Efficacy
of Methylphenidate
Among
Mentally
Retarded
Children
With Attention
Deficit
Hyperactivity
Disorder
Benjamin
L. Handen,
PhD*t;
Anna
Marie
Breaux,
PhDt;
Amy
Gosling,
MD*t;
Dianna
L. Ploof,
EdD;
and Heidi
Feldman,
MD, PhD*t
From the CUniversity of Pittsburgh School of Medicine; Departments of tPediatrics and jPsychiatry and §Chlld Development Unit, Children’s Hospital of Pittsburgh, Pennsylvania
ABSTRACT. Twelve children with IQ scores of 50 to 74 (educable mental retardation) who met rigorous diagnos-tic criteria for attention deficit hyperactivity disorder
participated in a double-blind crossover study of the
efficacy of two doses of methylphenidate compared with
placebo. Dependent measures included behavioral
rat-ings, classroom work output, laboratory measures of
at-tention and learning, and direct observations of social
behavior. Improvement with medication on the Conners
Hyperactivity Index was observed in 75% of subjects.
Significant increases in work output, on-task behavior, and attentional skills were associated with
methylpheni-date. However, gains in measures of attention were not
associated with improvement in learning, as measured by
a paired associate learning task. Additionally, no signifi-cant increases in appropriate social interactions during
free play were associated with methylphenidate. The
results suggest that mentally retarded children with at-tention deficit hyperactivity disorder respond to methyl-phenidate at similar rates and in similar domains to that of the nonretarded population. Pediatrics 1990;86:922-930; methyiphenidate, attention deficit hyperactivity dis-order, mental retardation.
ABBREVIATIONS. ADHD, attention deficit hyperactivity
dis-order; EMR, educable mentally retarded; MPH,
methylpheni-date.
Attention deficit hyperactivity disorder (ADHD)
affects 3% to 5% of elementary school-age children
and is characterized by significant attentional
weaknesses, impulsivity, and hyperactivity.’ In
ad-dition to these core deficits, secondary traits may
Received for publication Jul 12, 1989; accepted Jan 10, 1990.
Reprint requests to (B.L.H.) Child Development Unit,
Chil-dren’s Hospital of Pittsburgh, Pittsburgh, PA 15213.
PEDIATRICS (ISSN 0031 4005). Copyright © 1990 by the
American Academy of Pediatrics.
include learning problems, poor peer relations, and
low self-esteem. The most common treatment for
ADHD is stimulant medication. Despite a wealth
of research on ADHD, most studies have
specifi-cally excluded mentally retarded children.2
There-fore, little is known about the efficacy of stimulant
medication as a primary treatment modality in this
population.
A study published in 1985 suggested that
approx-imately 7.5% of educable mentally retarded (EMR)
children are currently receiving stimulant
medica-tion.3 This rate is considerably higher than a 1981
stimulant medication treatment prevalence
esti-mate of 1% to 2% among nonretarded elementary
school children.4 However, a more recent report,
published in 1988, documented that almost 6% of
public elementary school students are presently
prescribed stimulants.5 The rate of stimulant
med-ication use was reported to be approximately 3%
among trainable mentally retarded children and 1%
among severely/profoundly retarded children.3
De-spite this relatively high level of stimulant use
among the EMR population, it is not clear that all
of these children meet criteria for ADHD. A recent
study conducted by Epstein et al6 indicated that
18% of a sample of EMR students were rated at 15
points or above on the Abbreviated Conners
Teacher Rating Scale,7 a well-accepted cutoff for
hyperactivity. Yet it is often difficult to
differen-tiate between behaviors indicative of a primary
attention deficit disorder and those that are
see-ondary to mental retardation per se.
In recent reviews of the use of stimulant
medi-cation among the mentally retarded, Gadow3 and
Gadow and Poling’ noted only four medication
studies involving public school EMR children
con-ducted since 1960811 and only three recent studies
Two additional studies were recently reported, one
examining the efficacy of stimulant medication
among children with fragile X syndrome’5 and the
other examining stimulant medication effects on
three children with dual diagnoses in an inpatient
psychiatric setting.’6 The findings of this small
body of research are equivocal, with some studies
reporting positive drug effects10’’14’6 and others
indicating limited or no response to
medica-tion.8’9”2’4 A number of methodologic problems can
be found in this literature. In particular, three
studies failed to specifically select children with
both ADHD and EMR,8’9”3 two studies based their
ADHD diagnoses solely on a total of 15 points or
greater on the Hyperactivity Index of the Conners
Teacher Rating Scale,’4”5 and one study used only
a psychiatric interview for diagnostic purposes.”
Other limitations included the use of a narrow
range of dependent measures (eg, scores on
behav-ior rating scales alone8”), the use of inappropriate dependent measures (eg, progress on a standardized
achievement test after drug treatment9”2”3), and
the administration of nonstandardized medication
doses (ie, subjects receiving the identical doses
re-gardless of weight8”3’16).
