THE PREDICTION OF DIFFERENTIAL RESPONSIVENESS
OF HYPERKINETIC CHILDREN TO METHYLPHENIDATE
Russell A. Barkley
A Dissertation
Submitted to the Graduate College of Bowling Green State University in partial fulfillment of the requirements for the degree of
DOCTOR OF PHILOSOPHY
June 1977
Gr »resentative li
ABSTRACT
The present study attempted to ascertain the effects of methylphenidate on the activity level and attention of hyper active children. This research also focused on the deter mination of which variables predicted the degree to which hyperactive children improved during drug treatment.
A total of 36 boys ranging in age from 5 to 12 years and having IQs greater than 80 were used in this study. Of these, 18 were children referred to local pediatricians, diagnosed as hyperkinetic, and placed on methylphenidate. A second group of 18 boys was obtained from the local community as a control group and were matched in age and IQ with the hyperactive children. All children were observed on three occasions with each being separated by a 7 to 14 day interval. The hyperactive children participated in a double-blind drug- placebo crossover design during these three occasions. On the first occasion, they were evaluated while off all medica tion. On the second and third occasions, they received the drug or placebo in a randomized fashion such that half received the drug first while the other half received the placebo first. The hyperactive children received 10 milli grams of methylphenidate orally ingested within 3 hours prior to their evaluation, or received a placebo. The control children did not receive any drugs during this study. On each of the three occasions, all children were evaluated using a variety of measures of activity level and attention taken across several structured and free play settings. Parental ratings of activity level as well as tests of math and reading ability were also obtained.
The results indicated that methylphenidate significantly improved a variety of types of activity level across all of the settings in the hyperkinetic children. Attention span and concentration to tasks were also improved. Pretreatment levels of the inability to concentrate on structured tasks were the best predictors of global improvement in the hyper kinetic children during drug treatment. This study also found that hyperkinetic children were significantly more active, had shorter attention spans, were less able to con centrate on tasks, were less able to inhibit locomotor activity, and were viewed by their parents as more active than normal children. They were also observed to increase their task-irrelevant activity over time. Despite the positive drug effects, clinical observations suggested that the drug may have been reducing the hyperactive child's responsiveness to his environment. Ill
ACKNOWLEDGEMENTS
The author wishes to express his sincere appreciation to Douglas G. Ullraan, Ph.D., committee chairman, for his superlative guidance and supervision throughout the course of this research project, and to H. Wesley Brown, M. D., for his assistance in obtaining the hyperkinetic children and in providing the drug and placebo substances for this study. The assistance of William Roberts, M. D., and Marjorie Conrad, M. D., in providing several of the hyper kinetic children is also gratefully acknowledged. The author would also like to thank Donald Kausch, Ph.D., Jaak Panksepp, Ph.D., and Stephen Hood, Ph.D., members of the committee for their comments on an earlier version of this paper and for their assistance in this project, and Thomas L. Jackson, Jr. for assisting in the collection of the reliability data on several measures. And, of course, I am continually grateful to my wife, Pat, for her kind ness, understanding, and support throughout this arduous endeavor.
It should also be noted that several sections of this manuscript have recently been accepted for publication in scientific journals. Appendix A, Predicting the Response of Hyperactive Children to Stimulant Drugs: A Review, has been accepted for publication in a special issue of the Journal of Abnormal Child Psychology on Hyperactivity in Children, to be edited by Virginia Douglas, Ph.D., 1976, (in1 press). In addition, Appendix B, A Review of Stimulant Drug Research with Hyperkinetic Children, has also been accepted for publication in the Journal of Child Psychology and Psychiatry, 1976, (in press).
Funds for this project were provided in part by a grant from the National Science Foundation and by the Department of Psychology, Bowling Green State University. 77/
iv
TABLE OF CONTENTS
Page
INTRODUCTION...... 1
METHOD...... 12
Subjects...... 12
Medication...... 14
Design ...... 15
Apparatus...... 16
Procedures...... 19
Dependent Measures...... 22
RESULTS...... 26
Comparison of Hyperactive and Normal Children ... 26
Changes in NormalC hildren Over Time...... 31
The Effects of Methylphenidate on Hyperkinetic Children...... 34
Predicting Drug Responding in Hyperkinetic Children...... 42
DISCUSSION...... 48
Effects of Methylphenidate on Hyperkinesis...... 49
Predicting Drug Responses to Methylphenidate ... .53
Hyperactive Versus Normal Children...... 55
Clinical Observations on Drug Responding...... 56
Limitations of the Present Study...... 58
SUMMARY...... 59
REFERENCES...... 60
APPENDIX A...... 64
APPENDIX B...... 101
APPENDIX C...... 165 V
LIST OF TABLES
Table No. Contents Page
TABLE 1. Raw Means, Standard Deviations, and 13 Ranges for Age, IQ, and Reading and Arithmetic Scores for Each Group of Children
TABLE 2. List of Dependent Measures by Experi- 20 mental Session and Construct Being Measured
TABLE 3. Raw Means and Analyses of Variance 28 for Hyperactive Versus Control Comparisons on Baseline Measures
TABLE 4. Summary of Measures Discriminating 30 Hyperactive From Normal Children as Categorized by Constructs
TABLE 5. Raw Means, Standard Deviations, and 32 Analyses of Variance on Each Measure for Normal Children Under Each Occasion of Assessment
TABLE 6. Raw Means, Standard Deviations, and 35 Analyses of Variance on Each Measure for Hyperactive Children Under Each Treatment Condition
TABLE 7. Analyses of Variance for Pairwise 38 Comparisons of Treatment Conditions on Measures Found to Have Significant Differences Among Treatments
TABLE 8. Summary of Measures Found to be 39 Significantly Different Between Placebo and Drug Conditions
TABLE 9. Averaged Intercorrelations Among 45 Pretreatment and Drug Response Constructs -1-
The Prediction of Differential Responsiveness
of Hyperkinetic Children to Methylphenidate
The present research attempted to determine the effects R of methylphenidate (Ritalin ), a stimulant drug, on the
activity level and attention of hyperkinetic children.
Previous research in this area suggested that the major
effect of this drug was on attention span or concentration.
It was therefore predicted that the measures of attention
utilized in this study would show the greatest degree
of improvement in response to methylphenidate. Of additional
importance to this study was the determination of which of a
variety of measures predicted differential responsiveness to
this drug. That is, which characteristics of these children
predicted their degree of improvement while on methylpheni
date. Again, the measures of attention were predicted to
be the best indicants of such responsiveness. A review of
the literature on predicting differential responsiveness of hyperkinetic children to stimulant drugs is .provided in
Appendix A. A considerably larger review of the literature on the effects of stimulant drugs on hyperactive children
in general is provided in Appendix B.
Children diagnosed as hyperkinetic have been described as extremely overactive, distractible, inattentive, impulsive uncoordinated, and difficult to discipline in comparison to normal children (Cantwell, 1975; Douglas, 1972; Wender, 1971)
The present study focused on two of the most frequently cited -2-
symptoms of this disorder — overactivity and difficulties in attention.
Previous attempts at defining these constructs have met with only limited success. Some investigators have regarded overactivity as activity level which exceeds two standard deviations above the mean for the normal child on some ob jective measure (Werry, 1968). Another approach at defini tion appears to focus on specific types of activity, since efforts to arrive at a single, global measure of activity have not been successful (Cromwell, Baumeister, & Hawkins,
1963). That is, since there appear to be differences among the various measures of activity depending at least upon the part of the body engaged in the activity and the type of measure used, many investigators have narrowed their definition to some specific type of activity (Pope, 1970).
Attempts have therefore been made to measure wrist activity
(Kasper et. al., 1971), locomotor activity (Pope, 1970), ankle activity (Rie et. al., 1976), total body activity
(McFarland et. al., 1966), or seat movements (Sprague et. al., 1970). Others (Cromwell, Baumeister, & Hawkins, 1963;
Ellis et. al., 1974) have described overactivity as excessive activity which exceeds that required in a situation. Thus, the situational appropriateness of activity level is seen as important in this definition of overactivity. Within this conceptualization of overactivity, a further distinction has been made (Conners, 1972; Sroufe et. al., 1973) between activity which is relevant to the accomplishment of a task -3-
and that which is not. In summary, then, efforts to assess
activity level in hyperactive children have focused on the amount of general activity, the type of activity, such as wrist, ankle, locomotor, etc., the situational appropriate ness of the activity, and its relevance to the demands of an assigned task. To be comprehensive, the present study included measures of several types of activity taken in several types of formal and informal settings.
A similar state of affairs exists for definitions of attention as well. Douglas (1974) has chosen to investigate attention in these children by studying what a child must do when he is asked to selectively focus on a specific task.
She and her colleagues (See Douglas, 1972, 1974) have there fore chosen reaction time, maze coordination, vigilance, and continuous performance types of tasks as measures of attention, which she refers to as concentration. In this particular case, attention is felt to be the ability to concentrate on a structured task and to inhibit impulsive responding while doing so. Various parameters of task performance serve as the dependent measures. In contrast, others (Barkley 8s
Ullman, 1975; Pope, 1970; Rapoport et. al., 1971; Routh et. al., 1973) have regarded attention as the amount of time spent in contact with or manipulating objects in a relatively demand free setting. Thus, measures such as the number of toy changes or activity changes made during free play or the time spent per toy or activity in that interval have been used to assess attentiveness in hyperactive children. -4-
As such, attention is seen as the degree to which self-ini-
tiated investigation or manipulation of the environment is
focused to one or a limited number of stimuli within a given
time interval. Given this emphasis on average time per
change in activity or number of manipulations per unit time,
this approach appears to focus on the "length of attention"
or attention span. Although other definitions of attention
have been used, research with hyperactive children has most
frequently focused on the two described above. Since pre
vious research has shown that measures derived from these
two definitions frequently fail to intercorrelate (Barkley
& Ullman, 1975), the present study included both types of measures of attention, with measures of the first definition
referred to as concentration to task while measures of the second are referred to as attention span.
