A New Standard of Treatment By William W. Dodson, M.D.

Belief vs. Evidence in Medical Care <p align="justify">Until recently the standard of care for the diagnosis and treatment of AD/HD was based on several BELIEFS held by both clinicians and laypersons and perpetuated by the lay media. Among those assumptions were the beliefs that AD/HD:

1) Was a minor disorder if it existed at all,

2) Affected almost solely males (i.e. only half of the population was at risk to begin with) ,

3) Had little impact beyond grade school,

4) Went away spontaneously sometime in adolescence.¹

<p align="justify">Accordingly, there has been a prevailing belief that AD/HD was:

1) Over-diagnosed and that the diagnosis was thrown at any child who was energetic or "different" and that medication was only a form of chemical control.

2) Mis-diagnosed when the real problem was poor parenting, situational stress, or rigid, misguided teachers.

3) Over-treated by physicians who were using powerful and potentially addicting drugs to treat a minor and temporary ailment.

<p align="justify">This produced a pattern of treatment in which clinicians commonly did not use medications at all or, when they did:

1) Used low doses,

2) Treated only Monday through Friday,

3) Treated only during school hours,

4 Gave drug holidays on weekends, holidays and vacations, and

5 Stopped medications altogether in adolescence.²

<p align="justify">The problem is that not a single one of these beliefs or assumptions is true and there currently exists an abundance of EVIDENCE to the contrary. This presentation will review the evidence to date and how that scientific data translates into an entirely different EVIDENCE-BASED standard of care.

<p align="justify"> Genetics and Persistence Through the Life Cycle

<p align="justify">Once upon a time a rational person could have had honest misgivings about whether AD/HD actually existed at all. AD/HD was first diagnosed in children who could not articulate their experiences. Consequently, virtually all of our early formulations were based on second hand information from parents and teachers who filled out scales for researchers they oftentimes never met. The diagnosis was further complicated by the inconsistent nature of the impairments that could rise and fall over time and with the level of interest and challenge experienced by the individual. The Church of Scientology fed on these difficulties to create controversy, misgivings, and fear. Nonetheless, by 1998 the scientific response to all of this controversy had created a body of research on AD/HD that led the American Medical Association to call ADHD "one of the best-researched disorders in medicine, and the overall data on its validity are far more compelling than for many medical conditions."³

<p align="justify">Perhaps the most compelling of this data came from the research that demonstrated the clear genetic basis of AD/HD. The strongest data come from the ten twin studies that reported heritability between 0.6 and 0.9 (1.0 means a solely genetic pattern of transmission) across various sets of diagnostic criteria.⁴Adoption and family studies (see review by Faraone and Biederman⁵) support the concept that there is little contribution from the environment. AD/HD usually runs in families. Stressors and bad parenting can make the manifestations and impairments worse but they do not cause AD/HD.

<p align="justify">The evidence that AD/HD was a brain-based, genetic developmental disorder has far-flung implications. Just as no other genetically based developmental disorder disappears with age, neither does AD/HD. Its manifestations and the patient's compensation to the disorder change throughout the lifespan.⁶The basic features, impairments, and treatments, however, are very similar for both children and adults. People do not "outgrow" AD/HD just as no one outgrows any other genetic disorder or any other developmental disorder. All people develop better abilities to pay attention and control impulses as they grow older. Most patients will benefit from lifelong medication even if they have "learned to cope with ADD" because life stresses increase rather than diminish with age.

<p align="justify"> STANDARD OF CARE #1: Since AD/HD is a condition that runs in families and persists for a lifetime, the clinician must:

1) consider the diagnosis in patients of all ages and not just in children and adolescents,

2) screen all members of the family for the presence of AD/HD, not just the identified patient,

3) educate the patient on the lifelong nature of the disorder and the benefits of lifelong treatment.

<p align="justify"> IMPAIRMENT

<p align="justify">By DSM-IV definition the symptoms of AD/HD must be consistently and persistently impairing in at least two areas of life functioning. In other words, the diagnostic criteria are much more than endearing personality traits and quirks. They must significantly impair major aspects of day to day functioning in order to rise to the level of a diagnosis. Over the last decade these domains of impairment have been carefully researched.

<p align="justify"> Academics : Perhaps no area of dysfunction is as well documented as the impairment of school performance by the symptoms of AD/HD. Failure to perform academically is the single most common cause for referral for children and adolescents. Weiss and Hechtman⁷in follow-up studies at 5-, 10-, and 15-year intervals demonstrated AD/HD children performed poorly on achievement tests and failed grades/courses significantly more often than children of similar ability who did not have AD/HD. Children with AD/HD completed on average 3 fewer years of education than matched controls and were more likely not to graduate high school in spite of having more than adequate ability.⁸When AD/HD co-occurs with significant learning disabilities as it does in more than 30% of cases the academic impairment is usually profound.

