?         3.4% developed definite ADHD (DSM-III-R), and 2.7% ADHD-NOS (Not Otherwise Specified), for a total of 6.1% - figures consistent with other reports of incidence.

?         Among those treated with stimulants, however, 57% did not fulfill criteria for ADHD, and 29.3% of these had no ADHD symptoms at all.  The possibility that this simply indicated successful eradication of symptoms with medication was eliminated, since 56% of the treated, non-ADHD subjects began their treatment after the initial diagnostic interview.  Seventy-one percent of these subjects had no parent-reported ADHD symptoms (Angold, Erkanli, Egger, & Costello, 2000).

 

Basic Nature of ADD/ADHD

            It is fair to say, considering the above, that definitional and diagnostic precision are lacking. The very nature of ADD/ADHD is similarly unclear.  Although widely assumed to stem from a biological or neurological cause, with a significant genetic heritability factor, recent conclusions and statements from authoritative sources reveal the lack of evidence to support this assumption.  Reliance upon such expert consensus to interpret the current state of the science on ADD/ADHD is reasonable, because as pointed out in Attention Deficit Hyperactivity Disorder  State of the Science (2002b, p. xxi), "literally thousands of studies have been conducted on ADHD and its various predecessors prior to the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994)."  The sheer volume of published studies precludes reliance upon comprehensive literature review.  Even systematic reviews and meta-analyses of the literature (Schacter 2001, Schachar 2002) are fraught with numerous sources of methodological flaws, contamination of findings, and a tendency to exaggerate effects of treatment as will be discussed later.

?                     From the 1998 NIH Consensus Development Conference: ?There is no independent valid test for ADHD . . . Although research has suggested a central nervous system basis for ADHD, further research is necessary to firmly establish ADHD as a brain disorder? (NIH Consensus Development Panel, 2000, p.183).

?                     From the Agency for Health Care Research and Quality (AHRQ): ?The etiology of ADHD is unknown, and the disorder may have several different causes.? (Agency, 1999a, p.#1).  The AHRQ report is based upon a review of the 87 highest quality published articles from among 2,405 citations produced by an exhaustive search.

?                     From Attention Deficit Hyperactivity Disorder   State of the Science: "As recently as the 1998 National Institutes of Health Consensus Development Conference on the Diagnosis and Treatment of ADHD, consensus panelists concluded that the etiology of ADHD is unknown.  As the chapters in this section make clear, that situation has not changed (Jensen and Conners, 2002, p. P2-1)."   Carey further states: "The assumption that the ADHD symptoms arise from cerebral malfunction has not been supported even after extensive investigations (Carey, 2002, p. 3-2).

 

Brain Differences

            Reports of differences in various brain structural or functional measures between subjects considered to be normal and those considered to have ADD/ADHD have led some to believe that these measurable differences establish a central nervous system basis for the syndrome.  For several reasons, the reported differences do not justify this conclusion.

            The first and foremost flaw in this interpretation is that selection of subjects begs the question of how to establish that the syndrome group has the disorder and that the normal group does not, since (1) there is no test to determine the presence of ADD/ADHD, and (2) the diagnostic criteria are subjective, as established above.  The behavioral criteria upon which the diagnosis is made have been modified in an unending series of revisions, as found in DSM II, DSM III, DSM-III-R, and DSM IV. 

            Beyond this fundamental flaw, even assuming diagnostic precision for the respective groups being studied, finding a measurable difference in brain structure or function between two groups begs the question of causality.  Such measurable differences could represent antecedent measures or differences in structure or function as a result of the behaviors defining the syndrome.  Available research supports this possibility.

            Serotonin concentrations in whole blood in a 1971 study of 25 hyperactive children were reported to be significantly lower than in 150 control normal children, with no hyperactive child having a level above the lowest level among the controls.  The two most extreme cases were placed in a clinical research unit, and their 5-hydroxyindole levels rose toward normal as their behavior changed while in the unit.  These levels then decreased to pre-hospital values as their behavior reverted back to baseline following return to their home environment (Coleman, 1971).

            Although a study demonstrating measurable brain changes following behavioral management did not involve ADD/ADHD subjects, its findings suggest that brain changes may be induced by behavior changes.  Nine adults with DSM-III-R criteria for Obsessive-Compulsive Disorder (OCD) were treated in one or two weekly one-hour sessions with individualized exposure and response-prevention exercises, home assignments, and cognitive counseling while remaining medication free.  Positron emission tomography (PET) scans were performed at baseline and repeated after 8 to 12 weeks of therapy.  Significant decreases  were found in caudate glucose metabolic rates among responders to treatment that were greater than those seen in non-responders.  Changes in cerebral glucose metabolism from behavioral therapy alone were found to be comparable to those found from prior study of medication therapy (Schwartz, Stoessel, Baxter, Martin, & Phelps, 1996).                                                              Similarly, Furmark and colleagues (2002) studied 18 previously untreated adult patients who fulfilled DSM-IV criteria for social phobia disorder for neurofunctional changes associated with anxiety alleviation following cognitive-behavioral group therapy (CBGT) and citalopram medication treatment.  PET scans were used to assess regional cerebral blood flow (rCBF) during a public speaking task, before and after 9 weeks of medication or CBGT therapy, and in a waiting list (WL) control group.  In CBGT- and citalopram-treated patients, symptom improvement was accompanied by a significantly reduced rCBF in several areas of the brain, while no significant change was observed in the WL controls.  Thus significant and similar changes in cerebral blood flow were shown to occur as a consequence of either behavioral or medication treatment.  These authors speculated further, based on previously reported research, that reduced prefrontal and cingulate activity could have stemmed from an alteration of the emotional experience or a reduction in catastrophic or negative thinking among their subjects.

            Volkow  and colleagues, leaders in the field of brain imaging and drug effects, have studied the effects of methylphenidate on normal adult volunteers with PET scans.  She has commented: "We know that social interactions can increase dopamine receptors, but whether better interplay also affects transporter levels is unknown" (Vastag, 2001, p. 906).  Reiman (1997) used PET scans to study regional cerebral blood flow (CBF) during normal human emotion and found significantly increased CBF in several areas of the brain in response to picture-generated positive and negative emotion. 

            Physiological effects upon blood levels of catecholamine were shown to follow exposure of adults with a phobic dread of spiders to experimental tasks corresponding to varying strength of perceived self-efficacy (Bandura, Taylor, Williams, Mefford, & Barchas, 1985).   Plasma levels of norepineprine following interaction with a phobic object were found to be low in the presence of high perceived self-efficacy, while they were increased in subjects with moderate perceived self-inefficacy.  Plasma levels of dopac, a degradation product of dopamine, were shown to rise after exposure of subjects to tasks for which they held perceived deficient coping ability.   Neurotransmitters dopamine and norepineprine have been implicated in the theoretical pathophysiology for ADHD, and form the basis for current pharmaceutical research justifying use of stimulant medications in treating ADHD (Shire, 2002).  In discussing stimulant medication treatment, it is stated, "Medications sometimes referred to as stimulants are the most successful treatments for ADHD.  These medicines are thought to correct the chemical imbalance in the brain by making more dopamine and norepinephrine (two neurotransmitters) available (p.14)."  It is therefore reasonable to assume that changes in neurotransmitter levels might be the result of cognitive or emotional processes rather than represent the cause of observed behaviors defining ADHD.  

