulants and antidepressants; and medication can benefit up to

60 % of patients. In a randomized controlled study (n = 162), Wilens et al

(2005) concluded that bupropion XL is an effective and well-tolerated non-

stimulant treatment for adult ADHD. Adler et al (2005) stated that the

results of an interim analysis (97 weeks) of an ongoing, open-label study

(n = 384) support the long-term safety, effectiveness, and tolerability of

another non-stimulant, atomoxetine, for the treatment of adult ADHD.

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In a meta-analysis on the use of EEG biofeedback for the treatment of

ADHD, Monastra and colleagues (2005) critically examined the empirical

evidence, applying the efficacy guidelines jointly established by the

Association for Applied Psychophysiology and Biofeedback (AAPB) and

the International Society for Neuronal Regulation (ISNR). On the basis of

these scientific principles, EEG biofeedback was deemed to be "probably

efficacious" for the treatment of ADHD. Although significant clinical

improvement was reported in about 75 % of the patients in each of the

published research studies, additional randomized, controlled group

studies are needed in order to provide a better estimate of the percentage

of patients with ADHD who will demonstrate such gains in clinical

practice.

van As and colleagues (2010) stated that neurofeedback is a method of

treatment that is being used increasingly in the Netherlands, particularly in

psychological practices. Many psychiatric and somatic symptoms are

currently being treated with the help of neurofeedback. In particular,

neurofeedback is being used more and more to ADHD. Despite its

growing popularity, neurofeedback is still a relatively unknown treatment

method in psychiatric practices. These investigators examined the

scientific evidence for treating ADHD with neurofeedback. They searched

the literature for reports on controlled trials that investigated the

effectiveness of neurofeedback on ADHD. A total of 6 controlled trials

were located. The studies reported that neurofeedback had a positive

effect on ADHD, but all the studies were marred by methodological

shortcomings. The authors concluded that on the basis of currently

available research results, no firm conclusion can be drawn about the

effectiveness of treating ADHD by means of neurofeedback. In view of

the fact that neurofeedback is being used more and more as a method of

treatment, there is an urgent need for scientific research in this field to be

well-planned and carefully executed.

Actigraphy is the process of measuring physical movement of an

individual over time to assess the degree of motor activities. Jensen and

Kelly (2004) examined the effects of yoga on the attention and behavior of

boys with ADHD. Subjects were randomly assigned to a 20-session yoga

group (n = 11) or a control group (cooperative activities; n = 8). They

were assessed pre- and post-intervention on the Conners' Parent and

Teacher Rating Scales-Revised: Long (CPRS-R:L & CTRS-R:L), the Test

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of Variables of Attention (TOVA), and the Motion Logger Actigraph. Data

were analyzed using 1-way repeated measures analysis of variance

(ANOVA). Significant improvements from pre-test to post-test were found

for the yoga, but not for the control group on 5 subscales of the Conners'

Parents Rating Scales (CPRS): Oppositional, Global Index Emotional

Lability, Global Index Total, Global Index Restless/Impulsive and ADHD

Index. Significant improvements from pre-test to post-test were found for

the control group, but not the yoga group on 3 CPRS subscales:

Hyperactivity, Anxious/Shy, and Social Problems. Both groups improved

significantly on CPRS Perfectionism,DSM-IV Hyperactive/ Impulsive, and

DSM-IV Total. For the yoga group, positive change from pre- to post-test

on the Conners' Teacher Rating Scales (CTRS) was associated with the

number of sessions attended on the DSM-IV Hyperactive-Impulsive

subscale and with a trend on DSM-IV Inattentive subscale. Those in the

yoga group who engaged in more home practice showed a significant

improvement on TOVA Response Time Variability with a trend on the

ADHD score, and greater improvements on the CTRS Global Emotional

Lability subscale. Results from the Motion Logger Actigraph were

inconclusive. The authors noted that although these data did not provide

strong support for the use of yoga for ADHD, partly because the study

was under-powered, they did suggest that yoga may have merit as a

complementary treatment for boys with ADHD already stabilized on

medication, particularly for its evening effect when medication effects are

absent. They stated that yoga remains an investigational treatment, and

this study supported further research into its possible uses for this

population. The authors stated that these findings need to be replicated

on larger groups with a more intensive supervised practice program.

Working memory (WM) capacity is one's ability to retain and manipulate

information during a short period of time. This ability underlies complex

reasoning and has generally been regarded as a fixed trait of the

individual. Children/adolescents with ADHD represent one group of

patients with a WM deficit, attributed to an impairment of the frontal lobe

(Martinussen et al, 2005). Cogmed and RoboMemo WM training are

software-based approaches designed for children and adolescents with

ADHD to improve their ability to concentrate and use problem solving

skills after training.

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Klingberg and colleagues (2005) conducted a multi-center, randomized,

controlled, double-blind study to examine the effect of improving WM by

computerized, systematic practice of WM tasks. A total of 53 children

with ADHD (9 girls, 44 boys; 15 of 53 inattentive subtype), aged 7 to 12

years, without stimulant medication were included in the study. The

compliance criterion (greater than 20 days of training) was met by 44

subjects, 42 of whom were also evaluated at follow-up 3 months later.

Participants were randomly assigned to use either the treatment computer

program for training WM or a comparison program. The main outcome

measure was the span-board task, a visuo-spatial WM task that was not

part of the training program. For the span-board task, there was a

significant treatment effect both post-intervention and at follow-up. In

addition, there were significant effects for secondary outcome tasks

measuring verbal WM, response inhibition, and complex reasoning.

Parent ratings also showed significant reduction in symptoms of

hyperactivity/impulsivity, and inattention, both post-intervention and at

follow-up. The authors concluded that the findings of this study show that

WM can be improved by training in children with ADHD. This training also

improved response inhibition and reasoning and resulted in a reduction of

the parent-rated inattentive symptoms of ADHD.

It is interesting to note that improvements with WM training lasted for 3

months following treatment. However, how long these improvements

might persist is unclear. Furthermore, whether continued training is

needed to maintain these gains over a longer duration has yet to be

ascertained. Additionally, this study had several dr awbacks: (i) only 9 of

53 subjects in this small study were girls, so that a larger study with

more girls is needed to better assess overall efficacy and applicability

of this therapy to girls with ADHD; (ii) because individuals with

depression and/or co-occurring oppositional defiant disorder were

excluded, the extent to which these findings could be extrapolated to

children/adolescents with ADHD and these behavioral conditions is

unknown. Since many children/adolescents with ADHD also have

these conditions, it will be important to determine if WM training is

beneficial to these children/adolescents as well; (iii) the absence of

teacher-reported improvements is of particular concern. Although

these investigators suggested that parental ratings are more reliable

because they were consistent with the executive functioning results, the

basis for this suggestion is unclear. Since an objective of ADHD therapy

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is to improve patients' functioning at school, demonstrating that WM

training achieves this goal is important.

Preliminary data suggested that computerized training of WM may be an

effective treatment for children/adolescents with ADHD. However, more

research is needed to establish the effectiveness of this approach.

Rickson (2006) compared the impact of instructional and improvisational

music therapy approaches on the level of motor impulsivity displayed by

adolescent boys (n = 13) who have ADHD. A combination of a multiple

contrasting treatment and an experimental control group design was

used. No statistical difference was found between the impact of the

contrasting approaches as measured by a Synchronized Tapping Task

(STT) and the parent and teacher versions of Conners' Rating Scales

Restless-Impulsive (R-I) and Hyperactive-Impulsive (H -I) subscales. The

author noted that while no firm conclusions can be drawn, there are

indications that the instructional approach may have contributed to a

reduction of impulsive and restless behaviors in the classroom. In

addition, over the period of the study, both music therapy treatment

groups significantly improved accuracy on the STT, and teachers reported

a significant reduction in Conners' DSM-IV Total and Global Index

subscale scores. The author concluded that these findings tentatively

suggested that music therapy may contribute to a reduction in a range of

ADHD s ymptoms in the classroom, and that increasing accuracy on the

STT could be related to improvement in a range of developmental areas-

not specifically motor impulsivity.

Altunc et al (2007) evaluated the evidence of any type of therapeutic or

preventive intervention testing homeopathy for childhood and

adolescence ailments. Systematic literature searches were conducted in

MEDLINE, EMBASE, AMED, CINAHL, Cochrane Central, British

Homeopathic Library, ClinicalTrials.gov, and the UK National Research

Register. Bibliographies were checked for further relevant publications.

Studies were selected according to pre-defined inclusion and exclusion

criteria. All doubl e-blind, placebo-controlled randomized clinical trials of

any homeopathic intervention for preventing or treating childhood and

adolescence ailments were included. According to the classification of

the World Health Organization, the age range defined for inclusion was 0

to 19 years. Study selection, data extraction, and assessment of

methodological quality were performed independently by 2 reviewers. A

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http://ClinicalTrials.gov


total of 326 articles were identified, 91 of which were retrieved for detailed

evaluation. Sixteen trials that assessed 9 different conditions were

included in the study. With the exception of ADHD and acute childhood

diarrhea (each tested in 3 trials), no condition was evaluated in more than

2 double-blind randomized clinical trials. The evidence for ADHD and

acute childhood diarrhea is mixed, showing both positive and negative

results for their respective main outcome measures. For adenoid

vegetation, asthma, and upper respiratory tract infection each, 2 trials are

available that suggest no difference compared with placebo. For 4

conditions, only single trials are available. The authors concluded that the

evidence from rigorous clinical trials of any type of therapeutic or

preventive intervention testing homeopathy for childhood and

adolescence ailments is not convincing enough for recommendations in

any condition.

The Good Vibrations device is a radio-frequency instrument whose

main objective is to teach children to pay better attention in class.

It supposedly achieves this goal through the sending and receiving of

gentle, pager-like vibrations from teacher to student. This device consists

of 2 units: (i) a sending unit (teacher unit), and (ii) a receiving unit

(student unit -- wristwatch). The teacher can send 2 types of vibrational

signals -- one when the toggle switch is pressed down, triggering a long

vibration (the reminder vibration) and the other when the button is

pressed up, which triggers 4 short vibrations (the positive vibration. There

is a lack of evidence regarding he effectiveness of this device in treating

children with ADHD.

Karpouzis et al (2009) stated that the Neuro-Emotional Technique (NET),

a branch of chiropractic, was designed to address the biopsychosocial

aspects of acute and chronic conditions including non-musculoskeletal

conditions. Anecdotally, it has been suggested that ADHD may be

managed effectively by NET. A placebo-controlled, double-blind,

randomized clinical trial was designed to assess the effectiveness of NET

on a cohort of children with medically diagnosed ADHD. Children aged 5

to 12 years who met the inclusion criteria were randomixed to one of 3

groups -- the control group continued on their existing medical regimen

and the intervention and placebo groups had the addition of the NET and

sham NET protocols added to their regimen respectively. These 2 groups

attended a clinical facility twice-weekly for the first month and then once-

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monthly for 6 months. The Conners' Parent and Teacher Rating Scales

(CRS) were used at the start of the study to establish baseline data and

then in 1 month and in 7 months time, at the conclusion of the study. The

primary outcome measures chosen were the Conners' ADHD Index and

Conners' Global Index. The secondary outcome measures chosen were

the DSM-IV: Inattentive, the DSM-IV:Hyperactive-Impulsive, and the

DSM-IV:Total subscales from the Conners' Rating Scales, monitoring

changes in inattention, hyperactivity and impulsivity. Calculations for the

sample size were set with a significance level of 0.05 and the power of 80

%, yielding a sample size of 93. The authors concluded that the present

study should provide information as to whether the addition of NET to an

existing medical regimen can improve outcomes for children with ADHD.

Neale and colleagues (2010) noted that although twin and family studies

have shown ADHD to be highly heritable, genetic variants influencing the

trait at a genome-wide significant level have yet to be identified. As prior

genome-wide association studies (GWAS) have not yielded significant

results, these researchers conducted a meta-analysis of existing studies

to boost statistical power. They used data from 4 projects: (i) the

Children's Hospital of Philadelphia (CHOP); (ii) phase I of the

International Multicenter ADHD Genetics project (IMAGE); (iii) phase II

of IMAGE (IMAGE II); and (iv) the Pfizer-funded study from the

University of California, Los Angeles, Washington University, and

Massachusetts General Hospital (PUWMa). The final sample size

consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study,

these investigators imputed HapMap single nucleotide polymorphisms,

computed association test statistics and transformed them to z-scores,

and then combined weighted z-scores in a meta-analysis. No genome-

wide significant associations were found, although an analysis of

candidate genes suggests that they may be involved in the disorder. The

authors concluded that given that ADHD is a highly heritable disorder,

theser negative results suggested that the effects of common ADHD risk

variants must, individually, be very small or that other types of variants,

e.g., rare ones, account for much of the disorder's heritability.

