Attention Deficit/Hyperactivity Disorder (ADHD)

Attention Deficit/Hyperactivity Disorder (ADHD)

1 Overview

Summary and Quick Facts

  • The diagnosis of attention deficit/hyperactivity disorder (ADHD) is controversial and evokes passionate debate among healthcare professionals, policy makers, educators and parents. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM), ADHD is a neuropsychiatric disorder that includes inattentiveness, impulsivity and hyperactivity.
  • Upon reading this protocol you will acquire a basic understanding of ADHD. Several innovative and emerging ADHD management strategies and scientifically studied integrative interventions will be presented.
  • The good news is that several integrative interventions have been shown to help maintain focus and attention. For example, supplementation with omega-3 fatty acids, vitamin B6 and magnesium, as well as undergoing neurofeedback therapy, have benefited those affected by ADHD in studies.

The diagnosis of attention deficit/hyperactivity disorder (ADHD) is controversial and evokes passionate debate among healthcare professionals, policy makers, educators, and parents. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM), ADHD is a neuropsychiatric disorder that includes inattentiveness, impulsivity, and hyperactivity.

The good news is that several integrative interventions have been shown to help maintain focus and attention. For example, supplementation with omega-3 fatty acids, vitamin B6 and magnesium, as well as undergoing neurofeedback therapy, have benefited those affected by ADHD in studies.

Causes and Risk Factors

No single factor has been identified as a definitive cause of ADHD, instead it is more likely due to several variables:

  • Genetics
  • Environmental factors
  • Brain injury
  • Diet
  • Sleep disorders, which may also be a cause of ADHD-like symptoms

Signs and Symptoms

ADHD is defined primarily by persistent impulsivity, hyperactivity, and inattention.

Symptoms of impulsivity include:

  • blurting out an answer before a question is finished
  • difficulty waiting one’s turn
  • interrupting or intruding on others during conversations

Symptoms of hyperactivity include:

  • fidgeting with hands or feet
  • leaving one’s seat inappropriately, like during a meeting
  • difficulty working quietly

Symptoms of inattention include:

  • making careless mistakes during work
  • difficulty staying focused during work
  • difficulty organizing tasks and activities

Diagnosis

There is no single diagnostic test for ADHD; instead, diagnosis is a process that rules out factors such as learning disabilities and anxiety, which may cause similar symptoms.

Conventional Treatment

  • The most widely used drugs to treat ADHD are brain stimulants, including methylphenidate (available in many forms, including Ritalin).
  • Amphetamine-based drugs including Dexedr

Novel and Emerging Strategies

  • Neuropsychiatric EEG-Based Assessment Aid monitors brain waves to aid ADHD diagnosis.

Dietary and Lifestyle Considerations

  • A growing body of research indicates dietary changes can substantially improve ADHD symptoms:
    • Avoid foods high in sugar as it may help limit reactive low blood sugar symptoms, which may mimic ADHD symptoms
    • Eat a nutritious breakfast
  • In one study on children and adolescents, neurofeedback was as effective as methylphenidate in treating attention and hyperactivity symptoms.
  • Exercise may have a positive impact on ADHD symptoms in both adults and children.

Integrative Interventions

  • Omega-3 fatty acids: A UK-based study on school children found that omega-3 fatty acid insufficiency was very common and associated with ADHD-related symptoms.
  • Phosphatidylserine: Phosphatidylserine supplementation in children diagnosed with ADHD resulted in significant improvement in ADHD symptoms including inattention, impulsivity, and short-term memory.
  • Acetyl L-carnitine: In a randomized double-blind trial, acetyl L-carnitine had a beneficial effect on hyperactivity and social behavior in individuals with ADHD.
  • Vitamin B6 and magnesium: A study on children with ADHD found that supplementation with magnesium and vitamin B6 led to improvements in hyperactivity and school attention.
  • Zinc: Children with ADHD treated with Ritalin for six weeks received better behavioral ratings from teachers and parents when they also took zinc sulfate compared with children who received Ritalin and a placebo.

2 Introduction

The diagnosis of attention deficit/hyperactivity disorder (ADHD) is fraught with controversy involving passionate debate between healthcare professionals, policy makers, educators, and parents.

Using Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria, ADHD is characterized as a neuropsychiatric disorder that includes inattentiveness, impulsivity, and hyperactivity. Based upon DSM diagnostic criteria, estimates suggest that anywhere from 5–10% of school-aged children may have ADHD; however, adults can also exhibit signs and symptoms consistent with DSM-IV diagnostic criteria (Scahill 2000).

