AUGUST 1990
`
`yOLUME 86
`NUMBER 2
`
`HEAL TH SCIENC~S LIBP "· r' ·
`University of Wiscc,'
`AUG 1 ~3 1990
`
`1305 Linden C;-
`
`,'.lQ,~IJl_(j,;_ 5.-':tZQF. ----'
`
`,\ ,~
`
`- - -
`ARTICLES
`coa gulase-Negative Staphylococci in Young Infants- J. W. St Geme Ill et al
`5ubdural Effusion and Neurologic Sequelae of Meningitis- J. D. Snedeker et al
`sreast-Feeding in First 24 Hours After Birth in Full-Term Neonates- Y.
`yamauchi and I. Yamanouchi
`Infant Mortality: Analysis of Leading Causes and Risk Factors-C. Dollfus et al
`Side Effects of Methylphenidate in Children With Attention Deficit Hyperactivity
`Disorder- R. A. Barkley et al
`increased Fetal Hemoglobin Synthesis in Bronchopulmonary Dysplasia- H.
`Bard and J. Prosmanne
`cosleeping in Sample of 2- and 3-Year-Old Children- D. Madansky and C.
`Edelbrock
`Dexamethasone and Adrenal Function in Very Low Birth Weight Infants- A. L.
`Alkalay et al
`Urinary N-Acetyl-,8-glucosaminidase in Urinary Infection- C. E. Johnson et al
`oral Habilitation of Child With No Response on Brainstem Audiometry- P. K.
`Connolly et al
`Should Promethazine Be Avail.able Without Prescription?- G. B. Hickson et al
`Long-Acting Stimulant Efficacy on Children With Attention Deficit-Hype.ractivity
`Disorder~ W. E. Pelham Jr et al
`~ · Desmopressin Therapy in Sickle Trait Chronic Hematuria- L. A. Baldr3e et al
`:ti14 Sucrose and Delinquency: Behavioral Assessment- J. Bachorowski et al
`154 Sucrose and Delinquency: Oral Sucrose Tolerance Test and Nutritional
`Assessment- D. A. Gans et al
`·253 Carbamazepine Loading in Critically Ill Patients- M. V. Miles et al
`'J67 Play and Imitation in Autistic Children- W. L. Stone et al
`213 Turner's Syndrome and Partial Anomalous Pulmonary Venous Drainage- J.
`W. Moore et al
`
`l217 Direct Hyperbilirubinemia Associated With Chloral Hydrate Administration- G.
`C Fathers' Hospital Visits as Predictor df Father-Infant Relationship and Infant
`I 2 Pediatric Cardiopulmonary Arrests in Rural Populations- J. E. Thompson et al
`
`H. Lambert et al
`ii Children in Sauna: Cardiovascular Adjustment- E. Jokinen et al
`
`Development- R. Levy-Shiff et al
`Effect of Multidisciplinary Management on Outcome in Pierre Robin
`~ Sequence- M. J. Bull et al
`
`EXPERIENCE AND REASON
`E coli Sepsis and Prolonged Hypophosphatemia After Exertional Heat Stroke(cid:173)
`M. A. Kay and E. D. B. McCabe
`Growth Hormone Deficiency in 8-Year-Old Girl With Human Immunodeficiency
`Virus Infection- N. Jospe and K. R. Powell
`Influence of Perinatal Instruction About Breast-Feeding on Neontal Weight
`Loss- A. Avoa and P.R. Fischer
`Psychogenic Stridor: Adolescent Conversion Disorder- R. Geist and S. E.