The Quotient ADHD System consists of an infrared motional tracking

system (similar to a computer kiosk) that includes a head reflector (used

for individuals of all ages) and a leg reflector (used for individuals older

than age 13) to measure motion, attention and attention state. Integrated

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composite scores of 19 indices purport to indicate the level and severity of

inattention, hyperactivity and impulsivity compared with individuals of the

same age and gender. The Quotient ADHD system/test takes 15 mins

for children under the age of 13 years, or 20 mins for adolescents and

adults. The system collects data on the person’s ability to sit still, inhibit

impulsivity and respond accurately to images on a computer screen. The

report provides analysis of motion, attention and shifts in attention states.

Integrated composite scores report the level and severity of inattention,

hyperactivity and impulsivity compared to other people of the same age

and gender. The data are uploaded via a secure internet portal and the

report is available within minutes. The clinician integrates the Quotient

ADHD test report with information from other assessment tools and the

clinical evaluation to help guide the discussion on treatment plan. There

is a lack of scientific evidence regarding the validity of the Quotient ADHD

test as a management tool for ADHD.

In a case-control study, Gilbert et al (2011) examined if transcranial

magnetic stimulation (TMS)-evoked measures, particularly short interval

cortical inhibition (SICI), in motor cortex correlate with the presence and

severity of ADHD in childhood as well as with commonly observed delays

in motor control. Behavioral ratings, motor skills, and motor cortex

physiology were evaluated in 49 children with ADHD (mean age of 10.6

years, 30 boys) and 49 typically developing children (mean age of 10.5

years, 30 boys), all right-handed, aged 8 to 12 years. Motor skills were

evaluated with the Physical and Neurological Examination for Subtle

Signs (PANESS) and the Motor Assessment Battery for Children version

2; SICI and other physiologic measures were obtained using TMS in the

left motor cortex. In children with ADHD, mean SICI was reduced by 40

% (p < 0.0001) and less SICI correlated with higher ADHD severity (r =

-0.52; p = 0.002). Mean PANESS motor development scores were 59 %

worse in children with ADHD (p < 0.0001). Worse PANESS scores

correlated modestly with less SICI (r = -0.30; p = 0.01). The authors

concluded that reduced TMS-evoked SICI correlates with ADHD

diagnosis and symptom severity and also reflects motor skill development

in children. They noted that "[t]his study was cross-sectional, and a

longitudinal study might provide more readily interpretable insights into

the relationship between age-related motor development,motor

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physiology, and ADHD...Such studies in ADHD in children might further

enhance our understanding of SICI as a quantitative, biologically based

marker of ADHD symptoms".

In a randomized controlled trial (the INCA Trial), Pelsser et al (2011)

examined if there is a connection between diet and behavior in an

unselected group of children. The "Impact of Nutrition on Children with

ADHD (INCA)" study consisted of an open-label phase with masked

measurements followed by a double-blind cross-over phase. Patients in

the Netherlands and Belgium were enrolled via announcements in

medical health centers and through media announcements.

Randomization in both phases was individually done by random

sampling. In the open-label phase (1st phase), children aged 4 to 8 years

who were diagnosed with ADHD were randomly assigned to 5 weeks of a

restricted elimination diet (diet group) or to instructions for a healthy diet

(control group). Thereafter, the clinical responders (those with an

improvement of at least 40 % on the ADHD rating scale [ARS]) from the

diet group proceeded with a 4-week double-blind cross-over food

challenge phase (2nd phase), in which high-IgG or low-IgG foods

(classified on the basis of every child's individual IgG blood test results)

were added to the diet. During the 1st phase, only the assessing

pediatrician was masked to group allocation. During the 2nd phase

(challenge phase), all persons involved were masked to challenge

allocation. Primary end points were the change in ARS score between

baseline and the end of the 1st phase (masked pediatrician) and between

the end of the 1st phase and the 2nd phase (double-blind), and the

abbreviated Conners' scale (ACS) score (unmasked) between the same

time points. Secondary end points included food-specific IgG levels at

baseline related to the behavior of the diet group responders after IgG-

based food challenges. The primary analyses were intention-to-treat for

the 1st phase and per protocol for the 2nd phase. Between November 4,

2008 and September 29, 2009, a total of 100 children were enrolled and

randomly assigned to the control group (n = 50) or the diet group (n =

50). Between baseline and the end of the 1st phase, the difference

between the diet group and the control group in the mean ARS total score

was 23.7 (95 % confidence interval [CI]: 18.6 to 28.8; p < 0·0001)

according to the masked ratings. The difference between groups in the

mean ACS score between the same time points was 11.8 (95 % CI: 9.2 to

14.5; p < 0·0001). The ARS total score increased in clinical responders

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after the challenge by 20.8 (95 % CI: 14.3 to 27.3; p < 0.0001) and the

ACS score increased by 11.6 (7.7 to 15.4; p < 0.0001). In the challenge

phase, after challenges with either high-IgG or low-IgG foods, relapse of

ADHD symptoms occurred in 19 of 30 (63 %) children, independent of the

IgG blood levels. There were no harms or adverse events reported in

both phases. The authors concluded that a strictly supervised restricted

elimination diet is a valuable instrument to assess whether ADHD is

induced by food. Moreover, the prescription of diets on the basis of IgG

blood tests should be discouraged.

van Ewijk and colleagues (2012) stated that diffusion tensor imaging (DTI)

allows in-vivo examination of the microstructural integrity of white matter

brain tissue. These researchers performed a systematic review and

quantitative meta-analysis using GingerALE to compare current DTI

findings in patients with ADHD and healthy controls to further unravel the

neurobiological underpinnings of the disorder. Online databases were

searched for DTI studies comparing white matter integrity between ADHD

patients and healthy controls. A total of 15 studies met inclusion criteria.

Alterations in white matter integrity were found in widespread areas, most

consistently so in the right anterior corona radiata, right forceps minor,

bilateral internal capsule, and left cerebellum, areas previously implicated

in the pathophysiology of the disorder. The authors concluded that while

more research is needed, DTI proves to be a promising technique,

providing new prospects and challenges for future research into the

pathophysiology of ADHD.

VandenBerg (2001) noted that children described as having attention

deficit hyperactivity disorder often demonstrate inability to sustain visual

attention during classroom fine motor activities. This study investigated

the effect of wearing a weighted vest (deep-pressure sensory input) on

children's on-task behavior in the classroom. A total of 4 students with

documented attention difficulties and hyperactivity were timed with a stop-

watch to measure their on-task behavior during fine motor activities in the

classroom. All 4 students were timed for 6 15-min observations without

wearing a weighted vest and for 6 15-min observations while wearing a

weighted vest. On-task behavior increased by 18 % to 25 % in all 4

students while they were wearing the weighted vest. Additionally, 3 of the

4 students frequently asked to wear the vest other than during the

observation times. The authors concluded that these preliminary findings

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supported the hypothesis that wearing a weighted vest to apply deep

pressure increases on-task behavior during fine motor activities. These

preliminary findings need to be validated by well-designed studies.

The Dore program (also known dyslexia-dyspraxia attention treatment

[DDAT]) is a drug-free, exercise-based program that is employed for the

treatment of patients with ADHD, Asperger’s syndrome, dyslexia,

dyspraxia, and other learning difficulties. It consists of a specialized

neurological evaluation and series of patient-specific exercises designed

to improve the functioning of the cerebellum, based on Dore's belief that

the cerebellum facilitates skill development and thus plays an essential

role in the learning process. The theory is that the size and function of the

cerebellum are related to a group of learning disorders referred to as

cerebellar developmental delay (CDD). Currently, there is insufficient

evidence to support the effectiveness of the Dore program for the

treatment of patients with ADHD.

In a review on “Curing dyslexia and attention-deficit hyperactivity disorder

by training motor co-ordination”, Bishop (2007) noted that “the published

studies are seriously flawed. On measures where control data are

available, there is no credible evidence of significant gains in literacy

associated with this intervention. There are no published studies on

efficacy with the clinical groups for whom the programme is advocated”.

The author stated that the publication of 2o papers in peer-reviewed

scientific journal (Dyslexia) has been presented as giving further

credibility to the treatment. However, the research community in this area

has been dismayed that work of such poor standard has been published.

Bishop also noted that the research purporting to show effectiveness of

the treatment does not show sustained gains in literacy scores in treated

versus control children. Furthermore, the intervention has not been

evaluated on the clinical groups for which it is recommended.

Furthermore, Rack et al (2007) stated that Reynolds and Nicolson

(Dyslexia: An International Journal of Research & Practice, 2007)

reported follow-up data 12 and 18 months after a period of intervention

consisting of an exercise-based treatment program (DDAT). The findings

suggested the treatment had effects on bead threading, balance, rapid

naming, semantic fluency and working memory but not on reading or

spelling. These investigators argued that the design of the study was

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flawed, the statistics used to analyze the data were inappropriate, and

reiterated other issues raised by them and others in 2003. The authors

concluded that current evidence provided no support for the claim that

DDAT is effective in improving children's literacy skills.

A metronome is a mechanical or electrical i nstrument that makes

repeated clicking sounds at an adjustable pace, used for marking rhythm.

With interactive metronome therapy, a computerized metronome

produces a rhythmic beat that patients attempt to match with hand or foot

tapping. It is theorized that matching the beat over repeated sessions will

reflect gains in motor planning and timing skills. In a case-report,

Bartscherer and Dole (2005) described a new intervention, the Interactive

Metronome (Sunrise, FL), for improving timing and coordination. A 9-year

old boy, with difficulties in attention and developmental delay of

unspecified origin underwent a 7-week training program with the

Interactive Metronome. Before, during, and after training timing, accuracy

was assessed with testing procedures consistent with the Interactive

Metronome training protocol. Before and after training, his gross and fine

motor skills were examined with the Bruininiks-Oseretsky Test of Motor

Proficiency (BOTMP). The child exhibited marked change in scores on

both timing accuracy and several BOTMP subtests. Additionally his

mother relayed anecdotal reports of changes in behavior at home. This

child's participation in a new intervention for improving timing and

coordination was associated with changes in timing accuracy, gross and

fine motor abilities, and parent reported behaviors. The authors stated

that these findings warrant further study.

Cosper et al (2009) examined the effectiveness of Interactive Metronome

training in a group of children with mixed attentional and motor

coordination disorders to further explore which subcomponents of

attentional control and motor functioning the training influences. A total of

12 children who had been diagnosed with ADHD, in conjunction with

either developmental coordination disorder (n = 10) or pervasive

developmental disorder (n = 2), underwent 15 1-hour sessions of

Interactive Metronome training over a 15-week period. Each child was

assessed before and after the treatment using measures of attention,

coordination, and motor control to determine the effectiveness of training

on these cognitive and behavioral realms. As a group, the children made

significant improvements in complex visual choice reaction time and

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visuo-motor control after the training. There were, however, no significant

changes in sustained attention or inhibitory control over inappropriate

motor responses after treatment. The authors concluded that these

findings suggested Interactive Metronome training may address deficits in

visuo-motor control and speed, but appears to have little effect on

sustained attention or motor inhibition.

An Institute for Clinical Systems Improvement’s clinical practice guideline

on “Diagnosis and management of attention deficit hyperactivity disorder

in primary care for school-age children and adolescents” (Dobie et al,

2012) as well as an UpToDate review on “Attention deficit hyperactivity

disorder in children and adolescents: Overview of treatment and

prognosis” (Krull, 2013) do not mention the use of Dore program/dyslexia-

dyspraxia attention treatment (DDAT), intensive behavioral intervention

programs (e.g., applied behavior analysis [ABA], early intensive behavior

intervention [EIBI], intensive behavior intervention [IBI], and Lovaas

therapy), and metronome training as treatment modalities.

On July 15, 2013, the Food and Drug Administration (FDA) allowed

marketing of the first medical device (Neuropsychiatric EEG-Based

Assessment Aid (NEBA) System, NEBA Health of Augusta, GA), based

on brain function to help assess ADHD in children and adolescents 6 to

17 years old. When used as part of a complete medical and

psychological examination, the device can help confirm an ADHD

diagnosis or a clinician’s decision that further diagnostic testing should

focus on ADHD or other medical or behavioral conditions that produce

symptoms similar to ADHD. The NEBA System is based on EEG

technology, which records different kinds of brain waves given off by

neurons and their frequency. The NEBA System is a 15- to 20-min non-

invasive test that calculates the ratio of 2 standard brain wave

frequencies, known as theta and beta waves. The theta/beta ratio has

been shown to be higher in children and adolescents with ADHD than in

children without it. The FDA reviewed the NEBA System through the de-

novo classification process, a regulatory pathway for some low- to

moderate-risk medical devices that are not substantially equivalent to an

already legally marketed device. However, there is currently insufficient

evidence that the NEBA system is effective in the diagnosis of ADHD.