            Researcher William T. Greenough reviews and summarizes animal and human research showing how experience can influence the developing and mature brain (Greenough, Black, & Wallace, 1987).  Valenstein (1998) further reviews research on the effects of experience on the  brain, citing Jacobs et al.?s work showing branching of neuronal dendrites in the language area of humans proportionate with the amount of education.  A developmental cognitive neuroscientist  has  pointed out that effects on the brain of learning experiences occur in humans as well as animals.  Nelson states, ?Overall, then, it appears that the human brain ? even the brain of an adult ? is capable of undergoing reorganization after certain kinds of experience? (Bloom, Nelson, & Lazerson, 2001, p.90)

            As cited by Diller (1998), Zametkin in 1990 reported PET scan findings of 8.1% lower glucose metabolic rates in parents of children with hyperactivity than in parents of normal children, taking measurements during an auditory-attention task.  Subsequent follow-up studies on adolescent boys and girls, however, failed to confirm the strength of his original findings. Furthermore, in later short- and long-term studies of adults with ADD, treatment with methylphenidate did not lead to correction of these patterns of glucose underutilization.

            In a review of research that has led to some to conclude that ADD/ADHD is a neurological condition, Jensen and Conners (2002, p. P2-1) state the following:  "This section presents substantial evidence that ADHD symptomatology has a central nervous system basis (as do all normal and abnormal behaviors, thoughts, and emotions) (emphasis added).  By way of caution, such brain-behavior correlations do not constitute proof that ADHD reflects a disordered physiological or anatomic state."

            A 20-year research project followed more than 100 people from age 2 to adulthood and studied the relationship between behavioral inhibition or uninhibition during childhood and subsequent emergence of features of externalizing or internalizing disorders in young adulthood (Schwartz, Wright, Shin, Kagan & Rauch, 2003).  Adults who had been categorized in the second year of life as inhibited, compared with those previously categorized as uninhibited, were found to show greater functional MRI signal response within the amydgala to novel versus familiar faces, as well as a tendency to develop internalizing or externalizing disorders, respectively.  The authors interpreted their study as supporting the hypothesis that some brain properties related to temperament are preserved from infancy into adulthood.  They make the following cautionary note, however, about interpretation: 

These results imply that discovery of a difference in brain activity between subjects with a psychiatric diagnosis and a control group should not always be regarded as a specific marker of the disorder.  The difference may reflect instead a temperamental risk factor, or diathesis, for the diagnostic category under study.

             In addition to the possibility of demonstrable structural, functional, or chemical brain changes in ADHD subjects being a consequence rather than a cause of behaviors, or simply reflecting basic temperament or personality differences, studies claiming a causal relationship fail to control for the confounding effect of drug treatment.  Castellanos et al. (1996, p. 614), though arguing for a causal relationship between MRI detected brain changes and ADHD, comment: "Because almost all (93%) subjects with ADHD had been exposed to stimulants, we cannot be certain that our results are not drug related."  They (Castellanos, 2002) have more recently reported findings from a prospective MRI study of 152 ADHD subjects and 139 controls, in which 49 ADHD subjects without prior exposure to stimulant medication were included.  Significantly smaller total cerebral volumes, total white matter volumes, and cerebellar volumes were found among ADHD subjects than among controls, and these differences, all stable over time, remained among ADHD subjects without stimulant medication treatment, leading the authors to conclude that decreased brain volumes in ADHD subjects are not due to drug treatment.  However, limitations of the study acknowledged by the authors include:

?        The use of referred samples for patients and highly screened controls that "may not be optimally representative. (p. 1747)"  

?        In ongoing longitudinal follow-up the authors acknowledge that global functioning outcome in the 64 ADHD subjects four years after their initial scans fails to show any significant relationship between the continuing anatomical differences on MRI and clinical follow-up status. 

?        The use of an analysis of variance, which is appropriate only with true randomization of groups, which as noted above by the authors was not the case.  

?        There was a significant age difference between ADHD and control groups, with the ADHD subjects being younger.  The authors did a statistical adjustment to correct for this difference, which violates fundamental principles of statistical analysis.  One cannot do a statistical adjustment on a dependent variable when the independent variable has already been contaminated.  One can only do a correlational analysis in such circumstances.  Leo and Cohen (2003)  point out that Castellanos et al.?s unmedicated subjects being younger, shorter, and lighter would be expected to have smaller brains than the medicated subjects, based on  previous research and quite apart from any considerations of effect of ADHD.

?        Leo and Cohen further point out the failure to provide information about dose, duration of treatment, or type of drug used, the authors stating only that 68% of the patients were being treated with psychostimulants at the time of the first scan. 

Therefore, the authors? earlier acknowledgement of the possibility of brain differences

representing drug effects do not appear to be satisfactorily resolved  by the current study.

            Robinson and Kolb (2001) reported an alteration of the morphology of neurons in the nucleus accumbens and prefrontal cortex in rats attributable to treatment with amphetamine.  They theorize from their experimental findings that the ability of amphetamine to alter patterns of synaptic connectivity in these structures may contribute to the amphetamine psychosis and addiction resulting from long-term repeated amphetamine use.  Stein (2001) has shown that of ten representative studies describing brain and nervous system dysfunction in ADD/ADHD subjects, similar central nervous system changes have been described as a consequence of drugs for eight.

                    A workshop held by the National Institute of Mental Health and the Food and Drug Administration to address concerns about the increasing use of psychotropic medication for preschool children concluded that: 

(1) Most medication use in preschoolers seems to be for the treatment of ADHD.

(2) The target of psychotropic medications is the brain, an organ that undergoes major developmental changes in the first few years of life.  The monoaminergic systems, on which psychotropics act, display great plasticity and rearrangement in early life.  The short- and long-term consequences of exposing the developing brain to pharmacologic agents are largely unknown (Vitiello, 2001, pp. 983-984).

These conclusions support the idea that changes in brain chemicals or function may be caused by exposure to stimulant medications in preschool years, if not in older children.

            In their comprehensive critical review of the ADHD neuroimaging literature, Leo and Cohen (2003) describe a number of serious methodological and interpretation flaws common to studies claiming or suggesting a causal relationship between neuroimaging differences and ADHD.  Among the most important is the failure to control for, or in many cases, even to discuss, prior treatment with stimulant or other psychotropic drugs.  This they find surprising since  ?an astronomical number of experimental and clinical studies on animals and humans find that almost every studied psychotropic drug has been consistently shown to produce subtle or gross, transient or persistent effects on the functioning and structure of the central nervous system.? (p. 31)  After discussing a number of these published studies, they conclude that ?it is critical to be able to rule out the probable impact on the brain of prior psychotropic drug use.? (p. 33)   They found that among 33 relevant neuroimaging studies, of the 29 that included a control group of normal subjects, only 19 reported on prior use of medication.  Although all but one of these found imaging differences between ADHD and control subjects, an average of 77% of the ADHD subjects had prior exposure to medication.  