Changes introduced in DSM-5 include broadening the definition of ADHD by including more examples of diagnostic behaviors and increasing the maximum age of symptom onset from 7 to 12 years, leading to concerns that normal developmental processes such as pubertal restlessness and distractibility could be misdiagnosed as ADHD. In addition, diagnostic criteria for adults with ADHD are present for the first time (Thomas 2013). These along with other changes incorporated into DSM-5 are predicted to increase the prevalence of ADHD in the years to come, mostly in adults and adolescents, but possibly also in children (Dalsgaard 2013).

ADHD is a complex and controversial condition that likely involves both biological and environmental factors (De La Fuente 2013). Genetics are thought to play an important role as children born to parents with ADHD have an increased risk of developing the condition (Franke 2012; Thapar 2013). There is also some evidence that brain structure and/or function is perturbed in ADHD (Hale 2000; Schneider 2006; Emond 2009; Kasparek 2013; del Campo 2013). For instance, alterations in brain networks that govern attention and emotion have been observed in patients with ADHD (De La Fuente 2013; Konrad 2010; Edel 2010; Gow, Sumich 2013). Up to 60% of school-age children with ADHD may continue to experience symptoms into adulthood (Burbach 2010; O'Neill 2013; Sims 2012; Pearson 2012; Parker 2013; Akinbami 2011).

Mainstream medicine relies heavily upon powerful stimulant drugs from the amphetamine drug class (eg, Adderall®) and methylphenidate (eg, Ritalin®) to treat ADHD symptoms. This is not ideal for several reasons, including the fact that methylphenidate may induce lipid damage in certain brain regions (Schmitz, Scherer, Machado 2012; Comim 2013) and may cause abnormalities in the developing brain (Urban 2013). Stimulant ADHD drugs may cause other side effects as well, such as growth suppression, sleep problems, loss of appetite, and increased blood pressure and heart rate (Parker 2013).

The good news is that several integrative interventions have been evaluated and show promise in helping maintain focus and attention. For example, supplementation with omega-3 fatty acids and magnesium as well as undergoing neurofeedback therapy have been shown to offer considerable benefit to those affected by ADHD (Hariprasad 2013; Rutledge 2012; Arns 2009; Arnold 2013; Mousain-Bosc 2006).

Upon reading this protocol you will acquire a basic understanding of ADHD. You will also learn how conventional medications work to treat ADHD and about their troublesome side effects. In addition, several novel and emerging ADHD management strategies and scientifically-studied integrative interventions will be presented.

3 Background

The concept of treating aberrant childhood behavior as a medical disorder dates as far back as the 1700s and has always been fraught with controversy regarding what constitutes a “disease” as opposed to typical, albeit difficult, childhood behavior (Taylor 2011). The diagnosis and treatment of ADHD, especially among children, continues to remain a hotly debated topic today as many aspects of the condition are subjective and different systems to classify the disease are often used by physicians from different countries (Parens 2009).

Technological advances in neuroimaging techniques have allowed scientists to observe the brains of children diagnosed with ADHD and compare them to those of adolescents without the condition. Several studies have identified subtle differences in brain structure or function among ADHD children. For example, a study employing functional magnetic resonance imaging (fMRI) showed that the brain networks in children with ADHD activate in different patterns compared to healthy children’s brains (Massat 2012). Other studies suggest that brains of ADHD children display variations in the volume or density of various brain regions compared with non-ADHD kids (De La Fuente 2013; Pastura 2011; Tomasi 2012).

Evidence suggests that several aspects of the variation in brain function observed in ADHD are attenuated by psychostimulant drugs such as methylphenidate. This has led some researchers to speculate that reversion of brain network structure and activity to normal may underlie the therapeutic benefits of psychostimulant drugs (Spencer 2013; Kasparek 2013).

4 Causes and Risk Factors

No single factor has been identified as a definitive cause of ADHD. Instead, most scientists believe that several variables influence ADHD risk. For example, genetics, exposure to stressors during pregnancy or infancy, early social interactions, and environmental toxins all appear to affect ADHD risk (Thapar 2013).

Genetics

A considerable portion of ADHD cases are thought to be attributable to genetics and heritability (Neale 2010). A number of specific genetic variations are associated with ADHD. These are predominantly related to the regulation of dopamine (ie, a chemical messenger used by brain cells) (Faraone 2006; Thapar 2013; Franke 2012). The importance of dopamine in ADHD is highlighted by the fact that methylphenidate is thought to treat ADHD symptoms in part by increasing dopamine signaling in the brain (Volkow 2005).

Environmental Factors

Environmental toxins such as polychlorinated biphenyls, some pesticides, and lead have been linked to ADHD development, but no studies have proven that they directly cause the condition (Thapar 2013).Other external factors, such as negative child-parent interactions and poor or lacking early social contact, have been found to have a contributory effect in ADHD onset (McLaughlin 2010; Thapar 2013). Some variables in utero (in the womb) are seen as risk factors, but not causative links to ADHD. These include maternal smoking during pregnancy, premature birth and/or low birth weight, and/or maternal stress (Thapar 2013).