<p align="justify"> Health and Injury: Accidents are the leading cause of death until 44 years of age. Without treatment adolescents with AD/HD have 400 % more injury producing accidents and 300 % more motor vehicle violations than do adolescents without AD/HD or adolescents with AD/HD who consistently take medication.⁹A 9-year study of medical utilization (beyond just the direct costs of treating the AD/HD) demonstrated that persons with AD/HD have more than double the cost of care as compared to controls.¹⁰

<p align="justify"> Substance Use: Many people with AD/HD try to self-medicate their illness. Left untreated, persons with AD/HD have more than three times the incidence of substance use disorder diagnosis than does the population at large. Biederman and his colleagues¹¹demonstrated in a prospective, longitudinal study that the risk of substance abuse by AD/HD individuals remains equal to that of controls until 15 years of age. Between the ages of 15 and 27, however, the rate of substance abuse severe enough to be diagnosed as a substance use disorder triples (47% vs. 15%) . Far from predisposing to later drug abuse, treatment of AD/HD with stimulant class medications actually protects against the development of substance use disorders (SUD's) . If the person with AD/HD is consistently treated with stimulant class medication, the risk of developing SUD is the same as the general population.

<p align="justify"> Psychosexual functioning: In the one of the longest longitudinal outcome studies¹²done thus far, Barkley has followed a cohort of AD/HD children into their mid-twenties. Their sexual lives give a grim look at the impact of untreated AD/HD. At the most recent follow-up more than half of the AD/HD group had been tested for HIV disease. No one in the matched control group had been tested. Of the 43 children born to participants in the study 42 had been born to the ADHD group limiting their academic and occupational attainment. Perhaps the most disturbing finding was that 54 percent of these parents had already lost custody of their children.

<p align="justify">Criminality:AD/HD has a high comorbidity with Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) .13This comorbidity coupled with an impulsive, high-risk lifestyle put AD/HD individuals at risk for legal problems of all sorts. A long-term study in New York found that people with AD/HD were more likely to arrested (39%vs. 20%) , and when they are arrested they are more likely to be convicted (28% vs. 11%) and much more likely to be jailed (9% vs. 1%) than were their non-AD/HD peers.¹⁴<

<p align="justify"> Social Functioning and Self Esteem: Research on adolescents with AD/HD demonstrates that the social problems of children with AD/HD persist into adolescence and usually get worse. Even when the data was controlled for the features of Conduct Disorder that can be significantly alienating by themselves, children and adolescents with AD/HD fare poorly socially. They have fewer friends, poorer social skills, are "last picked and first picked on", and have lower scores on assessments of self-esteem.¹⁵

<p align="justify">Adults with AD/HD report that they "just don't seem to get it." They do not have the intuitive understanding of how social and intimate relationships work. They tend to be tactless and blurt out things before thinking. This intuitive sense of how to navigate within a culture develops between 12 and 17 years of age and is one of the major developmental tasks to be accomplished. At this age teenagers come to the awareness that words alone no longer carry the meaning in interactions. The real meaning is often conveyed through non-verbal cues such as a look in the eye or a tone of voice. People who are inattentive or speeding from one stimulus to the next often miss this important subtext. If this intuitive understanding is missed at this crucial stage of development it is commonly missed forever. Adults with AD/HD may learn better social skills but it never comes naturally the way it does for others.

<p align="justify"> STANDARD OF CARE # 2: Treat the disorder.

<p align="justify">If left untreated, AD/HD is a devastating disorder associated with severe impairments in every area of life functioning. It is no longer appropriate to recommend "waiting to see if he grows out of it" or "trying harder." There are NO significant adverse consequences associated with treatment. All of the adverse consequences are associated with non-treatment.

<p align="justify"> STANDARD OF CARE # 3: Continue to treat the disorder all day, every day, lifelong

<p align="justify">.AD/HD requires treatment in every setting in which the individual experiences impairment. Although the DSM criteria require impairment in two major areas of functioning, in practical terms most patients experience impairment in every aspect of functioning. Treatment of AD/HD only during school hours is nonsensical.

<p align="justify">Just as AD/HD itself persists into adulthood and changes its presentations so do the impairments continue to develop and be manifest as the individual with AD/HD develops. Most importantly, the consequences of untreated AD/HD get more severe with age. A child can repeat the fourth grade with fewer and less severe long-term consequences than an adult who fails at a job that supports his family or the adult who has his life disrupted by substance abuse, multiple accidents, unplanned pregnancies, legal problems, and social/interpersonal ineptness.