            Baumeister and Hawkins (2001) have pointed out the inconsistencies among neuroimaging studies that have been reported in increasing numbers in recent years and used by some to claim a structural or functional brain basis for ADHD.  In their review of the literature, no specific abnormality in brain structure or function was supported by convincing evidence. 

 

Preschool Diagnosis and Treatment

            Leaving aside the many problems of operationalization of definition, and the ambiguity and subjectivity of diagnosis already discussed, there appears to be a trend to increasingly younger ages at which children are being diagnosed and treated.  This raises further concerns about potential detrimental effects of stimulant medication, especially when treatment is continued for prolonged periods of time, in many cases for years or even decades.

            Although data were not available to determine prevalence rates of diagnosis and treatment, a study of the Michigan Medicaid system for 1995-1996 found 223 children age 3 years or younger had been diagnosed with ADD/ADHD (Rappley & Mullan, 1999).  About one fourth of these children (60) were age 2 years or younger, and 10 were one year old or younger.  Among these children who were age 3 years or younger, 57% were treated with psychotropics, and 34.6% treated with two or three psychotropics simultaneously.

            Another study of Medicaid enrollees found a prevalence of 12.3/1000, including 1.23% of the children age 2 through 4 years (Zito, Safer, dosReis, Gardner, Boles & Lynch, 2000).  It was noted further that methylphenidate treatment prevalence increased 1.7-fold and 3.1-fold from 1991 to 1995 among two groups of children 2 years old or younger.  The authors reported that a national prescription auditing firm had reported to the DEA 4,000 methylphenidate prescriptions for children age 2 years or younger in 1998.

 

Genetic Heritability

            When looked for, ADD/ADHD behaviors are often found among immediate family members and other relatives, leading to a belief that ADD/ADHD is familial, and that this suggests a genetic transmission factor.  Research findings have been widely interpreted to support a significant genetic component to the development of ADD/ADHD.  This view is illustrated in the following comments from prominent researchers Swanson and Castellanos (2002), citing others: "Family and adoption studies suggest a strong genetic basis for ADHD/HKD (hyperkinetic disorder).  The twin study methods offer ways to test this hypothesis and to estimate heritability of ADHD, which Goodman and Stevenson estimated to be about 0.75." 

            Joseph (2003) shows how methodologically unsound research on twins and adoptees has led to the erroneous conclusion that there is a genetic basis for ADHD, and how textbooks typically repeat this unsupportable conclusion.  He has presented detailed arguments pointing out the flaws in this faulty interpretation of genetic research (Joseph, 2000a, 2000b).   

            Having considered the above, it is hardly surprising that leading researchers in the field offer inconsistent explanations for the basic nature of ADD/ADHD in their writing.  Barkley (1995) has offered two contrasting summary comments about the nature of ADHD in his widely used guide for parents:  ?I believe the disorder stems from underactivity in an area of the brain that, as it matures, provides us with ever-greater means of behavioral inhibition . . ." (p. 19).  Later he states, ?This means that ADHD should not be considered some grossly abnormal pathological condition - in fact it is a condition not qualitatively or categorically different from normal at all? (p. 65).  William B. Carey, co-editor of a pediatric developmental-behavioral text, in comments delivered at the 1998 NIH Consensus Conference on ADHD, states: ?What is now most often described as ADHD in the United States appears to be a set of normal behavioral variations.  This discrepancy leaves the validity of the construct (ADHD) in doubt? (Carey, 2000).  That inattentive and impulsive behaviors among children in schools is increasingly prevalent is beyond doubt.  As Carey's comment and the foregoing discussion suggest, however, to attribute these to a neurologically or biologically derived disorder cannot be supported by research.  Continued use of the term ADD or ADHD is useful only so long as it is recognized that it represents simply a behavioral pattern description and does not define an established disorder - let alone a disease.  This is the sense in which ADD/ADHD is used for the remainder of this discussion. 

 

Prevailing Conventional Management

            Conventional management of ADD/ADHD consists of stimulant medication treatment combined with a behavioral approach emphasizing the need for more immediate and stronger reinforcing responses to appropriate behavior as well as external provision of prompts, cues, and reminders.  Contingency response to target behaviors is primarily reward based, and punishment is considered to be counterproductive.  Recent reviews of available research and reports issued by experts raise serious questions about the efficacy of this approach.  Although stimulant medication provides substantial short-term improvement in target behaviors and inattentiveness in most treated subjects, this improvement is not specific for those with a diagnosis, data on long-term effectiveness or potential risks beyond 14 months is absent, behavioral gains during treatment fail to persist after discontinuation, and other concerns about long-term medication treatment exist. 

            The AHRQ summary report concluded:

Few studies followed children for a period of time equivalent to the length of time children typically remain on these treatments.  These studies show a trend to general improvement over time regardless of treatment and support the need for long-term-placebo-controlled studies . . . [Conventional] intensive behavior therapy, including child, family, and school-based interventions, adds little to the effects of long-term stimulant therapy (Agency for Health Care Policy and Research, 1999b, p. 1).

            The NIMH and Department of Education cosponsored a randomized clinical trial, the Multimodal Treatment Study of Children with ADHD in 1992 (MTA, 1999).  Outcome data obtained at 14 months has been said to represent the largest and most comprehensive, carefully designed study with the longest follow-up to date.   Behavioral treatment included parent training, child-focused treatment, and a school-based intervention organized and integrated with the school year.  Parent training was based on work by Barkley, Forehand and McMahon, involving 27 group (6 families per group) and 8 individual sessions per family.  The child-focused treatment was a summer treatment program (STP) developed by Pelham as a therapeutic summer camp consisting of an 8-week, 5 days-per-week, 9-hours-per-day intensive behavioral intervention utilizing counselors and aides.  School-based treatment included two components: (1) 10 to 16 bi-weekly teacher consultations focused on classroom behavior management strategies and (2) 12 weeks (60 school days) of a part-time behaviorally trained, paraprofessional aide working directly with the child.  A daily teacher report card itemizing the child?s successes for the day was brought home by the child, to be reinforced by the parent with home based rewards.

            In a commentary accompanying the MTA study report, Taylor (1999) points out, ?The (behavioral) regimen in this trial was admirable, extensive, and presumably, expensive.  In the context of a publicly provided mental health service, it is unlikely to be affordable? (pp. 1097-1099).  A careful analysis of the reported results casts doubt that even this intensive application of the conventional behavioral approach adds much to stimulant medication alone, even assuming the unlikely practicality of its widespread adoption.  The study found that the group receiving the closely monitored medication treatment, along with the intensive behavioral management, fared somewhat better than the group receiving conventional community management, which included stimulant medication in 67%.  Likewise the group receiving carefully monitored medication treatment alone had somewhat better outcomes than conventional community management.  Intensive behavioral management alone, however, added little to medication treatment alone (MTA, p. 1078).

