The Benefits of Going Beyond Conventional Therapies for ADHD Benefits of Going Beyond...

The Benefits of Going BeyondConventional Therapies for ADHD

Gary Null, Ph.D., and Martin Feldman, M.D.'

IntroductionAttention deficit/hyperactivity disor-

der (ADHD) has the distinction of being themost thoroughly studied of all thebehavioral/emotional disorders of child-hood.' But despite the continuing focus onthis disorder, experts in the topic acknowl-edge that many aspects of ADHD—fi-om itsetiology to the best form of treatment-continue to be poorly understood or con-troversial.^'^

Two such controversies stem firom theADHD protocols of conventional medicine,which use subjective methods of diagnosisand mind-altering pharmaceuticals such asRitalin® and Adderall.® Although these drugsare central nervous system stimulants, in thecase of ADHD they have the paradoxical ef-fect of calming the patient. Unfortunately,they also put the growing number of childrenand adolescents who are diagnosed v«thADHD at risk of the adverse effects associ-ated with these drugs, particularly methylphe-nidate (Ritalin®, Concerta®, Metadate®,Focalin®, Methylin®). The negative effectsrange firom insomnia and decreased appetiteto movement disorders such as tics and thestunting of childrens grovirth. An analysis oforthodox medicines approach to diagnosingand treating ADHD will reveal the benefitsof using more natural methods of treating thecollection of symptoms now grouped underthe ADHD label.

Problems of DiagnosisADHD has become the most com-

monly diagnosed behavioral disorder ofchildhood, characterized by the core symp-toms of inattention, impulsivity and hyper-activity. Data on its prevalence vary. TheAmerican Psychiatric Association reports

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that 3% to 5% of school-age children haveADHD"; the American Academy ofPediatrics reports 4% to 12%.̂ The moststringent estimate in a recent study by theMayo Clinic puts the figure at 7.4% of chil-dren by age 19.' In a controversial develop-ment, the diagnosis of ADHD and use ofstimulant medications have been increas-ing among adults.' According to one expert,the literature suggests that 'ADHD is bestconceptualized as a lifelong disabilityrather than as a childhood disorder."*

However, the diagnosis of ADHD andits treatment with pharmaceuticals havebeen largely concentrated in the UnitedStates (and, to a lesser extent, Canada),'-'"making ADHD an American phenomenonand raising questions about whether it is atrue disorder. It is of interest that the useof methylphenidate for ADHD has in-creased sharply in many other countries—mostly European ones—as well, accordingto the International Narcotics ControlBoard. Consumption in countries such asBelgium, Germany, Iceland and the Neth-erlands increased by 150% to 350% in arecent five-year period. Consumption inAustralia and Canada, formerly main con-sumer countries of methylphenidate, hasleveled off or declined, although they arethe only countries besides the U.S. to re-port significant use of amphetamines forthe treatment of ADHD."

In diagnosing ADHD, physicians andpsychiatrists use a variety of assessmenttools and rating scales, such as theConners'/CADS scales and the diagnosticcriteria presented in the American Psychi-atric Association's Diagnostic and Statisti-cal Manual of Mental Disorders. DSM-IV(1994) defines three major subtypes ofthediagnosis of attention deficit/hyperactivitydisorder (ADHD): predominantly inatten-

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Journal of Orthomolecular Medicine Vol. 20, No. 2, 2005

tive, predominantly hyperactive-impulsive,and a combined type. (This condition alsois referred to as attention deficit disorder,ADD. The APA replaced its former diagno-sis of ADD—with or without hyperactiv-ity—with the unidimensional ADHD diag-nosis in 1987, then specified the threesubtypes in 1994.)'^-"

Children with ADHD may have one,two or all three of the core symptoms ofinattention, hyperactivity and impulsivity.Thus, a child may be diagnosed with ADHDeven if he or she is not hyperactive. Girls,for example, often fall into the inattentivesubtype.'" However, a 2000 review of thediagnosis of ADHD points out that theDSM-IV criteria for this disorder arephenomenologic rather than etiologic andare much more relevant for children thanfor adolescents and adults.'^

An easy-to-see problem with this ap-proach to diagnosis is that the assessmentsare not definitive. The National Institutesof Health (NIH) believes the diagnosis ofADHD can be made reliably using diagnos-tic interview methods, but it also said inits 1998 Consensus Statement on ADHDthat "there is no independent valid test forADHD.""* Although new testing methodsare being developed, the diagnosis ofADHD remains far less objective than thatof other abnormalities, where specific toolssuch as blood tests, x-rays and sonogramsare used to determine the presence of thedisorder.