`Tallett
`Apparent Proteinuria Due to Sodium Bicarbonate Ingestion- D. Wechsler et al
`
`COMMENTARY
`Coagulase-Negative Staphylococcal Bacteremia in Neonates- M. S. Edwards
`
`PEDIAU 86(2) pp. 157-330
`
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`

`

`AUGUST 1990 VOL. 86 NO. 2
`
`Pediatrics
`
`OFFICIAL PUBLICATION OF THE AMERICAN
`ACADEMY OF PEDIATRICS
`
`EDITOR
`Jerold F. Lucey, Burlington, VT
`
`ASSOCIATE EDITOR
`R. James McKay, Jr, Burlington, VT
`
`MANAGING EDITOR
`Jo A. Largent, Elk Grove Village, IL
`
`EDITORIAL BOARD
`Peter Berman, Philadelphia, PA
`Philip A. Brunell, Los Angeles, CA
`Marthe Bushore, West Palm Beach, FL
`Donald Cohen, New Haven, CT
`Donald Cornely, Baltimore, MD
`Jocelyn Elders, Little Rock, AR
`Ralph Feigin, Houston, TX
`Gilbert B. Forbes, Rochester, NY
`Berti! E. Glader, Stanford, CA
`Richard B. Goldbloom, Halifax, NS, Canada
`Alen B. Gruskin, Detroit, Ml
`Kenneth L. Jones, San Diego, CA
`Stephen Joseph, New York, NY
`William Klish, Houston, TX
`Michael Kremer, Montrea~ Quebec
`Richard D. Krugman, Denver, CO
`David Nathan, Boston, MA
`James A. O'Neil, Jr, Philadelphia, PA
`Larry Pickering, Houston, TX
`Jeffrey Pomerance, Los Angeles, CA
`Roland B. Scott, Washington, DC
`Geil G. Shapiro, Seattle, WA
`Steven Shelov, Bronx, NY
`Merk Widome, Hershey, PA
`Lonnie K. Zeltzer, Los Angeles, CA
`
`CONSULTANTS
`William C. Montgomery, Detroit, MI
`Richard M. Nerkewicz, Burlington, VT
`Donald W. Schiff, Littleton, CO
`
`EX OFFICIO
`Birt Hervey, President
`James E. Strain, Executive Director
`
`PUBLISHER
`American Academy of Pediatrics
`Nancy Wechter, Copy Editor
`
`PEDIATRICS (ISSN 0031 4005) is owned and con(cid:173)
`trolled by the American Academy of Pediatrics. It is pub(cid:173)
`lished monthly by ebe American Acndemv af Pediatrics,
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`0 AmeriC!m l\.cadorny or Pediatrics, 1990. i\lJ Righbl
`Re,served. P rinted in USA. No part may b,, duplicated or
`reproduced "'i thout pti:rmission of tbe Ame-rican Academy
`or Pedurtrico.
`The publication of an advertisement neither constitut.ee
`nor implies o guarantee or endoncment by PEDIATRICS
`o, t:be Americon Academy of. Pediatrioa of the pn:,duct or
`·service advttrtiud or of the c::lnim11 made for tb"e proiluct or
`service by t he advertiser.
`POSTMASTER: Send oddre .. chang .. to PEDIAT(cid:173)
`RICS, American Acodotny or Pedistrics, 141 Northwest
`Point 81,·d, Elk Grove Villilge, IL 60009--0927.
`
`ARTICLES
`
`157 Distinguishing Sepsis From Blood Culture Contamination
`in Young Infants With Blood Cultures Growing Coagu(cid:173)
`lase-Negative Staphylococci-Joseph W. St Geme III, Louis
`M. Bell, Stephen Baumgart, Carl T. D'Angio, and Mary Cath(cid:173)
`erine Harris
`
`163 Subdural Effusion and Its Relationship With Neurologic
`Sequelae of Bacterial Meningitis in Infancy: A Prospec(cid:173)
`tive Study-Jeffrey D. Snedeker, Sheldon L. Kaplan, Philip R.
