Cigna Attention-Deficit/Hyperactivity Disorder (ADHD): Assessment and Treatment - (0231) Form

The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date Medical Coverage Policy: 0231 of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Each coverage request should be reviewed on its own merits. Medical directors are expected to exercise clinical judgment where appropriate and have discretion in making individual coverage determinations. Where coverage for care or services does not depend on specific circumstances, reimbursement will only be provided if a requested service(s) is submitted in accordance with the relevant criteria outlined in the applicable Coverage Policy, including covered diagnosis and/or procedure code(s). Reimbursement is not allowed for services when billed for conditions or diagnoses that are not covered under this Coverage Policy (see “Coding Information” below). When billing, providers must use the most appropriate codes as of the effective date of the submission. Claims submitted for services that are not accompanied by covered code(s) under the applicable Coverage Policy will be denied as not covered. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations. This Coverage Policy addresses services for the assessment and treatment of attention-deficit hyperactivity disorder. Coverage Policy Coverage for behavioral services varies across plans. Refer to the customer’s benefit plan document for coverage details. Services provided by a psychiatrist, psychologist or other behavioral health professionals may be subject to the provisions of the applicable behavioral health benefit. Assessment and treatment for comorbid behavioral health and/or medical diagnoses and associated symptoms and/or conditions may be covered under applicable medical and behavioral health benefit plans. Coverage of medications related to the treatment of ADHD is subject to the pharmacy benefit of the applicable benefit plan. When coverage is available, services for the treatment of ADHD are considered medically necessary when the criteria of the Diagnostic and Statistical Manual of Mental Health Disorders, Fifth Edition (DSM-5) are met. Services that are considered primarily educational or training in nature or related to academic or work performance are not covered under many benefit plans. The following services for the assessment and/or treatment of ADHD are considered primarily educational and training in nature and not covered or reimbursable: education and achievement testing, including Intelligence Quotient (IQ) testing • educational intervention (e.g., classroom environmental manipulation, academic skills training, and parental training) Each of the following procedures/services is considered not covered or reimbursable for the assessment and/or treatment of ADHD: Assessment: actigraphy Medical Coverage Policy: 0231 computerized electroencephalogram (EEG) (e.g., brain mapping, neurometrics, or quantitative electroencephalography [QEEG], Neuropsychiatric EEG-Based Assessment Aid [NEBA] System) computerized tests of attention and vigilance • event-related potentials (i.e., evoked potential studies) • hair analysis • neuroimaging (e.g., computerized tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET] and single-photon emission computerized tomography [SPECT]) Quotient ADHD Test/System Treatment: acupuncture/acupressure • anti-candida albicans and antifungal medications • anti-motion sickness medication • auditory integration therapy • brain training/cognitive programs/games • • • dietary treatments • Dore program/Dyslexia Dyspraxia Attention Treatment (DDAT) • EEG biofeedback/neurofeedback • herbal remedies • chiropractic manipulation cognitive rehabilitation intensive behavioral intervention programs (e.g., early intensive behavior intervention [EIBI] intensive behavior intervention [IBI], Lovaas therapy, applied behavior analysis [ABA]) megavitamin therapy • metronome training • movement therapy • Neuro-Emotional Technique (NET) • • • vision therapy sensory integration therapy transcranial magnetic stimulation/cranial electrical stimulation General Background Attention-deficit/hyperactivity disorder (ADHD) is a common disorder of childhood and adolescence that is characterized by symptoms of inattention and/or hyperactivity/impulsivity. In this disorder, the symptoms have persisted for at least six months, to a degree that is maladaptive and inconsistent with developmental level. The hyperactive-impulsive or inattention symptoms that cause impairment are present before age seven, although many individuals are diagnosed after the symptoms have been present for a number of years. Some impairment from the symptoms is present in two or more settings (e.g., at home and at school). The Diagnostic and Statistical Manual of Mental disorders, Fifth edition (DSM-5) notes that there are three subtypes of ADHD (American Psychiatric Association [APA]), 2013): Medical Coverage Policy: 0231 Diagnostic Criteria from Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) for: 314.01 (F90.2) Attention-Deficit/Hyperactivity Disorder, combined type: If both Criterion A1 (inattention) and Criterion A2 (hyperactivity/impulsivity) are met for the past six months. 314.00 (F90.0) Attention-Deficit/Hyperactivity Disorder, predominantly inattentive type: If Criterion A1 (inattention) is met but Criterion A2 (hyperactivity/impulsivity) is not met for the past six months. 314.01 (F90.1) Attention-Deficit/Hyperactivity Disorder, predominantly hyperactive- impulsive type: If Criterion A2 (hyperactivity/impulsivity) 1(inattention) is met but Criterion A1 (inattention) is not met for the past six months. A. A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development as characterized by (1) or (2): 1) Inattention: six (or more) of the following symptoms of inattention have persisted for at least six months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities: Note: The symptoms are not solely a manifestation of oppositional behavior, defiance, hostility, or failure to understand tasks or instructions. For older adolescents and adults (age 17 and older), at least five symptoms are required. a) Often fails to give close attention to details or makes careless mistakes in schoolwork, at work, or during other activities (e.g., overlooks or misses detail, work is inaccurate). b) Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused during lectures, conversations, or lengthy reading). c) Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, even in the absence of any obvious distraction). d) Often does not follow through on instructions and fails to finish school work, chores, or duties in the workplace (e.g., starts tasks but quickly loses