Brain Injuries

Traumatic brain injury has been linked to behaviors similar to those observed in ADHD (Eme 2012; NIH 2013a). Approximately 20–50% of children who suffer a traumatic brain injury develop a form of clinically relevant attention disorder termed secondary ADHD (Senior 2013; Ornstein 2013; Sinopoli 2011).

Diet

There is some evidence that deficiencies in certain nutrients, such as zinc, magnesium, and polyunsaturated fatty acids may be linked to ADHD (Thapar 2013). As will be discussed later in this protocol, studies have found evidence for insufficiency or imbalance of omega-3 and omega-6 fatty acids in people with ADHD (Colter 2008). Zinc and magnesium intake have also been found to be reduced in those with ADHD (Dura Trave 2013). Additionally, there is some evidence that high levels of ingested food additives such as artificial coloring (eg, tartrazine (E103), quinolone yellow (E104), sunset yellow (E110), carmoisine (E122), ponceau 4R (E124) and allura red (E129)) correlate with increased activity in children and therefore may exacerbate this symptom in those with ADHD (Stevens 2013). Excessive sugar intake has often been linked to ADHD as well, although the majority of research has largely debunked this as unsubstantiated; definitive evidence for a causal relationship is currently lacking (Johnson 2011). Nevertheless, it is generally advisable to limit sugar intake, as high sugar consumption may contribute to numerous other health detriments.

Sleep Disorders and ADHD

Several lines of evidence suggest a relationship between ADHD and sleep disorders such as sleep apnea. It has been reported that up to 95% of obstructive sleep apnea sufferers experience attentional deficits, and obstructive sleep apnea has been observed in up to 30% of individuals with ADHD. Moreover, successfully treating obstructive sleep apnea appears to relieve ADHD symptoms in some individuals (Youssef 2011). Overall, sleep disorders have been observed in up to 30% of children and 80% of adults with ADHD (Yoon 2012).

It is important for physicians to realize that symptoms of sleep disorders such as sleep apnea or restless leg syndrome can resemble those of ADHD in both children and adults. Otherwise, a person may be misdiagnosed with ADHD when their symptoms are actually the consequence of a sleep disorder (Philipsen 2006; Owens 2005).

Despite intensive study and an active body of research, it is not entirely clear whether sleep disorders directly cause ADHD or vise-versa, or if the conditions have a high rate of concurrence yet remain distinct entities (Stein 2012; Yoon 2012).

Sleep and ADHD must also be contemporaneously considered since stimulant medications like methylphenidate, which are used to treat ADHD, may contribute to impaired sleep patterns. In a study on 93 children with ADHD, methylphenidate treatment was shown to considerably delay bedtimes and lead to reduced total sleep duration (Lee 2012). On the other hand, some studies have found that methylphenidate treatment does not disrupt sleep habits and may lead to better sleep quality in certain populations (Tomas Vila 2010; Faraone 2009). Since the impact of methylphenidate on sleep patterns appears not to be uniform in all individuals, a reasonable approach is to carefully monitor sleep habits following treatment initiation. If signs of diminished sleep duration or quality emerge, consult with a healthcare provider about dose-adjustment or pursuing a different treatment option.

5 Signs and Symptoms

ADHD is defined primarily by persistent symptoms of impulsivity, hyperactivity, and inattention that can severely affect a person’s quality of life. Some people present mostly with symptoms related to inattention, others present mostly symptoms related to hyperactivity and impulsivity, while others have all three types of symptoms in combination (A.D.A.M. 2013).

Symptoms of inattention include (A.D.A.M 2013):

  • making careless mistakes during school work
  • difficulty staying focused during work or play
  • difficulty in paying attention/listening when spoken to
  • difficulty organizing tasks and activities
  • often losing toys, books, or tools used for activities
  • being easily distracted
  • forgetfulness during daily activities and tasks

Symptoms of hyperactivity include (A.D.A.M. 2013):

  • fidgeting with hands or feet
  • leaving one’s seat when it is expected to remain seated
  • running/climbing in inappropriate situations
  • difficulty working/playing quietly
  • often being "on the go"
  • talking excessively

Symptoms of impulsiveness include (A.D.A.M. 2013):

  • blurting out an answer before a question is finished
  • difficulty awaiting one’s turn
  • interrupting or intruding on others during conversations/play

Many children with ADHD struggle academically and in social situations. Also, symptoms are frequently accompanied by other problems, including depression, anxiety, and substance abuse (Hodgkins 2013; Wilens 2004).