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Lansbergen et al (2011) stated that ADHD was found to be characterized

by a deviant pattern of electro-cortical activity during resting state,

particularly increased theta and decreased beta activity. The first

objective of the present study was to confirm whether individuals with

slow alpha peak frequency contribute to the finding of increased theta

activity in ADHD. The second objective was to explore the relation

between resting-state brain oscillations and specific cognitive functions.

From 49 boys with ADHD and 49 healthy control boys, resting-state EEG

during eyes open and eyes closed was recorded, and a variety of

cognitive tasks were administered. Theta and beta power and theta/beta

ratio were calculated using both fixed frequency bands and individualized

frequency bands. As expected, theta/beta ratio, calculated using fixed

frequency bands, was significantly higher in ADHD children than control

children. However, this group effect was not significant when theta/beta

ratio was assessed using individualized frequency bands. No consistent

relation was found between resting-state brain oscillations and cognition.

The present results suggested that previous findings of increased

theta/beta ratio in ADHD may reflect individuals with slow alpha peak

frequencies in addition to individuals with true increased theta activity.

Therefore, the often reported theta/beta ratio in ADHD can be considered

a non-specific measure combining several distinct neurophysiological

subgroups such as frontal theta and slowed alpha peak frequencies. The

authors concluded that future research should elucidate the functional

role of resting-state brain oscillations by investigating neurophysiological

subgroups, which may have a clearer relation to cognitive functions than

single frequency bands.

Loo and Makeig (2012) noted that psychiatric research applications of

EEG, the earliest approach to imaging human cortical br ain activity, are

attracting increasing scientific and clinical interest. For more than 40

years, EEG research has attempted to characterize and quantify the

neurophysiology of ADHD, most consistently associating it with increased

fronto-central theta band activity and increased theta to beta (θ/β) power

ratio during rest compared to non-ADHD c ontrols. Recent reports

suggested that while these EEG measures demonstrate strong

discriminant validity for ADHD, significant EEG heterogeneity also e xists

across ADHD-diagnosed individuals. In particular, additional studies

validating the use of the θ/β power ratio measure appear to be needed

before it can be used for clinical diagnosis. In recent years, the number

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and the scientific quality of research reports on EEG-based neuro-

feedback (NF) for ADHD have grown considerably, although the studies

reviewed here do not yet support NF training as a first-line, stand-alone

treatment modality. In particular, more research is needed comparing NF

to placebo control and other effective treatments for ADHD. Currently,

after a long period of relative stasis, the neurophysiological specificity of

measures used in EEG research is rapidly increasing. It is likely,

therefore, that new EEG studies of ADHD using higher density recordings

and new measures drawn from viewing EEG as a 3-dimensional

functional imaging modality, as well as intensive re-analyses of existing

EEG study data, can better characterize the neurophysiological

differences between and within ADHD and non-ADHD subjects, and lead

to more precise diagnostic measures and effective NF approaches.

Liechti et al (2013) stated that the resting EEG reflects development and

arousal, but whether it can support clinical diagnosis of ADHD remains

controversial. These investigators examined if the theta power and

theta/beta ratio is consistently elevated in ADHD and younger age as

proposed. Topographic 48-channel EEG from 32 children (8 to 16 years)

and 22 adults (32 to 55 years) with ADHD and matched healthy controls

(n = 30 children/21 adults) was compared. Following advanced artefact

correction, resting EEG was tested for increased theta and theta/beta

activity due to ADHD and due to normal immaturity. Discriminant

analyses tested classification performance by ADHD and age using these

EEG markers as well as EEG artefacts and deviant attentional event-

related potentials (ERPs). No consistent theta or theta/beta increases

were found with ADHD. Even multi-variate analyses indicated only

marginal EEG power increases in children with ADHD. Instead,

consistent developmental theta decreases were observed, indicating that

maturational lags of fewer than 3 years would have been detected in

children. Discriminant analysis based on proposed simple spectral

resting EEG markers was successful for age but not for ADHD (81 versus

53 % accuracy). Including ERP markers and EEG artefacts improved

discrimination, although not to diagnostically useful levels. The authors

concluded that the lack of consistent spectral resting EEG abnormalities

in ADHD despite consistent developmental effects casts doubt upon

conventional neurometric approaches towards EEG-based ADHD

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diagnosis, but is consistent with evidence that ADHD is a heterogeneous

disorder, where the resting state is not consistently characterized by

maturational lag.

Clarke et al (2013) noted that past research has reported that a small

proportion of children with ADHD have excess beta activity in their EEG,

rather than the excess theta typical of the syndrome. This atypical group

has been tentatively labeled as hyper-aroused. The aim of this study was

to determine whether these children have a hyper-aroused central

nervous system. Participants included 104 boys aged 8- to 13-year old,

with a diagnosis of either the combined or inattentive type of ADHD (67

combined type), and 67 age-matched male controls. Ten and a half

minutes of EEG and skin conductance (SCL) were simultaneously

recorded during an eyes-closed resting condition. The EEG was Fourier

transformed and estimates of total power, and relative power in the delta,

theta, alpha, and beta bands, and the theta/beta ratio, were calculated.

ADHD patients were divided into an excess beta group and a typical

excess theta group. Relative to controls, the typical excess theta group

had significantly increased frontal total power, theta and theta/beta ratio,

with reduced alpha and beta across the scalp. The excess beta group

had significantly reduced posterior total power, increased central-posterior

delta, globally reduced alpha, globally increased beta activity, and globally

reduced theta/beta ratio. Both ADHD groups had significantly reduced

SCL compared to the control group, but the 2 groups did not differ from

each other on SCL. These results indicated that ADHD children with

excess beta activity are not hyper-aroused, and confirmed that the

theta/beta ratio is not associated with arousal.

Dupuy et al (2013) examined sex differences between the EEGs of

combined and inattentive types of ADHD within boys and girls aged 8 to

12 years. Subject groups included 80 ADHD combined type (40 boys and

40 girls), 80 ADHD inattentive type (40 boys and 40 girls) and 80 controls

(40 boys and 40 girls). An eyes-closed resting EEG was recorded and

Fourier transformed to provide estimates for absolute and relative power

in the delta, theta, alpha and beta frequency bands, as well as total power

and the theta/beta ratio. The boy ADHD groups, compared with boy

controls, had greater absolute and relative theta, greater theta/beta ratio,

reduced absolute and relative alpha, and reduced absolute and relative

beta. The girl ADHD groups, compared with girl controls, hadgreater

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absolute delta, greater absolute and relative theta, greater theta/beta

ratio, greater total power, and reduced relative delta and relative beta.

Between ADHD types, combined type boys had globally greater absolute

and relative theta, greater theta/beta ratio, and less relative alpha than

inattentive type boys. While topographical differences emerged, there

were no significant global differences between ADHD types in girls. That

is, EEG differences between ADHD types are dissimilar in boys and girls.

Different EEG maturational patterns between boys and girls also obscure

ADHD-related EEG abnormalities. The authors concluded that these

results have important implications for the understanding of ADHD in

girls. Ignoring such sex differences may have compromised the value of

previous ADHD investigations, and these sex differences should be

recognized in future research.

An UpToDate review on “Attention deficit hyperactivity disorder in children

and adolescents: Clinical features and evaluation” (Krull, 2014) states that

“The evaluation for ADHD does not require blood lead levels, thyroid

hormone levels, neuroimaging, or electroencephalography unless these

tests are indicated by findings in the clinical evaluation. Ancillary

evaluation -- Other evaluations are not routinely indicated to establish the

diagnosis of ADHD, but may be warranted to evaluate conditions

remaining in the differential diagnosis after the initial assessment. These

evaluations may include neurology consultation or

electroencephalography (neurologic or seizure disorder)”.

An UpToDate review on “Clinical and laboratory diagnosis of seizures in

infants and children” (Wilfong, 2014) states that “An EEG is

recommended in the evaluation of a child with suspected seizures or

epilepsy. In addition to providing support for the diagnosis of epilepsy, the

EEG also helps define the epilepsy syndrome and directs optimal

therapy. Obtaining a tracing in the awake and sleep states, in close

proximity to an event, and repeating the tracing can increase the

diagnostic yield of the study. Nonetheless, the sensitivity and specificity

of EEG is imperfect”.

Wiley and Riccio (2014) examined the current state of research using

functional near-infrared spectroscopy (fNIRS) imaging methods to

evaluate neurological activation patterns of ADHD populations. Informal

search procedures were used to identify potential articles. Searches were

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conducted using EBSCO Academic Search Complete, ProQuest, and

PsycINFO between March 1, 2014 and March 31, 2014. Search terms

used were "near-infrared spectroscopy", "NIRS" and "fNIRS". To be

included in the review, studies must have utilized an empirical design,

collected data using fNIRS imaging methods, and have a specifically

identified ADHD sample. A total of 10 studies were identified that met the

inclusion criteria. Results were evaluated for recurrent themes and

patterns of activation detected by fNIRS. Samples of ADHD displayed a

consistent trend of altered activation patterns. Specifically, ADHD

samples exhibited decreased levels of oxygenated hemoglobin levels

during tasks. A similar pattern emerged for deoxygenated hemoglobin

levels, but group differences were smaller. Results from studies

investigating the effects of methylphenidate stimulant medications

indicated that these altered activation patterns showed a normalization

trend when participants began taking methylphenidate medications. The

authors concluded that although fNIRS has been identified as a viable

imaging technique with both temporal and spatial resolution, few studies

have been conducted using fNIRS to evaluate neurological activation

patterns in participants with ADHD. The clinical value of fNIRS has yet to

be established by well-designed studies.

Furthermore, an UpToDate review on “Adult attention deficit hyperactivity

disorder in adults: Epidemiology, pathogenesis, clinical features, course,

assessment, and diagnosis” (Bukstein, 2015) does not mention functional

near-infrared spectroscopy as a management tool.

Maneeton et al (2014) summarized the effectiveness, acceptability, and

tolerability of bupropion in comparison with methylphenidate for ADHD

treatment. Included studies were randomized controlled trials (RCTs) that

compared bupropion and methylphenidate. Clinical studies conducted

between January 1991 and January 2014 were reviewed. MEDLINE,

EMBASE, CINAHL, PsycINFO, and the Cochrane Controlled Trials

Register were searched in January 2014. Additionally, clinical trials were

identified from the databases of ClinicalTrials.gov and the EU C linical

Trials Register. All RCTs of bupropion and methylphenidate reporting final

outcomes relevant to (i) ADHD severity, (ii) response or remission rates,

(iii) overall discontinuation rate, or (iv) discontinuation rate due to

adverse events were selected for analysis. Language restriction was not

applied. The relevant clinical trials were examined and the data of

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http://ClinicalTrials.gov


interest were extracted. Additionally, the risks of bias were also

inspected. The efficacy outcomes were the mean changed scores of

ADHD rating scales, the overall response rate, and the overall remission

rates. The overall discontinuation rate and the discontinuation rate due to

adverse events were determined. Relative risks and weighted mean

differences or standardized mean differences (SMDs) with 95 % CIs were

estimated using a random effect model. A total of 146 subjects in 4 RCTs

comparing bupropion with methylphenidate in the treatment of ADHD

were included. The pooled mean changed scores of the Iowa-Conner's

Abbreviated Parent and Teacher Questionnaires and the ADHD R ating

Scale-IV for parents and teachers of children and adolescents with ADHD

in the bupropion- and methylphenidate-treated groups were not

significantly different. Additionally, the pooled mean changed score in

adult ADHD between the 2 groups, measured by the ADHD Rating Scale-

IV and the Adult ADHD R ating Scale, was also not significantly different.

The pooled rates of response, overall discontinuation, and discontinuation

due to adverse events between the 2 groups were not significantly

different. The authors concluded that based on limited data from this

systematic review, bupropion was as effective as methylphenidate for

ADHD patients; tolerability and acceptability were a lso comparable.

However, they stated that these findings should be considered as very

preliminary results; further studies in this area are needed to confirm this

evidence.