Given the paucity of research conducted to date,
the limited scope of dependent measures examined,
inadequate sample selection, and equivocal findings
of drug effects, a number of questions remain about
the efficacy of stimulant medication in EMR
chil-dren with ADHD.’7’9 The present study was
con-ducted to obtain a more complete picture of the
efficacy of stimulant medication in EMR children
with ADHD by means of a range of laboratory and
classroom measures and a double-blind crossover
design with two medication doses and a placebo.
METHOD
Subjects
Twelve EMR children, who also met criteria for
ADHD, served as subjects. Inclusion criteria
con-sisted of (1) a score of 15 or more on the
Hyperac-tivity index of both the Conners Parent and
Teacher Rating Scales,7 (2) a diagnosis of ADHD
based on a semistructured interview with parent(s)
using DSM-III-R criteria,20 (3) intellectual
func-tioning within the mild-to-borderline range of
men-tal retardation (IQ score 50 to 74, mean = 65, EMR
in class placement) as measured either by the
Wechsler Intelligence Scale for Children-Revised (Full-Scale IQ score) or the Stanford-Binet: Fourth
Edition (Composite Index), and (4) adaptive
func-tioning within the mild-to-borderline range of
men-tal retardation as measured on the Vineland
Adap-tive Behavior Scale-Parent Version. Ages ranged
from 6 to 9 years and 11 subjects were boys. Seven
of the subjects had been prescribed stimulant
med-ication for a period of time before participation in
the study.
Setting
All subjects were participants in a 6-week
Sat-urday laboratory school program conducted at
Chil-dren’s Hospital of Pittsburgh.
Procedure
The study involved a double-blind, crossover
de-sign with two doses of methylphenidate (MPH) (0.3
mg/kg per dose and 0.6 mg/kg per dose) and a
placebo. Each dose was given twice daily (for a total
of 0.6 mg/kg per day and 1.2 mg/kg per day) for a
1-week period. The first 2 weeks of the study were
devoted to the taking of baseline measures and to
allow participants to acclimate to the new setting.
Children who had previously been prescribed
stim-ulants did not receive medication during this
period. During weeks 3 through 5 of the study, a
dose of medication was given twice daily, the first
dose with breakfast and the second dose at noon.
Drug-placebo order was randomly assigned.
Saturday morning doses were given by parents at
8:15 AM, as confirmed by project personnel, with
the noon dose given by program staff. In addition,
each school nurse was contacted every Monday
morning to ensure that the correct medication dose
had been received. All 12 teachers and the parents
of each child were contacted weekly to respond to
questions and check compliance with the protocol.
Dependent Measures
Measures of behavior and performance were
taken in both the child’s regular weekday classroom and in the Saturday laboratory school.
Weekday Classroom Behavioral and Attentional Measures
Program staff met with the 12 weekday classroom
teachers to instruct them in the measures to be
taken. The following completed materials were
mailed to the project coordinator every Friday: Conners Teacher Rating Scale. The Conners
Teacher Rating Scale7 is a 28-item behavior
prob-lem checklist in which each item is rated as to
frequency of occurrence on a 4-point scale (0 = “not
at all” to 3 = “very much”). The following four
indices were obtained, each represented by a mean
ranging from 0 to 3: (1) Conduct Problems,
con-sisting of 8 items; (2) Hyperactivity, consisting of
items; and (4) Hyperactivity Index, consisting of 10
items. The Conners was completed by the
class-room teacher at the week’s end for each drug
con-dition.
CAP Behavior Checklist. The CAP Checklist2’ is
a 12-item behavior problem checklist in which each
item is rated as to frequency of occurrence on a
3-point scale (0 = “not true” to 2 = “very true”). The Inattentive scale comprises seven items, with a total
score ranging from 0 to 14. The Overactive scale
comprises five items, with a total score ranging
from 0 to 10. The CAP was completed by the
classroom teacher at the week’s end for each drug
condition.
Side Effects Checklist. A 16-item side effects
checklist was completed weekly by the classroom
teacher. Items were taken from the list of possible
side effects contained in the Physician’s Desk
Ref-erence.22 The same checklist was completed by each subject’s parent.
Five-Minute Work Sample. Each subject was
given an individualized 5-minute daily work sample
to complete independently. Examples of tasks
in-cluded single-digit addition problems,
match-to-sample tasks, and copying paragraphs. Tasks were
individualized for each child after review of the
child’s individual education plan and in
consulta-tion with the weekday classroom teacher. The tasks
involved work that had recently been mastered. A
parallel version of the same task was presented
each weekday. Measures included total number of
items attempted and percent correct.
Saturday Laboratory Program Attentional and
Behavioral Measures
Eight-Minute Work Sample. This was conducted
in the same manner as the 5-minute work sample
described above, with tasks representing recently
mastered material. Task difficulty was checked
dur-ing baseline sessions to assure appropriateness of
material. Subjects were placed side-by-side in pairs
to simulate a classroom setting and each subject
was given an independent task. Measures included
total number of problems attempted and percent
correct.
Observation of Eight-Minute Work Sample.
