POPULATION-SPECIFIC CONCERNS

Verle Valentine, MD, Report Editor

Attention Deficit/Hyperactivity Disorder (ADHD) in Athletes Jeffrey B. Kreher, MD • Massachusetts General Hospital for Children

Definition of Attention-Deficit/ Hyperactivity Disorder (ADHD) ADHD is a common neuropsychiatric disorder. Prevalence estimates range from 5–10% of school age children and adolescents1-3 and 4–6% of adults.4 Recognition of ADHD pervasiveness and persistence into adolescence and adulthood has brought ADHD and its treatment to the attention of the sports medicine community. This is apparent by the recent Position Statement from the Key Points American Medical Society for Sports Medicine ADHD is a common condition that is found (AMSSM)5 and a couple within the athletic population at all ages. review articles.6,7 Simply put, ADHD is “characterTreatment of ADHD with psychostimulants may put the athlete at risk for heat injury ized by the inability to but does not appear to increase the risk for maintain attention span sudden cardiac death. and focus concentration ability at a normal Many governing bodies have regulations developmental level.” concerning the treatment of ADHD with Diagnostic criteria can psychostimulants. be found in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) but, in short, consist of the following: symptoms before age 7, symptoms present in two or more settings, symptoms that impair functioning, and six of nine symptoms in the impulsivity/hyperactivity and/or inattentive domains. ADHD is a clinical diagnosis, and there are no blood tests or imaging studies that are appropriate for diag-

nosis. Table 1 presents ADHD characteristics that are pertinent to the care of athletes who have been diagnosed as having the condition. In managing athletes with ADHD varied behavioral approaches are indicated: • Identifying strengths and challenges is helpful to the athlete, athletic trainer, and coach. • Establishing a predictable schedule and structure with clear expectations of athlete conduct helps to manage ADHD athletes. • Both positive reinforcement and judicious and consistent loss of privileges if indicated help provide a favorable environment for success in athletics. • Avoidance of excessive criticism and highlighting failures for ADHD athletes with comorbid anxiety proves to be essential. The leading hypothesis of ADHD pathophysiology suspects a dysfunction of catecholamines (epinephrine and norepinephrine) and dopamine. Hence, drugs that are catecholamine agonists or psychostimulants, such as methylphenidate and amphetamine salts, are effective in treating symptoms of ADHD.8,9 Approximately 56% of patients with ADHD receive pharmacologic treatment,10 and of those, a majority receives psychostimulants. Psychostimulant medications have been found to be helpful in over 75% of patents.11-13 Some theories also suspect a systemic dopamine deficit.14 © 2012 Human Kinetics - IJATT 17(3), pp. 15-19

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Table 1. Traits Common to Athletes With ADHD Without Treatment5 Poor attention span Difficulty initiating or completing tasks in activities they find boring or nonengaging Too much attention to novel situations Difficulty waiting one’s turn Increased risk-taking behaviors Inability to manage own time Difficulties with unstructured time Lack of organizational skills Common comorbidities: anxiety, depression, disruptive behavior, learning disorders, substance abuse disorders, and psychotic disorders

NCAA Perspective on ADHD Treatment Effective August 1, 2009, the National Collegiate Athletic Association (NCAA) required those student athletes who have ADHD, take stimulant medication, and are subject to their regulation to have a documented prescription by a physician and support of diagnosis by clinical assessment. The main goals for the policy are (a) ensure clearer documentation of evaluation, (b) educate student athletes and those involved in their care, (c) ensure fair play, and (d) provide quality healthcare to athletes. The NCAA News summarizes the NCAA memorandum as follows: Under the stricter application of medical exceptions, documentation for stimulants prescribed to treat ADHD must include evidence that the student athlete has undergone clinical assessment to diagnose the disorder, is being monitored routinely for use of the stimulant medication, and has a current prescription on file.15 Many sports medicine programs have already formulated individualized responses to the NCAA regulation; however, the position statement from the AMSSM addresses NCAA regulation and covers WADA/ IOC regulations.5

Effect of Exercise on ADHD Exercise leads to a stimulation of the hypothalamicpituitary-adrenal and noradrenergic systems. 16 16  may 2012

Therefore, some theorize that exercise could be a treatment for ADHD; however, the exercise stimulus appears to be deficient in athletes with ADHD. Wigal et al.17 found a peripheral increase in norepinephrine and epinephrine in non-active ADHD(–) children and ADHD(+) children. The increase was significantly less, however, than control athletes despite completing a normalized work rate. Dopamine did not increase with exercise in ADHD(+) children as it did in controls. In addition, they found an attenuate lactate response at peak work.17 However, this study evaluated peripheral changes in catecholamines and dopamine levels and not central nervous system (CNS) levels. Anecdotally, some athletes believe exercise minimizes their ADHD symptoms. Indirectly, sport participation helps ADHD athletes learn to control behavior and give them a sense of mastery. Respect for authority figures is also enhanced through rules of conduct in practice and competition. In ADHD athletes with anxiety, sport can help overcome their fears and anxieties while also assisting with their aversion to risk taking.18 Studies on the treatment of ADHD with exercise have not documented clinically meaningful levels of improvement of ADHD symptoms and reported evidence of benefit has been derived from case reports.19-22