In a Cochrane review, Otasowie (2014) evaluated the effectiveness of

tricyclic antidepressants (TCAs) in the reduction of ADHD symptoms

within the broad categories of hyperactivity, impulsivity, and

inattentiveness in young people aged 6 to 18 years with established

diagnoses of ADHD. On September 26, 2013, these investigators

searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, CINAHL, 7

other databases, and 2 trials registers. They also searched the reference

lists of relevant articles, and contacted manufacturers and known experts

in the field to determine if there were any ongoing trials or unpublished

studies available. Randomized controlled trials, including both parallel

group and cross-over study designs, of any dose of TCA compared with

placebo or active medication in children or adolescents with ADHD,

including those with co-morbid conditions were selected for analysis.

Working in pairs, 3 review authors independently screened records,

extracted data, and assessed trial quality. They calculated the SMD for

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continuous data, the odds ratio (OR) for dichotomous data, and 95 % Cis

for both. These researchers conducted the meta-analyses using a

random-effects model throughout. They used the Cochrane 'Risk of bias'

tool to assess the risk of bias of each included trial and the GRADE

approach to assess the quality of the body evidence. The authors

included 6 RCTs with a total of 216 participants; 5 of the 6 trials compared

desipramine with placebo; the remaining trial compared nortriptyline with

placebo. One trial compared desipramine with clonidine and placebo,

and another compared 2 TCAs (desipramine and clomipramine) with

methylphenidate and placebo. Of the 6 trials, 1 RCT primarily assessed

the effectiveness of TCA in children with ADHD and co-morbid tic or

Tourette disorder, and another 1 trial was in children with co-morbid tic

disorder. Randomized controlled trials that met the inclusion criteria

varied both in design and quality, and none was free of bias. The quality

of the evidence was low to very low according to the GRADE

assessments. Tricyclic antidepressants out-performed placebo regarding

the proportions of patients achieving a pre-defined improvement of core

ADHD symptom severity (OR 18.50, 95 % CI: 6.29 to 54.39, 3 trials, 125

participants, low quality evidence). In particular, there was evidence that

desipramine improved the core symptoms of ADHD in children and

adolescents as assessed by parents (SMD - 1.42, 95 % CI: -1.99 to -0.85,

2 trials, 99 participants, low quality evidence), teachers (SMD - 0.97, 95 %

CI: -1.66 to -0.28, 2 trials, 89 participants, low quality evidence), and

clinicians (OR 26.41, 95 % CI: 7.41 to 94.18, 2 trials, 103 participants, low

quality evidence). Nortriptryline was also effective in improving the core

symptoms of ADHD in children and adolescents as assessed by clinicians

(OR 7.88, 95 % CI: 1.10 to 56.12). Desipramine and placebo were similar

on "all-cause treatment discontinuation" (RD -0.10, 95 % CI: -0.25 to 0.04,

3 trials, 134 participants, very low quality evidence). Desipramine

appeared more effective than clonidine in reducing ADHD symptoms as

rated by parents (SMD -0.90, 95 % CI: -1.40 to -0.40, 1 trial, 68

participants, very low quality evidence) in participants with ADHD and co-

morbid tics or Tourette syndrome. Although this Cochrane Review did not

identify serious adverse effects in patients taking TCAs, it did identify mild

increases in diastolic blood pressure and pulse rates. Also, patients

treated with desipramine had significantly higher rates of appetite

suppression compared to placebo, while nortriptyline resulted in weight

gain. Other reported adverse effects included headache, confusion,

sedation, tiredness, blurred vision, diaphoresis, dry mouth, abdominal

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discomfort, constipation, and urinary retention. The authors concluded

that most evidence on TCAs relates to desipramine. They noted that

findings suggested that, in the short-term, desipramine improves the core

symptoms of ADHD, but its effect on the cardiovascular system remains

an important clinical concern. Thus, evidence supporting the clinical use

of desipramine for the treatment of children with ADHD is low.

Ghanizadeh et al (2015) reviewed the available evidence regarding the

effectiveness of reboxetine in the treatment of ADHD. The databases of

PubMed/Medline, Google scholar, SCOPUS and Web of Science were

searched using the keywords: "reboxetine", "ADHD" and "attention deficit

hyperactivity disorder". The reference lists of the included studies were

screened to find any possible other relevant articles. All the non-

controlled and controlled clinical trials were included. The current

evidence mainly consists of un-controlled studies, such as case series.

Only 3 of 33 studies were controlled clinical trials. They are from single

sites and included a sub-sample of patients with ADHD. The author

concluded that non-controlled studies and controlled trials support the

promising effectof reboxetine in treating ADHD in a sub-sample of

patients that are without co-morbid psychiatric disorder and mental

retardation. They stated that reboxetine is well-tolerated; however, more

controlled trials are needed to reach any firm conclusion.


and adolescents: Overview of treatment and prognosis’ (Krull, 2015a)

states that “In addition to elimination diets and fatty acid supplementation,

other complementary and alternative (CAM) therapies that have been

suggested in the managementof ADHD include vision training,

megavitamins, herbal and mineral supplements (e.g., St. John's wort),

neurofeedback/biofeedback, chelation, and applied kinesiology, among

others. Most of these interventions have not been proven efficacious in

blinded randomized controlled trials”.


and adolescents: Treatment with medications” (Krull, 2015b) does not

mention bupropion, reboxetine, desipramine and nortriptyline as

therapeutic options.

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There are insufficientdata to support sensory integration therapy for

ADHD. Sensory integration therapy is a form of therapy in which special

exercises are used to strengthen the patient’s sense of balance and to

teach the brain to better react and integrate the sensory input it is

receiving through structured and constant movement, such as with the

use of recreational equipment that spins or rolls.

S NA P2 5 Gene Polymorphisms T esting

Liu et al (2017) analyzed the possible association between 6

polymorphisms (rs3746544, rs363006, rs1051312, rs8636, rs362549, and

rs362998) of SNAP25 and ADHD in a pooled sample of 10 family-based

studies and 4 case-control studies by using meta-analysis. The combined

analysis results were significant only for rs3746544 (p = 0.010) with mild

association (OR = 1.14). Furthermore, the meta-analysis data for rs8636,

rs362549, and rs362998 were the first time to be reported; however, no

positive association was detected. The authors concluded that there is

some evidence supporting the association of SNAP25 to ADHD.

Moreover, they stated that future research should emphasize genome-

wide association studies in more specific subgroups and larger

independent samples.

A c u puncture

Ni and colleagues (2015) evaluated the safety and effectiveness of

acupuncture in treating children with ADHD. These researchers

performed a literature search to retrieve RCTs of acupuncture in treating

ADHD covering the period of the years of establishment of the databases

to January 2014 from database of CBM, CNKI, PubMed, Cochrane

Library by using key words "attention deficit hyperactivity disorder",

"hyperactivity", "minimal brain dysfunction", and "acupuncture". Two

independent researchers extracted data from located articles in a pre-

defined structured way, and consulted the third researcher if necessary. A

total of 13 original trials including 1,304 cases of children with ADHD were

obtained in this study. In these trials, acupuncture intervention alone, or

acupuncture plus pharmacotherapy (methylphenidate (Ritalin),

haloperidol) or acupuncture plus behavioral therapy were compared with

simple pharmacotherapy or behavioral therapy alone. Results of the

meta-analysis indicated that the total effective rate and Conners' index of

hyperactivity (CIH) score-reduction rate in the acupuncture group were

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significantly superior to those of the other treatment groups [OR = 2.22,

95 % CI: 1.65 to 3.00), Z = 5.22, p < 0.00001] [SMD = -0.94, 95 % CI:

-1.41 to -0.47), Z = 3.89, p < 0.0001]. Acupuncture treatment was more

effective than haloperidol in reducing the score of Conners' Rating Scale

for ADHD [SMD = -7.28, 95 % CI: -8.32 to -6.23), Z = 13.62, p <

0.00001]. Acupuncture was similarly effective as methylphenidate in

improving the Chinese medicine syndrome (liver-kidney yin hypo-activity)

of children with ADHD [SMD = -1.14, 95 % CI: -2.53 to 0.25), Z = 1.60, p

= 0.11]. Less severe adverse effects were reported with acupuncture

therapy than the pharmacotherapy (poor appetite, dry mouth, nausea and

constipation). These effects were not likely due to publication bias

(approximately symmetry funnel plot, Egger's test p > 0.1). The authors

concluded that acupuncture is an effective and safe therapy in treating

ADHD, combined administration of acupuncture and pharmacotherapy or

behavioral therapy is more effective than the pharmacotherapy or

behavioral therapy alone. However, they stated that more rigorously

designed and high-quality RCTs are needed to confirm the above

conclusion.

M in e ra l Supplementa tion

Hariri and Azadbakht (2015) reviewed the evidence regarding the effects

of minerals in prevention and management of ADHD. These investigators

searched PubMed/Medline, Google Scholar, Ovid, Scopus, and ISI web of

science up to June 2013. "iron", "iron supplementation", "magnesium",

"magnesium supplementation", "zinc", "zinc supplementation", and

"attention deficit hyperactivity disorder" were used as the keywords. A

total of 11 RCTs were eligible to be included in the systematic review.

This review showed that there is no predominant evidence regarding the

use of mineral supplementation on children with ADHD. The authors

concluded that there is a need for more evidence for indicating the effect

of iron, magnesium, and zinc supplementation in the treatment of ADHD

among children.

Vayarin (Phosphatidylserine-Containing Omega3 Long-Chain Polyu nsa turated Fatty Acids)

In a double-blind, placebo-controlled trial, Manor et al (2012) examined

the safety and effectiveness of phosphatidylserine (PS)-containing

omega3 long-chain polyunsaturated fatty acids attached to its backbone

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(PS-Omega3) in reducing ADHD symptoms in children. This 15-week,

double-blind, placebo-controlled phase was followed by an open-label

extension of additional 15 weeks. A total of 200 ADHD children were

randomized to receive either PS-Omega3 or placebo, out of them, 150

children continued into the extension. Efficacy was assessed using

Conners' parent and teacher rating scales (CRS-P,T), Strengths and

Difficulties Questionnaire (SDQ), and Child Health Questionnaire (CHQ).

Safety evaluation included adverse events monitoring. The key finding of

the double-blind phase was the significant reduction in the

Global:Restless/impulsive subscale of CRS-P and the significant

improvement in Parent impact-emotional (PE) subscale of the CHQ, both

in the PS-Omega3 group. Exploratory subgroup analysis of children with

a more pronounced hyperactive/impulsive behavior, as well as mood and

behavior-dysregulation, revealed a significant reduction in the ADHD-

Index and hyperactive components. Data from the open-label extension

indicated sustained efficacy for children who continued to receive PS-

Omega3. Children that switched to PS-Omega3 treatment from placebo

showed a significant reduction in subscales scores of both CRS-P and the

CRS-T, as compare to baseline scores. The treatment was well-

tolerated. The authors concluded that the findings of this 30-week study

suggested that PS-Omega3 may reduce ADHD symptoms in children.

They stated that preliminary analysis suggested that this treatment may

be especially effective in a subgroup of hyperactive-impulsive, emotionally

and behaviorally-dysregulated ADHD children. Moreover, they stated that

the observations of this study were encouraging and could assist in

planning future large-scale, placebo-controlled trials evaluating the

effectiveness of PS-omega3 in ADHD children.

The main drawbacks of this study were: (i) in the double-blind phase, no

superiority was obtained in the primary outcome measure CRS-T, (ii)

the subgroup analysis was not planned prior to study initiation, rather

it was conducted following significant interactions found; (iii) in the

open-label extension phase, there is the lack of a corresponding

placebo controlled group and the relatively high percentage of

missing data in the CRS-T, due primarily to summer vacation during

which teachers could not rate the participants’ behavior, (iv) because

of the exploratory nature of the study, these researchers chose not to

correct for multiple testing.

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and adolescents: Overview of treatment and prognosis” (Krull, 2016)

states that “Essential f atty acid supplementation -- We do not suggest

essential fatty acid supplementation for children with ADHD. Some

studies have noted decreased fatty acid concentrations in the serum of

children with ADHD. However, evidence that fatty acid supplementation

improves core sym ptoms in children with ADHD is limited. In a 2012

meta-analysis of randomized and quasi-randomized trials comparing

omega-3 and/or omega-6 fatty acid with placebo supplementation in

children with ADHD ( diagnosed with validated criteria), there were no

differences in parent- or teacher-rated ADHD symptoms (overall),

inattention, or hyperactivity/impulsivity. Pooled analysis of two small trials

(97 participants) found some evidence of improvement in overall ADHD

symptoms or parent-rated ADHD symptoms among children

supplemented with both omega-3 and omega-6 fatty acids (risk ratio 2.19

95 % CI 1.04 to 4.62). Few of the studies included in the meta-analysis

were of high quality. Methodologic limitations included small sample size,

variable inclusion criteria, variable type and dose of supplement, and

short duration of follow-up. In a 2011 meta-analysis of 10 randomized

trials (699 participants), omega-3-fatty acid supplementation was

associated with improved ADHD symptoms in children with a diagnosis of

ADHD or symptoms of ADHD. The effect size was small to moderate

compared with that of pharmacologic therapies (0.31 versus

approximately 1.0 and 0.7, respectively). Possible explanations for the

variable findings in the two meta-analyses include differences in

population (children diagnosed with ADHD versus children with ADHD

diagnosis or symptoms) and outcome measures (separate versus pooled

parent- and teacher-reported symptoms)”.