focus and is easily sidetracked). e) Often has difficulty organizing tasks and activities (e.g., difficulty managing sequential tasks; difficulty keeping materials and belongings in order; messy, 2) Hyperactivity-impulsivity: six (or more) of the following symptoms of hyperactivity- impulsivity have persisted for at least six months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities: Note: the symptoms are not solely a manifestation of oppositional behavior, defiance, hostility, or a failure to understand tasks or instructions. For older adolescents and adults (age 17 and older), at least five symptoms are required. a) Often fidgets with or taps hands or feet or squirms in seat. b) Often leaves seat when remaining seated is expected (e.g., leaves his or her place in the classroom, in the office or other workplace, or in other situations that require remaining in place). c) Often runs about or climbs in situations in where it is inappropriate (Note: in adolescents or adults, may be limited to feeling restless). d) Often unable to play or engage in leisure activities quietly. e) Is often "on the go" acting as if "driven by a motor" (e.g., is unable to be or uncomfortable being still for extended time, as in restaurants, meetings; may be experienced by others as being restless or difficult to keep up with). f) Often talks excessively. g) Often blurts out an answer before a question has been completed (e.g., completes people’s sentences’ cannot wait for turn in conversation). Medical Coverage Policy: 0231 disorganized work; has poor time management; fails to meet deadlines). f) Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g., schoolwork or homework; for older adolescents and adults, preparing reports, completing forms, reviewing lengthy papers). g) Often loses things necessary for tasks or activities (e.g., school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, mobile telephones). h) Is often easily distracted by extraneous stimuli (for older adolescents and adults, may include unrelated thoughts). i) Is often forgetful in daily activities (e.g., doing chores, running errands, for older adolescents and adults, returning calls, paying bills, keeping appointments). h) Often has difficulty waiting his or her turn (e.g., while waiting in line). i) Often interrupts or intrudes on others (e.g., butts into conversations, games, or activities; may start using other people’s things without asking or receiving permission; for adolescents and adults, may intrude into or take over what others are doing). B. Several inattentive or hyperactive-impulsive symptoms were present prior to age 12 years. C. Several inattentive or hyperactive-impulsive symptoms are present in two or more settings (e.g., at home, school, or work; with friends or relatives; in other activities). D. There is clear evidence that the symptoms interfere with, or reduce the quality of social, academic, or occupational functioning. E. The symptoms do not occur exclusively during the course of schizophrenia or other psychotic disorder and are not better explained by another mental disorder (e.g., mood disorder, anxiety disorder, dissociative disorders, personality disorder, substance intoxication or withdrawal). It should be specified if the condition is in partial remission: when full criteria were previously met, fewer than the full criteria have been met for the past six months, and the symptoms still result in impairment in social, academic or occupational functioning. The severity should be specified: Mild: Few, if any, symptoms in excess of those required to make the diagnosis are present and symptoms results in no more than minor impairments in social or occupational functioning. Moderate: Symptoms or functional impairment between “mild” and “severe” are present. Severe: Many symptoms in excess of those required to make the diagnosis, or several symptoms that are particularly severe, are presents, or the symptoms results in marked impairment in social or occupational functioning. The DSM-5 notes that the designation of “other specified” (DSM-5 code 314.01) (F90.8) applies to presentation in which symptoms characteristic of attention-deficit/hyperactivity disorder that cause clinically significant distress or impairment in social, occupational or other important areas of functioning predominate but do not meet the full criteria for attention-deficit/hyperactivity disorder or any of the disorders in the neurodevelopmental disorders diagnostic class. The other specified attention-deficit/hyperactivity disorder category is used in situations n which the clinician chooses to communicate the specific reason that the presentation does not meet the criteria for attention-deficit/hyperactivity disorder or any specific neurodevelopmental disorder. This is done by recording “other specified attention-deficit/hyperactivity disorder” followed by the specific reason (e.g., “with insufficient inattention symptoms”). Medical Coverage Policy: 0231 The DSM-5 notes that the designation of “not otherwise specified” (NOS) (DSM-5 code 314.01) (F90.9) applies to presentations in which symptoms characteristic of attention-deficit/hyperactivity disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but not meet the full criteria of attention-deficit hyperactivity disorder or any of the disorder in the neurodevelopmental disorders diagnostic class. This should be used in situations in which the clinician chooses not to specify the reason that the criteria are not met for attention-deficit hyperactivity disorder or for a specific neurodevelopmental disorder and includes presentations in which there is insufficient information to make a more specific diagnosis. Health Equity Attention-deficit/hyperactivity disorder is diagnosed less often and medication treatment is used at a lower rate for children from racial and ethnic minority backgrounds, adolescents, and those experiencing poverty (Barbaresi, et al., 2020). It is important for the treating clinician to be aware that parents from different racial and ethnic backgrounds may have differing experiences, perceptions, and attitudes about ADHD and its treatment. Motivational interviewing strategies, assistance in reducing barriers to care, opportunities for social support and problem solving among peers, and increased coaching during behavior therapy may be helpful in improving family engagement and therefore treatment outcomes (Barbaresi, et al., 2020). Similar findings were found in a retrospective U.S. national birth cohort study (Shi, et al., 2021) that utilized insurance claim data to evaluate the impact race and ethnicity has on diagnosis and treatment of ADHD. Out of 238,011 children in the cohort, 48.8% were female, 6.7% were