Pharmacologic Treatment of ADHD There are many choices for pharmacologic treatment of ADHD, including methylphenidate (Ritalin®, Methylin®, Metadate®, Concerta®, etc.), amphetamine salts (Adderall®), buproprion (Wellbutrin®), atomoxetine (Strattera®), and most recently, modafinil (Provigil®). Table 2 presents mechanism of action for each of these medications. Treatment of ADHD with psychostimulants during sport participation has not been studied; however, such treatment has been proven beneficial in school and in homes that are relatively unstructured.14,15 Enhanced concentration is often helpful in sport, but athletes may resist losing some of their impulsive behaviors during athletic events. Some athletes are better served by treatment during sport participation, whereas others do better without medication. Each situation requires an individualized approach.18 Psychostimulants (i.e., methylphenidate and amphetamine salts) are the most commonly prescribed medicines for ADHD. Possible side effects of psychostimulants include appetite suppression, sleep international journal of Athletic Therapy & training

TABLE 2. Common Drugs Used in Treatment of ADHD Drug

Mechanism(s) of Action

Methylphenidate (Ritalin®, etc)

Dopamine reuptake inhibitor

Amphetamine salts (Adderall®, etc)

Dopamine releaser, dopamine reuptake inhibitor, monoamine oxidase inhibitor

Buproprion (Wellbutrin®, Zyban®)

Dopamine and norepinephrine reuptake inhibitor (2× > affinity for dopamine over norepinephrine)

Atomoxetine (Strattera®)

Selective norepinephrine reuptake inhibitor

Tricyclic agents (i.e. amitriptyline (Elavil®), nortriptyline (Norvil®), etc) — rarely used in athletes

Inhibits norepinephrine and serotonin reuptake

Modafinil (Provigil®)

Unsure: alpha-1 adrenergic agonist, GABA release inhibitor, “psychostimulant”, “cognitive enhancer”

Clonidine and guanfacine — rarely used in athletes

Alpha-2 adrenergic agonist

disturbance, irritability, gastrointestinal complaints, palpitations, tachycardia, hypertension, anxiety, tremor, and possible risk of serious cardiovascular events. In a survey of child psychiatrists with interest in sport, Conant-Norville and Toffler18 found the most commonly reported adverse effect was “over-focus.” Other complaints reported by athletes include “decline in athletic performance,” “decreased enjoyment,” “lack of creativity,” and “irritability.”15 Implicit in the NCAA position on ADHD treatment is consideration of nonstimulant medicines, primarily atomoxetine. Atomoxetine is the only FDA-approved medication for ADHD that is permitted during competition, yet it has not been studied in athletes. The adverse reactions to atomoxetine reported by athletes primarily consist of nausea, lethargy, palpitations, tremulousness, and sweating.18

Stimulants and Cardiac Risk Some concern has been raised about cardiovascular effects associated with psychostimulants. These drugs have been shown to increase heart rate and blood pressure. Safer23 reported methylphenidate to elevate heart rate by 11 beats per minute in methylphenidatenaïve patients, compared to 4 beats per minute with continued use. In addition, the clinical significance of a 1-5 mmHg increase in blood pressure (still below hypertensive levels) is disputed.15,24 The FDA reviewed sudden deaths related to 25 cases associated with use of methylphenidate or amphetamine. Seventeen of the cases were pediatric, and seven involved those on methylphenidate. The international journal of Athletic Therapy & training

adjusted estimate of sudden death per million prescriptions in the pediatric population is 0.16 for methylphenidate and 0.36 for amphetamine. For adults, the adjusted rates were 0.07 for methylphenidate and 0.53 for amphetamine. Among cases that involved autopsy, nearly two-thirds (12 of 19) were found to have a structural cardiac defect. Concerns about sudden death risk in Canada led to a 2005 removal of amphetamine salts, only to be subsequently reinstated the same year. In 2006, the FDA Advisory Panel suggested a black box warning on psychostimulants for sudden death and cardiovascular events (i.e., stroke and myocardial infarction); however, the estimated rate of sudden death in psychostimulanttreated ADHD patients does not appear to exceed risk of sudden death in the general population. The suggestion for the black box warning was opposed by the FDA Pediatric Advisory Committee, but the rate of sudden death can reach 6% in those with congenital heart disease. As a result, a package insert advises against psychostimulant use in ADHD children and adolescents with preexisting heart disease or symptoms consistent with cardiovascular disease. Finally, Winterstein et al.25 found that current exposure to psychostimulants lead to a 20% increase in ED visits for cardiac causes or symptoms (i.e., syncope, dysrhythmia, tachycardia/palpitation, and elevated blood pressure), and they subsequently reported that methylphenidate and amphetamine salts resulted in similar risks of ED visit for cardiac complaints.26 Of note, there were no sudden cardiac deaths reported during 42,612 person-years stimulant use. 24 In summary, it remains prudent to periodically monitor blood pressure and may 2012  17

heart rate along with exertional symptoms in athletes on psychostimulants.