E le ctroencephalography Theta/Beta Power Ratio for the Diagnosis of A D H D

On behalf of the American Academy of Neurology (AAN), Gloss and

colleagues (2016) evaluated the evidence for EEG theta/beta power ratio

for diagnosing, or helping to diagnose, ADHD. These researchers

identified relevant studies and classified them using American Academy

of Neurology (AAN) criteria. Two Class I studies assessing the ability of

EEG theta/beta power ratio and EEG frontal beta power to identify

patients with ADHD correctly identified 166 of 185participants. Both

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studies evaluated theta/beta power ratio and frontal beta power in

suspected ADHD or in syndromes typically included in an ADHD

differential diagnosis. A bi-variate model combining the diagnostic studies

showed that the combination of EEG frontal beta power and theta/beta

power ratio has relatively high sensitivity and specificity but is insufficiently

accurate. The authors concluded that it is unknown whether a

combination of standard clinical examination and EEG theta/beta power

ratio increases diagnostic certainty of ADHD compared with clinical

examination alone.

A A N R e commendation

Clinicians should inform patients with suspected ADHD and their

families that the combination of EEG theta/beta power ratio and

frontal beta power should not replace a standard clinical

evaluation. There is a risk for significant harm to patients from

ADHD mis-diagnosis because of the unacceptably high false-

positive diagnostic rate of EEG theta/beta power ratio and frontal

beta power. (Level B recommendation: Indicates a

recommendation that “should” be done)

Clinicians should inform patients with suspected ADHD and their

families that the EEG theta/beta power ratio should not be used to

confirm an ADHD diagnosis or to support further testing after a

clinical evaluation, unless such diagnostic assessments occur in a

research setting. (Level R recommendation: Should be applied

only in research settings)

In an editorial that accompanied the afore-mentioned study, Ewen (2016)

stated that “Whether TBR (the theta:beta ratio) specifically withstands the

test of replication …. We can hope that solid experimental design will

prove or disprove the utility of these techniques with little controversy”.

E va luation of Iron Status (e.g., M easurement of Serum Iron and Fe rritin Levels)

Wang and colleagues (2017) stated that ADHD is one of the most

common psychiatric disorders in children. However, the pathogenesis of

ADHD remains unclear. Iron, an important trace element, is implicated in

brain function and dopaminergic activity. Recent studies have

investigated the association between iron deficiency and ADHD, but the

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results are inconsistent. These researchers performed a systemic search

of Medline, Embase, Web of Science and Cochrane Library databases

was supplemented by manual searches of references of key retrieved

articles. Study quality was evaluated using the Newcastle-Ottawa Scale.

The SMD and 95 % CIs were calculated using a random-effects model.

H2 and I2 were used to evaluate the heterogeneity, and sensitivity,

subgroup and meta-regression analyses were conducted to explore the

reason of heterogeneity. The search yielded 11 studies published before

July 25, 2016. Of these, 10 studies, comprising 2,191 participants and

1,196 ADHD cases, reported serum ferritin levels, and 6 studies,

comprising 617 participants and 369 ADHD cases, reported serum iron

levels. Serum ferritin levels were lower in ADHD cases (SMD = -0.40, 95

% CI: -0.66 to -0.14). However, these investigators found no correlation

between serum iron levels and ADHD (SMD = -0.026, 95 % CI: -0.29 to

0.24). Meta-regression analysis indicated that publication year, age,

gender, sample size, and hemoglobin levels did not significantly influence

the pooled estimates of serum ferritin. The authors concluded that the

findings of this meta-analysis showed that serum ferritin levels were lower

in patients with ADHD than in healthy controls, which suggested that

serum ferritin is correlated with ADHD. However, these investigators

failed to find a correlation between serum iron and ADHD. This is likely

due to the fact that serum iron is affected by various factors that were not

completely considered in the included studies. The authors noted that

there is a need for more high-quality studies with larger sample sizes,

assessed using the same assay techniques, and multiple indices of iron

status to provide more conclusive results; the mechanisms leading to iron

deficiency in ADHD, and the correlation between brain iron and peripheral

iron levels also needs further research.

Ph a rmacogenetic Testing of Drug R esponse in Individuals with A D H D

Park et al (2013) examined the associations between the MspI and DraI

polymorphisms of the alpha-2 A-adrenergic receptor gene (ADRA2A) and

treatment response to methylphenidate according to subtype of ADHD.

These researchers enrolled 115 medication-naïve children with ADHD into

an open label 8-week trial of methylphenidate. The participants were

genotyped and evaluated using the Clinical -Global Impression (CGI),

ADHD rating scale, and Continuous Performance Test (CPT) pre- and

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post-treatment. There was no statistically significant association between

the MspI or DraI genotypes and the relative frequency of CGI-

improvement (CGI-I) 1 or 2 status among any of the groups (all types of

ADHD, ADHD-C, or ADHD-I). However, among the children with ADHD-

C, those subjects with the C/C genotype at the ADRA2A DraI

polymorphism tended to have a CGI-I 1 or 2 status post-treatment (odds

ratio [OR] 4.45, p = 0.045). The authors concluded that the findings of

this study did not support the association between the MspI or DraI

genotypes and treatment response to methylphenidate in ADHD.

However, the results suggested that subtypes might influence

pharmacogenetic results in ADHD.

Hegvik et al (2016) noted that ADHD is a common childhood onset

neuropsychiatric disorder with a complex and heterogeneous

symptomatology. Persistence of ADHD symptoms into adulthood is

common. Methylphenidate (MPH) is a widely prescribed stimulant

compound that may be effective against ADHD symptoms in children and

adults. However, MPH does not exert satisfactory effect in all patients.

Several genetic variants have been proposed to predict either treatment

response or adverse effects of stimulants. These investigators conducted

a literature search to identify previously reported variants associated with

MPH response and additional variants that were biologically plausible

candidates for MPH response. The response to MPH was assessed by

the treating clinicians in 564 adult ADHD patients and 20 genetic variants

were successfully genotyped. Logistic regression was used to test for

association between these polymorphisms and treatment response.

Nominal associations (p < 0.05) were meta-analyzed with published data

from previous comparable studies. In this analyses, rs1800544 in the

ADRA2A gene was associated with MPH response at a nominal

significance level (OR 0.560, 95 % confidence interval [CI]: 0.329 to

0.953, p = 0.033). However, this finding was not affirmed in the meta-

analysis. No genetic variants revealed significant associations after

correction for multiple testing (p < 0.00125). The authors concluded that

these findings suggested that none of the studied variants are strong

predictors of MPH response in adult ADHD as judged by clinician ratings,

potentially except for rs1800544. They stated that pharmacogenetic

testing in routine clinical care is not supported by this analyses; further

studies on the pharmacogenetics of adult ADHD are needed.

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Kim and colleagues (2017) examined the possible association between 2

NMDA subunit gene polymorphisms (GRIN2B rs2284411 and GRIN2A

rs2229193) and treatment response to methylphenidate (MPH) in ADHD.

A total of 75 ADHD patients aged 6 to 17 years underwent 6 months of

MPH administration. Treatment response was defined by changes in

scores of the ADHD-IV Rating Scale (ADHD-RS), clinician-rated Clinical

Global Impression-Improvement (CGI-I), and CPT. The association of the

GRIN2B and GRIN2A polymorphisms with treatment response was

analyzed using logistic regression analyses. The GRIN2B rs2284411 C/C

genotype showed significantly better treatment response as assessed by

ADHD-RS inattention (p = 0.009) and CGI-I scores (p = 0.009), and there

was a nominally significant association in regard to ADHD-RS

hyperactivity-impulsivity (p = 0.028) and total (p = 0.023) scores, after

adjusting for age, sex, IQ, baseline Clinical Global Impression-Severity

(CGI-S) score, baseline ADHD-RS total score, and final MPH dose. The

GRIN2B C/C genotype also showed greater improvement at the CPT

response time variability (p < 0.001). The GRIN2A G/G genotype was

associated with a greater improvement in commission errors of the CPT

compared to the G/A genotype (p = 0.001). The authors concluded that

these results suggested that the GRIN2B rs2284411 genotype may be an

important predictor of MPH response in ADHD.

Furthermore, an UpToDate review on “Attention deficit hyperactivity

disorder in children and adolescents: Treatment with medications” does

not mention pharmacogenetic testing.

A FF2 G ene T esting

An UpToDate review on “Attention deficit hyperactivity disorder in adults:

Epidemiology, pathogenesis, clinical features, course, assessment, and

diagnosis” (Bukstein, 2018) does not mention AFF2 testing.

M e a s ureme nts of Peripheral Brain-D erived Neurotrophic Fa ctor

Zhang and colleagues (2018) noted that studies suggested that

dysfunction of brain-derived neurotrophic factor (BDNF) is a possible

contributor to the pathology and symptoms of ADHD. Several studies

have found changes of peripheral BDNF levels in ADHD, but findings are

inconsistent. In a meta-analysis, these researchers evaluated the

association between peripheral BDNF levels and ADHD. A systematic

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search of PubMed, Web of Science and China National Knowledge

Infrastructure identified 10 articles totaling 1,183 individuals. Meta-

analysis was performed in a fixed/random effectmodel by using the

software Review Manager 5.2. The results suggested that peripheral

BDNF levels did not differ significantly between ADHD and controls with

the SMD of 0.62 (95 % CI: -0.12 to 1.35, p = 0.10). However, it is

interesting that BDNF levels were significantly higher in males with ADHD

compared with controls (SMD = 0.49, 95 % CI: 0.14 to 0.84, p = 0.006),

whereas there was no difference in BDNF levels between ADHD female

patients and control groups (SMD = 0.21, 95 % CI: -0.44 to 0.86, p =

0.53). The authors found that although there was no significantly

difference in peripheral BDNF levels between ADHD patients and control

groups overall, BDNF levels were significantly higher in males with ADHD

compared with controls. They stated that these findings suggested a sex-

specific association between peripheral blood BDNF levels and ADHD

male patients. The main drawback of this study was that high

heterogeneity was noted across sampled studies, which may be a

function of sample size, participants sampled, variations in study design,

or other factors.

M e a s ureme nts of Serum Lipid Patterns

Pinho and colleagues (2019) noted that ADHD is a multi-factorial,

complex and the most common neurodevelopmental disorder in

childhood. In this analysis, these researchers tested the hypothesis that

altered serum lipid patterns are associated with ADHD. Using data from

the nationwide, population-based German Health Interview and

Examination Survey for Children and Adolescents (KiGGS), these

investigators compared serum levels of total cholesterol, high-density

(HDL) and low-density lipoprotein (LDL) cholesterol, and also

triglycerides, in participants with physician-diagnosed and/or suspected

ADHD, as defined by a value of greater than or equal to 7 on the

hyperactivity-inattention subscale of the Strengths and Difficulties

Questionnaire (SDQ), with non-ADHD controls. Among 6,898 participants

aged between 11 and 17 years, 666 (9.7 %) had a physician-based

diagnosis of ADHD and/or suspected ADHD. These researchers found

correlations between the parent-rated SDQ scores on the hyperactivity-

inattention subscale and concentrations of triglycerides (r = 0.064, p <

0.001), total cholesterol (r = -0.026, p = 0.033), HDL cholesterol (r

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= -0.059, p < 0.001) and LDL cholesterol (r = -0.027, p = 0.031). In multi-

variate models, low serum levels of LDL cholesterol remained a

significant predictor of ADHD (Exp(β) = 0.382, 95 % CI: 0.165 to 0.888, p

= 0.025). The authors concluded that these findings in a large, nationwide

and representative sample of German adolescents demonstrated a small,

but significant and inverse link between LDL cholesterol levels and

symptoms of ADHD. Moreover, they stated that further studies are

needed to decipher the biochemical mechanisms behind this relationship.