In-dependent work periods were coded live with
ob-servers behind a one-way mirror for on-task,
in-seat, and disruptive behaviors. A 10-second
ob-serve/S-second record interval recording procedure
was used. Primary measures represent the
percent-age of intervals a subject was rated for each
cate-gory. Additionally, global ratings of restlessness and task interest, based on a 5-point Likert Scale, were
completed by each observer at the end of the
ses-sion. An overall score for each measure was
deter-mined by averaging the individual observer ratings. Observation of Group Instruction. Group instruc-tion activities were also coded live for on-task,
in-seat, and disruptive behaviors using a 10-second
observe/5-second record interval coding procedure.
Groups were conducted with either three or four
students for a 12-minute period and were designed
to simulate a classroom group-instructional setting.
Observers rotated among subjects every 90 seconds
to ensure a sampling of behavior of each subject
during the beginning, middle, and end of the
in-structional period. Primary measures represent the
percentage of intervals a subject was rated for each
category. Global ratings of restlessness and task
interest were again obtained as described above.
Continuous Performance Test. The Continuous Performance Test23 was given for 4#{189}minutes
dur-ing each drug condition to assess attentional skills
and impulsivity. The Continuous Performance Test
involved presentation of a variety of colored shapes
on a computer monitor at individually determined
interresponse rates ranging from 0.8 to 2.0 seconds,
designed to approximate a 50% correct rate at
base-line. The subject was instructed to depress a key
whenever the target stimulus (a blue square)
ap-peared. Measures include percent correct and
num-ber of commission errors.
Saturday Laboratory Program Learning Measure
The Paired Associate Learning Task24 was given
during each drug condition to assess the rate of
acquisition of new material (auditory-visual
asso-ciations). The Paired Associate Learning Task
in-volved the presentation of a set of 8 to 12 animal
pictures, each assigned to a specific number or
common object. As each card was presented, the
paired number was stated by the instructor and
repeated by the subject. Cards were then shuffled
and presented again. The subject was asked to recall
the name or the number paired with each stimulus
cared. If correct, the instructor provided praise. If
incorrect, the correct response was provided and
the subject was asked to repeat the name of the
assigned number. The number of cards were
mdi-vidually determined during the baseline sessions so
that a 30% to 60% correct rate was established
across 10 trials. Sessions lasted a maximum of 10
trials per set of pictures or until a perfect response
was obtained on 2 consecutive trials, whichever
occurred first. Parallel versions of pictures were
used for each session. The primary measure was
Saturday Laboratory Program Social Behavior Measures
A 22-minute play session (involving three or four
subjects) was conducted during each drug condition
with live coding from behind a one-way mirror.
Coding involved a 10-second observe/S-second
rec-ord system with coders shifting observation of
stu-dents every 2#{189}minutes to ensure a sampling of
behavior at the beginning, middle, and end of the
session for each subject.
Measures were taken in three categories:
appro-priate play, inappropriate play, and play intensity.
Appropriate play was divided into three ordinal
measures: solitary play, interactive play, and rough
and tumble play. Inappropriate play was divided
into three ordinal measures: rule breaking, negative
interaction, and aggression. The six measures
corn-prising appropriate and inappropriate play were
mutually exclusive. A play-intensity measure
(in-tense or nonintense) was used to provide a more
qualitative measure of each student’s behavior.
Pri-mary measures were the mean percentage of
inter-vals rate for each category.
Additionally, global ratings of social behavior, level of activity, and level of aggressive behavior,
based on a S-point Likert Scale, were completed by
each observer at the end of the session. An overall score for each measure was determined by averaging the individual observer ratings.
Reliability
Interrater reliability was calculated on 33% of
observation intervals based on percent agreement
across coders. Percent agreement ranged from
86.9% to 97.9% over the six primary coding
do-mains used. Because of the high rate of agreement, the initial coders’ decisions were used for analysis.
A seventh domain, disruptive behavior, was
ex-cluded from the analysis because of inability to
obtain interrater reliability above 75%.
Data Analysis
A multivariate repeated-measures ANOVA was
used to analyze differences among the three drug
conditions on all dependent variables. As is
gener-ally recommended, percentile data were
trans-formed using an arcsine-square root
transforma-tion; numeric data (eg, number of problems
corn-pleted) were transformed using a square root
transformation. Results of the sphericity test
mdi-cated that conditions were not met for the preferred
method of univariate repeated-measures
AN-OVA.25’26 Scheff#{233}post hoc comparisons were
con-ducted on the significant multivariate
repeated-measures ANOVAs.27 All post hoc comparisons
were performed at the .05 level.
RESULTS
Table 1 presents the means and standard
devia-tions for each dependent variable across drug
con-ditions. Table 2 presents the Hotelling’s T2
statis-tic, P value, and significant post hoc comparisons for each dependent variable.
Weekday
Measures
These measures included a weekly Conners
Teacher Rating Scale, weekly CAP Checklist, and
daily work samples from the weekday classroom.
Based on the results of standardized behavioral
checklists, 9 (75%) of 12 subjects improved at either
the 0.3-mg/kg or 0.6-mg/kg medication dose. As
described in Table 2, weekday behavioral measures
indicate significant improvement at both the
0.3-mg/kg and 0.6-mg/kg doses of MPH (in comparison
with placebo) for the majority of dependent
meas-ures. In no cases were significant differences
re-ported between the two drug doses. The Conners
Teacher Rating Scale and CAP Checklist appeared
to be equally sensitive to medication effects. On the
weekday classroom independent work sample,
sig-nificant drug effects failed to be obtained for both
number of items completed and percent correct.