6 Diagnosis

There is no single diagnostic test for ADHD; instead, diagnosis is a stepwise process that also has to take into consideration several other conditions, such as anxiety, learning disabilities, and anxiety, which may cause similar symptoms (CDC 2013a).

The first national survey that asked parents about ADHD was completed in 1997. Since then, there has been an increase in the number of parentally-reported ADHD diagnoses as well as in prescribing rates. However, it is difficult to tell whether this represents an increase in the number of children diagnosed or an increased number of children who developed this condition (Thomas 2013; CDC 2013a).

It is thought that some important contributors to the increasing rate of diagnosis are the lack of consistent criteria to objectively assess the severity of symptoms and the shift observed over the years in ADHD diagnostic criteria (Thomas 2013).

Diagnostic criteria describe three types of ADHD. Previously, the predominantly inattentive type included individuals with six or more symptoms of inattention and less than six symptoms of hyperactivity or impulsivity. The predominantly hyperactive-impulsive type included individuals with six or more symptoms of hyperactivity-impulsivity and less than six symptoms of inattention. The combined type included individuals with symptoms across both these dimensions (Willcutt 2012). One of the changes incorporated in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (adopted in 2013) is that for people over 17, five instead of six symptoms are sufficient for diagnosis (Prosser 2013; Thomas 2013).

7 Conventional Treatment

The traditional treatment strategy for ADHD is two-pronged, involving both medication and psychological support (Antshel 2011).

Stimulants

The most widely used drugs to treat ADHD are brain stimulants, of which there are several available (Chavez 2009).  Although these drugs have long been used in clinical medicine, their mechanisms of action have only recently started to be better understood. These drugs change the levels and signaling by neurotransmitters (eg, norepinephrine and dopamine) in the brain (Berridge 2011).

Methylphenidate. Methylphenidate is the most common stimulant medication used to treat ADHD. Many different forms of methylphenidate are available, including Ritalin®, Methylin®, Metadate®, Concerta®, and Daytrana®, which vary in dosage, delivery system (capsule, tablet, or patch), and rate of drug delivery. Dexmethylphenidate (Focalin®) consists of a specific structural form of methylphenidate thought to be better absorbed and more chemically active in the brain (Greydanus 2009; Liu 2006).

Daytrana®, the methylphenidate patch first released in the United States in 2006, is a relatively new development in ADHD treatment. It releases the drug through the skin, giving it the advantage of once-daily administration, flexibility in its removal, and suitability for children who cannot swallow pills; however, it can cause skin reactions where applied (Elia 2011).

Methylphenidate Drugs Induce Oxidative Stress

Aside from known side effects such as heart problems and growth suppression, methylphenidate also causes oxidative stress. Oxidative stress is the metabolic process by which reactive molecules damage cells and tissues. Oxidative stress is implicated as a contributing factor in several diseases and the aging process (Wang 2013; Kim 2013).

Animal studies have shown that methylphenidate treatment leads to an increase in the production of tissue-damaging reactive oxygen species in certain brain regions (Schmitz, Scherer, Machado 2012). Alarmingly, one animal experiment showed that brains of young animals were especially prone to the increased oxidative stress caused by methylphenidate, suggesting children may be more susceptible to this phenomenon than adults (Martins 2006).

Ironically, although methylphenidate is used as a treatment for ADHD, some evidence suggests that oxidative stress actually contributes to the development and progression of several psychiatric disorders, including ADHD (Ceylan 2012; Ng 2008; Kawatani 2011).

This is concerning, especially considering that evidence shows methylphenidate exposure during development likely has lasting neurological consequences that may impact brain health in later life. Conventional physicians are often quick to prescribe methylphenidate to children with ADHD despite a lack of thorough understanding of its long-term developmental effects (Urban 2013).

Amphetamines. Amphetamine drugs including dextroamphetamine (Dexedrine®) and Adderall® (a combination of amphetamine and dextroamphetamine) are also popular, and some people with ADHD may respond better to these alternatives (Chavez 2009).

Another amphetamine, lisdexamfetamine (Vyvanse®), is a relatively recent addition to the arsenal of stimulant drugs for ADHD. It was first approved by the Food and Drug Administration (FDA) for the treatment of ADHD in children in 2007 and is currently also approved for adolescents and adults. Unlike other stimulants prescribed for ADHD, lisdexamfetamine is a "prodrug," an inactive precursor converted to the active form of the drug after ingestion. This property is claimed to give the drug a smoother effect throughout the day with fewer rebound symptoms. It may also help prevent addiction or abuse (Madaan 2013).