B u p ropion for t he Tre atment of A DHD

Verbeeck and colleagues (2017) evaluated the safety and effectiveness of

bupropion for the treatment of adults with ADHD. These investigators

searched the Cochrane Central Register of Controlled Trials (CENTRAL),

Medline, Embase, and 7 other databases in February 2017. They also

searched 3 trials registers and 3 online theses portals. In addition, these

researchers checked references of included studies and contacted study

authors to identify potentially relevant studies that were missed by their

search. They included all RCTs that evaluated the effects (including

adverse effects) of bupropion compared to placebo in adults with ADHD.

Two review authors independently screened records and extracted data

using a data extraction sheet that they tested in a pilot study. These

researchers extracted all relevant data on study characteristics and

results. They assessed risks of bias using the Cochrane “Risk of bias”

tool, and assessed the overall quality of evidence using the GRADE

approach. They used a fixed-effectmodel to pool the results across

studies. The authors concluded that the findings of this review, which

compared bupropion to placebo for adult ADHD, indicated a possible

benefit of bupropion. They found low-quality evidence that bupropion

decreased the severity of ADHD symptoms and moderately increased the

proportion of participants achieving a significant clinical improvement in

ADHD symptoms. Furthermore, these investigators found low-quality

evidence that the tolerability of bupropion was similar to that of placebo.

In the pharmacological treatment of adults with ADHD, extended- or

sustained-release bupropion may be an alternative to stimulants. The

low-quality evidence indicated uncertainty with respect to the pooled

effect estimates. They stated that further research is very likely to change

these estimates; more research is needed to reach more definite

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conclusions as well as clarifying the optimal target population for this

medicine. The authors noted that there is also a lack of knowledge on

long-term outcomes.

S yn tonic Photothe rapy for the Tre atment of A DHD

Syntonic phototherapy, also known as optometric phototherapy, uses

visible light frequencies to enhance visual attention and the ability to

understand what we see. Syntonic phototherapy is designed to balance

the autonomic nervous system, which controls our perceptual visual

fields. This procedure has been clinically used for many years; however,

there is a lack of evidence regarding its effectiveness in the treatment of

ADHD.

Ne u rofe edba ck

In a systematic review, Razoki (2018) evaluated the efficacy of NF

compared to stimulant medication in treating children and adolescents

with ADHD. Included in this review were 8 RCTs that compared an NF

condition, either alone or combined with medication, to a medication

condition, which was mainly methylphenidate. Outcome measures

included behavioral assessments by parents and teachers, self-reports,

neurocognitive measures, EEG power spectra and ERPs. When only

trials were considered that include probably blinded ratings or those that

were sham-NF or semi-active controlled or those that employed optimally

titration procedures, the findings did not support theta/beta NF as a

standalone treatment for children or adolescents with ADHD.

Nevertheless, an additive treatment effect of NF was observed on top of

stimulants and theta/beta NF was able to decrease medication dosages,

and both results were maintained at 6-month follow-up. This review

concluded that the present role of NF in treating children diagnosed with

ADHD should be considered as complementary in a multi-modal

treatment approach, individualized to the needs of the child, and may be

considered a viable alternative to stimulants for a specific group of

patients. Particularly patients with the following characteristics may

benefit from NF treatment: low responders to medication, intolerable side

effects due to medication, higher baseline theta power spectra and

possibly having no co-morbid psychiatric disorders. The authors

concluded that future research should prioritize the identification of

markers that differentiate responders from non-responders to NF

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treatment, the potential of NF to decrease stimulant dosage, the

standardization of NF treatment protocols and the identification of the

most favorable neurophysiological treatment targets.

M e a s ureme nt of Blood a nd Hair M agnesium Levels

Effatpanah and associates (2019) stated that current research suggests

conflicting evidence surrounding the association between serum

magnesium levels and the diagnosis of ADHD. In a systematic review

and meta-analysis, these investigators examined the published literature

addressing this topic. They performed an exhaustive literature search on

Scopus and PubMed for all the relevant observational studies published

up to August 2018. A meta-analysis using a random-effects model was

used to summarize the overall association between serum magnesium

level and ADHD from the available data. These researchers identified 7

studies that reported the mean and standard deviation (SD) of

magnesium concentration in both ADHD and control gr oups. The

random-effects meta-analysis showed that subjects with ADHD had

0.105 mmol/L (95 % C I: -0.188 to -0.022; p < 0.013) lower serum

magnesium levels compared with to their healthy controls. Moreover,

they observed striking and statistically significant heterogeneity among

the included studies (I2 = 96.2 %, p = 0.0103). The authors concluded

that evidence from this meta-analysis supported the theory that an

inverse relationship between serum magnesium deficiency and ADHD

exists. Moreover, they noted that high heterogeneity among the included

studies suggested that there is a residual need for observational and

community-based studies to further examine this issue.

Huang and colleagues (2019) noted that the pathophysiology of ADHD is

still obscure. Some studies have discussed that magnesium levels are

lower in the serum and erythrocytes of children with ADHD. However,

these findings are controversial. In a systematic review and meta-

analysis, these researchers examined if magnesium levels are in fact

lower in children with ADHD. They carried out a thorough search of the

literature and examined the connection between magnesium insufficiency

and ADHD. A total of 12 studies were included into the current meta-

analysis. The results of this meta-analysis found that peripheral blood

magnesium levels, either in plasma, serum, or whole blood, of children

diagnosed with ADHD were significantly lower than those in controls

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(k = 8, Hedges' g = -0.547, 95 % CI: -0.818 to -0.276, p < 0.001). The

subgroup meta-analysis with serum sample sources also suggested that

peripheral serum magnesium levels of children diagnosed with ADHD

were significantly lower than those in controls (k = 6, H edges' g = -0.733,

95 % CI: -0.911 to -0.555, p < 0.001). The subgroup meta-analysis

focusing on subjects with ADHD diagnosed by definite diagnostic criteria

also suggested significantly lower peripheral serum magnesium levels in

ADHD c hildren than those in controls (k = 4, Hedges' g = -0.780, 95 %

CI: -0.985 to -0.574, p < 0.001). These investigators also noted that

magnesium levels in the hair of children diagnosed with ADHD were

significantly lower than those in controls (k = 4, Hedges' g = -0.713, 95 %

CI: -1.359 to -0.067, p = 0.031). The authors concluded that in this meta-

analysis, they found that children diagnosed with ADHD had lower serum

and hair magnesium levels than children without ADHD. Moreover, these

researchers stated that further study may be needed to examine the

behavioral influence on ADHD due to lower magnesium levels, the

association between brain and serum magnesium levels, and the effects

brought about by larger longitudinal cohort studies.



assessment, and diagnosis” (Bukstein, 2019) does not mention

measurement of blood and hair magnesium levels as a management tool.

T e s ting of Serotonin Re ceptor Fa mily G enetic Va ria tions

Hou and colleagues (2018) stated that ADHD is one of the most common

mental disorders in childhood, with a high heritability about 60 % to 90 %.

Serotonin is a monoamine neurotransmitter. Numerous studies have

reported the association between the serotonin receptor family (5-HTR)

gene polymorphisms and ADHD, but the results are still controversial.

These researchers conducted a meta-analysis of the association

between 5-HTR1B, 5-HTR2A, and 5-HTR2C genetic variants and ADHD.

The results showed that the 861G allele of 5-HTR1B SNP rs6296 could

significantly increase the risk of ADHD (OR = 1.09, 95 % CI: 1.01 to 1.18);

the 5-HTR2C gene rs518147 (OR = 1.69, 95 % CI: 1.38 to 2.07) and

rs3813929 (OR = 1.57, 95 % CI: 1.25 to 1.97) were all associated with the

risk of ADHD. Furthermore, these investigators also performed a case-

control study to examine the relevance between potential candidate

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genes 5-HTR1A, 5-HTR1E, 5-HTR3A and ADHD. The results indicated

that 5-HTR1A rs6295 genotype (CC+CG versus GG OR = 2.00, 95 % CI:

1.23 to 3.27) and allele (OR = 1.77, 95 % CI: 1.16 to 2.72) models were

statistically significantly different between case group and control group.

The authors concluded that this study was the first comprehensive

exploration and summary of the association between serotonin receptor

family genetic variations and ADHD, and it also provided more evidence

for the etiology of ADHD.



assessment, and diagnosis” (Bukstein, 2019) does not mention testing of

serotonin receptor family genetic variations as a management tool.

E x t ernal Trigemina l Nerve Stimulation (eTNS) System for the T re a tment of ADH D

In an 8-week, unblinded pilot study, McGough and associates (2019)

examined the potential feasibility and utility of trigeminal nerve stimulation

(TNS) for the treatment of ADHD in youth. A total of 24 participants aged

7 to 14 years with ADHD enrolled in an 8-week open trial of TNS

administered nightly during sleep, and were assessed weekly with parent-

and physician-completed measures of ADHD symptoms and executive

functioning as well as measures of treatment compliance, adverse events

(AEs), and side effects. Computerized tests of cognitive functioning were

administered at baseline and weeks 4 and 8. Significant improvements

were observed on the ADHD-IV Rating Scale (p < 0.0001) and parent-

completed Conners Global Index (p < 0.0001), as well as the majority of

scales on the parent-completed Behavior Rating Inventory of Executive

Functioning (BRIEF). Improvements were also noted on the

computerized Attention Network Task (ANT) Incongruent Reaction Time

(p = 0.006), suggesting that TNS has positive effects on response

inhibition. The authors concluded that TNS therapy for youth with ADHD

appeared to be both feasible and without significant risk. Subjective

improvements on rating scales and laboratory measures of cognition

suggested a potential role for TNS in treating ADHD that merited further

investigation. These researchers stated that future research in

anticipation of designing definitive controlled efficacy trials should

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evaluate time to onset of TNS response and durability of treatment effects

following TNS discontinuation, as well as validate an effective active sham

comparator suitable for blinded studies.

McGough and colleagues (2019) noted that TNS showed potential

benefits for ADHD in an open, unblinded study. In a blinded sham-

controlled pilot study, these researchers examined the safety and efficacy

of TNS for ADHD and potential changes in brain spectral power using

resting-state QEEG. A total of 62 children 8 to 12 years old, with full-

scale IQ of at least 85 and Schedule for Affective Disorders and

Schizophrenia-diagnosed ADHD, were randomized to 4 weeks of nightly

treatment with active or sham TNS, followed by 1 week without

intervention. Assessments included weekly clinician-administered ADHD-

RS and CGI scales and QEEG at baseline and week 4. ADHD-RS total

scores showed significant group-by-time interactions (F1,228 = 8.12, p =

0.005; week 4 Cohen d = 0.5); CGI-Improvement scores also favored

active treatment (χ21,168 = 8.75, p = 0.003; number needed to treat = 3).

Resting-state QEEG showed increased spectral power in the right frontal

and frontal mid-line frequency bands with active TNS. Neither group had

clinically meaningful AEs. The authors concluded that this study

demonstrated TNS efficacy for ADHD in a blinded sham-controlled trial,

with estimated treatment effect size similar to non-stimulants; TNS was

well-tolerated and had minimal risk. These investigators stated that

additional research should examine treatment response durability and

potential impact on brain development with sustained use.



prognosis” (Krull, 2019) does not mention external trigeminal nerve

stimulation as a therapeutic option.

On April 19, 2019, the FDA announced that they are permitting marketing

of the 1st medical device to treat ADHD for NeuroSigma’s Monarch

external Trigeminal Nerve Stimulation (eTNS) System. This eTNS system

is indicated for patients aged 7 to12 years old who are not currently taking

prescription ADHD medication and is the 1st non-drug treatment for

ADHD granted marketing authorization by the FDA.

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There is currently insufficientevidence to support the use of external

trigeminal nerve stimulation for the treatment of ADHD. The preliminary

findings from McGough and co-workers (2015, 2019) need to be validated

by well-designed studies especially to ascertain whether this approach

would result in a durable benefit or whether the effects wane over time.

Occu pational Therapy, Physical Therapy and Speech Therapy

Wilkes-Gillan and colleagues (2017) examined the pragmatic language

outcomes of children with ADHD in 2 feasibility studies. A total of 5

children with ADHD (aged 6 to 11 years), their parents, and 5 typically

developing peers completed an assessment 18 months after a therapist-

delivered intervention (Study 1). Participants then completed a parent-

delivered intervention (Study 2). Blinded ratings of peer-to-peer play

interactions documented changes in children's pragmatic language 18

months after the Study 1 intervention and before, immediately after, and 1

month after the Study 2 intervention. Non-parametric statistics and

Cohen's d were used to measure change. Children's pragmatic language

outcomes were maintained 18 months after the therapist-delivered

intervention and significantly improved from before to 1 month after the

parent-delivered intervention. The authors concluded that interventions

involving occupational therapist and speech-language pathologist

collaboration, play,and parent and peer involvement may facilitate

children's pragmatic language skills.