However, number of items completed did approach
significance (P < .076).
Saturday Laboratory School Measures
These measures included the independent task,
group instruction, individual testing, and social
in-teraction/play from the weekly laboratory school.
As described in Table 2, a significantly greater
number of items were completed during the
inde-pendent work sample at the 0.3-mg/kg dose than
placebo. No significant differences were noted
be-tween the 0.6-mg/kg dose and the placebo (although
the trend is in the same direction as the 0.3-mg/kg
dose) or between the 0.3-mg/kg and 0.6-mg/kg
doses. Significant drug effects were not observed
for percent correct. The percentage of intervals on-task was significantly greater at the 0.6-mg/kg dose
than placebo, but no significant difference was
ob-served between the 0.3-mg/kg dose and placebo
(although the trend is in the same direction as the
0.6-mg/kg dose). Medication effects were not
Measures Placebo 0.3 mg/kg 0.6 mg/kg
1.65 (0.62) 0.93 (0.76) 0.58 (0.37)
2.43 (0.74) 1.29 (0.87) 1.18 (0.72)
2.15 (0.49) 1.63 (0.55) 1.31 (0.73)
2.11 (0.68) 1.18 (0.67) 0.89 (0.51)
8.50 (3.75) 7.58 (4.34)
5.67 (3.45) 5.17 (3.38)
36.8 (30.7) 45.9 (34.2) 52.4 (42.2)
73.3 (26.4) 79.1 (25.0) 83.6 (18.3)
54.6 63.6 52.7 93.7 1.9 2.0 (48.4) (35.2) (21.0) (10.2) (1.1) (1.0) 52.3 70.9 59.4 98.7 1.4 2.2 (42.8) (31.1) (22.9) (3.2) (0.6) (1.0) 75.7 (24.1) 93.7 (7.1) 1.5 (0.87) 2.1 (0.87) 61.9 (28.2) 23.0 (39.0) 61.5 (27.3) 47.4 (38.4) 38.1 (29.8) 10.5 (19.6) 4.3 (3.5) 19.0 (17.4) 2.2 (1.3) 1.5 (1.5) 1.6 (0.7)
TABLE 1. Means (and Standard Deviations) for Dependent Measures Across Drug Conditions Weekday measures Teacher ConnersC Conduct Problems Hyperactivity Inattention/Passivity Hyperactivity index Teacher CAP* Inattention Overactivity Independent taskt
No. items completed
% items correct Saturday measures
Independent task4’ No. items completed
% items correct
% on-task behavior
% in-seat behavior Global restlessness Global interest Group instruction4’
% on-task behavior
% in-seat behavior Global restlessness Global interest Individual testing4’
CPT4 % correct CPT4 no. impulsive PAL, % correct Social interaction/playt
Solitary Interactive
Rough and tumble
Negative Intense Global measures/playt Active Social Aggressive
* n = 12. t n = 11.
:1:
Continuous Performance Test.§
Paired Associate Learning Task.11.83 (1.95) 9.25 (1.29) 20.4 (18.2) 58.5 (33.4) 35.8 (15.3) 84.4 (25.6) 2.6 (0.9) 1.2 (0.7) 59.5 (18.7) 77.9 (15.9) 2.8 (0.80) 1.8 (0.83) 47.5 (11.7) 32.3 (27.2) 61.0 (23.4) 40.7 (26.3) 37.5 (21.4) 15.7 (15.1) 6.5 (6.8) 28.6 (18.9) 2.7 (0.8) 0.8 (1.0) 1.9 (0.8) 89.2 (8.0) 96.7 (15.9) 1.3 (0.46) 2.6 (0.67) 61.2 (12.2) 9.2 (11.3) 61.2 (18.6) 40.2 (23.0) 52.6 (24.4) 2.9 (4.1) 4.5 (3.7) 12.9 (9.8) 1.8 (0.8) 1.2 (1.1) 1.4 (0.9)
the P value of .055 did approach significance.
Global ratings resulted in a significant difference
between the 0.6-mg/kg dose and placebo for
rest-lessness (indicating decreased activity when
receiv-ing medication) and significantly increased ratings
of task interest for both medication doses in
corn-parison with placebo. No significant differences in
global ratings were obtained between the two
med-ication doses for any of the independent task meas-ures.
On group instruction, significant differences
be-tween the 0.6-mg/kg dose and the placebo were
noted on all measures. The lower, 0.3-mg/kg drug
dose resulted in significantly greater in-seat
behav-ior and decreased restlessness (on global ratings)
than the placebo. Again, no significant differences
between the two drug doses were noted for any of
the group measures.
Individual testing resulted in significant
im-provement on the Continuous Performance Test
for the 0.6-mg/kg dose in comparison with placebo
for both percent correct and number of impulsive
responses. No differences were noted between the
0.3-mg/kg dose and placebo (although the trend is
in the same direction as the 0.6-mg/kg dose) or
between the 0.3-mg/kg and 0.6-mg/kg doses.