            Pelham and colleagues (2001), reporting the advantages of a long-acting form (Concerta ?) of methylphenidate (MPH) over three-times-daily dosing with MPH, state that in their study "the percentage of positive remarks on a child's daily (teacher) report card was used as an individualized behavioral measure of medication response"(p. e109). Their behavioral management component, consisting of at-home parent training and an in-school teacher component (point system, daily report card feedback and time out) combined with the medication treatment produced behavioral results that were comparable to those reported by Swanson's study in a different laboratory and community setting but without the behavioral interventions.  It appears that Pelham et al both found their (reward based) behavioral intervention failing to add benefit to medication treatment, as well as assuming that outcome in defining positive remarks on a child's daily teacher report card as representing a measure of medication response. 

            Leo (2002) has described several methodological and interpretation flaws in the MTA study which cast doubt even upon the significance of the positive effects of stimulant medication reported.  These include: (1) Participating families were not representative, since only parents who accepted the disease notion of ADHD and who were willing to have their child treated with stimulant medication were included, and of the original 289 children enrolled, 18 parents refused medication and withdrew their children from the study.  (2) Data sources included parents, teachers, and trained classroom raters who observed children in the classroom.  Only these direct observers were blind to which children were receiving medication, and they found no difference between the medication and behavior management groups.  (3) Parents said medication improved both attention and hyperactivity/impulsivity, while the teachers found improvement only in attention, not in hyperactivity.  Schachar, Jadad, Phil, Gauld, Boyle, & Cunningham (2002) in their systematic review point out that primary outcome measures were not blind to the treatment group in the MTA study. 

 

Beneficial and Adverse Effects of Stimulant Treatment

            In the absence of data on long-term effectiveness or potential adverse effects of different methods of treatment, it is prudent to consider carefully relative advantages and potential disadvantages of relying predominantly upon stimulant medication to manage ADD/ADHD behaviors.  Regarding beneficial effects of treatment, short-term behavioral improvement is immediate once an optimal dose is achieved, and is usually substantial, sometimes dramatic.  Reports of successful short-term amelioration of core ADHD behaviors range from 50% to as high as 95% (Barkley, 1998a), depending upon co-morbidity.  Greenhill and Ford (2002) in a review of more than 180 placebo-controlled trials found that approximately 70% of patients respond to stimulants compared with 13% for placebo.  Schachter and colleagues (2001) in their meta-analysis of 62 placebo-controlled randomized trials from 1981 to 1999 found a number of significant limitations of the studies, however, including low quality of study design, average intervention time of only 3 weeks and no trial lasting longer than 28 weeks.   They further found a strong indication of publication bias and lack of robustness of the short-term improvement from medication, especially with regard to core ADD behaviors. 

            Schachar, Jadad, Phil, Gauld, Boyle, & Cunningham (2002) undertook a systematic review of the literature on randomized treatment studies in which treatment was administerd for 12 weeks or longer.  A formal critical evaluation of existing systematic reviews and meta-analyses prior to their review revealed extensive flaws due to poor description of methods use to identify, select, assess, and synthesize information.  They found that of 13 prior reviews, only 2 had minimal flaws, and these had a narrow focus on treatment effects as measured on the Continuous Performance Task or on school-based interventions.  Their review of the 14 studies with  treatment for 12 weeks or longer, from their initial search yield of 2402 citations, found a limited number of high quality studies and significant heterogeneity of outcome measures, with only 5 considered adequate for methodological quality.  They furthermore found a wide range of outcome measures, and incomplete data reporting, leading to the conclusion that meta-analysis would be an inappropriate and inadequate method of summarizing the evidence.  They point out that trials with poor methodological quality are more likely to exaggerate treatment effects. 

            With regard to long-term stimulant treatment, Barkley found that ?Few studies employing rigorous methodology have evaluated the long-term efficacy of stimulant medications.  Those that have examined the issue have generally found little advantage of medication over no medication when evaluated over extended periods? (Barkley, 1998, p. 521).

            In addition to the observed short-term improvement in target behaviors, it has been suggested that medication for ADHD subjects may reduce the probability of substance use disorder (SUD) compared with the risk among unmedicated ADHD subjects.   Biederman (1999) reported that among medicated ADHD subjects the odds ratio (OR) was 0.15 compared with non-medicated ADHD subjects.  A meta-analysis of studies with data on the development of SUD in adolescence or adulthood among stimulant treated and untreated ADHD subjects  found 5 prospective, longitudinal studies among a total of 6 studies from the United States and Germany (Wilens, Faraone, Biederman, & Gunawardene, 2003).  Four of the odds ratios (ORs) from 2 studies suggested an adverse impact of stimulants, but these were not statistically significant.  Seven of the ORs from 4 studies suggested a protective effect, and 5 of the ORs were statistically significant.  Barkley (2003) reported no greater risk of drug use by adolescence or adulthood among stimulant treated ADHD subjects than among untreated ADHD subjects in another prospective study.   Despite conflicting data (see ahead), the weight of evidence from  prospective studies, therefore, suggests that stimulant treatment of ADHD in childhood may provide some protective effect against SUD during adolescence or adulthood, compared with the rate of SUD among untreated ADHD subjects. 

              Certain components within the overall domain of language processing (Tannock, 2000) and cognitive function difficulties (Solanto, 2000) have also been found to improve on stimulant medication.  Pelham and colleagues (2001) replicated earlier studies finding short-term academic gains in the form of daily classroom activities including arithmetic tasks and individualized classroom goals.  They go on, however, to point out that: "Unfortunately, these acute effects, despite the fact that they continue in adolescence, have not yet been shown to translate into long-term gains in academic achievement, even with long-term stimulant use." (p. 11) The MTA study found no favorable  treatment effect on arithmetic and spelling, and the modest improvement in reading test scores with MPH treatment (in the range of 0.1 SD) was no greater than effect sizes for placebo treatment (Schachar, 2002). 

            An advantage of stimulant medication treatment is its widespread availability in pharmacies and the ability of most pediatricians and family physicians to prescribe it, insuring access.  The financial pressures of managed care have probably contributed to increasing rates of stimulant medication prescribing by primary care providers, likely at the cost, however, of contributing to the steadily increasing rates of stimulant treatment in various communities, and an accompanying increase in treatment in the absence of  criteria for ADHD, as illustrated earlier.

            With regard to side effects, Barkley (1998b) points out that one must distinguish between those attributable to the medication and identical symptoms observed among ADHD subjects in the absence of medication. Insomnia or diminished appetite are common and appear to be attributable to medication in many cases.  He comments that it is more difficult to ascertain with certainty whether other reported side effects such as anxiety, irritability, or proneness to crying can be attributed to the medication.  Breggin (1999a) summarizes data from mostly double-blind placebo controlled trials of stimulant medication, reporting severe adverse drug reactions in 8% of 359 children included in the studies.  Although significant long-term growth impairment has not been documented, a recent trend to using longer acting forms of stimulants and marketing by pharmaceutical companies encouraging treatment on weekends and during summers for the perceived advantages of medication on social behavior raise the question of whether such growth impairment effects may be found in the future.  Pelham and colleagues address this concern: "Whether long-term tid medication or Concerta will result in a reduction in growth velocity awaits assessment." (Pelham 2001, p. e116)