`Dodge, Sandra J. Holmes, and Ralph D. Feigin ·
`
`171 Breast-Feeding Frequency During the First 24 Hours Af(cid:173)
`ter Birth in Full-Term Neonates-Yoshitada Yamauchi and
`Itsuro Yamanouchi
`
`1 76 Infant Mortality: A Practical Approach to the Analysis of
`the Leading Causes of Death and Risk Factors-Catherine
`Dollfus, Michael Patetta, Earl Siegel, and Alan W. Cross
`
`184 Side Effects of Methylphenidate in Children With Atten(cid:173)
`tion Deficit Hyperactivity Disorder: A Systemic, Placebo(cid:173)
`Controlled Evaluation-Russell A. Barkley, Mary B. McMur(cid:173)
`ray, Craig S. Edelbrock, and Kathryn Robbins
`
`193 Elevated Levels of Fetal Hemoglobin Synthesis in Infants
`With Bronchopulmonary Dysplasia-Harry Bard and Janie
`Prosmanne
`
`197 Cosleeping in a Community Sample of 2- and 3-Year-Old
`Children-Deborah Madansky and Craig Edelbrock
`
`204 Hypothalamic-Pituitary-Adrenal Axis Function in Very
`Low Birth Weight Infants Treated With Dexametha(cid:173)
`sone-Arie L. Alkalay, Jeffrey J . Pomerance, Asha R. Puri, Ber(cid:173)
`wyn J. C. Lin, Arnold L. Vinstein, Naomi D. Neufeld, and Alan
`H. Klein
`
`211 Urinary N-Acetyl-/9-glucosaminidase and the Selection of
`Children for Radiologic Evaluation After Urinary Tract
`Infection-Candice E. Johnson, Christina V. Vacca, Deborah
`Fattlar, Doris J . Fulton, and Philip W. Hall
`
`217 Oral Habilitation of the Child With No Response on Brain(cid:173)
`stem Audiometry-Patrick K. Connolly, Gayle G. Stout, Susan
`T. Williams, Sheryl Jorgensen, and Richard J . H. Smith
`
`221 Should Promethazine in Liquid Form Be Available With(cid:173)
`out Prescription?-Gerald B. Hickson, William A. Altemeier,
`and Ellen W. Clayton
`
`A7
`
`

`

`Relative Efficacy of Long-Acting Stimulants on
`Children With Attention Deficit-Hyperactivity
`Disorder: A Comparison of Standard
`Methylphenidate, Sustained-Release
`Methylphenidate, Sustained-Release
`Dextroamphetamine, and Pemoline
`
`William E. Pelham, Jr, PhD; Karen E. Greenslade; Mary
`Vodde-Hamilton; Debra A. Murphy, PhD; Jonathan J. Greenstein, MS;
`Elizabeth M. Gnagy; Karen J. Guthrie, RN; Michele D. Hoover, MSN;
`and Ronald E. Dahl, MD
`
`From the Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania
`
`ABSTRACT. Twenty-two children with attention deficit(cid:173)
`hyperactivity disorder underwent a double-blind, pla(cid:173)
`cebo-controlled, crossover evaluation of the efficacy of
`standard methylphenidate twice a day and comparable
`doses every morning of a sustained-release preparation
`of methylphenidate (SR-20 Ritalin), a sustained-release
`form of dextroamphetamine (Dexedrine Spansule), and
`pemoline. The children were participating in a summer
`treatment program in which they engaged in recreational
`and classroom activities. Dependent measures include
`evaluations of social behavior during group recreational
`activities, classroom performance, and performance on a
`continuous performance task. Results revealed generally
`equivalent and beneficial effects of all four medications.
`Dexedrine Spansule and pemoline tended to produce the
`most consistent effects and were recommended for 10 of
`the 15 children who were responders to medication. The
`continuous performance task results showed that all four
`medications had an effect within 2 hours of ingestion,
`and the effects lasted for 9 hours. The implications of
`these results for the use of long-acting stimulant medi(cid:173)
`cation in children with attention deficit-hyperactivity
`disorder are discussed. Pediatrics 1990;86:226-237; atten(cid:173)
`tion deficit-hyperactivity disorder, long-acting stimulant
`medication, methylphenidate, dextroamphetamine, pemo(cid:173)
`line.
`
`ABBREVIATIONS. ADHD, attention deficit -hyperactivity dis(cid:173)
`order; b.i.d., twice a day; DS, Dexedrine Spansule; SR-20, Slow(cid:173)
`Release Ritalin; q.a.m., every morning; CPT, continuous per(cid:173)
`forma nce task; DSM-ill-R, Diagnostic and Statistical Manual
`of Mental Disorders, 3rd ed, revised.
`
`Received for publication Apr 12, 1989; accepted Aug 4, 1989.
`Reprint requests to (W.E.P.) Western Psychiatric Institute and
`Clinic, 3811 O'Hara St, Pittsburgh, PA 15213.
`PEDIATRICS (ISSN 0031 4005). Copyright © 1990 by the
`American Academy of Pediatrics.
