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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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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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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
CPB 0388 - Complementary and Alternative Medicine
(../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
CPB 0388 - Complementary and Alternative Medicine
(../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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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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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.
An UpToDate review on “Attention deficit hyperactivity disorder in children
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”.
An UpToDate review on “Attention deficit hyperactivity disorder in children
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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An UpToDate review on “Attention deficit hyperactivity disorder in children
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.
Furthermore, an UpToDate review on “Attention deficit hyperactivity
disorder in adults: Epidemiology, pathogenesis, clinical features, course,
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.
Furthermore, an UpToDate review on “Attention deficit hyperactivity
disorder in adults: Epidemiology, pathogenesis, clinical features, course,
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.
Furthermore, an UpToDate review on “Attention deficit hyperactivity
disorder in children and adolescents: Overview of treatment and
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.
Furthermore, an UpToDate review on “Attention deficit hyperactivity
disorder in children and adolescents: Overview of treatment and
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 16 5 each additional 15 minutes (List separately in addition
to code for primary service)
9 6 1 67 Health behavior intervention, family (with the patient
present), face-to-face; initial 30 minutes
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Code Code Description
+ 9 6 16 8 each additional 15 minutes (List separately in addition
to code for primary service)
9 6 1 70 Health behavior intervention, family (without the patient
present), face-to-face; initial 30 minutes
+ 9 6 17 1 each additional 15 minutes (List separately in addition
to code for primary service)
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 45 with 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
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Code Code Description
7 0 5 52 with contrast material(s)
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)
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Code Code Description
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
9 0 8 33 Psychotherapy, 30 minutes with patient and/or family
member when performed with an evaluation and
management service
9 0 8 34 Psychotherapy, 45 minutes with patient and/or family
9 0 8 36 Psychotherapy, 45 minutes with patient and/or family
member when performed with an evaluation and
management service
9 0 8 37 Psychotherapy, 60 minutes with patient and/or family
member
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Code Code Description
9 0 8 38 Psychotherapy, 60 minutes with patient and/or family
member when performed with an evaluation and
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
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Code Code Description
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
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Code Code Description
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
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Code Code Description
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
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Code Code Description
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
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Code Code Description
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
+ 9 7 13 0 each additional 15 minutes (List separately in addition
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
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Code Code Description
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:
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Code Code Description
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
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Code Code Description
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
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Attention Deficit/Hyperactivity Disorder - Medical Clinical Policy Bulletins | Aetna
Code Code Description
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
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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