Having briefly discussed the definitions and measures of the concepts of activity level and attention, it will now be important to discuss the role of stimulant drugs in the treatment of children with problems in these areas.
Since Bradley (1937-38) first described their potential utility, stimulant drugs have been used increasingly in the treatment of children's behavior disorders. In particular, these drugs have been frequently prescribed for that group of children known as hyperkinetic or minimally brain damaged.
Recent estimates (Krager & Safer, 1974) indicate that between
76 and 82 percent of the hyperactive children receiving drugs are using some type of stimulant, particularly methylpheni- -5-
date. The belief that stimulant drugs diminish or alleviate
the symptoms commonly associated with hyperkinetic children
is widespread among clinical opinion (Bradley, 1950; Wender,
1971) . The effect of these drugs has been referred to by
many as "paradoxical" in nature because of the apparent calm
ing of a seemingly overaroused child. This calming effect
is supposedly reflected in reduced activity level, restless
ness, impulsivity, as well as in increased attention span or
concentration.
However, results of studies employing objective measures
of these hyperkinetic symptoms suggest that the symptom primarily affected by these drugs is attention span, or con
centration (See Appendix B; Douglas, 1972, 1974; Conners,
1972) . Effects on other symptoms are equivocal suggesting that favorable changes in these other symptoms may stem indirectly from improvement in attention span or concentration
(Cohen, Douglas, & Morgenstern, 1971; Conners, 1972). This seems particularly true with respect to the symptom of over activity. Many investigators (Conners, 1972; Douglas, 1972;
Schleifer et. al., 1975; Sroufe et. al., 1973) have proposed that it is not total motor overactivity per se that is improved by stimulant drugs but the hyperkinetic child's ability to attend to and concentrate on a task when demanded by a situation. Reductions in activity level are believed to be due indirectly to increased concentration in that only task-irrelevant activity is reduced while task-relevant activity may remain unchanged. Furthermore, the type of -6-
setting in which activity level is assessed may also deter
mine whether or not improvement in this symptom is observed
during stimulant drug treatment. Excessive activity in a
structured setting, such as during testing, may be affected
more by the stimulant drugs than free play activity (See
Appendix B).
The support for this notion remains tentative, however,
due to a major problem which exists in the comparison of
studies on this topic. This problem is the diversity of
measures used to assess activity level and attention span
or concentration across these studies. As previous research
has demonstrated (Barkley 8s Ullman, 1975), commonly used measures of these constructs, while significantly related,
have such low order intercorrelations that differences across
studies in their results could be due solely to the differ ences in their measuring techniques. The present study, therefore, attempted to examine the effects of methylpheni- date on the activity level and attention of hyperkinetic children using a variety of commonly used measures of these constructs.
Of particular importance to the current study was the identification of those variables which are useful in pre dicting the degree to which hyperkinetic children improved on medication. The determination of these variables would be of great clinical utility in selecting children who are most likely to respond to stimulant drug therapy with the greatest degree of improvement. Although many studies have -7-
found the majority of hyperkinetic children to improve on
stimulant drugs, some of them do not. It appears that approx
imately 75 percent of the children treated with these drugs
respond favorably while 25 percent remain unchanged or
their symptoms are exacerbated by them (See Appendix B).
It is possible that part of the variation in response to
stimulant drugs may be due to the fact that hyperkinetic
children comprise a rather heterogeneous group with regard to symptomatology. For instance, some of these children may be overactive, others may be more inattentive, and still others may show neither or both of these symptoms. In fact, this is suggested in the findings that overactivity and inattentiveness are not related to any significant degree in the hyperkinetic syndrome (Barkley & Ullman, 1975; Kasper et. al., 1971; Routh & Roberts, 1972). Possibly those hyper kinetic children who display relatively greater improvement on stimulant drugs are different from those showing less improvement. Perhaps the former are children whose major behavioral deficit is poor attention while the latter have major symptoms in behaviors other than attention. This hypothesis is, indeed, supported by a review of the litera ture on previous attempts to predict drug responsiveness in hyperkinetic children (See Appendix A). This review concluded that measures of attention and its correlates have consistently proven to be useful predictors in this area. However, continued research on clarifying the role of this and other variables in predicting improvement on -8-
drugs is warranted (Conners, 1972). Such research may find
a way of classifying the currently heterogeneous group of
hyperkinetic children into more homogeneous subgroups as a
function of their response to stimulant drugs. Thus, the present study attempted to determine which of a variety of measures of activity level, attention span, and concentration best predicted differential responding to methlyphenidate
in hyperkinetic children.
A major source of difficulty with most of the previous research on this topic has been the issue of what to consider as "improvement" when a child is placed on drugs. As noted in Appendix A, much of the research has relied primarily on one of several criteria of improvement. Some investiga tors have used the opinion of social agents, such as parents and teachers, while others used changes in the ratings of scales completed by these agents. Still others used changes in objective laboratory measures as a criterion of improve ment during drug treatment. A relatively few studies (Safer
& Allen, 1974; Satterfield et. al., 1972) used a numerical criterion which had to be exceeded by these change scores in order to be considered as improvement. The fact that these studies differed as to the criterion arbitrarily chosen to define improvement sorely limits the extent to which their results can be compared with research using a different criterion.
Each of the aforementioned improvement criteria are problematic in some respect. If a social agent's opinion of improvement is used, then it is difficult to ascertain -9-
which aspect(s) of a child's behavior that agent was respond
ing to in making his decision. It is also difficult to
compare children so defined as improved in one study with
those of another study in which improvement was defined by
some other method. Nor is it likely that such an opinion
in one study will necessarily agree with the opinions of
other agents in other studies (Loney & Ordona, 1975).
If a rating scale is used, and changes on the scores of the scale as a result of drug treatment are considered
as "improvement," then other problems emerge. For one thing,
it is hard to know just which behavior(s) of the child changed in response to drug treatment. And, for another, it cannot be determined whether the child's behavior changed at all or whether or not it was merely the rater's opinion that changed. Further, changes in rating scales may have little relationship to different criteria used by other social agents in other studies, such as parental opinion or clini cian's ratings of improvement. Additionally, whether or not such rating scales are related to objective laboratory mea sures of the same construct has been recently called into question (Barkley & Ullman, 1975).
Yet, if changes in objective laboratory measures are considered "improvement," it is difficult to know to what extent they are related to the opinions of improvement given by other social agents in the child's natural setting. In other words, a decline in a score on an open field measure of activity may or may not agree with a parent's opinion -10-
that the child's overactivity has improved at home. Thus,
no one criterion appears to be any more useful as a standard
of improvement in drug research with hyperkinetic children
than any other. It is therefore necessary for future research
to use several criteria of improvement in examining the issue
of predicting drug responding in hyperactive children.
The present study addressed these problems by utilizing
the following criteria of improvement; (a) changes in
parental ratings of the child's behavior during drug treat
ment, and (b) changes in objective laboratory measures of
activity level, attention span, concentration, and other
variables. Differences in the results were then examined as
a function of the criterion used to define improvement.
A related issue in drug research with hyperactive children
is the difficulty created by the statistical artifact of
regression-to-the-mean. If a study does not use a placebo
and fails to counterbalance the order in which children receive the drug or placebo, then it is difficult to deci pher whether or not the child changed in response to drug treatment or merely because his initial score on a measure was exceedingly above or below the mean and regression-to- the-mean occurred on subsequent evaluations with that measure.
Thus, it is customary to attempt to control for this phenom enon by utilizing a crossover drug-placebo design in which the order of administering the drug and placebo is counter balanced across subjects.
A second source of difficulty in previous research has -11-
been in their design and measurement procedures. Problems in
this area have been discussed in greater detail in Appendix
A, but briefly they include: (a) use of poorly controlled
experimental designs, (b) failure to use double blind and
placebo procedures, and (c) use of only one or a limited num
ber of measures of the constructs under study. The present
study attempted to control for these problems by using a
double-blind, drug-placebo crossover design in which a variety
of measures of both activity level and attention were used.
Additionally, both normal and hyperkinetic children were
employed. The normal children served as a comparison group
to determine if practice effects occurred on any measures as
a result of repeated assessment. Further, they served as a
control population against which the hyperactive children
were compared to ascertain whether or not initial differences
existed between these groups on any of the measures.
In summary, then, the present study attempted to deter mine the effects of methylphenidate on a variety of measures of activity level, attention span, concentration, and other variables in hyperkinetic children. It was anticipated that the drug would have its greatest influence on the measures of
attention. Reductions in activity level, if obtained, were predicted to vary as a function of the type of activity being assessed, the setting in which it was measured, arid the relevance of the activity for the task being accomplished.
This research also attempted to ascertain which of these measures best predicted the degree to which hyperkinetic -12-
children improved on methylphenidate. It was expected that
the baseline measures of attention would be the best predic
tors of differential drug responsiveness in these hyperactive
children.
Method
Subjects.
A total of 36 boys between the ages of 5 and 12 years,
with at least average intelligence (IQ greater than 80)
served as the subjects. All subjects were drawn from a
generally white, middle class community and all participated
voluntarily in these procedures, with the parents signing
informed consent statements to that effect. These children
comprised two groups; a hyperactive and a community control
group. The means, standard deviations, and ranges for age,
IQ, reading, and arithmetic achievement scores for the two groups are presented in Table 1. The IQ estimates were obtained from the Peabody Picture Vocabulary Test, while the reading and arithmetic achievement scores were obtained from the Peabody Individual Achievement Tests. The first group consisted of 18 boys who were diagnosed as hyperkinetic by area pediatricians and placed on methylphenidate. The children were obtained from a total of 3 different pediatri cians in the Bowling Green and North Baltimore, Ohio area.