Asian, 6.2% were Black, 9.8% were Hispanic, and 72.7% were white. A total of 11,401 were diagnosed with ADHD. At age 12, White children had the highest incidence of ADHD (14.19%) compared to Black children (11.76%) and Asian children (6.08%). White children were significantly more likely to receive some kind of treatment within the first year after diagnosis (p<0.001) compared to all other groups. The authors stated that the findings are not fully understood and that future studies are needed to determine the reasons behind the disparity. Assessment The diagnosis is clinical, based on findings that are derived from the history, physical and patient/family interviews. There are no specific diagnostic tests for ADHD. The established diagnostic tools used in the assessment of ADHD include: parent/child interview (to rule out other psychiatric or environmental causes of symptoms) • medical evaluation with a complete medical history and physical examination (to assess for co-existing conditions) electroencephalogram (EEG) or neurological consult when the presence of focal signs or clinical findings is suggestive of a seizure disorder or a degenerative neurological condition The use of the DSM-5 criteria is a standard of care for practitioners of all types (e.g., primary care, subspecialty, psychiatry and non-physician mental health providers) to use in the assessment and diagnosis of ADHD (APA, 2013). Diagnosis usually requires several steps, and clinicians will generally need to carry out the evaluation in more than one visit, often two to three visits. The behaviors must adversely affect functioning in school or in a social setting. Information obtained from the parent and school can assist the physician in assessing the effects that the symptoms are having on classroom performance, self-esteem, and family and social relationships. American Academy of Pediatrics (AAP): The AAP published updated clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and Medical Coverage Policy: 0231 adolescents. The guidelines include the following key action statements (Wolraich, et al., 2019) addressing assessment: The pediatrician or other (primary care clinician) PCC should initiate an evaluation for ADHD for any child or adolescent age four years to the 18th birthday who presents with academic or behavioral problems and symptoms of inattention, hyperactivity, or impulsivity. (Grade B: strong recommendation.) To make a diagnosis of ADHD, the PCC should determine that DSM-5 criteria have been met, including documentation of symptoms and impairment in more than one major setting (i.e., social, academic, or occupational), with information obtained primarily from reports from parents or guardians, teachers, other school personnel, and mental health clinicians who are involved in the child or adolescent’s care. The PCC should also rule out any alternative cause. (Grade B: strong recommendation.) In the evaluation of a child or adolescent for ADHD, the PCC should include a process to at least screen for comorbid conditions, including emotional or behavioral conditions (e.g., anxiety, depression, oppositional defiant disorder, conduct disorders, substance use), developmental conditions (e.g., learning and language disorders, autism spectrum disorders), and physical conditions (e.g., tics, sleep apnea). (Grade B: strong recommendation.) Agency for Healthcare Research and Quality (AHRQ): The AHRQ published a Comparative Effectiveness Review titled Attention Deficit Hyperactivity Disorder: Diagnosis and Treatment in Children and Adolescents (Kemper, et al., 2018). (An update is in progress per AHRQ Research Protocol published July 01, 2022.) A total of 19 studies examined the comparative diagnostic accuracy of approaches used to diagnose ADHD. Across the 19 diagnostic comparative studies, 14 different assessment tools were evaluated, including electroencephalography (EEG), integrated visual and auditory computerized performance test (IVA-CPT), continuous performance function tests (CPFT), event-related potentials (ERP), magnetic resonance imaging (MRI) of caudate body volume, Test of Variables of Attention (TOVA), CANTAB, ATTEX, CHEXI, electro interstitial scans (EIS), Disruptive Behavior- Diagnostic Observation Schedule (DB-DOS), neurological subtle signs (NSS), Kiddie-Disruptive Behavior Disorder Schedule (K-DBDS), and Strengths and Difficulties Questionnaire (SDQ). Among executive function tests, Attention and Executive Function Rating Inventory (ATTEX) and Childhood Executive Function Inventory (CHEXI) performed better than Cambridge Neuropsychological Testing Automated Battery (CANTAB) for individuals aged 7–17 (strength of evidence [SOE]=low). This systematic evidence review identified limited studies with variable and inconsistent findings for diagnostic accuracy for all other diagnostics tools evaluated, including imagining and EEG-based tests (SOE=insufficient). UpToDate: According to the literature, several medical screening tests and laboratory measures have been proposed to evaluate children with suspected ADHD. Although some additional testing may be warranted to evaluate comorbid conditions or conditions remaining in the differential diagnosis after the initial assessment, the following evaluations are not routinely indicated to establish the diagnosis of ADHD: Speech and language evaluation (language or communication disorder) • Occupational therapy evaluation (motor coordination disorder) • Mental health evaluation (mood disorder, anxiety, oppositional defiant disorder, conduct disorder, obsessive-compulsive disorder, posttraumatic stress disorder, adjustment disorder) Medical Coverage Policy: 0231 Blood lead level (lead poisoning) • Thyroid hormone levels (thyroid disorder) • Genetic testing and/or genetics consultation (fragile X syndrome) • Overnight polysomnography for children with symptoms suggestive of and/or risk factors for obstructive sleep apnea syndrome, restless legs syndrome, or circadian rhythm disorder Neurology consultation or EEG (electroencephalography; neurologic or seizure disorder) • Psychological or neuropsychological testing – Psychological testing (ie, cognitive and academic testing) is not necessary in the routine evaluation for ADHD and does not distinguish children with ADHD from those without ADHD. It may be recommended in the evaluation for complex ADHD. Quantitative electroencephalography (EEG) is not routinely recommended (UpToDate/Krull, et al., 2023). Federal Drug Administration (FDA): Some assessment tools have received FDA marketing approval. These tests have in common a claim to improve the objectivity of ADHD assessment compared to traditional behavioral rating scales and diagnostic interviews currently