Complementary and Alternative Treatments for ADHD: What the Evidence Suggests

©Donskarpo

Premiere Date: October 20, 2019
Expiration Date: April 20, 2021

This activity offers CE credits for:
1. Physicians (CME)
2. Other

All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.

ACTIVITY GOAL

The goal of this activity is to provide an understanding of the evidence for the use of complementary and alternative (CAM) treatments for ADHD.

LEARNING OBJECTIVES

At the end of this CE activity, participants should be able to:

• Discuss the limitations of conventional treatment and how CAM therapies are used as adjuncts to stimulants;

• Describe the effects of certain food products and how they might affect ADHD symptoms as well as the evidence for the use of the oligoantigenic diet;

• Explain EEG biofeedback protocols and the strategies to address various symptoms of ADHD;

• Identify which nutritional and herbal supplements have the best evidence for treating symptoms of ADHD.

TARGET AUDIENCE

This continuing medical education activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

CREDIT INFORMATION

CME Credit (Physicians): This activity has been planned and implemented in accordance with the Essential Areas and policies of the
Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of CME Outfitters, LLC, and Psychiatric Times. CME Outfitters, LLC, is accredited by the ACCME to provide continuing medical education for physicians.

CME Outfitters designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Note to Nurse Practitioners and Physician Assistants: AANPCP and AAPA accept certificates of participation for educational activities certified for AMA PRA Category 1 Credit™.

DISCLOSURE DECLARATION

It is the policy of CME Outfitters, LLC, to ensure independence, balance, objectivity, and scientific rigor and integrity in all of their CME/CE activities. Faculty must disclose to the participants any relationships with commercial companies whose products or devices may be mentioned in faculty presentations, or with the commercial supporter of this CME/CE activity. CME Outfitters, LLC, has evaluated, identified, and attempted to resolve any potential conflicts of interest through a rigorous content validation procedure, use of evidence-based data/research, and a multidisciplinary peer-review process.

The following information is for participant information only. It is not assumed that these relationships will have a negative impact on the presentations.

James Lake, MD, has received received travel support from Blackmores Institute Visiting Fellowship and royalty payments from Norton, American Psychiatric Publishing, Thieme Medical, and Blue Poppy Press.

Professor Sarris has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from Integria Healthcare & MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Grunbiotics, Australian Natural Therapies Group, Kantar Consulting, Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship. He also receives support from a NHMRC Clinical Research Fellowship (APP1125000).

Patricia Gerbarg, MD, (peer/content reviewer) has no disclosures to report.

Applicable Psychiatric Times staff and CME Outfitters staff have no disclosures to report.

UNLABELED USE DISCLOSURE

Faculty of this CME/CE activity may include discussion of products or devices that are not currently labeled for use by the FDA. The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational uses (any uses not approved by the FDA) of products or devices. CME Outfitters, LLC, and the faculty do not endorse the use of any product outside of the FDA-labeled indications. Medical professionals should not utilize the procedures, products, or diagnosis techniques discussed during this activity without evaluation of their patient for contraindications or dangers of use.

For content-related questions email PTEditor@mmhgroup.com; for CME credit questions call 877.CME.PROS (877.263.7767) Call us at 877.CME.PROS (877.263.7767)

Recent surveys suggest that 7% to 8% of children and 4% to 5% of adults meet ADHD criteria.^1,2 The rate at which ADHD is diagnosed and treated has increased dramatically since the syndrome was recognized by DSM as a specific disorder in the 1970s. It is estimated that fewer than 20% of adults with ADHD have had a correct diagnosis and have thus incurred significant social and occupational risk. Almost half of those who have ADHD never graduate from high school and fewer than 5% complete a 4-year university degree program.³ A diagnosis of ADHD has been associated with 35 days of lost work on average per year, which suggests US$19 billion in lost productivity and 120 million lost work days annually.⁴

Limitations of conventional treatment

Because stimulants are usually classified as scheduled or restricted medications (depending on the country), prescriptions are often limited to a small supply, which results in treatment interruptions and transient worsening of when refills are not obtained on timely basis. Adverse effects of stimulants include insomnia, decreased appetite, abdominal pain as well as occasional stimulant-induced psychosis; chronic use can increase the risk for slow growth. Moreover, stimulants and other pharmacologic treatments for adult ADHD may be only half as effective as they are in children.