             Psychotic behavioral episodes have been observed in some patients while taking stimulant medication.  Shire US (2001), the manufacturer of Adderall ? (mixed amphetamine salts), states in the package insert for the new extended release form of the drug, ?Central nervous system adverse effects that have been associated with amphetamine use include psychotic episodes at recommended doses.? Although psychotic symptoms attributable to stimulant treatment are widely believed to be infrequent, a recent retrospective study found that 6% of 98 children treated with methylphenidate developed psychotic or mood-congruent psychotic symptoms during treatment (Cherland & Fitzpatrick, 1999).  None of these six were diagnosed with any other psychiatric disorder before or after treatment, and the symptoms resolved following discontinuation of stimulant medication.  Symptoms included paranoia, visual and auditory hallucinations, and bizarre behavior.  As pointed out by the authors, the study is retrospective and cannot determine the frequency with which such side effects of stimulant medication occur, but the nature of the study is more likely to underestimate than to overestimate prevalence.  They call for prospective studies in order better to ascertain the frequency with which this complication of therapy occurs.  The Associated Press (1999) reported a North Dakota incident in which a 24-year old father fatally shot his 5-week old daughter before wounding himself and recovering.  A murder charge was dismissed by the judge following court hearings in which psychiatrists testified that the killing resulted from a psychotic state caused by Adderall within days of beginning the medication for treatment of ADHD. 

            Additional reported adverse effects of stimulant medication treatment of ADHD include obsessive-compulsive behaviors and explosive behavioral outbursts.  Kouris (1998) described an eight-year-old male with onset of severe obsessive-compulsive (OC) behaviors within two weeks of beginning methylphenidate for ADHD.  These problematic behaviors were of sufficient severity to discontinue medication, and gradually and completely resolved over two to three months.  The child remained off medication and experienced no recurrence of OC behaviors at one year follow-up.  Adrian (2001) described the development of explosive episodes of aggressive and violent behavior in a seven-year-old male coincident with treatment with methylphenidate.   He also developed obsessive-compulsive behavioral symptoms of sufficient severity to lead to discontinuing his medication, and both the explosive and obsessive-compulsive behaviors resolved off medication. It was felt that these behavioral problems were induced by methylphenidate rather than being a feature of the underlying clinical disorder of ADHD.    Breggin (2001) summarizes data from eight controlled trials of stimulant medication for ADHD, revealing a significant incidence of stereotypical behaviors, personality change, and in one study, over-focused obsessive-compulsive reaction in 42%. 

            Increasing reports of abuse of Ritalin? or other stimulants have been reported in research literature and in the lay press.  A recent major segment of NBC Dateline (1/18/01) reported widespread abuse of Ritalin? among students, according to investigative reporters interviewing students at several major colleges in different areas of the country.  A national survey found that 2.8% of high school seniors in 1997 had used Ritalin? without a physician?s prescription the previous year (Sannerud & Feussner, 2000).  In testimony before Congress, Drug Enforcement Administration (DEA) representative Terrance Woodworth (2000) reported that 3% of high school seniors had used Ritalin? without a doctor?s prescription in 1999.  Klein-Schwartz & McGrath, (2003) cite a survey of 6,000 public school students in Massachusetts finding that 13% of high school students admitted to having used methylphenidate without a prescription at some time.  A tenfold increase in emergency room mentions for methylphenidate (MPH) among children 10 to 14 years old in the Drug Abuse Warning Network (DAWN) from 1990 to 1996 made abuse of MPH as likely as use of cocaine (Sannerud & Feussner, 2000).  These same authors point out the pharmacological and animal experimental similarity of methylphenidate to cocaine when used by the same route of administration. The reinforcing, discriminative-stimulus, or subjective effects of methylphenidate were found to be comparable to those of d-amphetamine and cocaine in 48 of 60 animal and human studies (Kollins & MacDonald, 2001)  Pressure on students taking prescribed stimulant medication for diversion is substantial, as reflected in a survey of 161 children five years after being identified as Ritalin responders.  Sixteen percent of the children had been approached to sell, give away, or trade their medication (Musser, Ahmann, Theye, Mundt, Broste & Mueller-Rizner, 1998).

            Although Biederman reported a marked reduction in SUD among ADHD subjects treated with stimulant medication compared with untreated subjects (see above), and a meta-analysis suggests a possible protective effect, conflicting data has been reported.  Lambert and Hartsough (1998) reported their findings from a longitudinal study of 175 ADHD participants receiving stimulant medication and 68 ADHD control participants not receiving stimulant medication, along with 159 age-mate normal controls selected from the same classrooms as the ADHD subjects.  They found a significant increase in cocaine and tobacco dependence among treated compared with untreated ADHD subjects, with a linear relationship between the amount of stimulant treatment and the likelihood of either tobacco or cocaine dependence.  Their study had advantages over the Biederman study in having a larger untreated ADHD control group (68 versus 19), being community based, and in using non clinic-referred samples.  Shire US (2001) states in the Adderall XR? package insert that:  ?Amphetamines have been extensively abused.  Tolerance, extreme psychological dependence, and severe social disability have occurred."   These statements suggest that concerns about the possibility of drug dependence are realistic. 

            Volkow and colleagues at the Brookhaven National Laboratory have done extensive research on the effects of drugs of addiction on the brain using PET scans.  They found that, while cocaine blocks about 50% of the dopamine transporters and thereby leading to a surfeit of dopamine in the synapse, methylphenidate given to normal adult volunteers at 0.5 mg/kg doses blocked 70% of dopamine transporters.  They noted the relative lack of clinical reports of addiction to stimulants among those treated for ADHD, but caution that:

The long-term dopamine effects of taking methylphenidate for years, as many do, are unknown.  The only two large epidemiological studies conflict.  One reports more drug addiction in children with ADHD who took methylphenidate compared with children with ADHD who took no drug; the other shows the opposite result. . . . Could chronic use of Ritalin make you more vulnerable to decreased dopamine brain activity as cocaine does?  It's a key question nobody has answered (Vastag, 2001, p. 906).

The possibility of cognitive toxicity from stimulant medication treatment has been raised,

with varying results from different studies.  Dyme (1982) reported an increase in perseveration in four of five hyperactive children treated with methylphenidate at 1.0 mg/kg doses and concluded that "clinicians should be aware that psychomotor stimulant drugs may produce over-focusing of attention or perseveration in hyperactive children." (p. 272)   Solanto and Wender (1989) studied the effects upon cognitive function of methylphenidate at doses of 0.3, 0.6, and 1.0 mg/kg in 19 subjects with ADHD (DSM-III).  Although they found that the ADHD group as a whole did not exhibit drug-induced constriction, a subgroup of eight of the 19 subjects did show a perseverative quality and decreased lucidity in some of their responses.  The spontaneous speech of some of these children was also characterized by repetitiveness and lessened cohesiveness following drug administration compared with baseline.