The diagnosis of hyperkinesis was based upon parental com-'* plaints of longstanding hyperactivity, distractibility, impulsivity, difficulty in disciplining", and behavior problems -13-
TABLE 1
Raw Means, Standard Deviations, and Ranges for Age, IQ, and
Reading and Arithmetic Scores for Each Group of Children
Subj e c t Group s: Hyperactive Control Variable Mean S.D. Range Mean S.D. Range
Age (months) 94.7 18.0 68-124 92.7 20.7 61-133
IQ 104.7 12.9 83-124 109.9 12.3 88-128
Arithmetic 25.5 13.9 5-46 27.7 11.5 14-49
Reading 25.5 9.7 10-46 26.8 11.8 15-51 -14-
in school as well as the physician's own clinical impressions
of the children. These children varied in the length of time
they had been receiving methylphenidate, ranging from 1 week
to several years.
The second group consisted of 18 boys who served as a
normal community control group. They were obtained by tele
phone solicitation to their parents and were approximately
equated in age and IQ with the hyperkinetic boys. The control
child was considered matched in age if his age fell within
6 months on either side of the age of the hyperactive child
while IQ was considered equivalent if it fell within 10 points
on either side of that for the hyperactive child. These
groups, then, were not significantly different in age or IQ
(All Fs<1.00). Neither were the groups significantly differ
ent in the related variables of arithmetic and reading achieve
ment scores as measured by the Peabody Individual Achievement
Tests (All Fs<1.00). The control group did not receive any
drug or placebo during this study but were merely evaluated
on the dependent measures at approximately the same time
intervals as the hyperkinetic children.
Medication.
The drug used was methylphenidate as commercially produced by the CIBA-GEIGY Pharmaceutical Company under R the brand name of Ritalin . All of the hyperkinetic
children were evaluated within 3 hours following oral
ingestion of either 10 milligrams of methylphenidate or
a placebo (sugar pill). Both pills were supplied by a pediatri -15-
cian, with the placebo being approximately the same size,
shape, and color of the drug. The child, parent, and experi
menter were "blind" as to whether or not the child was
receiving the drug or placebo at the time of evaluation.
Only the pediatrician was aware of the drug or placebo code.
Design.
The experimental design consisted of a drug-placebo
crossover procedure in which half of the hyperactive children
received the placebo first followed by the drug while the other half received the drug first followed by the placebo.
Thus, each hyperactive child served as his own control. The hyperactive children were evaluated on three separate days, with each being separated by a 7 to 14 day interval. They were removed from their regular dose of methylphenidate at least 20 hours prior to participating in each of the three evaluations (baseline, placebo, and drug). This time interval was felt to be an adequate "washout" period for the drug as indicated by the fact that the primary behavioral effects of this drug are known to dissipate within 4 to 6 hours following an oral dose (Baldesirini, 1972; Iversen & Iversen,
1975). The children were removed from their regular medica tion only for that day's evaluation. On the first evaluation, the children remained off their drugs while on the second and third evaluations, they received the drug or placebo in a counterbalanced crossover fashion. This design permitted the children to remain on their regular medication during the school week while participating in these procedures on weekends -16-
Apparatus.
Grid-Marked Playroom. A playroom was divided into four
parts by black plastic tape on the tile floor. Each quadrant
contained a table and chair placed such that the child, when
seated, faced a wall at a 90 degree angle from the wall con
taining the one-way observation mirror. On each table, in a
row from the child's left to right, were the following four
toy types: a metal toy car, an Etch-A-Sketch drawing toy, a
box of crayons and two blank sheets of white paper, and a
Tinker Toy set. This room also contained a two-way communica
tions system connected with the adjacent observation room.
Movie Viewing Room. Nearby to the playroom, a smaller
room was used for the child to observe the videotape atten
tion test. The room contained a chair placed such that the
child, when seated, faced the observation mirror at a 45
degree angle. On the table, directly in front of the child
and also at a 45 degree angle from the observation mirror, was a 23 inch screen videotape monitor on top of which was the videotape player. Another table was placed along a wall to the child's left, when seated, and contained the apparatus needed to administer the reaction time, finger tapping, and maze Coordination tests.
Actometers. Two Timex Motion Recorders (No. 32) were used as the actometers to measure the child's wrist and ankle activity. The actometers were modified self-winding wrist watches with the internal winding pendulum attached directly to the hands on the watch face. The device measured force -17-
applied in the plane parallel to the watch face. The acto- meters were placed on the child's preferred arm and ankle and were attached such that the face of the watch was in a plane parallel to the back of the child's hand. The child's score on this measure was the number of "minutes" of activity during a given experimental period. Separate scores were kept for wrist and ankle activity.
Reaction Time Task. A simple reaction time task was used which consisted of a small metal box containing four lights with a push button located underneath each light. On the other side of a 1 foot square wooden panel was another metal box containing 4 electrical switches used to signal the panel of lights. Attached to the control panel was an electric timer. In an experimenter-paced procedure, the child received 20 trials each of which consisted of the experimenter signaling one of the four lights in a random order. This activated the timer which stopped when the child pushed the button underneath the signaled light.
Electric Finger Tapper. This device consisted of an electric counter affixed to a small wooden base. The counter was activated by the depression of a 2i inch metal arm attached to an electric switch. Depressing the arm closed the switch thereby sending a brief electric pulse to the counter advancing it one increment. The child was asked to tap the tapping arm as rapidly as possible during a 10 second interval using only his index finger while keeping the rest -18-
of his fingers flat on the base. Three such trials were given
for each hand with the child's score for each hand being the
average of the trials.
Maze Coordination Test. This test was composed of a |
inch raised metal maze which was connected to an electric
timer and counter. Also attached to the maze was a metal I pen. The child was required to move the pen through the maze as quickly as possible without touching the sides of the maze.
The apparatus automatically scored the number of contacts made by the child and the total time spent in contact with the sides of the maze. The total time taken for the trial was scored using a hand-held stopwatch. The child was required to perform the task once for the dominant hand and once for the non-dominant hand. Three scores were derived for each hand consisting of the number of contacts, the total time spent in contact with the sides of the maze, and the time to complete the trial.
Stabilimetric Chair. The chair in which the child sat during the movie viewing period and testing session was specially designed to record the child's restlessness while sitting in the chair. Attached to the underside of the chair; and thus suspended from the bottom of the chair, was a stabilimeter platform manufactured by the Lafayette Instru ment Company. The device is typically used for measuring animal activity in a cage placed on top of the platform.
This stabilimeter platform operates on vibrations which disturb an electro-magnetic coil centered in the middle of the platform. Disruption of the electro-magnetic field in the coil triggers electrical impulses which are then amplified
and recorded on an electric counter some distance from the
platform. So placed on the chair, the platform was sensitive
to any movement made by the child while seated in the chair.
Caution is require in interpreting the results for this device
as its reliability remains to be established.
Procedures.
During the pre-drug or baseline evaluation, each child was observed while off all drugs. Each child was then given two initial measures (Peabody Picture Vocabulary Test and
Peabody Individual Achievement Test). Following this, the child received the following four experimental periods in the same order on each of the three separate evaluations
(pre-drug, placebo, and on-drug). The total time taken for the administration of all the repeated measures on each occasion was approximately 1 hour. These measures are set forth in Table 2 and will be discussed later in this paper.
Free Play Period. The child was taken into the large playroom, the actometers were placed on the preferred wrist and ankle, and the child was instructed to play freely in the room for 6 minutes. The experimenter then left the room and entered the adjacent observation room where he scored the measures taken during this session. At the end of the
6 minute period, he returned to the playroom, recorded the actometer scores, and began the next session.
Movie Viewing Period. The child was then taken to the -20-
TABLE 2
List of Dependent Measures by Experimental Session and Construct Being Assessed
Occasion of List of Measures by Construct: Assessment and Experimental Setting Activity Level Attention Other
Initial Assessment Peabody Picture Vocabulary Test
Peabody Achievement Test
Repeated Assessments :
Free Play Number of Quad Number of Toy rant Changes Changes
Ankle Actometer Mean Time per Toy
Wrist Actometer
Movie Setting Ankle Actometer Time Distracted From Movie Wrist Actometer Retention Test Seat Movements
Test Setting Ankle Actometer Mean Reaction Time Finger Tapping Speed
Wrist Actometer Maze Coordination Test
Seat Movements Visual Discrimina tion Test
Restricted Play Ankle Actometer Number of Toy Changes
Wrist Actometer Mean Time per Toy
Times to First Toy Number of Quad and Quadrant Change rant
Parental Ratings Werry-Weiss-Peters Activity Rating Scale -21-
small movie viewing room for the attention test movie. He was
instructed to remain seated and to observe the movie as
questions might be asked about its contents later. He was
also told not to play with any of the equipment in the room.
After turning on the tape player, the experimenter left the room and entered the adjacent observation room in order to score the time the child spent attending to the movie.
Following this three minute period, the experimenter returned to the room, administered the retention test, and then recorded the seat movement and actometer scores. This period lasted approximately 5 minutes.
Structured Test Period. For this period, the child remained seated on the stabilimetric chair but the chair was moved to the table containing the testing apparatus. The experimenter then introduced the reaction time test. Follow ing the 20 reaction time trials, the finger tapping test was administered, after which the maze coordination and visual discrimination tests were given. At the end of these tests, the child's seat movement and actometer scores were recorded and the next experimental period began.
Restricted Play Period. The child was then taken back to the large playroom and told that he could play there for
6 minutes. However, this time he was instructed to remain in one part of the room, not crossing any of the grid-lines, and to play with only one toy type during this time. The experimenter then left the room, again entering the adjacent observation room to score the various measures for this period. -22-
At the end of the 6 minutes, he returned to the playroom,
recorded the actometer scores, and returned the child to his
parents. At the end of the study, all parents were provided
with a written summary of the results of this research.
Dependent Measures.
The response measures taken consisted of 3 initial and
33 repeated measures. These are set forth in Table 2 under
the experimental period in which they were taken. The 3
initial measures were taken only during the pre-drug evalua
tion and were as follows:
1. Peabody Picture Vocabulary Test (PPVT): Used as a
measure of intelligence.
2-3. Peabody Individual Achievement Tests (PIAT): Only
the mathematics and reading recognition subtests were adminis
tered.