<p align="justify"> WHAT WORKS IN THE TREATMENT OF AD/HD?

<p align="justify">While it is true that medication is only the beginning of the treatment of the many facets of AD/HD, it must be emphasized that it is the essential one. As the results of the five-year, multicenter, Multimodal Treatment Study of AD/HD (MTA)¹⁶become available, it is becoming more and more clear that medications are the treatment of choice. The initial reports indicate that medication alone and medication plus intensive behavioral treatment were nearly identical and that both were significantly superior to behavior management alone on 18 out of 19 outcome measures. The community treatment arm of the MTA also showed that 1/3 of these children with clearly documented "screaming" AD/HD received no treatment whatsoever and that those who did get treatment of some sort were almost always under-dosed on their medication. The MTA is just the most recent evidence that ADHD remains grossly under-treated.

<p align="justify">It is important to be clear about what the MTA study means and does not mean. It DOES NOT mean that adjunctive treatments such as behavioral management are not effective or not needed. These treatments are often absolutely necessary to teach the self control and social awareness that was not learned at age appropriate times due to the interference of AD/HD. The MTA clearly demonstrates that behavior management and "trying harder" do not treat the major impairment domains of inattention, impulsivity and motor restlessness.

<p align="justify">It DOES mean that:

1) AD/HD is not the result of bad parenting skills. These were good, involved parents who got even better. It just didn't make any difference.

2) AD/HD is not the result of a defect in character or laziness. Trying harder even with the intensive support of specialists in the field was ineffective.

<p align="justify"> STANDARD OF CARE # 4: Stimulant medications are where everyone should start, not the treatment of last resort when everything else has failed. Start medication as early as possible before the person has fallen hopelessly behind academically and maladaptive coping mechanisms and self-image issues have become ingrained. NEW DELIVERY SYSTEMS

<p align="justify">The minor stimulant class medications methylphenidate and amphetamine clearly work well and have become the treatment of choice for AD/HD. In real life the problem is how to actually get the medications that work so well into the patient at the right time. By definition people with AD/HD are poorly structured, forgetful, have trouble carrying through with a course of action, lose things, and get distracted from important activities. It is unreasonable to expect rigorous compliance from this patient population unless extended release delivery systems are utilized.

<p align="justify">The last 18 months has seen six new delivery systems enter the market that attempt to extend the action of either amphetamine or methylphenidate and to smooth out their kinetics. Methylphenidate has an onset of action that is abrupt and sometimes leaves the body so suddenly that patients "crash" or "Ritalin rebound" -- a condition that is described as an odd combination of lethargy, irritability, and confusion that lasts for 20-60 minutes after the last dose of the day wears off. Rebound occurs with all minor stimulants but is more dramatic with immediate release methylphenidate products.

<p align="justify">Amphetamine Delivery Systems:

1) Dexedrine Spansule has been on the market for more than 20 years. It delivers just the right-handed isomer of amphetamine by using the same enteric coated "tiny time pills" used in the over the counter Contac cold remedy. The Dexedrine Spansule comes in 5 mg, 10 mg, and 15 mg dosage strengths and is relatively difficult to fine-tune the dose due to the inability to divide the capsules. The only post marketing study of Dexedrine spansule by Brown and colleagues¹⁷found that the spansules and the tablets had the same duration of action.

2) Adderall XR is a beaded technology that reliably and steadily releases four different salts of both left and right-handed isomers of amphetamine over 10 to 12 hours. It is available in 10 mg, 20 mg, and 30 mg strengths. It is often advantageous to open the capsules to fine-tune the dose in half capsule increments despite the FDA-approved package insert stating that this should not be done. Other dosage strengths are promised before the end of 2002 (5 mg, 15 mg, 25 mg, and 40 mg) that will make fine-tuning of the dose and compliance easier.

<p align="justify">Methylphenidate Delivery Systems:

1) Ritalin SR is unreliable because Novartis and the generic manufacturers embed the MPH in a wax matrix and compressed the tablet more tightly for its long acting kinetics. This delays the onset of action by two hours but does not actually extend the duration of action much beyond the usual four hours. Ritalin SR only comes in one strength, 20 mg, which cannot be divided to fine tune the dose. No studies actually demonstrate that it has superior efficacy over immediate release methylphenidate preparations¹⁸

2) Metadate ER and Methylin ER use a "lumpy gravy" mechanism of retarding the release of methylphenidate. These two nearly identical products can be divided and fine-tuned to the individual patient but rarely provide more than 6 or 7 hours of effective action and are, therefore, still too short in duration to get a child all the way through a school day.