widely used by mental health professionals to determine an ADHD diagnosis. These assessment tools are not included in the latest DSM-5 Revision. They are not supported by well-designed, peer-reviewed, large clinical trials or endorsed by professional societies (for example, best practice guidelines of the American Psychological Association or American Academy of Pediatric) (Arns, et al., 2016). Examples include: Neuropsychiatric EEG-Based Assessment Aid (NEBA) System (NEBA Health, Augusta, GA) • Quotient ADHD Test/System (previously OPTAx System) (Pearson Education, Inc., Westford, Massachusetts) QBTest and QbCheck (Qbtech AB, Sweden) Genetic testing: When another condition is present along with ADHD, genetic testing may be considered. While there is ongoing research into the genetic causes of ADHD, it is preliminary and currently there is no established role for genetic testing, in the assessment of this condition. Treatment Types of treatment for ADHD include behavior therapy, including training for parents; and medications. The FDA has approved two types of medications – stimulants and non-stimulants – to help reduce the symptoms of ADHD and improve functioning in children as young as age 6. Examples of FDA approved non-stimulant pharmacotherapy includes Stattera® (atomoxetine), Intuniv (guanfacine), Kapvay (clonidine) and Qelbree® (viloxazine) (FDA, August 2023). In August 2023, the FDA approved several first generics of Vyvanse (lisdexamfetamine dimesylate) capsules and chewable tablets for attention-deficit/hyperactivity disorder (ADHD) in patients six years and older. American Academy of Pediatrics (AAP): The AAP published updated clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. The guidelines include the following key action statements (Wolraich, et al., 2019) addressing treatment: ADHD is a chronic condition; therefore, the PCC should manage children and adolescents with ADHD in the same manner that they would children and youth with special health care needs, following the principles of the chronic care model and the medical home. (Grade B: strong recommendation.) Recommendations for treatment vary depending on the patient’s age and are presented for the following age ranges:  preschool-aged children: age 4 years to the sixth birthday; Medical Coverage Policy: 0231  elementary and middle school–aged children: age 6 years to the 12th birthday; and  adolescents: age 12 years to the 18th birthday. For preschool-aged children (age 4 years to the sixth birthday) with ADHD, the PCC should prescribe evidence-based behavioral PTBM and/or behavioral classroom interventions as the first line of treatment, if available (grade A: strong recommendation). Methylphenidate may be considered if these behavioral interventions do not provide significant improvement and there is moderate-to-severe continued disturbance in the 4- through 5-year-old child’s functioning. In areas in which evidence-based behavioral treatments are not available, the clinician needs to weigh the risks of starting medication before the age of 6 years against the harm of delaying treatment. (Grade B: strong recommendation.) For elementary and middle school–aged children (age 6 years to the 12th birthday) with ADHD, the PCC should prescribe US Food and Drug Administration (FDA)–approved medications for ADHD, along with PTBM and/or behavioral classroom intervention (preferably both PTBM and behavioral classroom interventions). Educational interventions and individualized instructional supports, including school environment, class placement, instructional placement, and behavioral supports, are a necessary part of any treatment plan and often include an Individualized Education Program (IEP) or a rehabilitation plan (504 plan). (Grade A: strong recommendation for medications; grade A: strong recommendation for PTBM training and behavioral treatments for ADHD implemented with the family and school.) For adolescents (age 12 years to the 18th birthday) with ADHD, the PCC should prescribe FDA-approved medications for ADHD with the adolescent’s assent (grade A: strong recommendation). The PCC is encouraged to prescribe evidence-based training interventions and/or behavioral interventions as treatment of ADHD, if available. Educational interventions and individualized instructional supports, including school environment, class placement, instructional placement, and behavioral supports, are a necessary part of any treatment plan and often include an IEP or a rehabilitation plan (504 plan). (Grade A: strong recommendation.) The PCC should titrate doses of medication for ADHD to achieve maximum benefit with tolerable side effects. (Grade B, strong recommendation) The PCC, if trained or experienced in diagnosing comorbid conditions, may initiate treatment of such conditions or make a referral to an appropriate subspecialist for treatment. After detecting possible comorbid conditions, if the PCC is not trained or experienced in making the diagnosis or initiating treatment, the patient should be referred to an appropriate subspecialist to make the diagnosis and initiate treatment. (Grade C, recommendation) Grades of recommendations: grade A: consistent level A studies; • grade B: consistent level B or extrapolations from level A studies; • grade C: level C studies or extrapolations from level B or level C studies. The supplemental information published along with the AAP guidelines includes information regarding complementary and unproven therapies that may include: megavitamins and other dietary alterations, vision and/or visual training, chelation, EEG biofeedback, and working memory (e.g., cognitive training) programs. The report notes, “there is insufficient evidence to suggest that these therapies lead to changes in ADHD’s core symptoms or function. For many complementary and alternative therapies, limited information is available about their safety. Both chelation and megavitamins have been proven to cause adverse effects and are contraindicated. For these reasons, complementary and alternative therapies are not recommended” (AAP 2019). Medical Coverage Policy: 0231 Cochrane Systematic Review: In a Cochrane Review, Storebø et al. (2023) assessed the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. The authors concluded: Our updated meta-analyses suggest that methylphenidate versus placebo or no- intervention may improve teacher-rated ADHD symptoms and general behavior in children and adolescents with ADHD. There may be no effects on serious adverse events and quality of life. • Methylphenidate may be associated with an increased risk of adverse events considered non serious, such as sleep problems and decreased appetite. However, the certainty of the