`
`226
`
`PEDIATRICS Vol. 86 No. 2 August 1990
`
`Medication with a central nervous system stim -
`ulant has been the most common treatment for
`children with attention deficit-hyperactivity disor(cid:173)
`der (ADHD) for 20 years. Numerous studies have
`demonstrated the short-term efficacy of central
`nervous system stimulants-usually methylpheni(cid:173)
`date-in the treatment of ADHD (for reviews, see
`References 1 and 2). These studies have shown that
`methylphenidate improves the classroom function(cid:173)
`ing of children with ADHD, as reflected in de(cid:173)
`creases in observed disruptive behavior, increases
`in academic productivity and accuracy, and im(cid:173)
`provement
`in
`teacher ratings. 3
`4 Furthermore,
`•
`methylphenidate improves the performance of chil(cid:173)
`dren with ADHD on a variety of cognitive tasks,
`including measures of attention, learning, and
`memory.5
`6 Although considerably less research has
`•
`been conducted with them, similar findings have
`been reported for dextroamphetamine and pemo(cid:173)
`line. 7-12 Thus, medication with a central nervous
`system stimulant-usually methylphenidate and
`far less often dextroamphetamine-has become the
`most common treatment for ADHD.
`At the same time, pharmacotherapy with the
`standard preparations of stimulant has several lim -
`itations. For example, methylphenidate's brief half(cid:173)
`life means that it must be administered at least
`twice daily-a morning and a noon dose-to ensure
`adequate treatment throughout a child's school day.
`Its rapid onset and its brief half-life mean that a
`child with ADHD on the standard twice a day
`(b.i.d.) dosing regimen will be maximally affected
`for only part of a typical school day. This lack of
`pharmacologic coverage throughout the school day
`may account for the apparent failure of stimulants
`
`

`

`to affect some key domains of functioning in chil(cid:173)
`dren with ADHD. For example, it has been specu(cid:173)
`lated that one reason why stimulant effects have
`not been found on measures of long-term achieve(cid:173)
`ment is that methylphenidate's narrow window of
`effect on cognitive performance (60 to 180 minutes
`after pill ingestion) often does not overlap with
`time when medicated children are performing aca(cid:173)
`demic tasks in school.6·13·14 A child who takes a pill
`at 7:00 AM with breakfast and again at noon with
`lunch (a common regimen) may be in an active
`medication state that would facilitate performance
`on academic tasks only between 8:00 AM and 10:00
`AM and between 1:00 PM and 3:00 PM. If school
`lasts from 8:45 until 2:45, a child medicated with
`standard methylphenidate may be effectively med(cid:173)
`icated for only 3.5 hours out of the 6-hour school
`day. A child receiving methylphenidate on this
`schedule would not be expected to benefit from a
`reading group or independent seatwork after 10:00
`AM or during unstructured late-morning and mid(cid:173)
`day activities, such as recess and lunch, which are
`often difficult for children with ADHD.
`An additional difficulty associated with the
`standard methylphenidate regimen is that the child
`must be given a pill at school, an event that some
`children with ADHD and some school personnel
`actively avoid.15 In our locality (metropolitan Pitts(cid:173)
`burgh), some schools have policies that prohibit
`school personnel from administering psychoactive
`medication. Some of the young children with
`ADHD in our outpatient clinic must, therefore, take
`methylphenidate to school in their lunch boxes and
`remember themselves ·to take their midday pill.
`This no doubt contributes to the poor compliance
`that has characterized stimulant treatment of
`ADHD.16-1s
`Dextroamphetamine has a longer half-life than
`methylphenidate, 19 and controlled studies have doc(cid:173)
`- 10 Despite these studies,
`umented its effectiveness. 0
`dextroamphetamine has been widely thought to
`have a higher incidence of side effects than
`methylphenidate20 and perhaps to be less effec(cid:173)
`tive.21 It is, therefore, used far less often than
`methylphenidate-in only 5% of medicated chil(cid:173)
`dren, compared with 90% for methylphenidate.22
`These limitations of methylphenidate and dextro(cid:173)
`amphetamine led to interest in stimulants with
`longer effective spans of action. Three such medi(cid:173)
`cations are available: Dexedrine Spansule (DS, a
`sustained-release form of dextroamphetamine),
`Slow-Release Ritalin (SR-2O), andpemoline. There
`has been limited research with these long-acting
`preparations. Only two studies have examined the
`effectiveness of DS. Rapoport et al23 examined the
`effects of 10 mg of DS on clinic playroom activity
`and teacher ratings in 19 hyperactive children and
`
`reported improvement on the playroom measures
`and on the hyperactivity factor of the Conners
`Teacher Rating Scale.24 Brown et al25 conducted a
`time course study of DS (O.5 mg/kg). The results
`showed that DS had a later peak plasma level that
`lasted longer than standard dextroamphetamine,
`but that "the significant [clinical] response appears
`to be shorter."25 (P234l This is the only time course
`study of DS, and significant differences from pla(cid:173)
`cebo were reported only at 2 hours postingestion.