Side Effects of Stimulant ADHD Medications

Up to 30% of children with ADHD either do not respond to stimulants or cannot tolerate their side effects (CDC 2013b; Akhondzadeh 2003). The side effects of stimulant use can range from mild to severe. Adverse effects include headache, insomnia, decreased appetite, rapid heart rate, abdominal pain and growth suppression (long-term use) (Medscape 2013; ePOCRATES 2013). They should not be used in people with hypertension, heart or vascular disease, hyperthyroidism, glaucoma, psychosis, or those taking monoamine oxidase inhibitors (MAOIs), which are sometimes prescribed for depression. Because of their potential for abuse and effects on addiction-related pathways in the brain (through dopamine), they are also not suitable for people with substance abuse disorders. Stimulants can worsen tics in people with Tourette’s syndrome (three-fourths of whom also have ADHD), and some of them induce tics in people who did not have them previously. They can also induce mania or psychosis in people who have not previously shown signs of bipolar disorder or schizophrenia (Greydanus 2009). In rare cases, sudden death has been reported after the use of methylphenidate and amphetamines. Especially before taking stimulants, individuals should be screened for a history of cardiovascular risks.

In light of incidents of sudden death after taking ADHD medication, in 2008 the American Heart Association went so far as to recommend that all children have an electrocardiogram to rule out any undetected developmental defects to the heart before beginning stimulant medication for ADHD (Perrin 2008).

Non-Stimulant Medications

Non-stimulant ADHD medications are an effective alternative for some individuals. There are only a few non-stimulant ADHD drugs approved by the FDA. The first is atomoxetine (Strattera®), which inhibits reuptake of the neurotransmitter norepinephrine. Others include clonidine (Catapres®, Kapvay®) and guanfacine (Tenex®, Intuniv®), which counter the effects of the sympathetic nervous system (Cruz 2010; Antshel 2011; Christman 2004).

Use of atomoxetine avoids some of the complications associated with stimulants, notably tics and sleep disturbances, but there is an increased risk of suicidal thinking in children and adolescents given the drug, so people in these age groups should be carefully monitored for the first few months after beginning treatment or changing dosage (Purper-Ouakil 2005; FDA 2005).

Antidepressants. Although not FDA-approved for the treatment of ADHD, antidepressants, including venlafaxine (Effexor®) and the tricyclic antidepressant bupropion (Wellbutrin®), have also shown some promise in treating ADHD (Greydanus 2009; NIH 2013b). In one double-blind randomized trial, bupropion was found to be comparable in effect to methylphenidate (Jafarinia 2012).

Other agents. Modafinil (Provigil®), a wakefulness- and cognition-promoting drug, has also been used to treat ADHD and has shown promise in clinical trials on both children and adults with ADHD (Greydanus 2009; Kumar 2008). It is not FDA-approved for ADHD treatment as of the time of this writing (Spiller 2013).

8 Novel and Emerging Strategies

Monitoring Brain Waves to Aid ADHD Diagnosis

In July of 2013, the FDA approved the use of a new brain-wave-monitoring system to assist physicians in diagnosing ADHD in children and adolescents aged 6 to 17. The system is called the Neuropsychiatric EEG-Based Assessment Aid (NEBA). The non-invasive test takes about 15 to 20 minutes and involves placement of sensors on the scalp of the individual to monitor their brainwaves. Individuals with ADHD typically have a significantly higher theta/beta brainwave ratio, and the NEBA system can identify this phenomenon (Brauser 2013; FDA 2013).

However, not all physicians agree on the value of this new test. Some feel it could add value and improve ADHD diagnosis accuracy and possibly reduce unnecessary referrals, but others believe that current standards for ADHD diagnosis are sufficient. More evidence is needed before the value of the NEBA system can be stated unequivocally (Brauser 2013).

Dasotraline

Dasotraline, a novel compound being investigated for use in patients with ADHD, is believed to strongly inhibit the reuptake of both dopamine and norepinephrine, as well as weakly inhibit serotonin reuptake. Dasotraline is distinguished from stimulants used to treat ADHD by its slow absorption and long elimination time. Dasotraline is meant to be taken once per day and a steady blood concentration is achieved after 10‒14 days of daily use. These characteristics suggest dasotraline may have a sustained effect over 24 hours and likely has a low risk of being abused as a stimulant (Koblan 2015; Hopkins 2016; Sunovion 2014).

In a randomized controlled trial, 341 adults with ADHD received either 4 mg or 8 mg of dasotraline or placebo daily for four weeks. Those in the 8 mg group had significant improvement in an ADHD rating scale compared with placebo, while a trend towards improvement was observed in the 4 mg group. Mild-to-moderate side effects were frequent with both doses, with a greater prevalence in the high-dose group. The most common side effects were insomnia, decreased appetite, dry mouth, anxiety, and nausea. The most common severe side effects were insomnia, anxiety, and panic attack, all of which were more common in the higher dosage group. In a randomized controlled trial of 48 individuals who had used cocaine and other recreational stimulants, dasotraline showed a low potential for abuse compared with methylphenidate (Koblan 2016; Sunovion 2014).