            Barkley (1998) has suggested that high doses of stimulants conceivably may produce an over-focusing or constriction of attention, and that some children who show a positive behavioral response to medication may experience either no change or significant deterioration in academic performance.  Palladino (1999) has raised the question whether stimulant medication narrows a child?s wide range of creative thinking, perhaps working the way a zoom lens changes the focal point of a camera, ultimately leading to greater convergence, but less divergence.  Breggin (1999b) has described how both in animal research and in clinical studies of stimulant treatment of children, overly focused, obsessive-compulsive behaviors have been observed.  He further points out how these very over-focused and compulsive behaviors may be interpreted as improvements by teachers and parents in the face of prior impulsive and disruptive behavior.  In addition to possible stimulant induced cognitive constriction, Breggin (1999a) points out how diagnosing and medicating children to control their behavior may teach them to shift responsibility and the locus of control from within themselves to external sources.   He suggests that symptoms of depression and obsessive-compulsive behaviors developing while on stimulant medication may represent adverse medication effects rather than newly emerging co-morbid disorders among children with ADD/ADHD.                                                                                                                                                 

            Although long-term physiological effects such as blood pressure or cerebral blood flow changes have not been described, two reports of short-term changes suggest this possibility.  In a study of adults with ADHD treated with Dexedrine and methylphenidate, blood pressures were studied at 60 and 90 minutes following oral administration.   Following MPH 0.35 mg/kg systolic BP increased by 7% and 16.9% respectively, and diastolic BP increased by 9.9% and 12.3%.  Following Dextroamphetamine 0.24 mg/kg, systolic pressure increased by 13% and 13.9% (Matochik, Mordahl, Gross, Semple, King, Cohen, & Zametkin, 1993).  In a study of the effects of intravenous methylphenidate on cerebral blood flow in normal adult volunteers, Wang et al (1994) found from PET scans a significant decrease in cerebral blood flow throughout the brain.  Although the effects of oral methylphenidate would reasonably be expected to be lower than those following intravenous administration, the authors commented, " . . . though CBF changes after oral MP are probably smaller than with intravenous MP, its pharmacokinetics may be slower and the CBF decrements may last longer." (p. #144)

            Others have expressed concern about the possible long-term effect of stimulant medication on blood pressure in children.  Experts in public health and toxicological issues had the following to say:

Most clinical trials have reported small increases in blood pressure among those treated with stimulants.  In elementary school children under a relatively short course of medication, these changes may seem unimportant.  With longer periods of treatment extending through adolescence into adulthood, however, these small increases could accumulate and constitute a health risk.  Susceptible sub-populations may exist . . . In 1980 Satterfield, Schell, and Barb published one of the few studies on the long-term health effects of stimulant treatment in children.  These authors followed seventy children for one year and thirty-six children for three years.  After three years of follow-up, they found statistically significant increases in both systolic blood pressure (8 mm Hg) and diasolic blood pressure (5 mm Hg) among children with ADHD being treated with methylphenidate (Rowland, Umbach, O?Callaghan, Miller, & Dunnick, 2002a).

            Assuming the existence of an effective behavioral approach to managing ADD/ADHD (to be discussed below), it seems logical that reliance upon medication to curb behaviors for many years rather than learning effective coping strategies may perpetuate ADD/ADHD behaviors into adulthood.  The AHCPR Evidence Report/Technology Assessment points out that although it was previously thought that ADHD remitted by adolescence, up to 65% of adults continue to meet criteria (Agency for Healthcare Policy and Research, 1999b).  DeGrandpre  has written extensively about the possible role of electronic media exposure in America?s ADD/ADHD epidemic and  has suggested that ?medicating the child?s problems out of sight? may contribute to postponing dealing with issues and push into adulthood what used to be considered a childhood problem (DeGrandpre, 1999, p. #194).  Learning adaptive responses to impulsive or inattentive tendencies would appear to be more difficult in adulthood than at younger ages.

            Atomoxetine, or Strattera ?,  has recently been marketed for ADHD treatment as a non-stimulant without the abuse or addiction potential known to accompany treatment with the Schedule II stimulants.  It is predictable that other new medications will be introduced for managing ADHD behaviors, but inevitably will have their own risks separate from those of stimulant medications, and will share the fundamental disadvantage of relying upon external agency of a medication rather than teaching children adaptive mechanisms for dealing with the demands of their lives and circumstances.  It is interesting to consider how the putative ?biochemical? cause of ADHD is said to change as a succession of new drugs with differing mechanisms of action are marketed, each in turn allegedly correcting a new and different chemical (neurotransmitter) basis as the drug is shown to impact ADHD behaviors.  Methylphenidate and amphetamine derivatives, for example affect primarily dopamine and norepinephrine receptors, while atomoxetine affects predominantly the norepinephrine transporter system.  A promotional flyer distributed to physicians by Shire (2002), the pharmaceutical company that markets the long-acting Adderall XR ?, for example states: "Both dopamine and norepinephrine are believed to play critical roles in the pathology and treatment of ADHD."  Eli Lilly in its promotional material for physicians points out that Strattera ? is believed to produce its therapeutic effect by "selective inhibition of the pre-synaptic norepinephrine transporter (Eli Lilly, 2002)."

            Normal subjects have been shown to be affected similarly as ADHD subjects, at least with respect to stimulant medications.  If the interpretation of a neurochemical basis for ADHD is embraced simply because a medication is shown to cause a particular change in neurotransmitter function and also to lead to an improvement in behaviors that define a syndrome, one must logically accept the idea that normals  have a ?neurotransmitter or chemical imbalance?  as well!   

 

A New Paradigm

            It is reasonable to conclude that the current prevailing conceptualization of ADD/ADHD as a neurological or biological based entity for which optimal management consists of long-term treatment with stimulant medication combined with the conventional reward based behavioral approach is inadequate.  A number of observations and published works, to be considered following, suggest an alternate paradigm for ADD/ADHD.  This considers ADD/ADHD as largely an end product of a number of forces characteristic of, and in some cases unique to, our culture.  These include, though are not limited to, breakdown and increased mobility of the nuclear family, developmental considerations, parenting philosophy, widespread and increasing exposure of children at progressively younger ages to various forms of passive, electronic rapid stimuli, and increased stress on children from education reforms moving to earlier ages tasks not previously required of young children.  Perhaps a neurologically or biologically based ADD/ADHD syndrome is found in a small proportion of children who have a clearly defined pre-existing neurological insult. The majority receiving the diagnosis would then be culturally derived, and most cases with certain central nervous system dysfunctions secondary to behavioral or treatment issues rather than the converse.        

            The idea that ADD/ADHD behaviors may represent a developmental phenomenon that is largely preventable is suggested by two studies.  Carlson and colleagues reported findings from a prospective, longitudinal study of 191 firstborn children followed from infancy to end of sixth grade.  They found that for some hyperactive children, intrusive and over-stimulating care giving appeared to play a prominent role.  The authors suggested that development of early parenting skills and social support might play a preventive therapeutic role (Carlson, Jacobvitz, & Stroufe, 1995).  A qualitative study of a community parent training curriculum surveyed participants in the program and compared outcomes with nonparticipating subjects matched for parity and age.  The program taught a nurturing, but structured, traditional perspective on child-rearing characterized by clear rules and expectations for behavior with structured consequences, much in the manner of Baumrind?s authoritative parenting.  Participants who shared a dogmatic commitment to the principles upon which the curriculum was based had a substantially lower incidence of DSM-III-R ADHD criteria (5%) for their children at follow-up, when surveyed at age four to seven years, than children of non-participants (16%) (Wilson & Wilson, 1996). 