Gilboa and Helmer (2020) examined the effectiveness of self-

management intervention for attention and executive functions using

equine-assisted occupational therapy (STABLE-OT) for school-aged

children with ADHD. A pre-post design was used in the intervention. The

study was conducted at 2 riding school stables is Israel. A total of 25

children (3 girls, 22 boys, aged 7.8 to 12.3 years) diagnosed with ADHD

participated in a therapeutic equestrian riding intervention. The

intervention included structured 45-min sessions for 12 weeks, while

integrating child- and family-centered strategy acquisition and immediate

feedback principles. Their executive function (EF) and occupational

performance were evaluated pre- and post-intervention, using the

Behavior Rating Inventory of Executive Function (BRIEF) and the

Canadian Occupational Performance Measure (COPM). Results showed

a significant improvement in EF, as reflected by statistically significant

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decreases in the Global Executive Composite (GEC; t = 2.801; p = 0.01),

metacognitive index (t = 3.873; p= 0.001), working memory (t = 2.476; p =

0.021), monitor (t = 2.359; p = 0.027), and initiation (t = 3.204; p = 0.004)

subscales of the BRIEF questionnaire. A statistically (p < 0.001) and

clinically significant improvementwas also found in the COPM

performance and satisfaction scales. The authors concluded that the

findings of this study provided key preliminary evidence supporting the

effectiveness of an individual equine-assisted OT intervention for children

with ADHD. It constituted an initial step toward clinical implementation of

such therapeutic approaches, and is expected to spark further research in

this area.



prognosis” (Krull, 2020) does not mention occupational therapy, physical

therapy and speech therapy as managementoptions.

*DSM-5 Criteria for ADHD

A. E it her 1 or 2

1. Five or more (17 years of age or older) or six or more (under 17

years of age) of the following symptoms of inattention have been

present for at least six months to a point that is disruptive and

inappropriate for developmental level:

Inattention

a. Often does not give close attention to details or makes

careless mistakes in schoolwork, work or other activities

b. Often has trouble keeping attention on tasks or play

activities

c. Often does not seem to listen when spoken to directly

d. Often does not follow instructions and fails to finish

schoolwork, chores or duties in the workplace (not due to

oppositional behavior or failure to understand instructions)

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e. Often has trouble organizing tasks and activities

f. Often avoids, dislikes or doesn't want to do things that take

a lot of mental effort for a long period of time (such as

schoolwork or homework)

g. Often loses things needed for tasks and activities (eg, toys,

school assignments, pencils, books or tools)

h. Is often easily distracted

i. Is often forgetful in daily activities

2. Five or more (17 years of age or older) or six or more (under 17

years of age) of the following symptoms of hyperactivity

impulsivity have been present for at least six months to an

extent that is disruptive and inappropriate for developmental

level:

Hyperactivity-impulsivi ty

a. Often fidgets with hands or feet or squirms in seat

b. Often gets up from seat when remaining in seat is expected

c. Often has trouble playing or enjoying leisure activities

quietly (in adolescents or adults this may be reported as

"feeling restless")

d. Often "on the go" or often acts as if "driven by a motor"

e. Often talks excessively

f. Often runs about or climbs when and where it is not

appropriate (adolescents or adults may feel very restless)

g. Often blurts out answers before questions have been

finished

h. Often has trouble waiting one’s turn

i. Often interrupts or intrudes on others (eg, butts into

conversations or games)

B. Some symptoms that cause impairment were present before age

12 years

C. Some impairment from the symptoms is present in two or more

settings (eg, at school/work and at home)

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D. There must be clear evidence of significant impairment in social,

school or work functioning

E. DSM-5 includes no exclusion criteria for people with autism

spectrum disorder, since symptoms of both disorders co-occur.

However, ADHD symptoms must occur exclusively during the

course of schizophrenia or another psychotic disorder and must

not be better explained by another mental disorder, such as a

depressive or bipolar disorder, anxiety disorder, dissociative

disorder, personality disorder or substance intoxication or

withdrawal.

CPT Codes / HCPCS Codes / ICD-10 Codes

Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":

Code Code Description

CPT codes covered if selection criteria are met:

9 0 7 91 Psychiatric diagnostic evaluation

9 0 7 92 Psychiatric diagnostic evaluation with medical services

9 6 1 56 Health behavior assessment, or re-assessment (ie,

health-focused clinical interview, behavioral

observations, clinical decision making)

9 6 1 58 Health behavior intervention, individual, face-to-face;

initial 30 minutes

+ 9 6 15 9 each additional 15 minutes (List separately in addition

to code for primary service)

9 6 1 64 Health behavior intervention, group (2 or more patients),

face-to-face; initial 30 minutes



9 6 1 67 Health behavior intervention, family (with the patient

present), face-to-face; initial 30 minutes

aetnet.aetna.com/mpa/cpb/400_499/0426.html#dummyLink2 Proprietary 50/76




9 6 1 70 Health behavior intervention, family (without the patient

present), face-to-face; initial 30 minutes



CPT codes n ot covered for indications listed in the CPB:

EEG theta/b eta power ratio - no specific code:

0 0 3 3U HTR2A (5-hydroxytryptamine receptor 2A), HTR2C

(5-hydroxytryptamine receptor 2C) (eg, citalopram

metabolism) gene analysis, common variants (ie, HTR2A

rs7997012 [c.614-2211T>C], HTR2C rs3813929

[c.-759C>T] and rs1414334 [c.551-3008C>G])

0 3 3 3T Visual evoked potential, screening of visual acuity,

automated

7 0 4 50 Computed tomography, head or brain; without contrast

material

7 0 4 60 with contrast material(s)

7 0 4 70 without contrast material, followed by contrast

material(s) and further sections

7 0 4 96 Computedtomographic angiography, head, with contrast

material(s), including noncontrast images, if performed,

and image post-processing

7 0 5 44 Magnetic resonance angiography, head; without contrast

material(s)


7 0 5 46 without contrast material(s), followed by contrast

material(s) and further sequences

7 0 5 51 Magnetic resonance (e.g., proton) imaging, brain

(including brain stem); without contrast material





7 0 5 53 without contrast material, followed by contrast

material(s) and further sequences

7 0 5 54 Magnetic resonance imaging,brain, functional MRI;

including test selection and administration of repetitive

body part movement and/or visual stimulation, not

requiring physician or psychologist administration

7 0 5 55 requiring physician or psychologist administration of

entire neurofunctional testing

7 6 3 90 Magnetic resonance spectroscopy

7 8 6 00 Brain imaging, less than 4 static views

7 8 6 01 with vascular flow

7 8 6 05 Brain imaging, minimum 4 static views

7 8 6 06 with vascular flow

7 8 6 07 Brain imaging, tomographic (SPECT)

7 8 6 08 Brain imaging,positron emission tomography (PET);

metabolic evaluation

7 8 6 09 perfusion evaluation

8 0 0 61 Lipid panel [serum lipid patterns]

8 1 1 71 -

8 1 1 72

AFF2 (AF4/FMR2 family,member 2 [FMR2]) (eg, fragile

X mental retardation 2 [FRAXE]) geneanalysis

8 1 4 01 Molecular pathology procedure, Level 2 (eg, 2-10 SNPs,

1 methylated variant, or 1 somatic variant [typically using

nonsequencing target variant analysis], or detection of a

dynamic mutation disorder/triplet repeat)




8 1 4 04 Molecular pathology procedure, Level 5 (eg, analysis of

2-5 exons by DNA sequence analysis, mutation

scanning or duplication/deletion variants of 6-10 exons,

or characterization of dynamic mutation disorder/triplet

repeat by Southern blot analysis)

8 2 7 28 Ferritin

8 2 7 84 Gammaglobulin (immunoglobulin); IgA, IgD, IgG, IgM,

each [assessment test for prescription of diet]

8 2 7 87 Immunoglbulin subclasses (ed, IgG1, 2, 3, or 4), each

[assessment test for prescription of diet]

8 3 5 40 Iron

8 3 5 50 TIBC

8 3 7 35 Magnesium

8 4 6 30 Zinc

8 6 0 01 Allergen specific IgG quantitative or semiquantitative,

each allergen [assessment test for prescription of diet]

8 8 3 18 Determinative histochemistry to identifychemical

components (e.g., copper, zinc)

9 0 8 32 Psychotherapy, 30 minutes with patient and/or family

member


member when performed with an evaluation and

management service




management service


member






management service

9 0 8 67 Therapeutic repetitive transcranial magneticstimulation

treatment; planning

9 0 8 68 delivery and management, per session

9 0 8 69 subsequent motor threshold re-determination with

delivery and management

9 0 8 75 Individual psychophysiological therapy incorporating

biofeedback training by any modality (face-to-face with

the patient), with psychotherapy (eg, insight oriented,

behavior modifying or supportive psychotherapy); 30

minutes

9 0 8 76 45 minutes

9 2 0 65 Orthoptic and/or pleoptic training, with continuing

medical direction and evaluation

9 2 5 07 Treatment of speech, language,voice, communication,

and/or auditory processing disorder; individual

9 2 5 08 group, two or more individuals

9 2 5 21 Evaluation of speech fluency (eg, stuttering, cluttering)

9 2 5 22 Evaluation of speech sound production (eg, articulation,

phonological process, apraxia, dysarthria)

9 2 5 23 with evaluation of language comprehension and

expression (eg, receptive and expressive language)

9 2 5 24 Behavioral and qualitative analysis of voice and

resonance

9 2 5 37 -

9 2 5 38

Caloric vestibular test with recording, bilateral; bithermal

or monothermal




9 2 5 40 Basic vestibular evaluation, includes spontaneous

nystagmus test with eccentric gaze fixation nystagmus,

with recording, positional nystagmus test, minimum of 4

positions, with recording, optokinetic nystagmust test,

bidirectional foveal and peripheral stimulation, with

recording, and oscillating tracking test, with recording

9 2 5 41 Spontaneous nystagmus test, including gaze and

fixation nystagmus, with recording

9 2 5 42 Positional nystagmus test, minimum of 4 positions, with

recording

9 2 5 44 Optokinetic nystagmus test, bidirectional, foveal or

peripheral stimulation, with recording

9 2 5 45 Oscillating tracking test, with recording

9 2 5 46 Sinusoidal vertical axis rotational testing

+ 9 2 5 47 Use of vertical electrodes (List separately in addition to

code for primary procedure)

9 2 5 48 Computerized dynamic posturography

9 2 5 50 Tympanometry and reflex threshold measurements

9 2 5 58 Evoked otoacoustic emissions, screening (qualutative

measurement of distortion product or transient evoked

otoacoustic emissions), automated analysis

9 2 5 67 Tympanometry (impedance testing)

9 2 5 68 -

9 2 5 69

Acoustic reflex testing

9 2 5 70 Acoustic immittance testing, includes typanometry

(impedance testing), acoustic reflex threshold testing,

and acoustic reflex decay testing

9 2 5 85 Auditory evoked potentials for evoked response

audiometry and/or testing of the central nervous system;

comprehensive




9 2 5 86 limited

9 2 5 87 Evoked otoacoustic emissions; limited (single stimulus

level, either transient or distortion products)

9 2 5 88 comprehensiveor diagnostic evaluation (comparison

of transient and/or distortion product otoacoustic

emissions at multiple levels andfrequencies

9 5 8 03 Actigraphy testing, recording, analysis, interpretation,

and report (minimum of 72 hours to 14 consecutive days

of recording)

9 5 8 12 Electroencephalogram (EEG) extended monitoring;

41-60 minutes [covered only for persons with signs of

seizure disorder or degenerative neurological condition]

9 5 8 13 greater than 1 hour [covered only for persons with

signs of seizure disorder or degenerative neurological

condition]

9 5 8 16 Electroencephalogram (EEG); includingrecording awake

and drowsy [covered only for persons with signs of

seizure disorder or degenerative neurological condition]

9 5 8 19 including recording awake and asleep [covered only

for persons with signs of seizure disorder or

degenerative neurological condition]

9 5 9 25 Short-latency somatosensory evoked potential study,

stimulation of any/all peripheral nerves or skin sites,

recording from the central nervous system; in upper

limbs

9 5 9 26 in lower limbs

9 5 9 27 in the trunk or head

9 5 9 28 Central motor evoked potential study (transcranial motor

stimulation); upper limbs

9 5 9 29 lower limbs




9 5 9 30 Visual evoked potential (VEP) testing central nervous

system, checkerboard or flash

9 5 9 54 Pharmacological or physical activation requiring

physician attendance during EEG recording of activation

phase (eg, thiopental ac tivation test)