9 Dietary and Lifestyle Considerations

Dietary Considerations

A growing body of research indicates that dietary changes can substantially improve ADHD symptoms, either alone or as a complement to medical therapies (Millichap 2012).

Some children have a high sensitivity to some food additives and preservatives, particularly food colorings. A 2007 trial from Southampton University called into question the safety of certain food dyes. The randomized controlled trial assessed the effects of certain food colorings (ie, tartrazine (E103), quinolone yellow (E104), sunset yellow (E110), carmoisine (E122), ponceau 4R (E124) and allura red (E129)) on 153 three-year-old and 144 eight-to-nine-year-old children. The researchers found these artificial colorings resulted in increased hyperactivity in this population when added to their diet. Although artificial food coloring has not been established as a primary causative factor for ADHD, a subgroup of children have shown significant improvement when provided food lacking these additives. Similarly, they developed symptoms reminiscent of ADHD when exposed to artificial food coloring. Children with sensitivity to food coloring are often also sensitive to foods such as milk, eggs, wheat, and soy (Stevens 2011).

Although the majority of research does not support a causative role for sugar intake and ADHD, many parents anecdotally report that foods high in sugar can make their child’s ADHD hyperactivity symptoms more pronounced. However, children are more vulnerable to the effects of reactive hypoglycemia (ie, low blood sugar following the rise in blood sugar from a high carbohydrate meal) on cognitive function. Avoiding foods high in sugar may help limit reactive hypoglycemia symptoms, which may mimic some aspects of ADHD symptoms, in sensitive children (Millichap 2012).

Studies indicate that children who eat a balanced breakfast containing proteins, vitamins, and minerals, such as found in whole grains, have less deterioration in attention levels during morning hours at school (Arnold 2013).

Lifestyle Considerations

Neurofeedback. Neurofeedback is a technique introduced in the 1960s that helps people regulate their own mental states by viewing an EEG (electroencephalogram) recording of their brain activity in real time. It utilizes sensors placed on the scalp that detect brainwaves and then graphs them on a computer screen that the test subject can visualize. This allows the subject to recognize ways of thinking that favorably alter their neurological function and can help them gain better control over their brain activity (Moriyama 2012).

This therapy aims to change the threshold that triggers brain activity in the cortex, which appears to be impaired in ADHD. The great majority of studies have been conducted on school-age boys, so it is still unclear whether its results are as promising in adults, younger children, and girls. Nevertheless, the majority of clinical studies conducted to date have reported promising, long-lasting results (Moriyama 2012). For example, in one study on children and adolescents aged 6–18 years, neurofeedback was as effective as methylphenidate in treating attentional and hyperactivity symptoms (Duric 2012). A comprehensive review of several studies examining the efficacy of neurofeedback for ADHD management concluded that it confers robust benefits for inattention and impulsivity and modest benefits for hyperactivity (Arns 2009).

Cognitive behavioral therapy. Cognitive behavioral therapy (CBT) uses behavioral skill training and interventions that target dysfunctional patterns of thought to improve functional performance (Knouse 2010). Many cognitive training programs for ADHD are commercially available, and the practice is growing in popularity. This method seems to be particularly effective during adolescence and has the advantage that it can be adapted to technologies like cell phones and tablets and is designed to be engaging to users (Rutledge 2012).

For children with ADHD, training of parents and educators can also be very effective at improving symptoms (Anastopoulos 1993). In a 2013 analysis of published studies on interventions for preschoolers with disruptive behavior including ADHD, parent behavior training had more evidence of effectiveness than methylphenidate and combined home/school interventions, with consistently good results and no adverse effects (Charach 2013). One trial involving canine assistance in addition to CBT achieved greater reduction of ADHD symptoms compared to cognitive therapy alone (Schuck 2013). A program for children aged 4 to 5, which involved games designed to reduce impulsivity, inattention, and improve memory achieved significant improvements in ADHD symptoms in a pilot study of 29 children. The positive effects were still present three months after treatment (Halperin 2012).

Physical activity. Exercise may have a positive impact on ADHD symptoms in both adults and children (Berwid 2012). Thirty adults with ADHD were enrolled in a study comparing frequent aerobic exercise with infrequent activity. The 'exercise' group showed a significant decrease in impulsive symptoms and anxiety (Abramovitch 2013). Another study showed that cognitive symptoms in children with ADHD were improved after just twenty minutes of moderate exercise (Pontifex 2013).

Yoga may also be helpful in reducing ADHD symptoms (Jensen 2004). A small-scale study in nine children demonstrated a significant improvement in ADHD symptoms as a result of learning and practicing yoga (Hariprasad 2013).