`The study has several limitations, however, includ(cid:173)
`ing an N of only 9 and the fact that the dependent
`behavioral measures included only an activity mon(cid:173)
`itor and the blood technician's ratings of the sub(cid:173)
`jects' behavior during blood draws.
`Pemoline has a much longer half-life than both
`methylphenidate and dextroamphetamine.26 This
`longer half-life presumably enables it to be admin(cid:173)
`istered in a single morning dosage to cover an entire
`school day. Several direct comparisons of pemoline
`with methylphenidate or dextroamphetamine have
`shown it to be similar in its efficacy.7·11 Further(cid:173)
`more, one acute study of the time of onset and time
`course of pemoline showed that pemoline exerts a
`clear behavioral effect within 2 hours of ingestion
`on the second consecutive day of administration
`and that its effects last for at least 6 hours.27 How(cid:173)
`ever, it remains widely believed that pemoline is
`less effective
`than methylphenidate or dex(cid:173)
`troamphetamine2 and that it takes weeks rather
`than hours or days before pemoline exerts an ef(cid:173)
`fect.21 As a result, it is also used far less often than
`methylphenidate-in only 2% of medicated chil(cid:173)
`dren, compared with 90% for methylphenidate.22
`Furthermore, although its longer half-life has been
`documented, the precise time course of the behav(cid:173)
`ioral and cognitive effects of pemoline has not been
`clearly established.
`Recently, a sustained-release preparation of
`methylphenidate, SR-2O, has been developed. Ac(cid:173)
`cording to its manufacturer, SR-2O is currently
`being prescribed to 11 % of the children younger
`than 10 years of age who are receiving Ritalin
`(personal communication, Timothy Horner, Ciba(cid:173)
`Geigy, September 30, 1988). Although Ciba-Geigy
`advertises that the preparation is equivalent to a
`b.i.d. schedule of 10 mg of methylphenidate, the
`only published, controlled comparison of SR-2O and
`standard methylphenidate did not support this con(cid:173)
`clusion.28 On most behavioral measures the two
`preparations had similar effects, but standard
`methylphenidate was more effective than SR-2O on
`several key measures of disruptive behavior. Al(cid:173)
`though the time courses of the two medications
`were similar, SR-2O had a slower onset of action on
`a cognitive measure, and its effects wore off more
`quickly on a measure of social behavior. Further-
`
`ARTICLES
`
`227
`
`

`

`more, analyses of individual responsivity to medi(cid:173)
`cation favored the standard preparation. As in the
`studies of DS, this study also had a small N-13
`for the first study and 9 for the analysis of time
`course.
`Thus, although there are clear potential advan(cid:173)
`tages to long-acting forms of central nervous system
`stimulants for treatment of ADHD, there have been
`few studies of the efficacy of the available prepa(cid:173)
`rations. Only one time course study is available for
`each medication, and these are not directly com -
`parable, as each used different settings and depend(cid:173)
`ent measures. Only one study each of behavioral
`effects is available for DS and SR-20, and only
`three are available for pemoline. Because there has
`never been a relative efficacy study of the long(cid:173)
`acting medications, there are no guidelines for prac(cid:173)
`ticing physicians regarding which long-acting med(cid:173)
`ication to prescribe when a long-acting drug would
`appear appropriate.