The 33 repeated measures were taken on each of the three
evaluations (pre-drug, placebo, on-drug) and were categorized
as measures of activity, attention, or other variables.
These measures were as follows:
Measures Of Activity Level:
1. Number of Quadrant Changes - The scoring of quadrant
changes followed those definitions outlined by Routh et. al.
(1974) who found intercoder reliabilities to range from .98 to 1.00. Scoring simply consisted of counting the number of times the child crossed a grid-line in the playroom. Two of these scores were taken, one during free play and the other during restricted play. -23-
2. Wrist and Ankle Actometer Scores - As stated earlier,
the child's score for this measure consisted of separate scores
taken for his wrist and ankle and was the number of "minutes"
registered on the face of the watch during each of the four
experimental periods. Thus, two scores were taken during each
experimental period.
3. Seat Movement Scores - The child's score for seat movements as recorded by the stabilimetric chair were taken during both the movie viewing and structured testing periods.
Thus, two scores were obtained.
Measures of Attention.
1. Number of Toy Changes - The scoring of toy changes also followed those definitions set forth by Routh et. al.
(1974) who found intercoder reliability estimates to range from .88 to .98. Scoring simply consisted of counting the number of different toy types the child touched during his stay in the playroom. Two scores were taken, one during free play and the other during restricted play.
2. Average Time per Toy Type - This score was obtained by timing the amount of time the child played with the toys in the playroom and dividing it by the number of toy changes made during the experimental period. Scores for this measure were taken during free play and restricted play periods.
3. Amount of Time Not Attending to the Movie - During the movie viewing period, the child was asked to watch a
2| minute videotape of an adult female teaching a school lesson on a fictional animal. An observer stood behind the -24-
one-way mirror during this time and recorded the time the
child spent with his eyes fixed on the video monitor using
a hand-held stopwatch. This was then deducted from the total time for the movie and the resultant was the child's distrac- tibility score. For five of the subjects, a second coder independently recorded this measure. Intercoder reliability was .97 suggesting a high degree of agreement among the scorers. However, it should be noted that the clicking of the stopwatches was audible and may have influenced these reliability data.
4. Movie Retention Test - Following the child's obser vation of the movie, the examiner asked him a series of
10 questions about the content of that film. The number of correct answers served as the child's score. Since there were 3 separate movies, one given on each occasion of assess ment (pre-drug, placebo, and on-drug), three separate tests were also constructed to parallel the content of each movie.
The facts and type of creature in each movie varied although the style of presentation and length of the movie remained approximately the same.
5. Mean Reaction Time - The child's average reaction time was taken across the 20 reaction time trials during the structured test period.
6. Maze Coordination Test - Three scores were obtained for each hand on this test', these being the number of contacts made with the sides of the maze, the time spent in contact -25-
with the sides, and the total time for each trial. This
yielded a total of six scores for this test.
7. Visual Discrimination Test - This test consisted of
a sheet of paper containing nine rows of 8 faces each. Half
of the faces were boys and the other half were girls. The
faces differed only in showing three different mouth expres
sions: turned up, turned down, or straight. The child was instructed to complete the test as rapidly as possible by going across each row and crossing out only the faces which were smiling. The child received three scores which were the number of correct faces crossed out, the number of incorrect faces crossed out, and the total time to complete the test.
8. Time to First Quadrant and First Toy Change - During the restricted play period, the child was instructed not to cross a grid line or touch another toy type. The times which elapsed between the beginning of the period and when the child violated the grid line restriction and the toy restriction respectively were taken.
Other Measures.
1. Finger Tapping - As noted earlier, the child's score on this test was the average tapping speed for the index finger of each hand taken during three 10 second trials
The score was the mean of the three trials for that hand.
2. Parental Rating Scale - The parents completed the
Werry-Weiss-Peters Activity Rating Scale (See Appendix C) on each of the three evaluations. This was a modified ver -26-
sion of the scale as reported by Routh et. al. (1974) and
contained 22 items regarding the child's activity in various
home situations. The items could be answered in multiple
choice format by circling NA (not applicable), SOME, MUCH, or
NONE. One point was allotted for all answers of SOME and
two for all answers of MUCH. The score was the total number
of points summed across all items.
In summary, then, a total of 3 initial and 33 repeated
measures were obtained on each child during the course of
this study.
Results
The present study was primarily concerned with two major
issues. The first was the extent to which methylphenidate af
fected the various measures of activity level, attention span, concentration, and other variables in the hyperkinetic sample while the second focused on the determination of which measures predicted the extent to which hyperkinetic children improved on methylphenidate. However, prior to addressing these issues, it was important to first determine how hyper active children differed from normal children in this study and then to ascertain the degree to which the normal children changed with repeated assessment.
Comparison of Hyperactive and Normal Children.
Before turning to the analysis of drug treatment effects, it was first necessary to ascertain in what ways the hyper kinetic children in this study differed from the control children on the various measures of activity level, attention 27-
span, concentration, and other variables. Prior to making
these comparisons, the pretreatment raw scores on all measures
were transformed using the following equation:
Y = Loge (X + 1)
This transformation served to reduce the substantial varia
bility observed to occur on most measures while making many
of the somewhat skewed distributions closer approximates to
normal. The transformed pretreatment scores on all measures
were then compared using one factor (groups) analyses of
variance. Since one might expect a number of intercorrela
tions among these dependent measures and thereby artificially
increase the chances of finding multiple differences, some
caution needs to be exercised in interpreting the results for
any single measure. It was not possible to use a multivariate
analysis of variance to eliminate this problem since the
large number of dependent measures exceeded the scope of the
multivariate program. Therefore, univariate analyses of
variance were used throughout. The results for these univar
iate analyses, along with the raw means for the measures for
each subject group are displayed in Table 3.
Of the 33 dependent measures, 17 were found to signifi
cantly differentiate between the hyperactive and normal
children with seven other measures showing trends (p< .10)
in discriminating these groups. All of these differences were in the expected direction. For ease of reviewing, these 24 dependent measures are set forth in Table 4 under the construct they appeared to assess. In general, results -28- TABLE 3
Raw Means and Analyses of Variance for Hyperactive Versus Control
Comparisons on Baseline Measures
Raw Means For Raw Means For F test for Hyperactive Normal Transformed Setting and Measure Children Children Scores P< Free Play:
Wrist Actometer 412.89 193.77 4.60 .05
Ankle Actometer 389.72 95.72 2.92 . 10
Quadrant Changes 16.11 1.89 13.90 .01
Toy Changes 3.44 1.11 8.08 .01
Mean Time/Toy (seconds) 115.33 243.28 13.96 .01
Movie Setting:
Wrist Actometer 107.61 50.22 3.48 .07
Ankle Actometer 112.83 25.67 3.95 .07
Seat Movements 113.94 34.66 6.67 .05
Time Distracted From the Movie 42.72 24.22 5.77 . 05
Retention Test Number Correct 5.73 7.89 12.32 .01
Test Setting:
Wrist Actometer 213.17 65.S9 21.47 .001
Ankle Actometer 260.89 48.72 4.65 .05
Seat Movements 322.89 71.78 14.81 .01
Mean Reaction Time (1/lOOth sec.) 101.28 77.06 7.54 .01
Finger Tapping Dominant Hand 32.72 34.83 1.74 -
Finger Tapping Nondominant Hand 29.55 30.72 1.00 -
Visual Discrimination Test:
Number Correct 30.17 31.77 1.19 -
Number Incorrect 6.56 0.89 9.66 .01
Total Time (seconds) 110.67 87.56 2.97 . 10
Maze Coordination Test - Dominant:
Total Time (seconds) 43.72 57.72 5.72 .05
Number of Contacts 40.33 22.56 3.06 . 10
Time in Contact with Sides 552.06 204.78 1.57 - (1/100th seconds)
Maze Coordination Test - Nondominant:
Total Time (seconds) 43.22 52.50 3.71 .07 -29-
Table 3 Continued Page
Raw Means For Raw Means For F test on Hyperactive Normal Transformed Setting and Measure Children Children Scores P< Number of Contacts 45.83 37.06 2.01 -
Time in Contact with Sides 787.06 362.11 1.82 -
Restricted Play:
Wrist Actometer 397.78 148.78 7.03 .05
Ankle Actometer 215.22 142.44 3.41 .07
Quadrant Changes 7.94 0.61 5.71 .05
Toy Changes 2.00 0.89 0.68 -
Mean Time/Toy (seconds) 251.44 289.33 1.29 -
Time to First Quadrant Change (sec.:) 224.44 317.78 5.26 .05
Time to First Toy Change (sec. ) 268.22 302.6? 1.41 - Parental Ratings of Activity 27.77 9.87 52.77 . 001 -30-
TABLE 4
Summary of Measures Discriminating Hyperactive From Normal Children As Categorized by Constructs
Construct Measures Setting
Activity Level Wrist Actometer Free Play Movie Setting Test Setting Restricted Play
Ankle Actometer Free Play Movie Setting Test Setting Restricted Play
Quadrant Changes Free Play Restricted Play
Seat Movements Movie Setting Test Setting
Attention Span Number of Toy Changes Free Play Restricted Play
Mean Time per Toy Free Play
Time to First Quadrant Restricted Play Change
Inability to Time Distracted from Movie Setting Concentrate Movie
Movie Retention Test Movie Setting
Mean Reaction Time Test Setting
Visual Discrimination Test Setting
Maze Coordination Test Test Setting
Parental Ratings Werry-Weiss-Peters Activity of Activity Rating Scale 31-
indicated that hyperactive children displayed more wrist and
ankle activity across settings, more locomotor activity in
free and restricted play, and greater seat restlessness during
both the movie and test periods as compared to normal children.
Additionally, hyperactive children made more toy changes
during free and restricted play, spent less time per toy
during free play, were more distracted from the televised
school lesson, had poorer recollections of the contents of
that lesson, had slower mean reaction times, and performed more poorly on the visual discrimination and maze coordination tests than normal children. Furthermore, they were less able to inhibit locomotor activity during restricted play and were viewed by their parents as significantly more active than normal children. In summary, hyperactive children were more active on a number of types of activity level across a variety of structured and informal settings, had shorter attention spans, and were less able to concentrate on structured tasks as compared to normal children.