evidence for all outcomes is very low and therefore the true magnitude of effects remain unclear. Due to the frequency of non-serious adverse events associated with methylphenidate, the blinding of participants and outcome assessors is particularly challenging. To accommodate this challenge, an active placebo should be sought and utilized. It may be difficult to find such a drug, but identifying a substance that could mimic the easily recognized adverse effects of methylphenidate would avert the unblinding that detrimentally affects current randomized trials. Future systematic reviews should investigate the subgroups of patients with ADHD that may benefit most and least from methylphenidate. This could be done with individual participant data to investigate predictors and modifiers like age, comorbidity, and ADHD subtypes (Storebø, et al., 2023). Agency for Healthcare Research and Quality (AHRQ): The AHRQ published a Comparative Effectiveness Review: Attention Deficit Hyperactivity Disorder: Diagnosis and Treatment in Children and Adolescents (Kemper, et al., 2018). (An update is in progress per AHRQ Research Protocol published July 01, 2022.) The review included 69 studies related to treatment, and no studies were identified regarding monitoring. Findings included: Limited additional evidence published since the original 2011 report was available on ADHD medications approved by the Food and Drug Administration (FDA) compared with placebo or compared to different FDA-approved ADHD medications (SOE=insufficient). For atomoxetine and methylphenidate, the most commonly reported adverse events were somnolence and mild gastrointestinal problems. Atomoxetine had slightly higher gastrointestinal effects than methylphenidate (SOE=low). Cognitive behavioral therapy improved ADHD symptoms (SOE=low). • Child or parent training improved ADHD symptoms (SOE=moderate) but made no difference in academic performance (SOE=low). Omega-3/6 fatty acid supplementation made no difference in ADHD symptoms (SOE=moderate). Across all treatments, little evidence was reported on the risk of serious adverse events, including cardiovascular risk. The review concluded that this targeted update found insufficient evidence regarding new approaches to the diagnosis (e.g., EEGs, neuroimaging). The authors noted that although cognitive behavioral therapy or child or parent training may decrease symptoms of ADHD, more information is needed regarding the relative benefit of these approaches compared to, or combined with, medication treatment; Omega-3/6 supplementation does not appear to improve ADHD outcomes; and, no information was identified regarding the optimal strategy for monitoring after diagnosis. Definition of strength of evidence grades: Medical Coverage Policy: 0231 Moderate: moderately confident that the estimate of effect lies close to the true effect for this outcome. The body of evidence has some deficiencies. The findings are likely to be stable, but some doubt remains. Low: limited confidence that the estimate of effect lies close to the true effect for this outcome. The body of evidence has major or numerous deficiencies (or both). The authors believe that additional evidence is needed before concluding either that the findings are stable or that the estimate of effect is close to the true effect. Insufficient: no evidence, unable to estimate an effect, or have no confidence in the estimate of effect for this outcome. No evidence is available, or the body of evidence has unacceptable deficiencies, precluding reaching a conclusion. Cochrane Systematic Review: In a Cochrane Review, Eaton et al. (2022) assessed the effect of stimulant and non-stimulant drugs on children and adults with ADHD and co-occurring epilepsy because ADHD can co-occur in up to 40% of people with epilepsy. The authors concluded: In children with a dual-diagnosis of epilepsy and ADHD, there is some evidence that use of the stimulant drug osmotic-release oral system methylphenidate (OROS-MPH) is not associated with significant worsening of epilepsy, but higher doses of it may be associated with increased daily risk of seizures; the evidence is of low-certainty. OROS-MPH is also associated with improvement in ADHD symptoms. However, this treatment was also associated with a large proportion of treatment withdrawal compared to placebo. In relation to the non-stimulant drug omega-3, there is some evidence for reduction in seizure frequency in children who are also on risperidone and ASM, compared to children who are on risperidone and ASM alone. Evidence is inconclusive whether omega-3 increases or decreases the risk of adverse drug events. We identified only two studies – one each for OROS-MPH and omega-3 – with low to high risk of bias. We assessed the overall certainty of evidence for the outcomes of both OROS- MPH and omega-3 as low to moderate. More studies are needed. Future studies should include: 1. adult participants; 2. a wider variety of stimulant and non-stimulant drugs, such as amphetamines and atomoxetine, respectively; and 3. additional important outcomes, such as seizure-related hospitalizations and quality of life. Clusters of studies which assess the same drug – and those that build upon the evidence base presented in this review on OROS-MPH and omega-3 – are needed to allow for meta-analysis of outcomes (Eaton, et al., 2022). Cochrane Systematic Review: In a Cochrane Review, Storebø et al. (2019) assessed the beneficial and harmful effects of social skills training in children and adolescents (aged 5 to 18 years) with ADHD. The review included 25 randomized clinical trials described in 45 reports. The trials included a total of 2690 participants aged between five and 17 years. In 17 trials, participants were also diagnosed with various comorbidities. The social skills interventions were described as: 1) social skills training, 2) cognitive behavioral therapy, 3) multimodal behavioral/ psychosocial therapy, 4) child life and attention skills treatment, 5) life skills training, 6) the "challenging horizon program", 7) verbal self instruction, 8) meta-cognitive training, 9) behavioral therapy, 10) behavioral and social skills treatment, and 11) psychosocial treatment. The control interventions were no intervention or waiting list. The duration of the interventions ranged from five weeks to two years. The authors found no significant differences between social skills training versus controls on social skills, emotional competencies, and general behavior as assessed by teachers. Compared with the children who had no social skills training, teachers rated those who had been in the social skills groups as having fewer ADHD symptoms at the end of treatment. Medical Coverage