9 5 9 57 Digital analysis of electroencephalogram (EEG) (eg, for

epileptic spike analysis) [neuropsychiatric EEG based

assessment aid (NEBA)]

9 6 0 20 Neurofunctional testing selection and administration

during noninvasive imaging functional brain mapping,

with test administered entirely by a physician or other

qualified health care professional (ie, psychologist), with

review of test results and report

9 6 1 05 Assessment of aphasia (includes assessment of

expressive and receptive speech and language function,

language comprehension, speech production ability,

reading, spelling, writing, e.g., by Boston Diagnostic

Aphasia Examination) with interpretation and report, per

hour

96116,

96121

Neurobehavioral status exam (clinical assessment of

thinking, reasoning and judgment, [eg, acquired

knowledge, attention, language, memory, planning and

problem solving, and visual spatial abilities]), by

physician or other qualified health care professional,

both face-to-face time with the patient and time

interpreting test results and preparing the report

9 6 1 30 -

9 6 1 31

Psychological testing evaluation services by physician or

other qualified health care professional, including

integration of patient data, interpretation of standardized

test results and clinical data, clinical decision making,

treatment planning and report, and interactive feedback

to the patient, family member(s) or caregiver(s), when

performed




9 6 1 36 -

9 6 1 37

Psychological or neuropsychological test administration

and scoring by physician or other qualified health care

professional, two or more tests, anymethod

9 6 1 38 -

9 6 1 39

Psychological or neuropsychological test administration

and scoring by technician, two or more tests, any

method

9 6 1 46 Psychological or neuropsychological test administration,

with single automated, standardized instrument via

electronic platform, with automated result only

9 6 9 02 Microscopic examination of hairs plucked or clipped by

the examiner (excluding hair collected by the patient) to

determine telogen and anagen counts, or structural hair

shaft abnormality

9 7 0 10 Application of a modality to 1 or more areas; hot or cold

packs

9 7 0 12 traction, mechanical

9 7 0 14 electrical stimulation (unattended)

9 7 0 16 vasopneumatic devices

9 7 0 18 paraffin bath

9 7 0 22 whirlpool

9 7 0 24 diathermy (eg, microwave)

9 7 0 26 infrared

9 7 0 28 ultraviolet

9 7 0 32 Application of a modality to one or more areas; electrical

stimulation (manual), each 15 minutes

9 7 0 33 iontophoresis, each 15 minutes

9 7 0 34 contrast baths, each 15 minutes

9 7 0 35 ultrasound, each 15 minutes




9 7 0 36 Hubbard tank, each 15 minutes

9 7 1 10 Therapeutic procedure, one or more areas, each 15

minutes; therapeutic exercises to develop strength and

endurance, range of motion and flexibility

9 7 1 12 neuromuscularreeducation ofmovement, balance,

coordination, kinesthetic sense, posture, and/or

proprioception for sitting and/or standing activities

9 7 1 13 aquatic therapy with therapeutic exercise

9 7 1 16 gait training (includes stair climbing)

9 7 1 24 massage, including effleurage, petrissage and/or

tapotement (stroking, compression, percussion)

9 7 1 29 Therapeutic interventions that focus on cognitive

function (eg, attention, memory, reasoning, executive

function, problem solving, and/or pragmatic functioning)

and compensatory strategies to manage the

performance of an activity (eg, managing time or

schedules, initiating, organizing, and sequencing tasks),

direct (one-on-one) patient contact; initial 15 minutes


to code for primary procedure)

9 7 1 40 Manual therapy techniques (e.g.,

mobilization/manipulation, manual lymphatic drainage,

manual traction), one or more regions, each 15 minutes

9 7 1 51 -

9 7 1 58

Adaptive Behavior Assessments and treatment

9 7 1 61 -

9 7 1 64

Physical therapy evaluation or reevaluation

9 7 1 65 -

9 7 1 68

Occupational therapy evaluation or reevaluation




9 7 5 30 Therapeutic activities, direct (one-on-one) patient

contact (use of dynamic activities to improve functional

performance), each 15 minutes

9 7 5 33 Sensory integrative techniques to enhance sensory

processing and promote adaptive responses to

environmental demands, direct (one-on-one) patient

contact by the provider, each 15 minutes

9 7 8 10 -

9 7 8 14

Acupuncture

9 8 9 40 Chiropractic manipulative treatment (CMT); spinal, 1-2

regions

9 8 9 41 spinal, 3-4 regions

9 8 9 42 spinal, 5 regions

9 8 9 43 extraspinal, 1 or more regions

Other CPT codes related to the CPB:

8 3 6 55 Lead level

9 6 1 27 Brief emotional/behavioral assessment (eg, depression

inventory, attention-deficit/hyperactivity disorder [ADHD]

scale), with scoring and documentation, per

standardized instrument

9 6 3 65 -

9 6 3 68

Intravenous infusion, for therapy, prophylaxis, or

diagnosis (specify substance or drug)

HCPCS codes not covered for indications listed in the CPB:




E x t ernal

t r ig eminal

n e rve

st imulation

for t h e

t re a tment

of A D H D-

no sp ecific

cod e

A 9 5 8 3 Injection, Gadofosveset Trisodium, 1 ml [Ablavar,

Vasovist]

A 9 5 8 5 Injection, gadobutrol, 0.1 ml

G 0 0 68 Professional services for the administration of

anti-infective, pain management, chelation, pulmonary

hypertension, and/or inotropic infusion drug(s) for each

infusion drug administration calendar day in the

individual's home, each 15 minutes

G 0 1 29 Occupational therapy requiring the skills of a qualified

occupational therapist, furnished as a component of a

partial hospitalization treatment program, per day

G 0 1 52 Services performed by a qualified occupational therapist

in the home health or hospice setting, each 15 minutes

G 0 1 53 Services performed by a qualified speech and language

pathologist in the home health or hospice setting, each

15 minutes

G 0 1 58 Services performed by a qualified occupational therapist

assistant in the home health or hospice setting, each 15

minutes

G 0 1 59 Services performed by a qualified physical therapist, in

the home health setting, in the establishment or delivery

of a safe and effective therapy maintenance program,

each 15 minutes




G 0 1 60 Services performed by a qualified occupational therapist,

in the home health setting, in the establishment or

delivery of a safe and effective therapy maintenance

program, each 15 minutes

G 0 1 61 Services performed by a qualified speech-language

pathologist, in the home health setting, in the

establishment or delivery of a safe and effective therapy

maintenance program, each 15 minutes

G 0 1 76 Activity therapy, such as music, dance, art or play

therapies not for recreation, related to the care and

treatment of patient' s disabling mental health problems,

per session (45 minutes or more)

G 0 2 95 Electromagnetic therapy, to one or more areas

H 1 0 1 0 Non-medical family planning education, per session

H 1 0 1 1 Family assessment by licensed behavioral health

professional for state defined purposes

J 0 4 70 Injection, dimercaprol, per 100 mg

J 0 6 00 Injection, edetate calcium disodium, up to 1,000 mg

J 0 8 95 Injection, deferoxamine mesylate, 500 mg

J 3 4 75 Injection, magnesium sulfate, per 500 mg

J 3 5 20 Edetate disodium, per 150 mg

M 0 3 0 0 IV chelation therapy (chemical endarterectomy)

P2 0 3 1 Hair analysis (excluding arsenic)

S 8 0 35 Magnetic source imaging

S 8 0 40 Topographic brain mapping

S 9 1 28 Speech therapy, in the home, per diem

S 9 1 29 Occupational therapy, in the home, per diem

S 9 1 31 Physical therapy; in the home, per diem





S 9 1 52 Speech therapy, re-evaluation

S 9 3 55 Home infusion, chelation therapy; administrative

services, professional pharmacy services, care

coordination, and all necessary supplies and equipment

(drugs and nursing visits coded separately), per diem

S 9 4 45 Patient education, not otherwise classified,

non-physician provider, individual, per session

S 9 4 46 Patient education, not otherwise classified,

non-physician provider, group, per session

T 1 0 18 School-based individualized education program (IEP)

services, bundled

ICD-10 codes covered if selection criteria are met:

F9 0 .0 -

F9 0 .9

Attention-deficit hyperactivity disorder

1. Acosta MT, Leon-Sarmiento FE. Repetitive transcranial magnetic

stimulation (rTMS): New tool, new therapy and new hope for

ADHD. Curr Med Res Opin. 2003;19(2):125-130.

2. Adler LA, Spencer TJ, Milton DR, et al. Long-term, open-label study

of the safety and efficacy of atomoxetine in adults with attention

deficit/hyperactivity disorder: An interim analysis. J Clin

Psychiatry. 2005;66(3):294-299.

3. Agency for Healthcare Research and Quality (AHRQ) Website.

Comparative Effectiveness Review. Attention deficit hyperactivity

disorder: Effectiveness of treatment in at-risk preschoolers; long

term effectiveness in all ages; and variability in prevalence,

diagnosis, and treatment. Rockville, MD: AHRQ; August 2014.

4. Altunc U, Pittler MH, Ernst E. Homeopathy for childhood and

adolescence ailments: Systematic review of randomized clinical

trials. Mayo Clin Proc. 2007;82(1):69-75.

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5. American Academy of Child and Adolescent Psychiatry. Practice

Parameter for the Assessment and Treatment of Children and

Adolescents with Attention-Deficit/Hyperactivity Disorder. J Am

Acad Child Adolesc Psychiatry. 2007;46(7):894-921.

6. American Academy of Pediatrics (AAP) Website. Policy Statement.

Cardiovascular monitoring and stimulant drugs for attention-

deficit/ hyperactivity disorder. Elk Grove Village, IL: AAP; August

2008.

7. American Academy of Pediatrics (AAP). ADHD: Clinical practice

guideline for the diagnosis, evaluation and treatment of

attention-defici t/ hyperactivity disorder in children and

adolescents. Elk Grove Village, IL: November 2011.

8. American Academy of Pediatrics. Clinical practice guideline:

Diagnosis and evaluation of the child with attention

deficit/hyperactivity disorder. Pediatrics. 2000;105(5):1158-1170.

9. American Heart Association (AHA) Website. Cardiovascular

monitoring of children and adolescents with heart disease

receiving medications for attention deficit/hyperactivity disorder.

Dallas, TX: AHA; April 21, 2008.

10. American Psychiatric Association (APA). Attention

deficit/hyperactivity disorder. Diagnostic and Statistical Manual of

Mental Disorders, Fifth Edition (DSM-5). Washington, DC:

American Psychiatric Association; 2013: 59-66.

11. ATHENA Association for Therapeutic Eurythmy in North America

[website]. Portland, OR: Artemisia; 2001. Available at:

http://www.artemisia.net/athena/index.htm. Accessed July 9,

2004.

12. Augustovski F, Pichon Riviere A, Alcaraz A, et al. Functional

magnetic resonance imaging for brain pathologies [summary].

Report IRR No. 50. Buenos Aires, Argentina: Institute for Clinical

Effectiveness and Health Policy (IECS); 2005.

13. Barry RJ, Clarke AR, Johnstone SJ. A review of electrophysiology in

attention-defici t/hyperactivi ty disorder: I. Qualitative and

quantitative electroencephalography. Clin Neurophysiol.

2003;114(2):171-183.

14. Barry RJ, Johnstone SJ, Clarke AR. A review of electrophysiology in

attention-defici t/hyperactivi ty disorder: II. Event-related

potentials. Clin Neurophysiol. 2003;114(2):184-198.

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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and

constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or

program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any

results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna

or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be

updated and therefore is subject to change.

Copyright © 2001-2020 Aetna Inc.

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AETNA BETTER HEALTH® OF PENNSYLVANIA

Amendment to Aetna Clinical Policy Bulletin Number: 0426

Attention Deficit/Hyperactivity Disorder

There are no amendments for Medicaid.

Physical therapy, occupational therapy, and speech therapy are covered by PA Medical Assistance when medical necessary under EPSDT. Children with ADHD may have co-morbid conditions which may require these services.

www.aetnabetterhealth.com/pennsylvania revised 04/22/2020

http://www.aetnabetterhealth.com/pennsylvania

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Attention Deficit/Hyperactivity Disorder · (e.g., schizophrenia, psychotic disorder,mooddisorder,anxiety disorder, or personality disorder) should be ruled out. Attention deficit