`Perhaps as a result of this lack of information,
`the long-acting forms of stimulant are used with
`only a small percentage of the children with ADHD
`who are receiving medication. Given the potential
`utility of an effective long-acting stimulant prepa(cid:173)
`ration, there is a need for a comprehensive study of
`the relative efficacy of comparable doses of the
`three long-acting forms of stimulant-pemoline,
`DS, and SR-20-compared with the standard meth(cid:173)
`ylphenidate preparation. This investigation has
`that purpose. The paucity of information about
`long-acting stimulants means that an acute, short(cid:173)
`term, crossover study appears more appropriate
`than a longer, between-group comparison. Thus, we
`designed
`a
`placebo-controlled,
`double-blind,
`within-subject study to compare 10 mg of methyl(cid:173)
`phenidate b.i.d., SR-20 every morning (q.a.m.),
`56.25 mg of pemoline q.a.m., and 10 mg of DS
`q.a.m., with midday placebos administered with the
`long-acting preparations and on placebo days. A
`wide range of dependent measures was used to
`expand on those that have been used in previous
`studies and to ensure a comprehensive assessment
`of effects. Furthermore, the most commonly used
`laboratory measure of stimulant response in chil(cid:173)
`dren with ADHD, a continuous performance task
`(CPT), was administered repeatedly on 1 day of
`each medication condition to track the relative time
`courses of the drugs.
`
`METHODS
`
`Subjects
`
`Twenty-two boys, aged 8.08 years to 13.17 years,
`participated in this study. Based on a structured
`parental interview, and parent and teacher rating
`
`228
`
`LONG-ACTING STIMULANTS
`
`scales, ADHD was diagnosed for all 22 subjects.
`Nine of the subjects also met the Diagnostic and
`Statistical Manual of Mental Disorders, 3rd ed,
`revised (DSM-III-R) criteria for a diagnosis of an
`oppositional/defiant disorder, and 4 others met
`DSM-III-R criteria for conduct disorder. Thirteen
`subjects had a discrepancy between their Wechsler
`Intelligence Scale for Children-Revised IQ and
`their Woodcock-Johnson Achievement scores of at
`least one full standard deviation in either reading,
`arithmetic, or written language, suggesting the
`presence of a learning disability. On the Swanson,
`Nolan, and Pelham Rating Scale (Pelham WE,
`Atkins MS, Murphy HA, and Swanson J, unpub(cid:173)
`lished data, 1986), which lists the symptoms of
`attention deficit disorder presented in the DSM(cid:173)
`III, teachers reported the presence of at least 8
`symptoms in each of 15 subjects. Of the 7 children
`who did not meet this criterion 5 were medicated
`when the teacher ratings were gathered. Teacher
`ratings were also obtained on the Iowa Conners
`Teacher Rating Scale, resulting in 8 subjects' ex(cid:173)
`ceeding the cutoff score for the aggression factor. 29
`No children had IQ scores below 80. One child had
`a concurrent seizure disorder for which he had
`received medication in the past, but he was not
`receiving medication at the time of the study.
`Means and standard deviations on several measures
`of subject characteristics are shown in Table 1.
`
`TABLE 1. Subject Characteristics
`Measure
`
`Mean (SD)
`10.39 (1.38)
`105.68 (14.81)
`
`Age, y
`Wechsler Intelligence Scale for
`Children-Revised IQ score
`Abbreviated Conners Rating Scale
`scores
`Teacher
`Parent
`Iowa Conners Teacher Rating Scale
`scores
`Inattention/Overactivity
`Aggression
`DSM-III-R Structured Interview for
`Parents*
`Attention deficit disorder items
`Oppositional/ defiant disorder
`items
`Conduct disorder items
`Woodcock-Johnson Achievement
`Test standard scores
`Reading
`96.45 (14.89)
`Mathematics
`99.82 (17.21)
`Language
`99.00 (14.19)
`* Number of symptoms endorsed by clinician. DSM-111·
`R, Diagnostic and Statistical Manual of Mental Disorders,
`3rd ed, revised.