Policy: 0231 However, this finding was questionable because our other analyses did not support it. We found no indications of harmful effects. All trials suffered from methodological problems such as overestimation of benefits and underestimation of harms. Many studies were also difficult to compare because they involved different interventions. The authors summarized that they were unable to conclude whether social skills training is beneficial or not for children with ADHD, noting the need for more randomized clinical trials on social skills training for children and adolescents with ADHD that have a sufficient number of participants and higher methodological quality. The evidence base regarding adolescents is especially weak (Storebø, et al., 2019). Cochrane Systematic Review: In a Cochrane Review, Gillies et al. (2023) compared the efficacy of polyunsaturated fatty acids (PUFA) to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents. The total number of studies included in the review to 37, including 2374 children and adolescents with ADHD. Thirty-six studies compared PUFA to placebo. Treatment with PUFA lasted between two weeks and six months. The authors noted that although there was some evidence that PUFA could improve ADHD symptoms in children and adolescents, most of the evidence indicated that PUFA did not improve ADHD symptoms such as inattention or hyperactivity-impulsivity. PUFA probably makes little to no difference to overall side effects or whether a person drops out of a study (i.e. does not complete it). The authors stated they are confident that PUFA has no effect on ADHD symptoms when compared to placebo. Although there was some evidence that ADHD symptoms may be more likely to improve in children and adolescents receiving PUFA compared to those receiving placebo, The authors stated they have little confidence in this finding (Gillies, et al., 2023). Agency for Healthcare Research and Quality (AHRQ): The AHRQ published a comparative effectiveness review: Attention Deficit Hyperactivity Disorder: Effectiveness of Treatment in At- Risk Preschoolers; Long-Term Effectiveness in All Ages; and Variability in Prevalence, Diagnosis, and Treatment (Charach, 2011). The conclusions of the review include: Overall, the most information about long-term outcomes applies to boys ages 7 to 9 years at intervention. Preschoolers with diagnosed ADHD, girls, teenagers, and adults have rarely been the focus of intervention research. Parent behavior training for preschoolers is efficacious and benefits appear to last, although many parents drop out of treatment. Medications can be efficacious in preschoolers but are not as well tolerated as in children over 6 years of age, or in adults. In addition, parents show decreasing adherence to medication use for their children over 12 months despite effectiveness. For children over 6 years of age, teenagers, and adults, medications remain the most thoroughly researched interventions, with most studies sponsored by industry. In addition to psychostimulant medications, two additional pharmacologic agents, atomoxetine (ATX) and guanfacine extended release (GXR), have been studied and appear effective and safe for one or more years at a time, with differing adverse event profiles. Classroom teacher-based interventions can improve academic and classroom behavior outcomes for both preschoolers and primary school children, but difficulties re-emerge 1 to 2 years following discontinuation of the intervention. For some subgroups of children, additional benefit may derive from combined medication and behavioral interventions, but not for all. There remains a lack of clarity about how long treatment may be required, of what type, and for whom. Medical Coverage Policy: 0231 For some, incremental improvement accrues with continued intervention over years; for others, medication interventions can be discontinued without symptom relapse. However, these observations are difficult to evaluate due to the absence of information regarding specific subgroups receiving treatment and details regarding co-interventions. Other Treatments American Academy of Pediatrics (AAP): The AAP published updated clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. The guidelines include the following key action statements (Wolraich, et al., 2019) addressing treatment. The supplemental information published along with the AAP guidelines includes information regarding complementary and unproven therapies that may include: megavitamins and other dietary alterations, vision and/or visual training, chelation, EEG biofeedback, and working memory (e.g., cognitive training) programs. The report notes, “there is insufficient evidence to suggest that these therapies lead to changes in ADHD’s core symptoms or function. For many complementary and alternative therapies, limited information is available about their safety. Both chelation and megavitamins have been proven to cause adverse effects and are contraindicated. For these reasons, complementary and alternative therapies are not recommended” (AAP 2019). Acupuncture/Acupressure: Evidence on the effectiveness of acupuncture therapy for ADHD patients is currently too limited to provide recommendations for its usage. More studies with the proper methodology are needed for the validation of AT interventions in treating children with ADHD (Ang, et al., 2023). Please refer to Cigna Coverage Policy Acupuncture (CPG 024) for additional information. Brain Training Games/Cognitive Training Programs: There is an increased interest in the use of computer-based cognitive training as a treatment of ADHD. Brain training video games are also being studied as treatment for symptoms of ADHD. These programs are computer-based and purport to improve cognitive, behavior and academic ability in ADHD. The duration of training session, number of sessions and frequency vary according to the specific protocol employed, although they typically involve a large number of sessions spread over several weeks. Training may be implemented at school, home, or clinic/research facility. The programs include but are not limited to: Project: EVO (Akili Interactive Labs, Boston,MA): computer game that purports to provide a targeted way to potentially improve cognition and disease symptoms through at-home videogame play. It is currently undergoing trials to validate each product in a variety of specific patient populations. Cogmed Working Memory Training® (Pearson Education, Indianapolis, IN): a computer- based program for attention problems caused by poor working memory. CogniPlus (Schuhfried, Austria): computer based program that is designed for training cognitive functions. RehaCom (Magdeburg, Germany): computer