Nei-ther medication dose resulted in significantly
im-proved learning on the Paired Associate Learning
Task in comparison with placebo.
27.85 20.13 13.50 25.23 .001811 .0055 II .0182i1 .002611 12.23 .02381/ 21.46 .004511 7.72 .0761 5.47 .1403 18.90 2.28 12.81 8.67 66.19 22.08 37.49 60.54 41.78 14.13 38.06 13.77 0.13 0.26 3.11 10.12 10.27 10.50 8.07 10.57 2.16 .0067! .3903 .02111/ .0547 .0001# .0041 II .00061/ .000111 .0004 II .0161// .0006# .0173// .9942 .8922 .2958 .04 .04161/ .0395// .0699 .0390// .4148 - P1 .4- P2
-..
P3-..
P4 - P5 -0 P6TABLE 2. Comparison of 0.3 mg/kg Methylphenidate,
0.6 mg/kg Methylphenidate, and Placebo on Dependent
Measures Hotelling’s Measure T2 Weekday measures Teacher Conners4’ Conduct Problems Hyperactivity Inattention/Passivity Hyperactivity index Teacher CAP4’ Inattention Overactivity Independent taskt
No. items completed
% correct Saturday measures
Independent task4’ No. items completed
% correct
% on-task behavior
% in-seat behavior Global restlessness Global interest Group instruction4’
% on-task behavior
% in-seat behavior Global restlessness Global interest Individual testing4’
CPT4 % correct CPT4 no. impulsive PAL, % correct Social interaction/playt
Solitary Interactive
Rough and tumble
Negative Intense Global measures/playt Active Social Aggressive
C df2,10; n = 12.
tdf2,9;n= 11.
:1:
Continuous Performance Test.§
Paired Associate Learning Task.II
0.3 mg/kg > placebo, P < .05; 0.6 mg/kg > placebo, P< .05.
#{182}0.3 mg/kg > placebo, P < .05. # 0.6 mg/kg > placebo, P < .05.
play during the playgroup observation, data form
the three categories comprising inappropriate play
were collapsed. No significant differences were
noted between the 0.3-mg/kg dose and placebo on
any of the social interaction measures. For the
higher, 0.6-mg/kg dose, significantly less rough and
tumble play and significantly less intense play were
noted in comparison with placebo. Global measures
of activity level also indicated significantly less
activity at the 0.6-mg/kg dose than placebo. No
differences between medication and placebo were
noted for solitary play, interactive play, or global
measures of appropriate social behavior, although
the latter measure did approach significance (P <
.069). Finally, negative play and global measures of
aggression also failed to evidence medication
ef-fects, probably because of the relatively low rates
of these behaviors at baseline.
Data from six children randomly selected from
the participant group (N = 12) were graphed using
the Hyperactivity Index of the Conners Teacher
Rating Scale and percent correct from the
Contin-uous Performance Test (based on a square root
data transformation). This was done to illustrate
individual differences among children because a
number of researchers have demonstrated a great
deal of variability both among children and for each
child on different measures of drug response.28’29 A
test of the equality of the regression lines indicated no significant differences between the slopes of the
dose-response curves from the 6 randomly selected
children and the entire group of 12 children.
Inspection of the first dose-response curve (Fig
1) indicates that four subjects exhibited clear,
dose-dependent decreases in Conners ratings. Subject 4,
while evidencing a large decrease in the Conners
rating at the 0.3-mg/mg dose, was well above the
1.5-point cutoff at the 0.6-mg/kg dose.
Interest-ingly, subject 1 was rated as having a good response
to placebo, with a slight increase in the Conners
rating at 0.3 mg/kg and a greater increase at the
0.6-mg/kg dose.
Inspection of Fig 2 demonstrates that two
sub-jects had dose-dependent increases in percent
cor-rect on the Paired Associate Learning Task. Two
additional subjects exhibited slight decreases in
percent correct at the 0.3-mg/kg dose but increased
:D
Placebo .3 mg/kg .6 mg/kg
Dose Level
Fig I. Conners Teacher Hyperactivity Index score for 6
children randomly selected from the total group (N =
12). Score based on a mean of 10 items for each drug
0
U 1 U
. P1
... P2
..
P3 -C. p4. PS
-0-
p4 0020
Placebo .3 mg/kg .6 mg/kg
Dose Level
Fig 2. Percent correct on Continuous Performance Test (CPT) across drug conditions for 6 children randomly
selected from the total group (N = 12).
to above placebo levels at the higher, 0.6-mg/kg
dose. The two remaining subjects evidenced the
opposite pattern, with improved performance at the
0.3-mg/kg
dose and a subsequent decrease in per-cent correct at the 0.6-mg/kg dose.Medication
Side Effects
A number of subjects exhibited adverse side
ef-fects during the medication trial. Teachers of six
subjects reported increased staring at either the
0.3-mg/kg or 0.6-mg/kg doses. Four of these
sub-jects also evidenced increased drowsiness, with a
fifth subject exhibiting drowsiness without staring.