Changes in Normal Children Over Time;
In order to determine the extent to which control children changed as a function of time, or repeated assess ment, scores across each of the three assessment occasions on all measures were first transformed using the aforementioned equation and then submitted to analysis using one-factor
(occasion of assessment) analyses of variance with repeated measures on that one factor. The results of these analyses are listed in Table 5 along with the raw means and standard -32- TABLE 5
Raw Means, Standard Deviations, and Analysis of Variance on Each Measure
for Normal Children Under Each Occasion of Assessment
Occasion of Assessment: F test on Transformed Setting and Measure Trial #1 Trial #2 Trial #3 Scores
Free Play:
Wrist Actometer Mean 193.77 178.56 150.06 1.00 __ S.D. 184.78 170.26 89.99
Ankle Actometer Mean 95.72 56.44 49.50 1.24 - S.D. 129.26 56.80 45.11
Quadrant Changes Mean 1.89 0.33 0.27 2.26 S.D. 4.36 1.03 0.57
Toy Changes Mean 1.11 1.11 0.89 1.00 - S.D. 1.53 1.49 2.02
Mean Time/Toy Mean 243.28 243.33 291.72 1.00 - (seconds) S.D. 123.09 124.29 117.32
Movie Setting:
Wrist Actometer Mean 50.22 27.22 24.22 1.01 - S.D. 111.03 36.64 24.36
Ankle Actometer Mean 25.67 30.50 38.11 1.00 - S.D. 25.44 35.09 55.99
Seat Movements Mean 34.66 54.61 59.11 2.12 S.D. 41.42 86.21 57.43
Time Distracted Mean 24.22 10.89 15.17 6.94 .01 From the Movie S.D. 22.82 13.85 18.01 (seconds)
Retention Test Mean 7.89 9.39 9.67 18.68 . 001 Number Correct S.D. 1.57 1.09 0.69
Test Setting:
Wrist Actometer Mean 65.89 59. 17 62.00 1.00 - S.D. 29.12 27.82 35.83
Ankle Actometer Mean 48,72 32.44 49.61 1.39 - S.D. 52.19 42.30 67.67
Seat Movements Mean 71.78 101.06 77.11 2.44 - S.D. 65.86 47.14 47.61
Mean Reaction Time Mean 77.06 75.00 74.56 1.00 - S.D. 11.99 12.60 14.00
Finger Tapping Mean 34.83 35.S3 36.05 1.30 - Dominant Hand S.D. 4.53 5.88 6.07
Finger Tapping Mean 30.72 31.72 32.00 2.40 - Nondominant S.D. 3.79 4.64 4.69
Visual Disc.rimina- tion Test:
Number Correct Mean 31.77 32.00 32.33 1.00 - S.D. 3.09 1.37 1.45
Number Incorrect Mean 0.89 0.61 0.44 1.00 - S.D. 1.27 0.91 0.51 -33-
Table 5 Continued Page
Occasion of Assessment : F test on Transformed Setting and Measure Trial #1 Trial #2 Trial #3 Scores P< Total Time Mean 87.56 76.27 70.44 17.77 .001 (seconds) S.D. 24.16 22.69 19.61
Maze Coordination Test - Dominant Hand:
Total Time Mean 57.72 61.11 53.50 1.34 - (seconds) S.D. 20.06 28.88 19.30
Number of Contacts Mean 22.56 21.72 17.78 5.63 .01 S.D. 10. 35 9.48 7.76
Time in Contact Mean 204.78 116.56 59.94 11.61 . 001 with Sides S.D. 161.42 125.89 73.10 (1/100th second)
Maze Coordination Test - Nondominant:
Total Time Mean 52.50 50.22 49.55 1.34 - (seconds) S.D. 16.28 17.75 18.64
Number of Contacts Mean 37. 06 33.11 35.28 1.00 — S.D. 18.67 13.59 14.61
Time in Contact Mean 362.11 258.55 257.06 2.33 with Sides S.D. 245.28 244.41 225.07 (l/100th second)
Restricted Play:
Wrest Actometer Mean 148.78 Ì52.83 166.61 1.00 - S.D. 113.91 147.27 138.78
Ankle Actometer Mean 142.44 71.38 115.56 1.00 S.D. 307.01 82.24 194.92
Quadrant Changes Mean 0.61 0.94 0.33 1.00 - S.D. i. 66 3.29 0.97
Toy Changes Mean 0.89 1.00 0.67 1.00 S.D. 1. 74 1.57 1.19
Mean Time/Toy Mean 289.33 261.50 277.30 1.00 - (seconds) S.D. 117.91 128.25 124.85
Time to First Mean 317.78 305.67 336.68 1.00 - Quadrant Change S.D. 96.78 125.15 79.40
Time to First Mean 302.61 253.50 288.61 2.00 - Toy Change S.D. .105.62 144.65 120.25
Parental Ratings of Mean 9.87 9.22 8.94 1.01 - Act ivity S.D. 5.49 5.98 5.49 -34-
deviations for each measure on each occasion of assessment.
As Table 5 indicates, only the measures of time distracted
from the movie, the movie retention test, total time to complete the visual discrimination test, and performance on the maze coordination test were significantly improved over time. Thus, with few exceptions, normal children remained essentially stable in their activity level, attention span, concentration, and parental ratings of activity over.the three assessment occasions. Those significant changes which were observed appeared to reflect a practice effect on those measures due to repeated testing.
The Effects of Methylphenidate on Hyperkinetic Children.
One of the major issues of importance to this study was the extent to which hyperkinetic children improved on a variety of measures as a function of treatment with methyl phenidate. Again, before analyzing these results, the scores on all measures across all of the treatment conditions
(baseline, placebo, drug) were transformed using the afore mentioned equation. Subsequently, all measures were analyzed using one-factor (treatments) analyses of variance with repeated measures on that factor. The results of these analyses along with the raw means and standard deviations for the measures are listed in Table 6. As this table shows, significant changes were observed on 20 of the 33 dependent measures as a function of the experimental treatments.
Hence, subsequent pair-wise comparisons between treatment conditions were conducted on the transformed scores for these -35- TABLE 6
Raw Means, Standard Deviations, and Analysis of Variance on Each Measure
for Hyperactive Children Under Each Treatment Condition
Treatment Conditions F test on Transformed Setting and Measure Baseline Placebo Drug Scores p<
Free Play:
Wrist Acto.eter Mean 412.89 555.11 233.00 4.55 .05 S.D. 335.60 445.98 185.00
Ankle Actometer Mean 389.72 442.22 97.33 5.85 .01 S.D. 457.83 626.11 105.11
Quadrant Changes Mean 16.11 8.89 1.94 13.42 .001 S.D. 20.82 12.76 4.76
Toy Changes Mean 3.44 3.32 1.44 4.56 .05 S.D. 2.36 3.04 1.25
Mean Time/Toy Mean 115.33 123.78 159.39 1.00 - (seconds) S.D. 98.75 98.08 123.05
Movie Setting:
Wrist Actometer Mean 107.61 114.28 54.00 5.64 .01 S.D. 233.38 76.67 38.40
Ankle Actometer Mean 112.83 153.50 78.22 11.56 . 001 S.D. 242.75 140.57 175.46
Seat Movements Mean 113.94 157.67 64.72 9.55 .01 S.D. 145.53 134.11 56.26
Time Distracted Mean 42.72 36.50 18.61 10.01 .001 from the Movie S.D. 26.68 23.58 18.11 (seconds)
Retention Test Mean 5.78 8.11 9.28 28.81 .001 Number Correct S.D. 1.96 1.94 1.07
Test Setting:
Wrist Actometer Mean 213.17 242.-33 143.39 5.23 .01 S.D. 215.17 155.54 86.15
Ankle Actometer Mean 260.89 212.44 148.00 5.38 .01 S.D. 426.22 178.13 286.22
Seat Movements Mean 322.89 213.00 168.78 2.31 - S.D. 361.72 166.78 145.04
Mean Reaction Time - Mean 101.28 105.39 87.56 5.48 .01 (1/lOOth seconds) S.D. 35.68 52.91 30.98
Finger Tapping Mean 32.72 33. 16 33.00 1.00 - Dominant Hand S.D. 6.31 6.86 6.93
Finger Tapping Mean 29. 55 30.17 30.22 1.63 - Nondominant Hand S.D. 6.15 6.10 5.35 -36-
Table 6 Continued Page 2
Treatment Conditions : F test on Transformed Setting and Measure Baseline Placebo Drug Scores P < Visual Discrimina tion Test :
Number Correct Mean 30.17 30.56 30.88 1.00 S.D. 6.20 5.69 5.17
. Number Incorrect Mean 6.56 2.61 4.22 5.42 .01 S.D. 9.51 5.74 9.29
Total Time Mean 110.67 83.17 85.11 7.75 .01 (second.'-) S.D. 50.19 34.09 43.91
Maze Coordination Test - Dominant Hand
Total. Time Mean 43.72 47.11 42.72 1.00 (seconds) S.D. 17.48 23.02 16.79
Number of Con- Mean 40.33 36.56 34.67 1.00 __ tacts S.D. 21.30 20.92 20.47
Time in Contact Mean 552.06 551.94 390.72 3.12 — with Sides S.D. 490.24 608.18 468.33 (1/lOOth seconds)
Maze Coordination Test - Nondominant:
Total Time Mean 43.22 41.28 42.67 1.00 — (seconds) S.D. 22.75 18.86 15.15
Number of Con- Mean 45.83 47.61 42.67 3.45 . U5 tacts S.D. 16.64 20.21 19.84
Time in Contact Mean 787.06 647.67 552.28 5.63 .01 with Sides S.D. 631.17 428.19 434.85
Restricted Play:
Wrist Actometer Mean 397.78 412.83 211.83 5.24 . 01 S.D. 261.53 245.02 185.55
Ankle Actometer Mean °15.22 396.17 189.00 6.06 .01 S.D. *98.54 355.48 245.28
Quadrant Changes Mean 7.94 7.89 2.11 2.72 S.D. 15.57 12.51 4.02
Toy Changes Mean 2.00 2.56 0.72 4.22 . 05 S.D. 3.93 2.45 1.22
Mean Time/Toy Mean 251.44 141.72 212.56 1.41 - (seconds) S.D. 140.31 123.42 152.08
Time to First Mean 224.44 192.61 253.67 1.00 - Quadrant Change S.D. 162.32 162.63 151.23
Time to First Toy Mean 268.22 198.17 277.11 1.49 - Change (seconds) S.D. 142.58 134.26 130.55
Parental Ratings of Mean 27. 77 24.78 14.78 8.94 .01 Act ivity S.D. 7.84 9.52 10.49 -37-
20 dependent measures. These comparisons were made using
one-factor (treatments) analyses of variance with repeated
measures on that one factor. Results for these contrast
analyses are displayed in Table 7.