Controlled-release stimulants, bupropion, and the SSRI antidepressants are being increasingly used in the adult ADHD population, however these medications may not be as efficacious as stimulants. Although atomoxetine is FDA-approved for the treatment of childhood ADHD, there are growing concerns about its adverse effects, including hypertension, tachycardia, nausea and vomiting, liver toxicity, and possibly increased risk of suicide.

CAM therapies are widely used to treat ADHD

Growing concerns about inappropriate prescribing or over-prescribing of stimulant medications and the incomplete understanding of risks associated with their long-term use have led to increasing acceptance of complementary or alternative medicine (CAM) therapies. CAM therapies in children with ADHD are used largely out of parental concerns over prescription drug safety. CAM therapies, including vitamins/minerals, dietary changes, and expressive therapies, are used although parents rarely disclose this to the child’s doctor. Although there is limited evidence to support most CAM therapies for treating ADHD, it is highly regarded by many patients’ parents.

Dietary modification

Early studies suggested that artificial food colors were associated with ADHD; however, a meta-analysis of studies spanning a 35-year period failed to confirm this relationship.⁵ One such diet, the oligoantigenic diet (OAD), is a highly restrictive multiple elimination diet that excludes food colors and additives, in addition to dairy products, sugar, wheat, corn, citrus, eggs, soy, yeast, nuts, and chocolate. The diet permits a limited number of hypo­allergenic foods like lamb, chicken, potatoes, rice, bananas, apples, cabbages, broccoli, brussels sprouts, carrots, peas, pears, and cucumber, as well as salt, pepper, calcium, and some vitamins. Reductions in hyperactivity were seen in children who were on the OAD regimen when specific food items were eliminated from the diet.⁶ Behavioral symptoms improved during the elimination and placebo phases and recurred when children were subsequently challenged with the eliminated food item.

Roughly one-third of hyperactive children may benefit from some form of an elimination diet.⁵ Although these findings are promising, they cannot be used to develop general ADHD treatment protocols because of study design flaws, including heterogeneity of patient populations, absence of standardized outcome measures, high dropout rates and, in some studies, non-blinded researchers.

The American Academy of Pediatrics does not endorse elimination diets because of inconsistent efficacy findings as well as concerns that highly restrictive diets do not provide balanced nutrition. Parents who are considering restrictive diets should consult with a qualified nutritionist. Highly restrictive diets should not be continued for longer than two weeks in the absence of noticeable improvements in ADHD symptoms.

EEG biofeedback

Many individuals with ADHD have abnormal patterns of brain electrical activity, including under-arousal in the frontal and midline cortical regions. Electroencephalogram (EEG) biofeedback is aimed at normalizing EEG activity to correct the brain’s state of relative under-arousal and improve cognitive and behavioral functioning. Two EEG biofeedback protocols have been extensively evaluated as treatments of ADHD.

Sensorimotor rhythm (SMR) training reinforces EEG activity in the faster beta frequency range (16-20 Hz) in the midline cortical regions, with the goal of reducing symptoms of impulsivity and hyperactivity. Theta suppression reduces EEG activity in the slower theta frequency range (4 to 8 Hz) and is primarily used to treat symptoms of inattention. An EEG biofeedback protocol directed at suppressing theta activity (4 to 8 Hz) over the midline regions is probably the most effective strategy when treating primarily symptoms of distractibility and inattention.

Controlled studies that compared EEG biofeedback with a stimulant medication versus a waitlist showed positive clinical effects and EEG normalization; however, it is not yet established whether improved alertness is associated with increased or decreased alpha activity (12 to 18 Hz).^7,8 A review of 14 randomized neurofeedback trials in children with ADHD consistently showed beneficial outcomes.⁹ Findings of neurofeedback research are limited by small study sizes, heterogeneous populations, absence of a control group, inconsistent outcome measures, and limited or absent follow-up. The potential benefits of neurofeedback are limited by expensive treatments that are seldom covered by insurance.