Social withdrawal was severe enough for one of the
above subjects at the 0.3-mg/kg dose that the
sub-sequent 0.6-mg/kg dose was not administered.
DISCUSSION
Consistent with reports of the use of stimulant
medication among nonretarded children, the
pres-ent study found that 75% of mentally retarded
subjects evidenced a positive response to MPH
based on behavioral checklists. This is particularly striking given the relatively short duration (1 week) of each drug dose, necessitated by the limitations
of a 6-week Saturday laboratory school program.
Questionnaires completed by weekday classroom
teachers indicated significant improvement in most
indices for both the 0.3-mg/kg and 0.6-mg/kg doses.
Weekday classroom work samples showed trends
in the correct direction.
Significant improvement in behavior was
corrob-orated during two simulated classroom settings
conducted during the Saturday laboratory program.
Methylphenidate was found to be associated with
improvement in on-task behavior as well as work
output, both considered to be measures of attention.
Global measures of restlessness and interest were
also significantly improved.
Controversy exists in the ADHD literature about
the long-term effect of stimulant medication on
achievement and learning. Two reviews of the
literature’9’30 concluded that there is little evidence
for improvement in achievement over time when
children with ADHD who have been or have not
been receiving medication are compared. However,
Pelham3’ describes a number of methodologic
in-adequacies with this research. Other research29’32
has consistently documented immediate
improve-ment in work output and accuracy after
adminis-tration of medication, a finding also observed in the
present study. This may suggest that learning has,
indeed, occurred. Although the present study found
significant improvement on a number of measures
of attention (eg, Continuous Performance Test,
work output, on-task behavior), this was not
nec-essarily associated with improvement in learning
as measured by the Paired Associate Learning
Task. This finding is in contrast to a number of
other studies which have documented significant
drug effects on Paired Associate Learning Task
performance with nonretarded children with
ADHD.33’34 It may be that performance on
previ-ously acquired material (eg, timed work samples)
requires a different level of attention and
organi-zational skill than that demanded with a novel
learning task. This may be especially true for
men-tally retarded children, many of whom have had
poor and frustrating learning histories. Therefore,
work output may be independent of learning, at
least with certain types of tasks.
The effect of stimulant medication on social
in-teractions of children with ADHD also remains an
area of some confusion in the literature. In general,
free-play observations, as contrasted with more
structured settings, have revealed relatively few
differences between normal children with ADHD
and control children.35 Whereas stimulant
medica-tion has been shown to decrease broad categories
of negative social behavior,36’37 little is known about
the positive effect of stimulants on behaviors that
lead to peer difficulties.35 In fact, there is some
evidence that medication may not enhance the
ac-quisition of appropriate social Skll5.m In the
pres-ent study, minimal improvement was observed in
social interactions during play group after the
in-troduction of MPH. In fact, no differences were
noted between the 0.3-mg/kg dose and placebo on
any social interaction measures. Those variables
for which a significant drug effect was documented were limited to measures that described the general intensity of play. At the higher dose, the children
as a group were significantly less active and rough.
However, this did not necessarily translate into increased appropriate interactive play or increased
social withdrawal. Although intensity of play may
decrease with the administration of MPH, the
little. Therefore, a child who chooses to engage in
isolated play when not receiving medication will
not necessarily become more socially involved after
administration of stimulant medication. It may be
that social interactions are less influenced by
med-ication in this population because of the presence of long-standing social skills deficits which are not
immediately ameliorated by stimulant medication.
Therefore, the use of alternative treatments, such
as social skills training or anger control,38 either
alone or in conjunction with stimulants should be
considered.
The relatively high number of reported adverse
drug side effects is unusual. It is possible that the
present study’s close scrutiny of potential side
ef-fects, both through checklists during the week and
observation during the Saturday laboratory school,
tended to increase the number of reports of unusual
behaviors over that commonly found in clinical
practice with nonretarded children. An alternative
explanation is that less well-developed cortical
functioning among the mentally retarded may make
this population more susceptible to adverse drug
side effects. This same explanation may also
ac-count for some reports of increased side effects
among preschoolers treated with stimulants.39’4#{176}
Of the nine children for whom MPH was
effica-cious, a 0.6-mg/kg dose was recommended for four
children and a 0.3-mg/kg dose was recommended
for the remaining five at the conclusion ofthe study.
Dosage decisions were based on individual response
patterns and consideration of adverse side effects.
While group data can guide clinical decision making
about the appropriateness of MPH for a particular
mentally retarded child, one must weigh individual
differences in terms of global responsivity,
improve-ment or lack of gains in specific subdornains, as
well as the presence of adverse side effects at higher dose levels.
ACKNOWLEDGMENTS
This investigation was supported by grants from the
Edith L. Trees Foundation and the Research Advisory
Committee of Children’s Hospital of Pittsburgh.