Of particular importance to the present study were those
comparisons of the drug and placebo conditions on each
measure as these provided information on the effects of
methylphenidate on hyperactive children as compared to treat
ment with placebo. As can be seen in Table 7 (Column 3: Drug
X Placebo), methylphenidate significantly improved the behavior
of hyperactive children on 18 of the 20 measures. Only the measures of number of incorrect responses and total time on
the visual discrimination test were not found to be signi
ficantly different between drug and placebo conditions. Again,
for ease of reviewing, these 18 measures are summarized in
Table 8 under the construct they were believed to assess.
Methylphenidate was found to significantly reduce the scores on all but one of the measures of activity level, regardless of the type of activity or the setting in which it was assessed. Wrist and ankle activity were significantly reduced across all settings by methylphenidate. Similarly, locomotor activity as measured by the number of quadrant changes was also significantly reduced during both free and restricted play. In addition, the measure of seat restlessness during the televised school lesson dramatically decreased during treatment with methylphenidate. Only seat restlessness during the test setting was not significantly reduced by drug treatment -38- TABLE 7
Analyses of Variance for Pairwise Comparisons of Treatment Conditions
on Measures Found to Have Significant Differences Among Treatments
Baseline x Drug Baseline x Placebo Drug x Placebo Setting and Measure F P< F P< F P< Free Play:
Wrist Actometer 2.63 - 1.00 - 16.89 . 001
Ankle Actometer 5.13 .05 1.00 - 12.68 . 001
Quadrant Changes 21.63 .001 2.27 - 14.69 . 001
Toy Changes 6.06 .05 2.08 - 5.31 .05
Movie Setting:
Wrist Actometer 1.46 - 4.13 .07 13.94 . 001
A'kle Actometer 1.50 - 10.28 .01 17.65 . 001
Seat Movements 1.43 - 7.0? .05 30.32 . 001
Time Distracted from Movie 13.88 .001 1.00 - 14.34 .001
Retention Test Number Correct 52.31 .001 19.49 .001 8.82 .01
Test Setting:
Wrist Actometer 1.97 - 2.80 - 13.21 . 001
Ankle Actometer 3.77 .07 1.73 - 9.88 . 01
Mean Reaction Time 7.51 .05 • 1.00 - 6.39 .05
Visual Discrimination Test:
Number Incorrect 6.85 .05 6.72 ,05 1.00 -
Total Time 24. '-'0 .001 11.26 01 1.00 -
Maze Coordination Test - Nondominant Hand:
Number of Contacts 3.71 . 10 1.00 - 5.25 . 05 Time in Contact with Sides of Maze 8.51 .01 1.00 - 6.00 .05
Restricted Play:
Wrist Actometer 4.43 .05 1.00 - 9.21 .01
Ankle Actometer 1.00 - 7.80 05 10.73 . 01
Toy 'Changes 1.17 - 2.48 - 10.53 .01
Parental Ratings of Activity Level 15.52 . 001 2.89 — 5.96 .05 -39-
TABLE 8
Summary of Measures Found to be Significantly Different Between Placebo and Drug Conditions
Construct Measures Setting
Activity Level Wrist Actometer Free Play Movie Setting Test Setting Restricted Play
Ankle Actometer Free Play Movie Setting Test Setting Restricted Play
Quadrant Changes Free Play
Seat Movements Movie Setting
Attention Span Number of Toy Changes Free Play Restricted Play
Inability to Time Distracted From Movie Setting Concentrate the Movie
Movie Retention Test Movie Setting
Mean Reaction Time Test Setting
Maze Coordination Test Test Setting Nondominant Hand
Parental Ratings Werry-Weiss-Peters Activity of Activity Rating Scale -40-
This was probably the result of the fact that the stabilimetric
chair was sensitive to most body movements and that some
body movement was required in the performance of the tasks
given in that setting. Thus, task demands may have set a
basal level of seat activity required for task performance below which methylphenidate was not likely to reduce this type of activity. Nevertheless, with this one exception, methylphenidate significantly reduced a variety of types of activity level in hyperactive children in comparison to treat ment with placebo.
In a similar manner, the measures of attention were also significantly improved by methylphenidate as compared to placebo. This was observed in a reduction in the number of toy changes made during both free play and restricted play settings, presumably reflecting increased attention span. The measures of concentration to structured tasks were also im proved by methylphenidate. This was noted in the decrease in the amount of time the child was distracted during the movie, and increase in correct responding on the movie retention test. In addition, significant decreases were also observed in mean reaction time, and errors in performance on the maze coordination test for both dominant and nondominant hands.
Thus, methylphenidate significantly improved the attention span and concentration of hyperactive children in comparison to treatment with placebo.
In addition to these changes on objective laboratory measures, significant improvement was also noted on the -41 parental ratings of activity. This suggested that parents were sensitive to the differences in their hyperactive child's behavior between drug and placebo treatments. Thus, taken together, these results indicated that methylphenidate signifi cantly reduced a variety of activity types in hyperkinetic children across a number of formal and informal settings while at the same time improving attention span and the ability to concentrate on structured tasks.
The results for the comparisons of the pre-treatment
(baseline) and placebo scores using these 20 measures (See
Table 7, Column 2: Baseline X Placebo) indicated that few of the measures changed significantly from baseline to placebo conditions. In fact, on a few of these measures, results indicated that the hyperactive children became more active in ankle activity during the movie and restricted play settings, and in wrist and seat activity during the movie setting from the baseline to placebo conditions. This finding contrasts with those for normal children in that the control children did not change in activity level over time. All of these types of activity can be regarded as essentially unnecessary to the demands of the movie and restricted play settings.
This suggested that as hyperkinetic children became more familiar with these initially novel settings, their level of task or situation irrelevant activity increased while that for normal children remained essentially unchanged.
In examining the comparisons of baseline and drug scores
(See Table 7, Column 1: Baseline X Drug), it is apparent that -42-
most of the measures found to be significantly different be
tween drug and placebo conditions were also significantly
different between baseline and drug conditions. A few, however,
were not. Wrist activity in free play, during the movie and
test settings, and ankle activity and seat restlessness during
the movie were not found to be significantly different from
baseline to drug conditions. A likely explanation for this
is the fact that hyperactive children became significantly
more active on these measures from baseline to placebo condi
tions thereby making their drug and placebo comparisons signi
ficant while their baseline and drug comparisons were not.
Thus, in comparison to baseline levels, these measures cannot
be considered to have improved as a function of drug treat
ment. That is, drug improvement occured on these measures
only in comparison to placebo as opposed to baseline conditions.
Nevertheless, aside from these few measures, most were observed
to be improved significantly by methlphenidate in comparison
to baseline levels.
Predicting Drug Responding in Hyperkinetic Children.
Having demonstrated that methylphenidate significantly
improved the behavior of hyperactive children, it was of
additional importance to this study to ascertain those variables
which usefully predicted the degree to which these children
improved during drug treatment. Previous studies in this
area have utilized several methods of answering this question.
One of these involves using pretreatment measures to predict
the degree of drug improvement on those measures. The other
consists of comparing children classed as "good" versus "poor" -43-
drug responders based on some criterion of drug responding,
typically parental or teacher opinion. The results derived
from these two methods will be discussed separately below.
Predicting Degree of Improvement from Drugs. This
method involves the correlation of pretreatment scores with
change scores on-those measures during drug treatment (Rie et.
al., 1976). Each of the 18 measures demonstrating drug im
provement were correlated with change scores on those measures.
The change scores were derived by subtracting the drug from
placebo scores on each measure and therefore represented
change on those measures as a function of drug treatment.
However, because of the vast number of correlations
generated by such an analysis relative to the small sample
size in this study, caution should be exercised in interpret
ing these findings. Certainly, cross validation will be needed to bear out these results. Nevertheless, some general relation ships are apparent.
In order to provide a more comprehensible picture of these relationships, an averaging procedure was applied to these correlations. Both pretreatment and drug response measures on which significant intercorrelations were noted were grouped into those constructs they appeared to measure. These were: ankle activity (ankle actometer scores collapsed across settings), general activity, (wrist actometer, seat movements, and quadrant changes collapsed across settings), attention span (toy changes and average time per toy collapsed across settings, and times to first quadrant and toy changes in -44-
restricted play), and inability to concentrate (time distracted
from the movie, movie retention test, mean reaction time,, visual discrimination test, and maze coordination test).
A separate construct of ankle activity was established since intercorrelations involving the ankle activity measures and other measures were inconsistent in the direction of their relationships. Hence, averaging them with the correla tions for other measures would have negated any predictive relationships with those measures.
Having classified the measures into constructs, those statistically significant intercorrelations among the measures within and between each construct were then averaged arith metically. The number of intercorrelations comprising each average correlation as well as the mean correlation itself are reported in Table 9. As this table demonstrates, the most robust and widespread pattern of relationships occurred on the construct of concentration which not only predicted improvement on itself but also on both activity constructs as well. That is, the greater the hyperactive child's pretreat ment inability to concentrate, the more he improved during drug treatment in his ability to concentrate and also in his activity level as well. Given the greater number of corre lations between concentration and these other constructs, pre treatment levels of the inability to concentrate appear to be the best predictors of general improvement in hyperkinetic children on methylphenidate.