Nutritional supplements

Children with ADHD have lower plasma concentrations of certain essential fatty acids (EFAs). However, findings from controlled trials of supplemented EFAs in ADHD are inconsistent. One study found no differential benefit of EFAs compared with stimulants.¹⁰ In another study, parents of children in the EFA-treatment group (n = 104) reported more improvement than parents of children who received a palm oil placebo.¹¹ This study has been criticized because a high dropout rate confounds findings in a positive direction. A meta-analysis (including studies from 1965 to 2010) confirmed positive effects of adjunctive EFAs in childhood ADHD; however, therapeutic benefits were significantly less compared with conventional pharmacological treatments.¹²

The use of olive oil as a placebo in certain studies may mask the beneficial clinical effects of EFAs because an active constituent of olive oil is converted into oleamide, which is known to affect brain function. Furthermore, the short durations and low doses of EFAs used in most studies may not be adequate to result in the long-term changes in neuronal membrane structure required for clinical improvement.

Some children with ADHD have abnormally low plasma zinc levels, which may interfere with optimal information processing and thereby result in difficulties maintaining attention. However, findings on zinc supplementation are inconsistent. In a large 12-week prospective controlled trial, children and adolescents randomized to zinc (150 mg/d) experienced significant improvements in hyperactivity and impulsivity over placebo but not inattention.¹³ However, a high dropout rate limited the significance of these findings. In contrast to these findings a more recent placebo-controlled study failed to show efficacy.¹⁴

Abnormally low serum ferritin levels may be associated with hyperactivity in children with non-anemic ADHD, but not with deficits in cognitive performance. A 2012 systematic review of studies on iron in children with ADHD found mixed results in the relationship between serum iron levels and symptom severity as well as inconsistent responses of ADHD symptoms to iron supplementation.

The amino acid acetyl-L-carnitine (ALC) is required for energy metabolism and synthesis of fatty acids. L-carnitine may significantly reduce the severity of ADHD symptoms; however, inconsistent findings and design flaws limit the significance of these findings. In a multisite 16-week pilot study, 112 children with ADHD were randomized to placebo versus ALC (500 to 1500 mg bid). Children in the ALC group with predominantly inattentive-type ADHD experienced greater improvement over placebo, but there was no differential benefit in children with combined-type ADHD.¹⁵

In a six-week placebo-controlled trial, children and adolescents were randomized to ALC (doses ranged from 500 to 1500 mg/d depending on weight) plus methylphenidate (20 to 30 mg/d) versus placebo plus methylphenidate. At the end of the study no differences were observed between the groups.¹⁶

Herbal supplements

The bioactive constituents of saffron may increase reuptake inhibition of dopamine and norepinephrine and may function as both N-methyl-D-aspartic acid (NMDA) receptor antagonists and gamma-aminobutyric acid (GABA)-a agonists.

In a six-week randomized double-blind study children and adolescents aged 6 to 17 years were randomized to methylphenidate (20 to 30 mg/d) or saffron capsules (20 to 30 mg/d). Participants who received saffron capsules showed equivalent improvement on both parent and teacher symptom rating scales.¹⁷ Both treatments were well tolerated. Large long-term placebo-controlled studies are needed to confirm these findings and to investigate the efficacy of saffron in individuals with comorbid mood and anxiety disorders.

In a four-week open label study, an herbal preparation containing Ginkgo biloba and Panax quinquefolium was added to existing ADHD medication.¹⁸ Beneficial effects were observed in 18 children (53%) taking the herbal combination after four weeks. However, the absence of a control group and the small size of the study limit the significance of these findings.