We gratefully acknowledge the staff of Children’s
Hos-pital of Pittsburgh, Saturday Education Program:
Kir-sten Bonvalot, Clare Flanagan, Sarah McAuliffe, Dale
Pope, David Ramally, Dedra Russ, MEd, and Wendy
Wallace. We also thank Janine Janosky, PhD, for her
consultation in conducting the statistical analysis and
Joseph Mazzotta, RPh, of the Children’s Hospital of
Pittsburgh Pharmacy Department for his assistance in
preparing the methyiphenidate doses.
REFERENCES
1. Barkley RA. Hyperactive Children: A Handbook for
Diagno-sis and Treatment. New York, NY: Guilford Press; 1981
2. Gadow KD, Poling AG. Pharmacotherapy and Mental
Re-tardation. Boston, MA: College Hill Press; 1988
3. Gadow KD. Prevalence and efficacy of stimulant drug use
with mentally retarded children and youth. Psychopharma-col Bull. 1985;21:291-303
4. Gadow KD. Prevalence of drug treatment for hyperactivity
and other childhood behavior disorders. In: Gadow KD,
Loney J, eds. Psychosocial Aspects of Drug Treatment for
Hyperactivity. Boulder, CO: Westview Press; 1981:13-76.
5. Safer DJ, Krager JM. A survey of medication treatment for
hyperactive-inattentive students. JAMA.
1988;260:2256-2270
6. Epstein M, Cullinan D, Gadow KD. Prevalence of
Hyper-activity Symptoms in Special Education Settings.
Unpub-lished manuscript. DeKalb, IL: Northern Illinois University,
Dept of Learning, Development and Special Education; 1984
7. Goyette CH, Conners CK, Ulrich RF. Normative data on
revised Conners Parent and Teacher Rating Scales. Abnorm
Child Psychol. 1978;6:221-236
8. Blacklidge V, Ekblad R. The effectiveness of
methylpheni-date hydrochloride (Ritalin) on learning and behavior in
public school educable mentally retarded children.
Pediat-rics. 1971;47:923-926
9. Blue AW, Lytton GJ, Miller OW. The effect of
methylphe-nidate on intellectually handicapped children. Am Psychol.
1960;15:393. Abstract
10. Schell RM, Pelham WE, Bender ME, Andree JA, Law T,
Robbins FR. The concurrent assessment of behavioral and
psychostimulant interventions: a controlled case study.
Be-hay Assess. 1986;8:373-384
11. Varley CK, Trupin EW. Double-blind administration of
methylphenidate to mentally retarded children with
atten-tion deficit disorder: a preliminary study. Am J Ment Defic.
1982;86:560-566
12. Alexandris A, Lundell EW. Effect of thioridazine,
amphet-amine, and placebo on the hyperkinetic syndrome and
cog-nitive area in mentally deficient children. Can Med Assoc J.
1968;98:92-96
13. Bell A, Zubek JP. Effects of deanol on the intellectual
performance of mental defectives. Can J Psychol.
1961;15:172-175
14. Christensen DE. Effects of combining methylphenidate and
classroom token system in modifying hyperactive behavior.
Am J Ment Defic. 1975;80:266-276
15. Hagerman RJ, Murphy MA, Wittenberger MD. A controlled
trial of stimulant medication in children with the fragile X
syndrome. Am J Med Genet. 1988;30:377-392
16. Payton JB, Burkhart JE, Hersen M, Helsel WJ. Treatment
ofADDH in mentally retarded children: a preliminary study.
J Am Acad Child Adolesc Psychiatry. 1989;28:761-767
17. Aman MG. Stimulant drug effects in developmental
disor-ders and hyperactivity: toward a resolution of disparate
findings. J Autism Dev Disord. 1982;12:385-398
18. Aman MG. Psychoactive drugs in mental retardation. In:
Matson JL, Andrasik F, eds. Treatment Issues and
Innova-tions in Mental Retardation. New York, NY: Plenum Press;
1983;455-513
19. Gadow KD. Relative efficacy ofpharmacological, behavioral,
and combination treatments for enhancing academic
per-formance. Clin Psychol Rev. 1985;5:513-533
20. American Psychiatric Association, Committee on
Nomen-clature and Statistics. Diagnostic and Statistical Manual of
Mental Disorders. 3rd ed., revised. Washington, DC:
Amer-ican Psychiatric Association; 1987
21. Edelbrock C. CAP Rating Scale. Worcester, MA: University
of Massachusetts Medical School, Dept of Psychiatry; 1986.
22. Physician’s Desk Reference. Oradell, NJ: Medical Economics Company Inc; 1987
23. Lindgrun 5, Lyons D. Pediatric Assessment of Cognitive
Efficiency (PACE). Iowa City, IA: University of Iowa, Dept
of Pediatrics; 1984
24. Swanson JM, Kinsbourne M. Stimulant-related
state-de-pendent learning in hyperactive children. Science.
25. Collier RO, Baker FB, Mandeville GK, Hoyes TF. Estimates of test size for several test procedures based on conventional
variance ratios in the repeated measures design.
Psycho-metrika. 1972;32:339-353
26. Davidson ML. Univariate versus multivariate tests in
re-peated measures experiments. Psychol Bull. 1972;77:446-452
27. Marascuilo LA, Levin JR. Multivariate Statistics in the
Social Sciences: A Researcher’s Guide. Monterey, CA: Brooks/Cole Publishing Co; 1983
28. Rapport MD, DuPaul GJ, Stoner G, Birmingham BK, Masse
G. Attention deficit disorder with hyperactivity: differential
effects of methylphenidate on impulsivity. Pediatrics.