Furthermore, the answers provided byparents and teachers on behaviour ratingscales-to questions such as how much achild fidgets or whether he/she is easilydistracted-are subjective. What one personviews as distractibility another may viewas natural inquisitiveness. Some of thequestions also are based on questionablevalues or assumptions. For example, theConners' Parent Rating Scale" asks whetherthe child "actively defies or refuses to com-ply with adults' requests." In some life situ-ations, though, disobedience is a virtue.

Another problem with the ADHD di-agnosis is that it may apply a medical labelto behaviours that fall at one end of a spec-trum of normal patterns. The NIH says inits Consensus Statement: "Clinicians whodiagnose this disorder have been criticizedfor merely taking a percentage of the nor-mal population who have the most evi-dence of inattention and continuous activ-ity and labeling them as having a disease.In fact, it is unclear whether the signs ofADHD represent a bimodal distribution inthe population or one end of a continuumof characteristics." The NIH observes thatone of the problems of diagnosis is to "de-termine the approriate boundary betweenthe normal population and those with

The American Psychiatric Associationstates itself that the diagnosis of ADHD isnot an easy one to make. The symptomsare similar to those of many other child-hood disorders." Psychiatrist AbramHoffer, M.D., Ph.D., has stated: "You cantake this same difficult child to ten psychia-trists and come back with ten differentdiagnoses. But no matter what the diagno-sis is, they all put him on Ritalin."^" To addto the complexity, approximately 65% ofpatients v«th ADHD may have one or morecomorbid disorders, such as anxiety, com-munication, mood, conduct, oppositionaldefiant and learning disorders andTourette's syndrome.^'

One researcher suggests that more ex-act diagnostic guidelines may emerge fromADHD-related tests of executive functioning,neuroimaging and genetics that have beendeveloped in recent years.̂ ^ But any such di-agnostic methods are likely to be contro-versial as well. According to a 2004 article,while the current evidence on the genetics ofADHD wiU provide important clues to itsetiology, it is not sufficient to justify the useof genetic screening tests. The authors addthat "genetic information on susceptibility toADHD has the potential to be abused and tostigmatize individuals."^'

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The Benefits of Going Beyond Conventional Therapies for ADHD

Also open to controversy are the re-sults of neuroimaging studies that haveidentified supposed abnormalities in struc-tural and functional aspects of the brainsof ADHD patients.̂ ** Researchers have in-terpreted these findings to mean that thedisorder may have a biological basis. Forexample, a 2003 study in the Lancet foundreduced regional brain sizes and grey-mat-ter abnormalities in cortical componentsof attentional systems that may help ac-count for ADHD symptoms.^^

Research associating ADHD with brainabnormalities does not withstand a criti-cal analysis, however. A review ofneuroimaging studies published in ClinicalNeuropharmacology in 2001 states thatwhile the results of such studies are oftenused to support a biological basis forADHD, "inconsistencies among the stud-ies raise questions about the reliability ofthe findings." At the time of publication, theresearchers found that "no specific abnor-mality in brain structure or function hasbeen convincingly demonstrated byneuroimaging studies." They concludedthat the neuroimaging literature "provideslittle support for a neurobiologic etiology

Some doctors are already using brain-scanning technologies in the assessment ofADHD, according to a Wall Street Journalarticle. One such method even exposes thepatient s brain to a small amount of radio-active material, which is used to illuminatebrain activity. However, most researchersbelieve the use of brain-scanning tech-niques to diagnose ADHD is premature andimpractical, given the expense of the testsand the lack of standard guidelines for in-terpreting the scans.^'

Another more objective test of ADHD isavailable. The Developmental BiopsychiatryResearch Program at Harvard's McLean Hos-pital has developed a diagnostic tool calledM-MAT that monitors fine body movementsduring a computerized task to measurehyperactivity, impulsivity and attention.