3) Concerta (methylphenidate in an osmotic release "oros" delivery system) has recently become available in dosage strengths that deliver 18 mg, 27 mg, 36 mg, and 54 mg doses over 8 to 12 hrs. Unfortunately, the release of the methylphenidate is constantly changing in a crescendo pattern that only gives the optimal dose for approximately two hours out of the total duration of action. It is the most heavily back loaded delivery system (28/72) and the complex mechanism is prone to failure.

4) Metadate CD is a beaded delivery system that delivers methylphenidate in a steady release over 8 to 10 hours. It comes in three dosage strengths, 10, 20, and 30 mgs, that are heavily back-loaded like Concerta.

5) Ritalin LA is the most reliable of the methylphenidate delivery systems. It is the only MPH product that divides the dose in a 50/50 split that mimics how a person would take an immediate release product. It comes in three dose sizes (20, 30, 40 mgs) with a lower and higher dose sizes promised in 2004.

6) On the near horizon is a two beaded delivery systems from Novartis of the pure right-handed isomer (Focalin LA) .

<p align="justify"> Standard of Care #5: This is a patient population that is notoriously forgetful and that has difficulty carrying through with a course of action. Therefore, whenever possible, use long-acting formats of stimulant class medications that are more convenient and give fewer times to forget a medication dose. 24-HOUR TREATMENT

<p align="justify">The DSM V is not expected until 2010 but work has already begun on the official criteria for adults with persistent AD/HD. It has long been recognized that while the inattentive criteria persist into adulthood, the impulsive/hyperactive criteria that discriminate well for children and early adolescents with AD/HD do not work well for adults at all.

<p align="justify">Sleep disorders are common in patients with AD/HD at all ages.¹⁹Sleep disturbances such as sleep walking, sleep talking, initiation insomnia, restlessness, fractured sleep architecture, and enuresis were diagnostic criteria in the DSM III but were dropped in transition to the DSM III-R because they were felt to be non-specific. It is now known that sleep disturbances in persons with AD/HD increase in both prevalence and severity with age. In prepubertal children the incidence of severe initiation insomnia is about 10 to 15 percent. The incidence reaches fifty percent by 12.4 years age and is almost seventy-five percent by the age of 30. Adults describe four different types of sleep disturbance:

<p align="justify">

1) 75% of late adolescents and adults with AD/HD describe themselves as "night owls." They experience a burst of energy when the sun sets and then have an initiation insomnia in which they are unable to turn off their mind to go to sleep. They describe that their thoughts "bounce" or "jump" from one concern or worry to another for, on average, one and half hours each night.

2) Once they do fall sleep they report that they have multiple awakenings and toss and turn until approximately 4 AM.

3) They have significant difficulty waking up and feeling mentally alert in the morning.

4) There is an intrusion of drowsiness or sleep when bored. This is often mistaken for narcolepsy. This phenomenon can be fatal if it occurs while driving.

<p align="justify">These sleep disturbances are the manifestations of the mental and physical restlessness of ADHD. Just as AD/HD does not go away in adolescence, it does not go away at night either. The treatment at night is the same as the treatment during the day... stimulant class medication. No behavior management techniques have been found to be effective with AD/HD patients for the initiation and maintenance of sleep. The fear among parents and adult patients is that the medication will keep them awake at night instead of continuing to provide the calmness, relaxation, and steadiness that it did during the day. The simple use of a no-risk trial in the form of a nap in the afternoon while on medication usually demonstrates that well-regulated stimulant class medication helps with the initiation and maintenance of sleep instead of hinders it.

<p align="justify">It is very important in the initial evaluation to take a careful history of sleep disturbances. Patients who report significant difficulty with initiating sleep or awakening in the morning will need more patient education and will need to take more doses of medication throughout the day. Later reports of sleep disturbances will need to be evaluated in light of this initial history to distinguish sleep disturbances due to AD/HD from those caused by the stimulant class medications used to treat the disorder.

<p align="justify"> STANDARD OF CARE # 6: Assess whether to treat with stimulant class medication 24 hours a day.

<p align="justify">AD/HD disrupts sleep in the majority of patients with the proportion having sleep disturbances due to the restlessness of AD/HD increasing with age. The history of consistent difficulty shutting down to fall asleep at night warrants a trial of nighttime medication.

<p align="justify"> SUMMARY

<p align="justify">AD/HD is a brain-based genetic disorder that, if left untreated, causes significant impairment in every area of life and throughout the lifespan. The current treatments are effective and safe. All of the adverse consequences are associated with NOT treating the disorder. Therefore, the current standard of care requires that the clinician:

1) Thoroughly assess all patients regardless of age for the diagnosis,

2) Assess all family members for AD/HD, not just the identified patient.