based program for cognitive therapy in areas of alertness, attention, memory, executive functions, visual Field, neglect Rapport et al. (2013) reported on a meta-analysis of 25 studies of facilitative intervention training (i.e., cognitive training) for children with ADHD on cognitive, academic, and behavioral outcomes. Inclusion criteria included that pre- and post-treatment metrics for dependent measures from which an effect size could be estimated were reported. Exclusion criteria included repeat data, single subject designs, non-empirical/review articles, and non-English articles. Random effects models corrected for publication bias and sampling error revealed that studies training short-term Medical Coverage Policy: 0231 memory alone resulted in moderate magnitude improvements in short-term memory, while training attention did not significantly improve attention, and training mixed executive functions did not significantly improve the targeted executive functions (both nonsignificant: 95% confidence intervals). Far transfer effects of cognitive training on academic functioning, blinded ratings of behavior (both nonsignificant), and cognitive tests were nonsignificant or negligible. Unblinded raters reported significantly larger benefits relative to blinded raters and objective tests. Critical examination of training targets revealed incongruence with empirical evidence regarding the specific executive functions that are most impaired in ADHD, and functionally related to the behavioral and academic outcomes these training programs are intended to ameliorate. The authors concluded that collectively, meta-analytic results indicate that claims regarding the academic, behavioral, and cognitive benefits associated with extant cognitive training programs are unsupported in ADHD. A review of the published literature for computerized cognitive training approaches, (e.g., working memory training) targeting both the symptoms and the underlying neuropsychological deficits in patients with attention-deficit/hyperactivity disorder (ADHD) (Sonuga-Barke et al. 2014). The review examined 14 randomized controlled trials (RCTs) with ADHD outcomes. the authors note given the inconsistency of extant findings, increased evidence from well-blinded trials are required before cognitive training can be supported as a frontline treatment of ADHD. The review concludes that future research should focus on ways to improve the content and implementation, and increase the scope, of these potentially therapeutic approaches. Dore Program/Dore Program for Attention Deficit Disorder: The Dore program, also known as Dore Program for Attention Deficit Disorder, or Dyslexia Dyspraxia Attention Treatment (DDAT), is an exercise-based program that was originally developed to treat dyslexia. The program is aimed at treating dyslexia, ADHD, dyspraxia and Asperger’s Syndrome. The program consists of a specialized neurological evaluation and series of patient-specific exercises designed to simulate the cerebellum or “hind brain.” The proponents of this program theorize that cerebellar size and function are related to a constellation of learning disorders that are referred to as cerebellar developmental delay (CDD). A review of this treatment (Bishop, 2007) notes that published studies regarding this program “are seriously flawed.” The review notes that two studies were published regarding this treatment for children with dyslexia. Regarding the use of the Dore program for ADHD, the review notes that, “There is nothing here to justify the claims made that the Dore Programme is more effective than state-of-the-art medication for ADHD, especially in view of the fact that only one child in the study had an ADHD diagnosis.” There is insufficient evidence to support the efficacy of the Dore program for treatment of ADHD. EEG Biofeedback/Neurofeedback: The AAP (2019) notes that there is insufficient evidence to suggest that these therapies (including EEG) lead to changes in ADHD’s core symptoms or function. Barth et al. (2021) conducted a randomized-controlled neurofeedback trial in adult patients with ADHD. the authors aimed to compare slow cortical potential (SCP)- and functional near-infrared spectroscopy (fNIRS) NF to a semi-active electromyography biofeedback (EMG-BF) control condition regarding changes in symptoms and the impact of learning success, as well as changes in neurophysiological parameters in an adult ADHD population. The patients were randomly assigned to SCP-NF (n = 26), fNIRS-NF (n = 21) or EMG-BF (n = 20). Outcome parameters were assessed over 30 training sessions (pre, intermediate, post) and at six-months follow-up (FU) including three booster sessions. EEG was recorded during two auditory Go/NoGo paradigms assessing the P300 and contingent negative variation (CNV). fNIRS measurements were conducted during an n-back- as well as a Go/NoGo task. All three groups showed equally significant symptom improvements suggesting placebo- or non-specific effects on the primary outcome measure. Only when differentiating between learners and non-learners, fNIRS learners Medical Coverage Policy: 0231 displayed stronger reduction of ADHD global scores compared to SCP non-learners at FU, and fNIRS learners showed specifically low impulsivity ratings. 30.8% in the SCP-NF and 61.9% of participants in the fNIRS-NF learned to regulate the respective NF target parameter. The authors concluded that some adults with ADHD learn to regulate SCP amplitudes and especially prefrontal hemodynamic activity during NF. There was no significant differences in outcome between groups when examining the whole sample; when evaluating learners only, there appeared to be superior effects as compared to non-learners. The study is limited by the small number of participant and lack of blinding. Cortese et al. (2016) performed meta-analyses of randomized controlled trials to examine the effects of neurofeedback on ADHD symptoms and neuropsychological deficits in children and adolescents with ADHD. The review included 13 trials (520 participants). Significant effects were found on ADHD symptoms rated by assessors most proximal to the treatment setting, that is, the least blinded outcome measure (standardized mean difference [SMD]: ADHD total symptoms = 0.35, 95% CI = 0.11−0.59; inattention = 0.36, 95% CI = 0.09−0.63; hyperactivity/impulsivity = 0.26, 95% CI = 0.08−0.43). Effects were not significant when probably blinded ratings were the outcome or in trials with active/sham controls. Results were similar when only frequency band training trials, the most common neurofeedback approach, were analyzed separately. Effects on laboratory measures of inhibition (SMD = 0.30, 95% CI = −0.10 to 0.70) and