Because a child can be retested after tak-ing a dose of medication, the test helpsdetermine whether the drug will be effec-tive for him or her. The researchers believethis test will address the concerns of manyphysicians that the diagnosis of ADHD is"too subjective, often pathologizes normalchildhood behavior, and maslcs the detec-tion of other important problems, such asa learning disorder."^"

Conventional Treatment of ADHDPsychostimulants have become the

primary treatment for those diagnosedwith ADHD, fueling what the NIH hascalled one of the major controversies re-garding this disorder. The agency noted in1998 that the grov^dng prescription of thesedrugs for the short- and long-term treat-ment of ADHD has led to intensified con-cerns about their potential overuse and

The stimulants used to treat ADHD in-clude methylphenidate, mixed salts of am-phetamine (Adderall®), dextroamphetaminesulfate (Dexedrine, Dextrostat) and, to amuch lesser extent, pemoline (Cylert®). Themethylphenidates and amphetamines areavailable in short- and long-acting versions.In late 2002, Eli Lilly and Co. introducedthe first nonstimulant medication ap-proved by the FDA for the treatment ofADHD. This drug, atomoxetine (Strattera®),is a selective norepinephrine reuptake in-hibitor. It had the strongest launch ever foran ADHD drug and was the first such medi-cation approved for the treatment of adultsas well as children and adolescents.™- '̂

Stimulant-type drugs still lead thismarket, however, and numerous studiesdocument their growing prescription dur-ing the 1990s.'2-3* One study found that theuse of psychotropic medications amongyoung people had reached nearly adult uti-lization rates in 1996, with stimulantsranked first in the three groups examined.^'Another study reported sizable increases inthe use of stimulants and other medica-

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tions among even 2- to 4-year-olds.38Perhaps most disconcerting is a four-

year analysis ofthe use of stimulants in anarea of North Carolina which found that themajority of 9- to 16-year-old children whotook these medications had never had anyimpairing ADHD symptoms reported bytheir parents. They did have nonimpairingsymptoms and behaviours that were clas-sified as ADHD, but "these typically fell farbelow the threshold for a DSM-III-R diag-nosis of ADHD," say the researchers.^'

One study finding evidence ofoverdiagnosis was conducted in southeast-ern Virginia, where the incidence of grade-school children receiving ADHD medica-tions was two to three times as high as theexpected rate ofthe disorder. By fifth grade,18% to 20% of Caucasian boys were takingADHD drugs.""" Meanwhile, a study of theprevalence of stimulant prescriptions in1999 found wide variations among states,ranging from a high of 6.5% in Louisianato a low of 1.6% in the District of Colum-bia. The authors suggest that areas of bothoveruse and underuse may exist.""

The use of stimulant-type drugs to treatADHD has grown despite a lack of under-standing of their therapeutic action. Meth-ylphenidate and amphetamines are stimu-lants ofthe central nervous system (10 mil-ligrams of Ritalin are equivalent to 5 milli-grams of amphetamine), yet in patients v«thADHD the drugs have a paradoxical effectand reduce the symptoms of inattention,hyperactivity and impulsive behavior.

Researchers acknowledge that stimu-lants' method of action in treating ADHDis not well understood.''^'" According to theJournal of the American Medical Associa-tion, Nora Volkow, M.D., a leading re-searcher in the imaging of drug effects inthe brain, said of methylphenidate in 2001:"As a psychiatrist, sometimes I feel embar-rassed about the lack of knowledge becausethis is, by far, the drug we prescribe mostfrequently to children.""^

A 2001 study by Dr. Volkow and col-

leagues provided direct evidence, for thefirst time, that therapeutic doses of meth-ylphenidate significantly increase extracel-lular dopamine in the human brain byblocking dopamine transporters. The re-searchers postulate that the drug's ampli-fication of weak dopamine signals in ADHDpatients enhances task-specific signaling,improving attention and reducingdistractibility.""*