`
`15.50 (6.52)
`19.32 (5.32)
`
`9.59 (3.81)
`5.86 (4.45)
`
`11.36 (1.92)
`5.36 (2.38)
`
`1.68 (1.73)
`
`

`

`setting
`The boys in this protocol were participating in
`the 1988 Western Psychiatric Institute and Clinic
`Attention Deficit Disorder Program's Summer
`Treatment Program. Children attended the Sum(cid:173)
`mer Treatment Program from 8:00 AM until 5:00
`pM on weekdays for 8 weeks. The children were
`divided into groups of 12 according to age. A broad(cid:173)
`spectrum behavior modification intervention was
`the primary treatment modality. A day in the Sum(cid:173)
`mer Treatment Program was divided into the fol(cid:173)
`lowing activities: two academic classroom periods,
`each staffed by a special education teacher and an
`aide; an art class (The oldest two boys in the study
`were in a group that participated in a group discus(cid:173)
`sion rather than an art class.); swimming; three
`supervised, group, outdoor recreational activities
`(eg, dodgeball); and lunch. For all activities except
`the academic classroom periods, five counselors
`supervised each group of 12 children and imple(cid:173)
`mented the treatment programs. The 22 children
`receiving the drug protocol described herein were
`distributed across five different age groups. The
`first 1.5 weeks of the program served as a period of
`adaptation for the children and staff, and medica(cid:173)
`tion assessments were conducted during the last 6.5
`weeks of the program.
`
`Procedure
`
`The clinical medication assessment procedure
`used in this study has been described in detail
`30 It was a double-blind, placebo-con(cid:173)
`elsewhere.28
`•
`trolled evaluation in which each child received, in
`random order for 3 to 6 days each, the following
`medications: placebo b.i.d., a standard regimen of
`10 mg of methylphenidate b.i.d., and comparable
`doses of SR-20 q.a.m., 56.25 mg of pemoline q.a.m.,
`and 10 mg of DS q.a.m. (The long-acting dosages
`were selected to be comparable with 10 mg of stand(cid:173)
`ard methylphenidate b.i.d. Empirical data have
`shown the comparability of this dose of pemoline
`11 while dextroam(cid:173)
`and 10 mg of methylphenidate,8
`•
`phetamine is generally considered to be twice as
`potent as methylphenidate. 1
`) Midday placebos were
`administered on long-acting medication days so
`that they could not be distinguished from standard
`methylphenidate days. Placebo, standard methyl(cid:173)
`phenidate, SR-20, and DS were randomized over
`single days, and pemoline was randomized in tri(cid:173)
`plets of days, with only the last 2 days of a triplet
`used for data. The average equivalent in milligrams
`per kilogram of body weight for a 10-mg dose of
`methylphenidate for these boys was 0.29. For 14 of
`the 22 boys, 10 mg was equivalent to 0.3 mg/kg,
`and the range for the other children was from 0.23
`to 0.37 mg/kg. Active medication and placebo were
`
`disguised in gelatin capsules and prepackaged in
`individual daily pill reminders. Medication was ad(cid:173)
`ministered either by parents with breakfast or by
`program staff on arrival at the program and by the
`program staff just before or just after lunch, de(cid:173)
`pending on the child's treatment group's daily
`schedule. The time and location of pill administra(cid:173)
`tion remained constant for each child. Four to 6
`days of data were gathered for placebo, standard
`methylphenidate, SR-20, and DS conditions, with
`the average number of days for each condition being
`5.0, 5.1, 4.9, and 4.9, respectively. Three to 5 days
`(mean= 4.5) of data were gathered for the pemoline
`condition. The risks and benefits of psychostimu(cid:173)
`lants were explained to all parents, and all parents
`signed treatment consents that described in detail
`the protocol and assessment procedures.
`
`Dependent Measures
`
`The reliabilities of all of the following dependent
`measures are acceptable and have been reported in
`detail in previous descriptions of our medication
`28
`30
`assessment. 3
`•
`•
`Daily Frequencies. As part of a behavior-modifi(cid:173)
`cation point system in effect in all settings except
`the academic classrooms, counselors recorded the
`frequencies with which numerous appropriate and
`inappropriate behaviors occurred daily. The follow(cid:173)
`ing five categories were derived: (1) following rules,
`(2) positive peer behaviors (eg, positive verbal state(cid:173)
`ments to others), (3) noncompliance, (4) conduct
`problems (eg, aggression), and (5) negative verbal(cid:173)
`izations ( eg, name-calling/teasing).
`Classroom Measures. Teacher-recorded rates of
`rule-following behavior were derived from a re(cid:173)
`sponse-cost procedure. Children lost points imme(cid:173)
`diately upon the occurrence of a classroom rule
`violation. The percentages of points that each child
`kept were measures of medication effects on class(cid:173)
`room rule-following behavior.