1985;76:938-943
29. Pelham WE, Hoza J. Behavioral assessment of
psychostim-ulant effects on ADD children in a summer day treatment
program. In: Prinz R, ed. Advances in BehavioralAssessment of Children and Families. Greenwich, CT: JAI Press; 1987;3:3-33
30. Barkley RA, Cunningham C. Do stimulant drugs improve
the academic performance of hyperkinetic children? Clin
Pediatr (Phila). 1978;17:85-92
31. Pelham WE. The effects ofpsychostimulant drugs on
learn-ing and academic achievement in children with
attention-deficit disorders and learning disabilities. In: Torgesen JK,
Wong YL, eds. Psychological and Educational Perspectives on Learning Disabilities. New York, NY: Academic Press; 1986:257-288
32. Pelham WE, Bender ME, Caddell JM, Booth 5, Moorer S.
Methylphenidate and children with attention deficit
disor-der: dose effects on classroom and social behavior. Arch Gen Psychiatry. 1985;42:948-952
33. Gan J, Cantwell DP. Dosage effects of methylphenidate on
paired associate learning: positive/negative placebo
re-sponders. J Am Acad Child Psychiatry. 1982;21:227-242
34. Swanson J, Kinsbourne M, Roberts W, Zucker K.
Time-response analysis of the effect of stimulant medication on
the learning ability of children referred for hyperactivity.
Pediatrics. 1978;61:21-29
35. Hinshaw SP, McHale JP. Stimulant medication and the
social interactions of hyperactive children: effects and
im-plications. In: Gilbert DG, Conley JJ, eds. Personality, Social Skills, and Psychopathology. New York, NY: Plenum Press; in press
36. Amery B, Minichiello MD, Brown GL. Aggression in
hyper-active boys: response to d-amphetamine. J Am Acad Child
Psychiatry. 1984;23:291-294
37. Whalen CK, Henker B, Collins BE, McAuliffe 5, Vaux A.
Peer interactions in a structured communication task:
com-parisons of normal and hyperactive boys and of
methylphe-nidate (Ritalin) and placebo effects. Child Dev. 1979;52:388-401
38. Hinshaw SP, Henker B, Whalen CK. Self-control in
hyper-active boys in anger-inducing situations: effects of
cognitive-behavioraltraining and ofmethylphenidate. JAbnorm Child
Psychol. 1984;12:55-77
39. Cohen NJ, Sullivan 5, Minde KK, Novak C, Helwig C.
Evaluation of the relative effectiveness of methylphenidate
and cognitive behavior modification in the treatment of
kindergarten-aged hyperactive children. J Abnorm Psychol.
1981;9:43-54
40. Schleifer M, Weiss G, Cohen N, Elman M, Cvejic H, Kruger
E. Hyperactivity in preschoolers and the effect of
methyl-phenidate. Am J Orthopsychiatry. 1975;45:38-50
TRANSPLANTING
THE
COST
OF ORGAN
TRANSPLANTS
Two years ago, in a controversial move, Oregon’s Legislature opted to use the
state’s limited Medicaid funds for prenatal programs instead of organ
trans-plants, effectively eliminating such procedures for the needy and working poor.
One early result, critics say, was the death of a seven-year-old boy with leukemia
who needed a $100,000 bone-marrow transplant.Now families are moving to
California from Oregon simply to qualify for California’s $7 billion MediCal
program, which still covers some transplants for uninsured patients. In recent
months, two San Francisco hospitals each performed a liver transplant on
former Oregon residents-including an 11-year-old girl-at a cost of $100,000
to $200,000 apiece. Oregon’s lawmakers set “a death sentence for children with
liver disease,” says Robert Dimand, medical director for the pediatric
liver-transplant program at the University of California Medical Center in San
Francisco.
Ruffenach G. Transplanting the cost of organ transplants. The Wall Street Journal. January 2,
1990;86;922
Pediatrics
Feldman
Benjamin L. Handen, Anna Marie Breaux, Amy Gosling, Dianna L. Ploof and Heidi
Deficit Hyperactivity Disorder
Efficacy of Methylphenidate Among Mentally Retarded Children With Attention
Services
Updated Information &
http://pediatrics.aappublications.org/content/86/6/922
including high resolution figures, can be found at:
Permissions & Licensing
http://www.aappublications.org/site/misc/Permissions.xhtml
entirety can be found online at:
Information about reproducing this article in parts (figures, tables) or in its
Reprints
1990;86;922
Pediatrics
Feldman
Benjamin L. Handen, Anna Marie Breaux, Amy Gosling, Dianna L. Ploof and Heidi
Deficit Hyperactivity Disorder
Efficacy of Methylphenidate Among Mentally Retarded Children With Attention
http://pediatrics.aappublications.org/content/86/6/922
the World Wide Web at:
The online version of this article, along with updated information and services, is located on
American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.