Other research in this area includes a2003 study that measured regional cerebralblood flow in ADHD patients while theywere on and off methylphenidate. The re-sults suggested that Ritalin reduces ADHDsymptoms by modulating regions of thebrain associated with motor function.''^ Astudy from Harvard Medical School foundevidence that methylphenidate alters activ-ity and attentiveness in children withADHD in a rate-dependent manner. Therewas a clear inverse association between theseverity of symptoms and the degree oftherapeutic response.***

Some recent evidence about the dosagesof stimulants prescribed to young people isof interest: While the common practice isto increase a child's dosage as he or shegrows, this may not be necessary for all pa-tients."" In one clinical trial, 40% of childrenwho took half the dose of methylphenidatethat had kept their symptoms stable, alongvdth a placebo, had equally good ADHDcontrol and fewer side effects.'" Anotherstudy found that the greatest benefit in aca-demic performance and classroom behaviorcame with the lowest dose studied,^' while athird reported that "adolescents with ADHDmay not necessarily require more medica-tion than younger children to achieve a simi-lar therapeutic

Questions Regarding ADHD DrugsIn addition to uncertainties about the

diagnosis of ADHD and the method of ac-tion of ADHD drugs, questions remainabout the quality of studies of stimulantmedications, the safety of these drugs and

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the implications of long-term use in youngpatients with developing brains.

In 2001, Howard Schachter and col-leagues pubhshed a meta-analysis of 62randomized trials ofthe efficacy and safetyof short-acting methylphenidate. The trialsinvolved 2,897 participants under age 18diagnosed v«th attention deficit disorder.Their treatment lasted three weeks on aver-age and 28 weeks at most. The meta-analy-sis found a significant effect of methylphe-nidate for each primary outcome. However,it also found that the collection of trials "ex-hibited low quality" based on scores fromtwo separate indices. The analysis concludedthat the drug's "apparent beneficial effectsare tempered by a strong indication of pub-lication bias and the lack of robustness ofthe findings, especially those involving coreADD features.""

An earlier meta-analysis of 77randomized controlled trials of both phar-macological and nonpharmacological in-terventions for ADHD also found that stud-ies of this disorder "have low reportingquality, methodological fiaws, and hetero-geneity across outcome measures andtests." This analysis makes a noteworthypoint about efficacy: It found that methyl-phenidate may reduce behavioural distur-bance in children vdth ADHD, but that"academic performance does not appear tobe improved with stimulants."'"* Likewise,the NIH consensus statement on ADHDrefers to the "consistent findings that de-spite the improvement in core symptoms,there is little improvement in academic orsocial skills."''

Research on the long-term effects andsafety of ADHD medications has been es-pecially lacking. Schachter's meta-analy-sis notes that while short-acting methyl-phenidate has a statistically significantclinical effect in the short-term treatmentof ADHD, the "extension of this placebo-controlled effect beyond 4 weeks of treat-ment has not been demonstrated."" In fact,the prescribing information for Adderall XR

and Concerta state that the effectiveness ofthe drug beyond three weeks and four weeks,respectively, has not been systematicallyevaluated in controlled trials. Even so, theaverage number of years children are beingtreated for ADHD is increasing.'^ And ac-cording to a study of psychotropic drugs(such as stimulants, sedatives and antide-pressants) used with preschoolers, earlierages of initiation and longer durations oftreatment mean that "the possibility ofadverse effects on the developing braincannot be ruled out."'*

One often cited study of longer-termADHD treatments, the Multimodal Treat-ment Study of Children vfith ADHD, lasted14 months. In this clinical trial, 64% ofchildren, aged 7 to 9.9 years, were reportedto have side effects from ADHD medica-tions (mild side effects for 49.8%; moder-ate for 11.4%; severe for 2.9%). Interestingly,the authors say that six ofthe 11 severe sideeffects-such as depression, worrying andirritability-"could have been due tononmedication factors."" But as psychia-trist and author Peter Breggin, M.D., pointsout, placebo-controlled double-blind clini-cal trials have shown that the three sideeffects mentioned above are common ad-verse reactions to stimulants.'"