An unexpected finding was that ankle activity was TABLE 9 1 Averaged Intercorrelations Among Pretreatment and Drug Response Constructs
Drug Response Constructs: Ankle General Inability to Pretreatment Activity Activity Inattentiveness Concentrate Construct No. Mean r No. Mean r No. Mean r No. Mean r
Ankle Activity 4 -.65* 5 + .29 3 -.52*
-.49* * -.54* General Activity 1 9 + .54 -- _ 6
* Inattentiveness — — 4 + .27 — — 6 -.55
Inability to Concentrate 5 + .52 11 + .55 6 + .62* — —
^The abbreviation "No." in the first column underneath each drug response construct refers to the number of statistically significant correlations averaged within that construct.
*p<.05
I cn l -46-
negatively related to improvement on itself and on concentra
tion during drug treatment. That is, the higher the pretreat
ment level of ankle activity, the less was the extent of drug
improvement on ankle activity and concentration to tasks.
Just why this should be the case is unclear at this time.
The construct of general activity was negatively related to
drug improvement on only one measure of ankle activity and
thus is hardly a meaningful pattern. But, general activity was positively related to drug improvement on itself — a
finding which is not surprising given the interrelationships among these activity measures (Barkley & Ullman, 1975). General activity, like ankle activity, also negatively predicted im provement in concentration indicating that the higher the hyperactive child's pretreatment level of general activity, the less he improved in ability to concentrate on structured tasks. Again, why activity level should be negatively re lated with improvement on concentration is uncertain at this time.
As for measures of attention span, they appeared to be unrelated to improvement in activity while negatively related to improvement in concentration. Apparently, children who were lower in attention span initially were less likely to improve in concentration to structured tasks during drug treatment. This result is also difficult to explain. No other pretreatment measures were observed to usefully predict change during drug treatment. In general, then, these results suggested that among these constructs of concentration, -47-
attention span, ankle activity, and general activity, concen
tration was the best predictor of drug responding in hyper
kinetic children. The greater the hyperkinetic child's
initial inability to concentrate on structured tasks, the more likely he was to improve in activity level and concen
tration during drug treatment. It is therefore concluded
that measures of concentration are the best predictors of global improvement in hyperactive children during drug treat ment .
Good Versus Poor Drug Responders. Another method for determining variables which may predict drug improvement in hyperactive children is to select a measure and to establish a criterion of change on that measure that will be considered as improvement. Children exceeding that criterion are grouped as good drug responders while those not doing so are classified as poor drug responders. These groups are subsequently com pared on other measures across placebo and drug conditions to determine if their drug responses on the measures differed as a function of their group placement. The present study used such a method in which 50 percent or more change from placebo to drug conditions on parental ratings was the criterion of improvement. Children showing 50 percent or more change during drug treatment on this measure were labeled as good drug responders while those not doing so were labeled as poor drug responders. This resulted in 9 hyperactive children being assigned to each group. The comparison of these groups on the other 18 measures on which drug improvement had -48-
originally been observed to occur revealed no significant
differences in the drug responses of these two groups (All
Fs < 1.00). In essence, good and poor drug responders as
defined by this method were not significantly different in
drug responses on any of the laboratory measures. This may
have resulted from the fact that all hyperactive children in
this study were all felt to be positive drug responders
originally given that they had been using methylphenidate for
some time prior to this study.
Discussion
In general, the present study found that methylphenidate
significantly improved the activity level, attention span,
and concentration to task in hyperactive children. In addi tion, these results indicated that the more the hyperactive
child was initially unable to concentrate on structured tasks, the greater was his global improvement on drugs. Further, this study found that hyperactive children were more active, inattentive, and unable to concentrate on tasks, as well as being unable to inhibit locomotor activity when requested in comparison to normal children. They were also viewed by their parents as more active and were observed to display greater task or situation irrelevant activity with time as compared to normal children.
These and other findings will be discussed in relation to the following issues: (1) the effects of methylphenidate on hyperkinetic children; (2) the characteristics of the hyper active children which were useful in determining their response to methylphenidate; (3) differences between the hyperactive -49-
and normal children in this study; and (4) clinical observa tions related to drug responding. These issues will be discussed separately below.
Effects of Methylphenidate on Hyperkinesis.
One of the major findings of the present study was that methylphenidate significantly reduced a number of types of activity level in hyperkinetic children while simultaneously increasing the attention span and ability to concentrate in these children. For the most part, reductions in activity level were not a function of the degree of setting structure or type of activity being measured. This is somewhat dis crepant with the expectation noted earlier that type of setting and type of activity would influence whether or not drug effects on activity level were realized. The reason for this discrepancy is unclear at present but may be related to the fact that this is the only study to investigate drug effects on activity level in a number of different settings. The expectation on the other hand had been culled from a number of different studies each using a different type of setting and measure (See Appendix A). It was predicted that only task irrelevant activity during structured settings would be reduced by methylphenidate. In contrast, this study found that activity level, regardless of its relevance to the task or its situational appropriateness, was reduced by methyl phenidate. Both wrist and ankle activity during free play, observation of a movie, performance of a number of structured tasks, and during restricted play were significantly reduced -50-
in comparison to treatment with placebo. Similarly, locomotor
activity in the playroom during free and restricted play was
reduced, as was seat activity during observation of the tele
vised school lesson. Seat movements during testing were not
significantly reduced by methylphenidate. This may have been
due to the fact that some body activity was necessary during
the performance of these tasks which cannot be reduced further
by methylphenidate without precluding task accomplishment.
Since the stabilimetric chair was sensitive to movements of
the body during testing, this may in fact account for the
lack of drug effects on this measure. In any case, this was
the only activity measure on which significant drug effects
in relation.to placebo effects were not observed. Finally,
parental ratings of activity level were also noted to be
significantly improved by methylphenidate indicating that
parents perceived changes in their children’s behavior as
a function of treatment with methylphenidate or placebo.
In summary, then, methylphenidate improved a variety of types
of activity level in hyperactive children across a variety of
structured and informal settings.
It is of interest to note, however, that several measures of activity level were improved by Ritalin as compared to placebo but were not improved in relation to pretreatment scores on these measures. This occurred for the measures of wrist, ankle, and seat activity during the movie, and wrist activity during free play and testing. It was also observed that hyperactive children became more active on only these -51-
measures over time. Most of these measures have in common
the fact that they assess activity which is irrelevant or
unnecessary to the demands of a task or setting. This suggests
that hyperactive children displayed increasing amounts of task
irrelevant activity over time when placed in an initially novel
setting, and only then were drug effects on this type of activity
apparent. Yet, this appears to be closely related to the type
of activity a practitioner might use to evaluate whether or
not a hyperactive child has responded to stimulant medication
— that is, whether or not the child's activity level was
appropriate or relevant to the clinical or office setting in which the child was initially evaluated. Extrapolating from the present results, it is possible that if untreated, the child's activity might increase, making the initial observation an underestimate. Thus, a practitioner who prescribed stimu lant medication for such a child during the child's first visit to his office may falsely conclude that their has been no noticeable improvement in behavior on a post-treatment visit. These results suggest that only if the practitioner had seen the child several times in that setting before prescribing medication for the child would he be likely to find that child's activity level noticeably improved by the drug. While more research is obviously needed before conclu sions can be reached on this speculation, these results raise the possibility that repeated evaluation of these children prior to medication may be an important consideration.
As for the measures of attention span and concentration, -52-
the results of this study were those anticipated from a re
view of previous research in this area (See Appendix B) —
methylphenidate was observed to significantly improve the
attention span and concentration to task in hyperkinetic child
ren. Results indicated significant reductions in the number
of shifts in play with different toys during both free and
restricted play; a finding in agreement with those of
Rapoport et. al. (1971). In addition, the time the child was
distracted from the televised teacher's lesson and the amount
of material recalled from that lesson were significantly
improved. These measures may have been sampling behaviors closely related to those required of a hyperactive child in a regular classroom setting. These results suggest then that concentration to lecture material in that setting might have been improved during drug treatment. Such a finding would not be unexpected given that Sprague et. al. (1970) noted methylphenidate to increase time spent attending to tasks in a natural classroom setting. The findings for mean reaction time also concurred with those of many previous studies using this measure (See Appendix B) in that mean reaction time was significantly reduced, or improved, during drug treatment. Similarly, improvement in performance of the maze coordination test also agrees with the results of other research using this measure (Garfinkel et. al., 1975; Knights
& Hinton, 1969). In summary, then, these findings for measures of attention span and concentration replicate and extend those of previous research in finding methylphenidate to substantially -53-
improve these abilities in hyperactive children (Appendix B;
Conners, 1972; Douglas, 1972, 1974; Werry, 1970).
Predicting Drug Responses to Methylphenidate.
Of particular importance to the present study were those
results bearing on the extent to which the various pretreatment
measures predicted drug improvement on those and other measures.
These results suggested that, in general, pretreatment levels
of activity level in hyperactive children were positively predictive of drug improvement only on activity level but were
negatively related to improvement in concentration. There
fore, the higher the hyperactive child's initial activity
level, the greater was his improvement in activity level but the less he improved in concentration to tasks during drug treatment. In contrast, pretreatment levels of the inability to concentrate on structured tasks were positively related to drug improvement not only on this ability, but also on activity level as well. That is, the greater the hyperkinetic child's initial inability to concentrate, the more he im proved in that ability and the greater the reduction he dis played in activity level during drug treatment. Thus, as anticipated, pretreatment levels of concentration to task in hyperactive children apparently were the best predictors of the extent to which they improved in both activity level and concentration during treatment with methylphenidate. Given the limited number of subjects and the large number of measures, it will be important to cross validate these results.