attention (SMD = 0.13, 95% CI = −0.09 to 0.36) were not significant. In most studies it was found that the risk of bias was unclear for many Cochrane Risk of Bias domains. The authors concluded that evidence from well-controlled trials with probably blinded outcomes currently fails to support neurofeedback as an effective treatment for ADHD and that future efforts should focus on implementing standard neurofeedback protocols, ensuring learning, and optimizing clinically relevant transfer. Intensive Intervention Programs: Intensive intervention programs, also known as early intensive behavior intervention (EIBI) intensive behavior intervention (IBI), Lovaas therapy, and applied behavior analysis {ABA}. These programs incorporate behavior modification and applied behavior analysis. The programs were developed initially to treat children with autism spectrum disorders (ASD) and have recently been proposed to treat children with learning disabilities and ADHD. These programs may be prescribed by school systems as an intervention that is part of the individualized educational plan (IEP). The program is intensive and usually involves hours of treatment (usually more than 15 hours per week) delivered over a long period of time. There is a lack of scientific evidence to support the efficacy of the programs for ADHD. Please refer to EVERNORTH Behavioral Health Coverage Policy on Intensive Behavioral Interventions (EN0499) for additional information. Neuro Emotional Technique (NET): NET has been described as methodology of finding and removing Neuro Emotional Complexes (NECs) which are defined as a subjective maladaptation syndrome adopted by the organism in response to a real or perceived threat to any aspect of its survival (Karpouzis, et al., 2009). NET has been proposed as a treatment designed to address negative distressing stimuli, by removing these patterns by accessing the nervous system via stimulation of the spine. It was first developed as a branch of chiropractic care, but is now being provided by other practitioners such as psychologists and licensed acupuncturists to treat many other disorders including ADHD. It is purported that there is a mind-body connection with these conditions that can be corrected with NET. There is insufficient evidence in published peer- reviewed scientific literature to support the efficacy of this treatment for ADHD. Transcranial magnetic stimulation (TMS)/cranial electrical stimulation (CMS): There is insufficient evidence in the published peer-reviewed literature to support the efficacy of TMS/CES for treatment of ADHD Medical Coverage Policy: 0231 A systematic review (Westwood, et al., 2020) examined repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) for a treatment alternative to stimulant medication for attention-deficit/hyperactivity disorder (ADHD). The review found that rTMS and tDCS showed positive effects in some functions but not others, and little evidence for clinical improvement and that the meta-analyses of one to five sessions of anodal tDCS over mainly the left or bilateral dlPFC showed trend-level improvements in inhibition and processing speed, but not in attention. The studies were limited by heterogeneity in stimulation parameters, patient age and outcome measures limited the interpretation of findings. Leffa et al. (2022) conducted a randomized controlled trial to evaluate the efficacy of tDCS on the treatment of inattention in adults (n=64) with ADHD. The mean age of participants was 38.3 years (18–60 years) with 47% being female. Adult participants were included if they had a diagnosis of ADHD with an inattentive or combined subtype and symptoms rated as moderate or severe according to the clinician-administered version of the Adult ADHD self-report scale version 1.1 (CASRS-I). Patients were excluded if they: currently used stimulant drug treatment, had current moderate to severe symptoms of depression or anxiety, had a diagnosis of bipolar disorder with a manic or depressive episode in the last year, had a diagnosis of a psychotic disorder (e.g., schizophrenia), or had a diagnosis of autism spectrum disorder. The intervention consisted of 30 minute daily sessions of home-based tDCS for four weeks totaling 28 sessions. Sham tDCS served as the comparator. The primary outcome evaluated was inattention scores as measured by the CASRS-I. Fifty-five participants completed follow-up at four weeks. A significant reduction in CASRS-I scores was noted in the intervention group compared to the sham group (p<0.001) at four weeks. Adverse events were reported as mild and included skin redness, headache, and scalp burn in the intervention group. Author noted limitations of the study included patient attrition and inability to generalize the findings to the general population (e.g., those taking stimulant or non-stimulant medications or with comorbid psychiatric conditions). Additional limitations included the small patient population and short-term follow-up. Additional, high-quality studies are needed to establish the safety and efficacy of tDCS for the treatment of inattention in patients diagnosed with ADHD. Please refer to EVERNORTH Behavioral Health Coverage Policy on Transcranial Magnetic Stimulation (EN0383) for additional information. Adult ADHD While ADHD is well studied in children, it is less studied in adults. An estimated 4.4% of adults aged 18-44 have ADHD. Although comorbid psychiatric disorders are common in both adults and children, the comorbidity rate is higher in adults; as many as 80% of adults with ADHD are reported to have at least one comorbid psychiatric disorder. In clinical adult ADHD samples, substance use disorder (SUD), mood disorder, anxiety disorder, and antisocial personality disorder (ASPD) are the most common comorbid disorders. A recent systematic literature review noted a higher prevalence of comorbid psychiatric disorders in adult ADHD subjects compared to non- ADHD adult subjects, whether they were previously diagnosed with other psychiatric disorders or not. Furthermore, their results suggested a complex association between the multiple comorbidities of ADHD (National Alliance on Mental Illness, 2023; Choi, et al., 2022). Unlike treatment for childhood ADHD, treatment for adult ADHD has not been well-established by randomized, controlled trials, nor are there any published treatment guidelines. Support groups, such as Children and Adults with Attention-Deficit/ Hyperactivity Disorder (CHADD) assist newly diagnosed adults by providing information about ADHD and available resources, including peer support groups. Coaching and training in organizational skills appear useful but remain unstudied (Goroll, 2009). Medical Coverage Policy: 0231