A clearer picture ofthe long-term con-sequences of stimulant use is beginning toemerge from animal studies conducted inthe past few years. These studies havefound, for example, that Ritalin has thepotential to cause long-lasting changes inbrain cell structure and function"; that arepeated, clinically relevant dose ofmethylphenidate markedly inhibits imme-diate-early gene expression in the brain";that chronic exposure to methylphenidateduring pre- and periadolescent develop-ment made the animals significantly lessresponsive to natural rewards than controlanimals and significantly more sensitive tostressful situations, with an increase inanxiety-like behaviours'^ and that early ex-posure to methylphenidate causes behav-

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ioural changes which last into adulthood,including some changes that may he hen-eficial (less sensitivity to cocaine reward)and others that may he detrimental (in-creases in depressive-like signs).*^

The lack of information on long-termeffects isn't the only worrisome factor inthe treatment of ADHD. Young people alsoare increasingly heing prescrihed multiplemedications at the same time. For exam-ple, a child prescrihed methylphenidate forADHD may also take a selective serotoninreuptake inhihitor (SSRI) antidepressant.''^A review hy researchers at Johns HopkinsMedical Institutions found that the datasupporting the use of concomitant psycho-tropic medication are hased almost entirelyon case reports and small-scale, non-hlindassessments.** Other studies also documentthe simultaneous use of multiplepsychoactive drugs hy children.'*^'''' TheJohns Hopkins review concludes: "Suhstan-tive systematic evidence is needed to clarifythis increasingly common, inadequatelyresearched child psychopharmacologicpractice."^'

Another shortcoming in the researchon pediatric drug use may underminesafety data as well: There is no commonmethod used to elicit and report data onadverse events in clinical studies, accord-ing to a 2003 review of 196 pediatric psy-chopharmacology articles puhlished overthe past 22 years. The inconsistency in theascertainment of safety data "is a majorlimitation that likely impairs the ahility topromptly and accurately identify drug-in-duced adverse events," state the reviewers."Research on how hest to standardizesafety methods should he considered a pri-ority in pediatric psychopharmacology."™

Adverse EffectsStimulant-type drugs generally are

descrihed as a safe treatment for ADHD,causing relatively mild side effects that mayhe related to dose and may decrease with

'̂ Yet as a review puhlished in 2002

notes, there is a suhstantial amount of vari-ation hoth in response to these drugs andin adverse drug reactions.'^ Although 75% to90% of ADHD patients respond well to am-phetamine and methylphenidate, says an-other review, there is a suhset of patients whoeither do not respond to the drugs or whoexperience side effects that preclude their use.These side effects include tics, a severe loss ofappetite and marked insomnia.'"*

In their analysis of 62 randomized tri-als, Schachter and colleagues conclude thatmethylphenidate "has an adverse eventprofile that requires consideration." For al-most all of the adverse events reported,patients taking methylphenidate had ahigher percentage of the effects than didthose taking placeho. According to dataderived from parent/self-reported adverseeffects, the numher of study participantsrequired for five prominent adverse eventsto he identified were as follows: four pa-tients for a decreased appetite, seven forinsomnia, nine for all stomachache events;10 all drowsiness events, and 11 for all diz-ziness events."

According to a 2002 review, side effectsof methylphenidate such as nervousness,headache, insomnia, anorexia and tachycar-dia increase linearly with dose, while over-doses can cause agitation, hallucinations,psychosis, lethargy, seizures, tachycardia,dysrhythmias, hypertension and hyperther-mia.'^ A study of long-acting methylpheni-date puhlished in 2003 found that only twoside effects, insomnia and decreased appe-tite, were more common at higher doses. Inthis group of 5- to 16-year-olds, younger andsmaller children were more likely to experi-ence sleep prohlems and a diminished ap-petite at higher dosages."