Other findings suggest that a standardized extract of Pinus pinaster (pycnogenol) bark may be beneficial for ADHD; however, only one controlled study has been published.¹⁹ Children and adolescents who received pycnogenol for one month experienced non-significant improvements in inattention, improved visual-motor coordination; however, no improvements were seen in symptoms of hyperactivity. Symptoms returned to pretreatment baseline levels after a one-month wash-out. Only one case of mild gastric discomfort was reported. These findings should be regarded as preliminary pending replication by large prospective studies.

In addition to singular vitamins or herbal medicines, various proprietary herbal and nutrient formulas have been used to treat ADHD; however, little research evidence supports their use. A four-month randomized double-blind placebo-controlled trial evaluated the efficacy of a patented, compound herbal preparation (Nurture and Clarity) in improving attention, cognition and impulse control in children (n = 120) with newly diagnosed ADHD.²⁰ At study end those who received the herbal formula showed statistically significant improvement in symptoms of inattention, impulse control and cognition in all four subscales of the test of variables of attention (TOVA) compared with no improvement in the control group. The herbal formula was well tolerated. These findings should be regarded as preliminary pending confirmation by large prospective placebo-controlled studies.

Acupuncture

A 2010 meta-analysis of acupuncture for ADHD revealed three studies that met inclusion criteria for sufficient methodological rigor and sample size.²¹ Positive results were seen with electroacupuncture given concurrently to behavioral therapy. A meta-analysis of two other studies of somatic acupuncture or auricular acupuncture combined with drug therapy showed significant differential effects of combined treatment.²² The findings, however, were inconclusive because of the small study size, its short duration (less than one month), the absence of blinding, and the absence of an intention-to-treat analysis.

Meditation and yoga

In a systematic review of studies on meditation and mind-body practices (eg, yoga, Tai chi, Qi gong) to treat ADHD, only four studies (83 participants total) met inclusion criteria for methodological rigor and sample size.²³ Two studies evaluated mantra meditation and two studies compared yoga with conventional drugs, relaxation training, non-specific exercise, or treatment as usual. However, design problems resulted in a high risk of bias in all studies and identified only one study that met criteria for formal analysis. In that small study (n = 15) the teacher rating ADHD scale failed to show significant outcome differences between the meditation group and the drug therapy group.²⁴

In a small pilot study (n = 19), children in a yoga group experienced greater improvement in symptoms over time compared with children who exercised. Children who continued on stimulants while practicing yoga experienced the greatest improvements.²⁵ Two small controlled studies suggest that yoga and regular massage therapy may reduce the severity of ADHD symptoms.^26,27

Summary and clinical recommendations

When stimulants fail to result in significant reductions in symptom severity or when adverse effects, toxicities, or comorbid substance abuse preclude their use, EEG biofeedback and select evidence-based CAM treatments may be considered. Restrictive diets are reasonable interventions in cases where impulsivity and distractibility may be related to sugar intake or food allergies. Parents of children with ADHD should first consult their child’s pediatrician before initiating a strict dietary regimen, and ideally with a qualified nutritionist who can provide them with expert guidance should be consulted.

When therapeutic doses of stimulants cannot be achieved with acceptable tolerance, the adjunctive use of EFAs and select herbals including Ginkgo biloba, Panax quinquefolium, Pinus pinaster, and Bacopa monnieri may improve response. The adjunctive use of acetyl-L-carnitine, zinc, and iron may be beneficial in some cases; however, these treatments are not substantiated by strong research findings. Regular yoga and massage therapy may help improve attention and hyperactivity in some cases. When a person diagnosed with ADHD fails to respond to pharmacological and CAM treatments it is prudent to rule out confounding psychiatric disorders, including learning disorders, depressed mood, and anxiety disorders, which are frequently comorbid with the syndrome and may interfere with treatment outcomes.

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Disclosures:

Dr Lake is a Psychiatrist in private practice in California; he is the author of An Integrative Paradigm for Mental Health Care: Ideas and Methods Shaping the Future. Professor Sarris is Deputy and Research Director, NICM Health Research Institute, Westmead, New South Wales and an honorary Principle Research Fellow, Professorial Unit, The Melbourne Clinic, Department of Psychiatry, Melbourne University, Richmond, VIC, Australia.

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