            Educational psychologist and former advocate of early childhood exposure to computers, Dr. Jane Healy (1990) has studied the effects on young children of rapid, passive, electronic stimuli as found with computers and television.  She cites the work of Dr. Marian Diamond in noting the impact upon brain structure and function from the environment.  Healy states, ?Fast-paced, nonlinguistic, and visually distracting television may literally have changed children?s minds, making sustained attention to verbal input, such as reading or listening, far less appealing than faster-paced visual stimuli? (Healy, 1998, p. 32).  DeGrandpre theorizes that early life exposure to rapid, passive stimuli such as from computers and television so prevalent in our culture produces a form of sensory addiction.  He postulates that stimulant medication might, in a sense, ?feed the addiction" (1999, p. 194).

            Among the Amish, who are well known for their rejection of most modern indulgences such as computers and television, ADD/ADHD may be uncommon.  Papolos reports that among 200 Amish children followed prospectively and compared with the non-Amish population at large for the development of bipolar disorder, symptoms of ADHD were unusual (Papolos & Papolos, 1999).

            Sax (2001) has written about the movement toward pushing academic instruction formerly characteristic of first grade into Kindergarten.  Lagging performance among U.S. students compared with other industrialized nations has contributed to the education reform movement.  This has resulted in an emphasis on standardized testing, pushing into Kindergarten much of the traditional first grade curriculum, and in the process replacing traditional Kindergarten year subjects such as music, gym, and recess time for free play with academic instruction.   He correlates this progressive education reform movement with higher rates of stimulant medication treatment and proposes that these changes subject young children to demands for which they are not developmentally ready (Sax, 2000).

            Campbell (1996) has reported resolution of ADD/ADHD behaviors in children who had been struggling to learn to read proficiently by providing them pure phonics based reading instruction.  Marked inattention, inability to stay on task, and classroom disruptive behavior virtually disappeared coincident with correcting these children's reading inability.  He theorizes that some children, when taught to read by methods other than basic phonics based instruction, experience frustration over their struggle to learn to read, become quickly "turned off" to reading, and react by becoming inattentive, distractible, and often disruptive in the school environment, especially during classes that place high reading demands.  He has regularly referred children in a pediatric practice who fit this description to private community resources where they could be taught basic reading skills through a phonics approach, and has seen often dramatic resolution of ADD/ADHD behaviors. 

            This possible etiological factor is supported by the findings of a study of all public school students in grades two through five in two adjacent Tidewater, Virginia cities.  LeFever, Dawson, & Morrow (1999) obtained data on prevalence of stimulant medication use among all students in the two public school systems.  While reporting overall prevalence rates among all students that were consistent with other reports, they found startling figures among  the students who were young-for-grade, or one year or more younger than the age expected for that grade in one of the communities.   Among all students, 8% and 10% respectively in the two communities received stimulant medication in school, with in-school medication administration increasing to 18% and 20% of white males by fifth grade.  Among 770 young for grade students in the second community, 62.7% were given medication during school, and taking into account a prior study cited by the authors that 79% of those receiving stimulant medication for ADD/ADHD received a dose during school, one can reasonably assume that 79% of these students in community B were likely on treatment.

            In a subsequent study, LeFever and colleagues (2002) examined the relationship between routine community treatment for ADHD and adverse educational outcomes of students in the region, as well as overall rates of stimulant treatment in the population by surveying parents in order to determine the rate of stimulant medication treatment administered outside of school.  They were able to obtain survey responses from parents of 63% of the 1,644 children in grades one through five in the selected schools.  In this representative sample of elementary students, 17% of all the children had been diagnosed with ADHD, including 28% of all boys and 11% of all girls.  With regard to their likelihood of being enrolled in special education, being suspended or expelled from school, or repeating a grade, ADHD children who received behavioral intervention or combined treat.ment could not be distinguished from those who did not receive these treatments. 

 

A New Behavioral Approach

            Stein (1999) has described a novel behavioral approach to managing ADD/ADHD behaviors and reported encouraging data on effectiveness of using this approach, without relying on stimulant medication.  The Caregivers Skills Program (CSP) underlying assumptions depart from those upon which conventional behavioral management is based.  These assume that ADHD children can be enabled and trained to develop those behavioral traits they lack, and that effective behavioral management relies upon avoiding material reinforcers, incentives, or token economy programs.  No rules are posted, and contingency responses to target behaviors are imposed upon the slightest sign of inappropriate behavior.   Accountability for appropriate behavior is transferred to the child.  Reinforcement for appropriate behavior is stressed, consisting of social reinforcement only.  The approach is considered strict, but not punitive.  The program depends entirely upon parental management of the target behaviors in the home environment and only involves the school in the small minority of cases where gains in the home environment do not generalize to the school.  Stein?s research has found that gains are realized whether behavioral problems are encountered primarily in the home or in school. 

            He found that 11 of 12 targeted ADHD behaviors improved dramatically or disappeared within four weeks among the 37 children fulfilling DSM-IV criteria for ADHD ages 5 to 11 years included in the study.  These gains were stable at follow-up one year after treatment.  In 81% of children, gains generalized to the school setting, and in the remaining 19% institution of a school component (daily report program) extended the behavioral improvement into the school setting.  Although the study is uncontrolled, the results appear to justify further clinical trials with control groups receiving alternative methods of management, considering the lack of evidence for long-term effectiveness of the prevailing medication centered approach and the virtual absence of risk of the CSP approach.  Pending such controlled trials, a delay of only a few weeks usually required to realize gains with the CSP approach before implementing medication therapy could not reasonably be construed as a significant risk. 

            Stein (1999) has provided a reasonable explanation for the failure of the reward-based popular behavioral approach, as implemented in the MTA trial, based on Barkley and Pelham's work .  He points out that prompting, reminding, warning, token economies, and providing other means of external control are based upon the flawed assumption that ADHD children are incapable of learning adequate self-monitoring and compliance skills.  He further observes that these forms of attention at the time of misbehavior may be reinforcing. Relying upon this type of intervention creates cognitive and emotional dependency and fosters an external locus of control, rather than building self-efficacy, the importance of which has been described by Bandura (1993).  Reliance upon medications, stimulants or otherwise, fosters this same process.

            The case report described at the beginning, although not technically fulfilling DSM-IV criteria due to absence of behavioral criteria for the school domain, illustrates the promise of this method of management.  The teachers and principal shared such concern about the child's functional impairment in school, DSM criteria notwithstanding, that barring substantive behavioral improvement in school, he would not be promoted.  The CSP program was offered to the parents of that child and instruction provided.  The child was removed from the public school and enrolled in a publicly funded charter school to assure advancement to the second grade, despite the position of his former public school principal, guidance counselor, and teacher that without stimulant medication he would be unable to succeed.  Follow-up at the end of the ensuing semester revealed that he was doing so well in the second grade that consideration was being given to advancing him to the third grade, and his behavior was considered to be exemplary. Several additional children who did fulfill DSM-IV criteria for ADD/ADHD have been successfully managed with the CSP program and remained medication free.  It appears that behavioral management alone may be effective for many children if predicated upon the assumptions and approach found in the CSP program.             