A study of even younger children, aged4.0 to 5.11 years, raises serious questionsahout the growing use of stimulants inpreschoolers. In this study of 11 young chil-dren with developmental disabilities andADHD, five who took methyplenidate ex-perienced significant adverse effects, such

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as severe social withdrawal, increased cry-ing, and irritability, especially at the higherdose of 0.6 mg/kg. The researchers state that"this population appears to he especiallysusceptible to adverse drug side effects." '̂

Another medication, Cylert, can causeacute and sometimes fatal hepatic failure.Its black box warning in the U.S. was revisedin 1999, stating that Cylert should not ordi-narily he considered a first-line drug treat-ment for ADHD.'' The drug also has heenwithdrawn from the UK and Canadian mar-kets (it is available with restrictions througha special access program in Canada).* *'

What follows is a discussion of someof the side effects associated with stimu-lant-type drugs used to treat ADHD, par-ticularly methylphenidate:

Mental EffectsStimulants can cause a variety of nega-

tive effects on mental functioning. In hishook Talking Back to Ritalin, Peter Breggin,M.D., discusses some of the adverse expe-rience reports for Ritalin submitted to theFDA's Spontaneous Reporting System from1985 through 1997. Among these data,which represent only a small fraction ofthetotal adverse events experienced by a drug'susers, were reports of depression (48 re-ports for depression, 11 for psychotic de-pression); personality disorders (89); agita-tion (55); hostility (50); abnormal thinking(44); hallucinations (43); psychosis (38); andemotional lability (33), along with reportsof amnesia, anxiety, confusion, nervous-ness, neurosis, stupor, paranoid reactionsand, in a few cases, manic reactions.'^

Dr. Breggin points out that stimulantsimpair the function of the basal ganglia inthe hrain, and this dysfunction can impedehigher mental functions and cause obses-sions, compulsions and abnormal move-ments. In two studies of stimulants, the rateof OCD symptoms was 51% and 25%, re-spectively." '̂̂ '' Another study found that42% of children experienced ohsessive over-focusing."^ Parents and teachers may mis-

takenly see these OCD symptoms as an im-provement says DE Breggin, but drug-inducedOCD is in fact a severe type of hrain dysfiinc-tion.** Case reports also document stimulant-induced obsessive compulsiveness.*"*^

The potential for psychotic behavior inRitalin users is included in the drug's pack-aging information. A 1999 chart review ofchildren with ADHD treated in an outpa-tient clinic found a 6% rate of psychotichehavior among stimulant users. Six ofthe98 children who took a stimulant (they werefollowed an average of 21 months) devel-oped psychotic or mood-congruent psy-chotic symptoms during treatment."'

As for mania, a study of 34 adolescentshospitalized for this disorder found thatpatients who had used stimulants in thepast had an earher age at onset for hipolardisorder (BD) than those without priorstimulant exposure. In fact, those who hadused at least two stimulants developed BDat a younger age than those who had beentreated with one such drug.'" The authorsof a 2004 article also hypothesize that theearlier age of onset for BD in the UnitedStates than in the Netherlands (where theprevalence among adults and adolescents,but not pre-pubertal children, is similar tothat of the U.S.) may be related to thegreater use of antidepressants and stimu-lants for depression or ADHD by Americanchildren."

Movement DisordersChildren taking methylphenidate may

develop involuntary muscle contractionsand limb movements. A 2003 review re-ports that the increased use of stimulants,antipsychotic agents and antidepressantsin children has inevitably led to more youngpatients experiencing side effects such asmovement disorders. Those associated withthese drugs include acute dystonic reactionand tardive dyskinesia. The reviewer states:"Unlike the isolated abnormal involuntarymovements associated vdth drugs pre-scribed for epilepsy or asthma, movement

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syndromes... associated with psychotropicdrugs are complex, difficult to recognize,and potentially seriously disabling."'^

In a retrospective chart review involv-ing 555 subjects, a total of 7.8% of thosetreated with stimulants developed tics (8.3%of methylphenidate users; 6.3% ofdextroamphetamine users; 7.7% of pemolineCylert users). The children who developedtics were significantly younger than thosewho did not.'^ Another cross-sectionalanalysis and chart review of 122 childrenwith ADHD treated vdth stimulants foundthat approximately 9% developed tics ordyskinesia. One child developed Tourette'ssyndrome.** Other studies and case reportsbear out the association between stimulantsand abnormal movements.^^"

The risk of tics in stimulant users isanother debated area of ADHD treatment,however. Several studies, for example, havefound that the proportion of subjects withADHD and chronic tic disorder whose ticsworsened was no higher for methylpheni-date than for placebo'* or that methylphe-nidate did not produce significantly moretics than did the placebo in children with orwithout preexisting mild to moderate tics.**

Growth EffectsAnother disturbing side effect of

stimulants is the stunting of growth thatoccurs in some children who take moder-ate to high doses over a period of years. Thisstunting occurs not only because stimu-lants can diminish a child's appetite butalso because they may alter the body's natu-ral balance of growth hormones.""