10 Integrative Interventions

Fatty Acids

An analysis of several published studies of “non-pharmacological” (ie, dietary and psychological) interventions for ADHD found that supplementation with free fatty acids and exclusion of artificial food coloring from the diet had statistically significant effects on reducing ADHD symptoms (Sonuga-Barke 2013). Considering that dopamine-producing nerve endings contain up to 80% omega-3 fatty acids (Rucklidge 2009), these molecules appear to have a role in the central nervous system and its functions.

Children with ADHD may have lower levels of omega-3 fatty acids in their blood (Colter 2008). While the typical Western diet often contains excessive levels of certain omega-6 fatty acids, it is lacking in omega-3 fats, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Patterson 2012; Carlson 2013). In children, the severity of ADHD symptoms are linked to lower levels of omega-3 and higher levels of omega-6 fatty acids. Hyperactivity and inattention in general are also linked to omega-3 deficiency, thus indicating that this may be a risk factor for ADHD (Arnold 2013). A UK-based study on 493 school children aged 7-9 years found that omega-3 fatty acid insufficiency was very common and associated with ADHD-related symptoms such as oppositional behavior and emotional instability (Montgomery 2013). Research from another group found that low blood levels of omega-3 fatty acids correlated with callous-unemotional behavior, antisocial traits, and impaired emotional processing (Gow, Sumich 2013; Gow, Vallee-Tourangeau 2013).

Swedish scientists studied the effects of combined omega-3 (558 mg EPA, 174 mg DHA daily) and the beneficial omega-6 fatty acid gamma linolenic acid (GLA) (60 mg daily) supplementation in 75 children and adolescents with ADHD over a 6-month period. They found that after 6 months, nearly half of subjects responded to omega-3/6 treatment with a reduction in ADHD symptoms (Johnson 2009). In a subsequent analysis of these study data, the same researchers found that subjects with at least a 25% reduction in symptoms exhibited a significantly greater decrease in the ratio of omega-6’s to omega-3’s in their blood at 3 and 6 months (Johnson 2012).

A comprehensive review conducted by researchers at Yale University examined evidence from 10 trials involving 699 children with ADHD. It was found that supplementation with omega-3 fatty acids modestly improved ADHD symptoms among study participants. In their concluding remarks, the researchers noted “…it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacologic interventions…” (Bloch 2011).

Blood fatty acid levels can be measured with blood tests, and people taking fatty acid supplements can have repeat blood tests to measure their effect.

Phosphatidylserine

Phosphatidylserine (PS) is a major component of cell membranes and is considered one of the most important brain nutrients. PS has a variety of functions within the brain including supporting cell membrane fluidity and beneficially influencing neurotransmitter systems (eg, acetylcholine, dopamine, serotonin). Several clinical trials have examined the role of PS on improving ADHD symptoms (Hirayama 2013).

In a 2013 randomized controlled trial, 36 children diagnosed with ADHD were given either 200 mg per day of PS or placebo for 2 months. PS supplementation resulted in significant improvement in ADHD symptoms including inattention, impulsivity, and short-term memory. No adverse effects were reported and the supplement was well tolerated (Hirayama 2013).

Another randomized controlled trial of 15 weeks duration studied the effects of PS combined with omega-3 fatty acids. In this study, 200 ADHD children were given either 300 mg of PS plus 120 mg EPA and DHA or placebo. The treatment resulted in significant improvement in ADHD symptoms. A subgroup analysis revealed this treatment may be especially effective in ADHD children with more pronounced hyperactive and impulsive behavior (Manor 2012).

Acetyl-L-carnitine

Acetyl-L-carnitine (ALC) is a natural derivative of L-carnitine. It serves a key role in the metabolism of fatty acids and cellular energy production (Torrioli 2008). Evidence from both animal and human studies suggests it may help alleviate ADHD symptoms. In an animal model of ADHD, long-term administration of ALC to rats consistently decreased impulsivity. This study also found that impulsive animals had altered levels of certain neurotransmitter metabolites, and ALC helped improve this imbalance (Adriani 2004). In a placebo-controlled trial on 112 subjects, ALC was found to improve symptoms in children with the inattentive ADHD subtype (Arnold 2007). In a separate randomized, double-blind trial, ALC was found to have a beneficial effect on hyperactivity and social behavior in 51 subjects with ADHD (Torrioli 2008).