            Others have described successful management of ADHD with counseling or psychotherapy, without relying on medication.  Oas (2001) describes his experience treating thousands of ADHD children over a period of over 20 years through a process of  psychotherapy, working closely primarily with the parents.   Glasser (1998) has used his Nurtured Heart approach in the Tucson, Arizona area for many years and describes successful management  of children with severe ADHD behavioral problems in his book for parents.  These latter, along with Stein?s CSP program, illustrate that successful management of ADHD is possible without resorting to stimulant medication or to other drugs that have been reported or that are in clinical trials.

             

Informed Consent

            It is recognized that some parents will likely be unable or unwilling to devote the consistency of effort required for successful implementation of the CSP approach.  Availability of other professionals who have experience successfully managing ADHD without medication like Oas and Glasser is limited.  Stimulant medication management therefore will likely retain a place in management, but prudence suggests that its use be restricted to subjects whose behaviors are more problematic and in circumstances where caretakers cannot or will not utilize the CSP approach successfully, and only after disclosure that an effective alternative behavioral approach may be available.  In view of the absence of data for long-term effectiveness and the potential adverse effects, informed consent should be revised to provide a more realistic and balanced picture of the potential benefits and risks of stimulant medication than is currently usual practice.  Lawsuits brought by attorneys who successfully litigated the tobacco industry, against Novartis Pharmaceutical Corporation and the American Psychiatric Association claiming a conspiracy to create a market for methylphenidate point to the wisdom of this latter suggested revision to customary practice (Charatan, 2000).

             To justify on an ethical basis the use of stimulant medication as the mainstay of management of ADD/ADHD behaviors, and to satisfy the obligation to provide informed consent, the following information, at a minimum, should be provided to caregivers prior to instituting stimulant medication treatment:

1.      ADD/ADHD as a clinical term describes a pattern of behaviors and does not represent an established neurologically or biologically derived disorder.

2.      The cause or causes of these behaviors are unknown, but likely include a number of cultural factors, as described above.  ADD or ADHD behaviors may be caused by proven, organic brain damage, but at most, this would account for only a very small minority of cases diagnosed clinically.

3.      Short-term effectiveness of stimulant medication in improving ADD/ADHD behaviors has been established, but long-term effectiveness (beyond 14 months) has not been proven compared with management without medication.

4.      The long term risk of adverse effects has not been established for stimulant medication.  Conflicting data exists about the possible long-term risk of increased use of illicit drugs among stimulant medication treated ADD/ADHD subjects compared with untreated ADD/ADHD subjects.  The prevalence of reported serious behavioral effects of stimulant medication such as psychosis, obsessive-compulsive behaviors, or explosive behavioral outbursts is unknown.  The incidence or significance of cognitive toxicity attributed to stimulant medication is unknown.

5.      Relying on stimulant medication to correct behavior for prolonged periods rather than modifying the environment and correcting them otherwise may postpone learning adaptive behaviors to an age when learning successful responses is less likely.

6.      The conventional reward-based behavioral approach to ADD/ADHD as designed by Pelham in the MTA study has been shown to be helpful only when used in conjunction with stimulant medication, and adds little to the effectiveness of stimulant medication alone in managing core symptoms of the syndrome.

7.      A behavioral approach (CSP, Stein) based on radically different assumptions about the nature of ADD/ADHD and incorporating behavioral management techniques in many ways opposite those underlying conventional behavioral management has been found effective in uncontrolled trials, and should be offered to caregivers as an alternative to stimulant medication for those who would prefer management without medication. 

            It is debatable that even inclusion of the above potential adverse effects of stimulant medication treatment represents true informed consent.   From the State of the Science - Best Practices text: "Neither the long-term effectiveness nor the long-term safety of stimulant medications has ever been demonstrated.  Yet, precisely this information is needed to effectively weigh the risks and benefits of treatment and to provide or receive truly informed consent (Rowland, Umbach, O'Callaghan, Miller, & Dunnick, 2002b, p.                     10-8)."            

                    Usual practice of informed consent seems to exaggerate potential benefits of stimulant medication treatment and often fails to disclose some of the potential risks outlined above.   Representative of inaccurate claims about the risks and benefits of stimulant treatment are the following:

?        A current popular book written for parents about the use of psychotropic drugs for children is Straight Talk about Psychiatric Medications for Kids (Wilens, 2001).  Although claiming to provide "honest and complete answers to the many complex questions" (p. 1) and "extensive details about side effects" (p. 4) of stimulant medication treatment of ADHD, reported adverse effects of treatment are omitted or dismissed.  Examples of this are the risk of psychotic episodes mentioned in the package insert for Adderall ? as sometimes occurring during treatment with normal doses, cognitive toxicity, and the risk of abuse leading to physical or psychological dependence, or addiction.  The author states that stimulants are classified as Schedule II drugs because of their "abuse potential (liability), either by the individual taking the drug or by others who may steal the medication (p. 193)."  He fails, however, to state that psychological or physical dependence may occur, one of the three criteria defining Schedule II (Drug Enforcement Administration, 2003).   This omission is surprising in view of the author's professional qualifications including being Board certified in child, adolescent, and addiction psychiatry.     

?        The AAP (American Academy of Pediatrics, 2003) has made available to pediatricians and other professionals an ADHD toolkit, containing a variety of materials for professionals and for parents of children with ADHD.  Included is a brochure written for parents ?Understanding ADHD ? Information for Parents About Attention-Deficit/Hyperactivity Disorder.?  With regard to treatment with stimulant medication, the following is stated: ?For most children, stimulant medications are a safe and effective (emphasis added) way to relieve ADHD symptoms (p. 10).?  In the ensuing discussion of side effects one might expect, common minor side effects are discussed, but the more serious reported adverse effects of psychotic episodes, cognitive toxicity, abuse potential and addiction liability are not mentioned, similar to omissions in the publication Straight Talk discussed above.  Contrary to numerous reports discussed earlier in this paper, it is stated that ?There is no evidence that children are getting high on stimulant drugs such as methylphenidate and amphetamine.  These drugs also do not sedate or tranquilize children and have no addictive properties (p. 20).?    It is noted that the enclosed promotional flyer for the toolkit, as well as the brochure under discussion are supported by an unrestricted educational grant from McNeil Consumer & Specialty Pharmaceuticals, the manufacturer and supplier of a major stimulant medication used to treat ADHD, Concerta ?.  These omissions and the funding support source suggest the possibility of a lack of objectivity and represent a conflict of interest.         

                    It is recognized that the approach of Stein, as well as the approaches of others like Oas and Glasser, are supported by uncontrolled data, but this is also true for conventional medication and combined medication and behavioral treatments from the standpoint of long-term follow-up for many years, as is increasingly characteristic of traditional management.  These non-medication based  approaches are free of significant risk, however, in contrast to the prevailing alternative of stimulant medication as the mainstay of management.  I encourage those in clinical behavioral research to implement well-designed controlled trials of Stein's behavioral medication approaches to caregivers as an alternative to stimulant medication unless such research might dictate otherwise.  We should adhere to the historic and traditional dictum of primum non nocere.

 

 

 

 

 

 

 

 

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