3) Recommend aggressive, multimodal treatment with the institution of stimulant class medications early in the process.

4) Start medications early in the process before maladaptive behaviors and poor self-esteem become ingrained.

5) Recommend treatment with stimulant class medications throughout the day and not just during school hours.

6) Recommend treatment seven days a week, 52 weeks a year.

7) Recommend continuous treatment with stimulant class medications lifelong.

8) Use long-acting delivery systems that maximize compliance and success.

9) Assess the efficacy of nighttime use of medications to improve the initiation and maintenance of sleep.

REFERENCES

<p align="justify">¹Goldman LS, Genel M, Bezman RJ, Slanetz PJ. Diagnosis and treatment of Attention Deficit/Hyperactivity Disorder in Children and Adolescents. JAMA 1998; 279(14) 1100-1107.

<p align="justify">²MTA Cooperative Committee. Moderators and mediators of treatment response for children with attention deficit / hyperactivity disorder. Arch Gen Psychiatry. 56:1088-1096, 1999.

<p align="justify">³Goldman LS, op cit.

<p align="justify">⁴Todd RD. Genetics of Attention Deficit/Hyperactivity Disorder. Am J Med Genetics 96:241-243, 2000.

<p align="justify">⁵Faraone SV, Biederman J. Genetics of Attention Deficit/ Hyperactivity Disorder. Child Adolesc Psychiatric Clinics N AM3:285-301.

<p align="justify">⁶Wender, P, The Hyperactive Child, Adolescent, and Adult-Attention Deficit Disorder Through the Life Span. Oxford University Press, New York, 1987.

<p align="justify">⁷Weiss G and Hechtman LT. Hyperactive Children Grown Up. 2nd Edition. New York, NY: Guilford Press; 1993.

<p align="justify">⁸Mannuzza S, Klein RG. Diagnosis and longitudinal course of Attention Deficit/ Hyperactivity Disorder. The Economics of Neuroscience 47-53, April, 2001.

<p align="justify">⁹Barkley RA, et. al. Driving-related risks and outcomes of Attention Deficit/Hyper-activity Disorder in adolescents and young adults: a 3-5 year follow-up survey. Pediatrics.92:212-218, 1993.

<p align="justify">¹⁰Leibson CL, et al. Use and costs of medical care for children and adolescents with and without Attention Deficit/Hyperactivity Disorder. JAMA 285(1) 60-66, 2001.

<p align="justify">¹¹Biederman J, Wilens T, Mick E, Spencer T, Faraone SV, Pharmacotherapy of Attention Deficit / Hyperactivity Disorder reduces risk for substance use disorder. Pediatrics 104(2) :1999.

<p align="justify">¹²Barkley RA, ADD Research: a look at today and tomorrow. ATTENTION! 1996; 8-11.

<p align="justify">¹³Biederman J, Faraone SV, Milberger S, et al. A prospective 4-year follow-up study of Attention Deficit/Hyperactivity Disorder and related disorders. Arch Gen Psychiatry53: 437-446, 1996.

<p align="justify">¹⁴Mannuzza S, Klein R, Konig PH, Giampino TLK. Hyperactive boys almost grown up:IV. Criminality and its relationship to psychiatric status. Arch Gen Psychiatry. 46:1073-1079, 1989.

<p align="justify">¹⁵Hechtman L, Weiss G, Perlman T. Hyperactives as young adults: self esteem and social skills. Can J Psychiatry25: 478-483, 1980.¹⁶MTA Cooperative Committee, A 14-month randomized clinical trial of treatment strategies for Attention Deficit / Hyperactivity Disorder. Arch Gen Psychiatry. 56: 1073-1086, 1999.

<p align="justify">¹⁷Brown GL, Ebert MH, Mikkelsen EI Hunt RD. Behavior and motor activity response in hyperactive children and plasma amphetamine levels following a sustained release preparation. J AM Acad Child Adolesc Psychiatry 1980:19, 225-239.

<p align="justify">¹⁸Solanto MV, Arnaten AFT, Castellanos FX, Eds. Stimulant Drugs and ADHD: Basic and Clinical Neuroscience . Oxford University Press, New York, 2001. pgs 50-52.

<p align="justify">¹⁹Corkum P, et al. Sleep problems in children with Attention-Deficit/Hyperactivity Disorder: impact of subtype, comorbidity, and stimulant medication. J Am Acad child Adolesc Psychiatry 1999; 38 (10) : 1285-1293.