Vitamins and Minerals

Vitamin B6 and magnesium. Vitamin B6 (pyridoxine) is involved in the production of serotonin, and B6 supplementation increases serotonin levels and may improve hyperactivity in ADHD (Pellow 2011). In a nutritional survey comparing 100 people with ADHD to 150 healthy individuals, vitamin B6 intake levels were significantly lower in those with ADHD (Dura Trave 2013). An 8-week study on 40 children with ADHD found that supplementation with magnesium and vitamin B6 led to improvements in hyperactivity and school attention. Interestingly, when the treatment regimen was discontinued, the children’s symptoms reappeared in a few weeks (Mousain-Bosc 2006). A similar regimen of vitamin B6 and magnesium therapy improved hyperexcitability symptoms in a previous study by the same researchers. In this study, the magnesium-B6 combination was given to 52 hyperexcitable children for 6 months, and symptoms such as physical aggressiveness and attention in school improved in all subjects during treatment (Mousain-Bosc 2004).

Studies have shown that magnesium deficiency is common among individuals with ADHD (Ghanizadeh 2013; Kozielec 1997). In a placebo-controlled trial, 200 mg magnesium per day for six months showed a significant decrease of hyperactivity in 7-12 year old children with ADHD (Starobrat-Hermelin 1997).

Zinc and iron. Zinc and iron are both involved in dopamine production, so deficiencies in these minerals could have effects on dopamine neurotransmission in ADHD (Patrick 2007). Children with ADHD treated with Ritalin® for six weeks received better behavioral ratings from teachers and parents when they also took zinc sulfate (55 mg/day) compared to children who received Ritalin® and a placebo (Akhondzadeh 2004).

Iron deficiency is present in a significant percentage of children with ADHD, and the severity of the iron deficiency is related to the severity of symptoms (Konofal 2004). Children who have ADHD in conjunction with sleep disorders such as restless leg syndrome have also been observed to have low iron levels (Cortese, Angriman 2012). A randomized, placebo-controlled study in 23 subjects aged 5–8 years showed that 80 mg iron daily for twelve weeks resulted in a significant decrease in symptoms (Konofal 2008). Another trial with fourteen subjects (7–11 years old) showed that 5mg/kg iron per day for 30 days significantly reduced parent ratings of ADHD symptoms (Sever 1997).  Higher doses of iron (such as those used in these trials) should only be used under medical supervision for iron deficiency.

Plant-Based Interventions

Ginkgo biloba and ginseng. Among plant-based supplements tested for ADHD, a combination of ginseng extract and Ginkgo biloba improved a range of symptoms from social problems to impulsivity (Lyon 2001). Ginkgo alone was shown to be effective in another trial. In this study, ginkgo (80-120 mg daily in 25 children with ADHD for 6 weeks) produced a significant improvement in subjective teacher and parent ratings; however, it did not outperform methylphenidate (20-30 mg daily under the same parameters) (Salehi 2010). In another trial, eighteen children (6–14 years old) received a 1000 mg dose of Korean red ginseng twice daily. At the end of the eight-week trial, a significant reduction in attentional symptoms and level of anxiety was observed (Lee 2011).

Pycnogenol. Pycnogenol is an extract from the French maritime pine, Pinus pinaster. It is often used in ADHD for its antioxidant and vasodilatory properties (ie, it may increase cerebral blood flow, a measure of brain activity, to affected regions). A double-blind, randomized trial on 61 children receiving 1 mg/kg Pycnogenol or placebo per day for 4 weeks showed a significant decrease in hyperactivity, improvement in attention, and increase in visual and motor coordination in the Pycnogenol group (Trebaticka 2006). Another double-blind, randomized, placebo-controlled trial showed that Pycnogenol decreased hyperactivity and oxidative stress in children with ADHD (Dvorakova 2007).

Study: Multinutrient Formula as Effective as Methylphenidate for ADHD Management

The multifactorial origins of ADHD suggest that an intervention targeting multiple specific underlying contributing factors might be beneficial. To test this hypothesis, researchers at McLean hospital in Massachusetts divided 20 children with ADHD into 2 groups. One group of 10 children received 5–15 mg of Ritalin® 2-3 times daily and the other received a comprehensive multi-nutrient formula designed to target several factors that possibly play a role in ADHD development (Harding 2003).

The multi-nutrient formula used in this study included gastrointestinal support (eg, lactobacillus acidophilus and bifidus), amino acids (eg, tyrosine, histidine, glutamine, glycine, methionine and cysteine), essential fatty acids and phospholipids (eg, EPA, DHA, and phosphatidylcholine), and vitamins and minerals.

A standardized assessment of visual and auditory attention was administered to the children at the beginning of the study to quantify their ADHD symptoms. Then, the children took either Ritalin® or the multi-nutrient formula for 4 weeks. At the end of the 4-week period, the researcher administered the same ADHD symptom assessment again.

Impressively, ADHD symptoms among children who took the multi-nutrient formula improved just as much as among those who received Ritalin®. Upon concluding their study, the researchers noted “Improvements … were … found to be significant and essentially identical in both groups…

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