Effect of Medications on Exercise and Performance Multiple medications used in treatment of ADHD have an effect on central catecholamines and dopamine. Buproprion is a relatively weak dopamine and norepinephrine reuptake inhibitor. Potency for dopamine is twice that for norepinephrine. Multiple groups have associated CNS fatigue with a decrease in central catecholamines. CNS fatigue is a hypothesized feed-forward mechanism—a means of limiting power output with increase in body temperature for avoidance of possible heat injury. In a cross-over study of endurance-trained males, Watson et al.27 found an improved time-trial performance of 9% in warm (30° C), but not temperate (18° C) conditions when acutely treated with buproprion. The improvements came with an increased heart rate and increased core temperature, despite having a similar rating of perceived exertion (RPE) as a nontreated trial. Less than 25% of untreated athletes, compared to greater than 75% of treated athletes, attained a core temperature > 40° C in the preloaded time trial.27 Dopamine has been implicated in control of body temperature28 and tolerance to exercise in the heat.29 Therefore, there is a concern that alteration in central catecholamines may put an athlete at risk for heat injury by attenuating the feed-forward protection induced by CNS fatigue. Buproprion may thwart the protection by maintaining a high central catecholamine level, particularly dopamine. Methylphenidate, which is a dopamine reuptake inhibitor, has also been found to increase performance in warm (30° C) but not in temperate (18° C) conditions. Roelands et al.30 found a 16% improvement in time-trial performance in eight well-trained, non-heat acclimatized, male cyclists/triathletes. Similar to the Watson et al.27 study with buproprion, core temperatures and heart rates were elevated in methylphenidate-treated athletes. This study used a low dose of methylphenidate, yet 50% of the athletes achieved core temperatures > 40° C, with one of them above 41° C after exercise. Once again, the athletes reported no difference in RPE despite the increased thermal stress. Both buproprion and methylphenidate appear to have ergogenic effects in warm environments that are not evident from the results of small studies performed in temperate environments. The results of these preliminary studies do establish a need to educate and observe athletes treated with pharmacologic agents 18  may 2012

that affect central catecholamines (i.e., methylphenidate, amphetamine salts, buproprion, etc.). In addition, one must be cognizant about the effect of elevated core temperatures on hydration status during prolonged exercise. Modafinil is a new drug labeled as a psychostimulant, much like amphetamine and caffeine, both of which can increase physical performance with acute ingestion. In a study by Jacobs and Bell,31 15 nontrained males taking modafinil were found to extend time to exhaustion and exhibited lower RPE despite HR increase. With modafinil, there was a 22% improvement over baseline and 14% improvement over placebo in performance—similar to the range reported with caffeine of 19.5–35% at similar workloads. Other studies have shown a mild increase in core temperature of 0.3-0.5° C at rest and with exercise after modafinil ingestion.32

Regulation of ADHD Treatment As with all medications with potential ergogenic effects, the regulatory bodies of various sports have established rules. The International Olympic Committee (IOC) banned amphetamines in 1968, secondary to a perception of an unfair competitive advantage and health risks. Research has not demonstrated clear benefit of amphetamine use in rested subjects, but there is evidence of obvious performance benefit in sleep-deprived subjects. Controlled studies on amphetamine use in sport are limited, but they may improve short-term power performance.33 The NCAA requires substantial documentation in the case of a positive drug test. Methylphenidate was banned in 1999 when the Olympic Movement Antidoping Code added a statement banning “related” products and substances. In 2000, the Olympic Oath included a reference to the non-use of all drugs. However, a high profile case of an American Olympic sprinter brought about the specific ban of modafinil and buproprion, which represent new and novel stimulants.34 The World Anti-Doping Agency and the International Olympic Committee do allow the use of stimulants with a “Therapeutic Use Exemption” (TUE).

Summary ADHD is a common condition that is found within the athletic population at all ages. Treatment of ADHD with psychostimulants may put the athlete at risk for international journal of Athletic Therapy & training

heat injury but does not appear to increase the risk for sudden cardiac death. 

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Jeffrey Kreher is a musculoskeletal and sports medicine specialist in the Department of Orthopaedic Surgery—Pediatric Orthopaedics, Massachusetts General Hospital for Children in Boston.

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