A study conducted at Yale UniversitySchool of Medicine, published in 2003, ex-amined the growth of 84 patients withADHD who took stimulants and comparedtheir height standard deviation (SD) scoreswith those of untreated biological siblings.The researchers found significant differ-ences in mean height SD scores betweentreated children and siblings after two yearsof treatment. These findings "suggest that

the prevalence of growth-suppressive ef-fects of methylphenidate is greater thanpreviously suspected."^"'

Another 2003 study in Australia tracked51 children treated with dexamphetamineor methylphenidate for six to 42 months. Inthe first six months, 86% ofthe patients hada height velocity below the age-correctedmean and 76% lost weight. The children'sheight and weight standard deviation score(SDS) showed a progressive decline that wasstatistically significant after six and 18months. During the first 30 months, heightvelocity was significantly attenuated (witha mean height deficit of approximately 1cm/year in the first two years).'"^

Other studies have reported thatstimulants do not have negative effects ongrowth for most children, that ADHD it-self may be associated with temporary defi-cits in height gain which may normalize bylate adolescence, or that most aspects ofmethylphenidate treatment are not asso-ciated with adult height or weight.'" '̂"*^

Cardiovascular EffectsSeveral recent studies have docu-

mented changes in cardiovascular func-tioning that can occur when children takestimulants. In a study of 17 boys takingmethylphenidate or Adderall, diastolicblood pressure load increased significantlywhile the subjects were on Adderall.Systolic blood pressure and heart rate alsodiffered between on and off medication.^"''A study of 14 healthy subjects found thatintravenous doses of methylphenidate sig-nificantly increased heart rate, systolic anddiastolic blood pressures and epinephrineconcentration in plasma. The blood pres-sure changes were significantly correlatedwith increases of dopamine in striatum andof plasma epinephrine levels caused by thedrug, supporting the hypothesis that meth-ylphenidate-induced blood pressure in-creases are due in part to the drug's cen-tral dopaminergic effects.'"'

The cardiovascular effects of methyl-

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phenidate can be deadly. According to FDAadverse reaction reports—which are noto-riously incomplete—there were 160 Ritalin-related deaths between 1990 and 1997,most of them related to cardiovascularfunctioning. Dr. L. Dragovic, OaklandCounty, Michigan, medical examiner, ex-plains that drugs such as methylphenidatestimulate the body's adrenergic system whenused repetitively, affecting everything thathas as its chemical pathway mediators andtransmitters such as adrenaline, noradrena-line and dopamine. The enhancement of theadrenergic system over many months oryears will produce changes in small bloodvessels. Some cells will be lost, and scarringwill occur as the body tries to repair the area.The blood vessels will narrow. "The changesthat we're seeing in kids who have been onRitalin for about eight years are basically thesame as the changes in someone that hasbeen abusing cocaine regularly over a periodof years," says Dr. Dragovic.̂ "^

Potential for Drug AbuseAccording to the U.S. Drug Enforce-

ment Administration (DEA), of all thepsychoactive drugs prescribed to youngchildren in the U.S., only two substancesthat are widely used to treat children aresubject to the Controlled Substances Act(CSA): methylphenidate and amphetamine.The DEA identifies these drugs as "power-ful stimulants" and places them in Sched-ule II of the CSA, which contains sub-stances that have the highest abuse poten-tial and dependence profile of all drugs withmedical utility.''"