`Each boy completed a 2-minute, timed, arithme(cid:173)
`tic drill and a 10-minute, timed, reading task, using
`materials selected as appropriate to his instruc(cid:173)
`tional level. The number of arithmetic problems
`and reading questions attempted and the percent(cid:173)
`age completed correctly within the allotted time
`served as the dependent measures. Other daily ac(cid:173)
`ademic tasks were also individualized according to
`each child's needs (eg, language, spelling, additional
`reading, and arithmetic). Accuracy (percentage cor(cid:173)
`rect) and productivity (percentage of assigned seat(cid:173)
`work completed) in these tasks were recorded daily.
`Rating Scales. Teacher ratings on the Abbrevi(cid:173)
`ated Conners Teacher Rating Scale were obtained
`for each child two to four times in each medication
`condition. Counselor ratings, also using the Abbre-
`
`ARTICLES
`
`229
`
`

`

`viated Conners Teacher Rating Scale, were gath(cid:173)
`ered two to four times per child per condition.
`Parent, teacher, and counselor side effects check(cid:173)
`lists were also gathered at least once per condition
`per child. If side effects were reported on that rating
`for a child, then side effect rating scales were re(cid:173)
`peated.
`Daily Report Card. A number of each child's
`individual behavioral and academic goals (typically
`three to five targets) were included on daily report
`cards. Positive daily report cards were rewarded at
`home and monitored throughout weekly parent(cid:173)
`training sessions. The percentage of days the child
`reached his daily report criterion was used as an
`individualized measure of drug response.
`Continuous Performance Task. In addition to the
`measures from our standard medication assess(cid:173)
`ment, the children in this protocol completed a
`CPT five times on 1 day of each medication con(cid:173)
`dition to provide information about the behavioral
`time courses of the drugs. Each subject received a
`morning dose of medication and then a midday dose
`(for standard methylphenidate) or placebo (for
`long-acting medications) 4 hours after the morning
`dose. The task was administered at the following
`time intervals after morning medication ingestion:
`1 hour, 2 hours, 4 hours, 6 hours, and 9 hours.
`The CPT was the same as that used in a previous
`study, 28 with minor modifications. The rate of stim(cid:173)
`ulus presentation was varied to control the level of
`difficulty and length of the task. Subjects performed
`the CPT in a group setting. All the computers were
`situated on desks that were placed around the pe(cid:173)
`rimeter of a classroom so that all the subjects were
`facing a wall. The task itself consisted of the re(cid:173)
`peated presentation of letters on a computer mon(cid:173)
`itor (Lindgren S and Lyons D, unpublished data,
`1985). The rate at which the letters were presented
`was predetermined by establishing a baseline when
`the subjects were unmedicated. To establish the
`baseline, the variable rate version of the task was
`used, in which the rate of stimulus presentation is
`varied as a function of the subject's error rate to
`achieve an optimal level of difficulty. A 20% to 40%
`error rate was selected to make this task compa(cid:173)
`rable with other laboratory tasks that have been
`used to study stimulant effects. 11
`31 The baseline
`•
`task was administered on two different occasions
`and the average ending rate for stimulus presenta(cid:173)
`tion was calculated. Each subject was then assigned
`a presentation rate of either 0.3, 0.6, or 0.9 seconds,
`whichever was closest to his average rate during
`baseline. The task lasted for a total of 15 minutes
`regardless of the stimulus rate chosen, and the same
`rate was used for all subsequent administrations of
`the task for a given child.
`The stimuli consisted of letters presented on a
`
`230
`
`LONG-ACTING STIMULANTS
`
`monitor with the target stimulus being the letter
`"H" followed by the letter "T." When this sequence
`occurred, the subject was instructed to respond by
`pressing the space bar. Errors of omission were
`recorded as the percentage of targets presented for
`which the subject failed to press the space bar.
`Errors of commission were recorded when the child
`responded to a nontarget stimulus. The percentage
`of errors of omission, along with the number of
`errors of commission, were the dependent measures
`for the task.
`
`RESULTS
`
`The results of the trial on the mean values of the
`dependent measures from the standard medication
`assessment protocol are shown in Table 2. A one(cid:173)
`way (drug) MANOVA on these measures r