In testimony before Congress in 2000,a DEA official reported that extensive re-search "unequivocally indicates that bothmethylphenidate and amphetamine havehigh abuse liabilities." The data show thatanimals and humans cannot tell the differ-ence between cocaine, amphetamine andmethylphenidate when they are taken inthe same way at comparable doses. "Inshort, they produce effects that are nearly

identical," he said. Improper use of methyl-phenidate (tablets can be abused orally,crushed and snorted, or dissolved in waterand injected) poses significant risks, withhigh doses producing agitation, tremors,euphoria, palpitations and other problems.Abuse of this drug also has been associatedwith psychotic episodes, paranoid delu-sions and hallucinations.""

According to one review of this topic,neuropharmacologic data suggest thatmethylphenidate has pharmacokineticproperties which reduce its abuse poten-tial compared with that of other stimulants,such as cocaine.'" And while there is disa-greement regarding the extent to whichpreteens and adolescents are abusing thisdrug,"^ some research indicates that thediversion of methylphenidate for illicit useincreased during the 1990s and, accordingto a recent survey, poses a potentially seri-ous public health issue.'"'"^ The DEA offi-cial concludes: "Probably the single mostdisturbing trend is that adolescents do notview abuse of this drug as serious."'"'

Natural Therapies for ADHDGiven the risks that children face in

taking stimulant-type drugs, it stands toreason that parents may want to use morenatural methods of treating ADHD symp-toms. In a 2003 survey, 54% of 114 parentsof children referred for evaluation of ADHDreported using complementary and alter-native medicine, such as vitamins and di-etary manipulation, to treat their child'sattention problems.'" Natural therapiesused to treat ADHD are introduced here,and they will be discussed more fiilly in afuture article.

Many nonpharmaceutical approachesto ADHD focus on eliminating food andenvironmental allergens that trigger symp-toms and using nutrient supplements toaddress deficiencies and provide the bodywith nutritional support. As a recent arti-cle reports: "Numerous studies suggest thatbiochemical heterogeneous etiologies for

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AD/HD cluster around at least eight riskfactors: food and additive allergies, heavymetal toxicity and other environmentaltoxins, low-protein/high-carbohydrate di-ets, mineral imbalances, essential fatty acidand phospholipid deficiencies, amino aciddeficiencies, thyroid disorders, and B-vita-min deficiencies.""'

A 2003 review of nutrition in the treat-ment of ADHD found that nutritional fac-tors such as food additives, refined sugars,food sensitivities/allergies and deficienciesof fatty acids have been associated with thisdisorder. The authors say there is growingevidence that "many children withbehavioral problems are sensitive to one ormore food components that can negativelyimpact their behaviour." They concludethat, in general, diet modification "plays amajor role in the management of ADHDand should be considered as part of thetreatment protocol."'^"

One study proving this statementfound that 19 of 26 children who met thecriteria for ADHD responded favourably toa multiple-item elimination diet. On openchallenge, all 19 reacted to many foods,dyes and/or preservatives. Sixteen of themcompleted a double-blind placebo-control-led food challenge, which found a signifi-cant improvement on placebo days com-pared with challenge days. The researchersstate that "dietary factors may play a sig-nificant role in the etiology of the majorityof children with ADHD."'"

The value of nutritional therapies inaddressing ADHD was demonstrated in arecent study comparing the effects ofRitalin with those of food supplements. Inthis study, 10 children with ADHD took thedrug and 10 took dietary supplements.Subjects in both groups showed significantgains on the outcome measures used, suchas the Intermediate Visual and Auditory/Continuous Performance Test. The supple-ments used in the study included a mix ofvitamins, minerals, phytonutrients, aminoacids, essential fatty acids, phospholipids

and probiotics that attempted to address thebiochemical risk factors of ADHD. The re-searchers concluded: "These findings supportthe effectiveness of food supplement treat-ment in improving attention and self-controlin children with AD/HD and suggest foodsupplement treatment of AD/HD may be ofequal efficacy to Ritalin treatment"'^^

Natural therapies for ADHD, such asthose discussed here, target the symptomsof this disorder vdthout posing the risks ofconventional treatment. Considering themany controversies surrounding ADHD-anunidentified cause, a subjective diagnosisand exposure to potentially harmful medi-cations-there is clearly room for treatmentoptions that avoid those considerable risks.

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