These findings also lend strong empirical support to -54-
the results of previous research which suggested that measures
of attention and its correlates are the most sensitive pre
dictors of stimulant drug responsiveness in hyperkinetic
children (See Appendix A). Such a result is consistent with
the notion that the stimulant drugs are primarily altering
the attention span or ability to concentrate in the hyper
active child with reductions in activity level possibly being
an indirect result of this improvement in attentional pro cesses (Conners, 1972; Douglas, 1972, 1974; Sroufe et. al.,
1973; Werry, 1970). Thus, applied practitioners might find such measures of attention useful in determining the extent to which a hyperactive child would be likely to improve from treatment with methylphenidate.
Interestingly, parental ratings of activity level were not found to predict improvement on an laboratory measures of activity level or attention. Nor was drug improvement on this measure found to be useful in classifying children as good or poor drug responders for the purposes of determining differences between them in drug responding on other measures.
These findings agree with the negative results of other studies using parental ratings of hyperactive children for this purpose (Rapoport et. al., 1971; Rie et. al., 1976;
Werry & Sprague, 1974). As noted earlier, this may have resulted from the fact that hyperactive children in this study were essentially good drug responders before partici pating in this study. Since they were using methylphenidate prior to this study and continued to use it afterwards, this would appear to be a reasonable assumption. -55-
Hyperactive Versus Normal Children.
Turning to the comparisons of hyperactive and normal
children, the results of this study agree with most previous
research in this area in finding hyperactive children tao be
significantly more active, have shorter attention spans, and
to be less able to concentrate on structured tasks as com pared to normal children. In addition, hyperactive children were found to be less able to inhibit locomotor activity when
instructed to do so as compared to normal children. The results for activity level concur with the findings of Pope
(1970) and Kasper et. al. (1971) while those for attention span agree with the findings of Conners and Rothschild (1968),
Sroufe et. al. (1973), and Douglas (1972,1974). Furthermore, this study found hyperactive children to be viewed by their parents as substantially more active than normal children, a result also in agreement with previous research (Barkley &
Ullman, 1975).
The present findings for laboratory measures, however, are not in complete agreement with a previous study (Barkley
& Ullman, 1975) which used a similar procedure and set of measures, yet found hyperactive children to differ from * normal children only in wrist and ankle activity during free play. In contrast, the present study found such differences in free play and structured settings while also finding differ ences in locomotor activity and attention span across a number of settings. One possible explanation for these discre pancies is that somewhat different populations appear to have -56-
been studied in these reports. Barkley and Ullman (1975)
used children referred to a psychological services center
for hyperactivity, only half of whom were eventually diagnosed
as such at that center. On the other hand, the present study
examined children already diagnosed as hyperactive and placed
on stimulant medication. The present population was there
fore more likely to be representative of children regarded
as hyperactive by the professional community.
Differences were also noted in the present study between
hyperactive and normal children in the extent to which their
behavior changed as a function of time, or repeated assess
ment. Normal children were observed, with a few exceptions,
to remain relatively stable in their activity level, attention
span, and concentration across the three assessment occasions.
Hyperactive children however, displayed significant increases
in task irrelevant activity during observation of the televised
school lesson with time. These observations may indicate that
as the hyperactive child becomes increasingly familiar with
an initially novel setting, an increase in unnecessary activity
is likely to result.
Clinical Observations of Drug Responding.
Apart from these results on objective measures of drug
responding, some clinical observations are worth noting. Like much of the previous research in this area, this study found many of the hyperactive children to be subdued during drug
treatment (See Appendix B). This was reflected in decreased
interest in and exploration of the environment. During drug
treatment, these children were observed to sit during both -57-
free and restricted play without once venturing to play with
any of the toys or to vigorously investigate and manipulate
other environmental objects as they had initially been ob
served to do. Similar reactions to methylphenidate were re
ported by Rie et. al. (1976) who viewed the behavior as re
flecting a decreased "responsivity" to the environment. While
not systematically investigated in this study, these clinical
observations suggest that although methylphenidate may be re
ducing the activity level and inattentiveness of the hyper
active child, it may be doing so at the expense of interest
or inquisitiveness in the environment — a result which has been observed to lead some parents to prefer to discontinue R the use of Ritalin with their hyperkinetic children.
On a more general level, the findings of improved activity level, attention span, and concentration during drug treat ment are difficult to reconcile with the results of followup studies on hyperactive children receiving stimulant medication over a number of years (See Appendix B). These follow-up studies found that stimulant medication alone did not appear to influence the later psychological, social, academic, or occupational adjustment of hyperactive children as compared to children not receiving the drug. This discrepancy between short and long term findings for the stimulant drugs is both surprising and disappointing. It suggests that the drugs are useful only in the short term manageability of hyperkinetic children while contributing little to their long term psycho logical or social adjustment. Rie et. al. (1976) have suggested that the positive changes in manageability resulting from these -58- drugs may be counteracted by their apparent negative effect on "responsiveness" to the environment. Thus, long term gains in adjustment are likely to be cancelled out by decreased responsiveness to the environment with the results of follow-up studies being essentially nil for the effect of these drugs. Certainly, this is an important area for future research to explore.
Limitations of the Present Study.
There are several limitations on the extent to which these findings can be generalized. First, the small number of hyperactive children and the criteria chosen to diagnose them as hyperkinetic are likely to limit the comparability of these results with those of other studies. Second, since the placebo pill was somewhat smaller than the methylphenidate pill, parents may have been provided with a cue to understand ing the drug-placebo code for their child. While this may have confounded their ratings of activity level, it is not likely to have had an effect on the vast majority of measures in this study which were taken by the experimenter who still remained blind to the drug-placebo code. However, a third and related difficulty with these results, which has been noted in other research (Werry & Sprague, 1974), is that the dramatic behavioral changes resulting from the drug permit the experimenter to guess the drug-placebo code with great accuracy. This, then, may confound his observations of the child. A fourth problem rests in the results regarding the -59-
prediction of drug responses in the hyperkinetic children.
The fact that these children were receiving methylphenidate
prior to the study suggests that most were probably good
drug responders. Their results, therefore, may not be repre
sentative of hyperkinetic children who are poor drug respon
ders. Certainly, these potential limitations of this study
need to be considered in interpreting the findings for the
hyperkinetic children.
Summary
In conclusion, the present study found methylphenidate
to significantly reduce several types of activity level in
hyperactive children across a number of types of assessment
settings. Methylphenidate was also noted to substantially
improve the attention span and concentration of hyperactive
children, again without regard to the type of setting. In determining which measures predicted improvement during drug treatment, pretreatment levels of the inability to concentrate were found, to be the best predictors of drug responding in the hyperactive children. Hyperkinetic children were also found to be more active, inattentive, and unable to concentrate as well as unable to inhibit locomotor activity when requested to do so in comparison to normal children. Despite these positive results for the drug, clinical observations suggested that the drug may have been decreasing the hyper active child's spontaneous interest in or responsiveness to his environment — a finding worthy of future research. -60-
References
Baldessarini, R. Pharmacology of the amphetamines.
Pediatrics, 1972, 49, 694-701.
Barkley, R. & Ullman, D. A comparison of objective measures
of activity and distractibility in hyperactive and
nonhyperactive children. Journal of Abnormal Child
Psychology, 1975, 3, 231-244.
Bradley, C. The behavior of children receiving benzedrine.
American Journal of Psychiatry, 1937, 94, 577-585.
Bradley, C. Benzedrine and dexedrine in the treatment of
children’s behavior disorders. Pediatrics, 1950, 5, 24-37.
Cantwell, D. (Ed.) The Hyperactive Child. New York:
Spectrum Publications, Inc., 1975.
Conners, C. Pharmacotherapy of psychopathology in children.
In H. Quay & J. Werry (Eds.) Psychopathological Disorders
of Childhood. New York: J. Wiley & Sons, 1972.
Conners, C. & Rothschild, G. Drugs and learning in children.
In Learning Disorders Volume 3. Seattle, Washington:
Special Child Publications, 1968.
Cromwell, R., Baumeister, A., & Hawkins, W. Research in
activity level. In N. Ellis (Ed.) Handbook of Mental
Deficiency. New York: McGraw-Hill Book Co., 1963.
Douglas, V. Stop, look, and listen: The problem of sustained
attention and impulse control in hyperactive and normal
children. Canadian Journal of Behavioral Science, 1972,
4, 259-282. -61-
Douglas, V. Sustained attention and impulse control:
Implications for the handicapped child. In Psychology
and the Handicapped Child. Washington, D. C.: U. S.
Department of Health, Education and Welfare, Office
of Education, 1974.
Ellis, M. , Witt', P., Reynolds, R. , & Sprague, R. Methylpheni
date and the activity of hyperactive children in the
informal setting. Child Development, 1974, 45, 217-220.
Garfinkel, B., Webster, C., & Sloman, L. Methylphenidate and
caffeine in the treatment of children with minimal brain
dysfunction. American Journal of Psychiatry, 1975, 132,
723-727.
Iversen, S. & Iversen, L. Behavioral Pharmacology. New York:
Oxford University Press, 1975.
Kasper, J., Millichap, J., Backus, R., Child, D., & Schulman,
J. A study of the relationship between neurological
evidence of brain damage in children and activity and
distractibility. Journal of Consulting and Clinical
Psychology, 1971, 36, 329.
Knights, R. & Hinton, G. The effects of methylphenidate on
the motor skills and behavior of children with learning
problems. Journal of Nervous and Mental Disease, 1968,
148, 643-653.
Krager, J., & Safer, D. Type and prevalence of medication
used in treating hyperactive children. New England
Journal of Medicine, 1974, 291, 1118-1120.
Loney, J. 8s Ordona, T. Using cerebral stimulants to treat -62-
minimal brain dysfunction. American Journal of Ortho
psychiatry , 1975, 45, 564-572.
Pope, L. Motor activity in brain injured children. American
Journal of Orthopsychiatry, 1970, 40, 783.
Rapoport, J., Abramson, A., Alexander, D., & Lott, I. Play
room observations of hyperactive children on medication.
Journal of the American Academy of Child Psychiatry,
1971, 10, 524-534.
Rie, H., Rie, E., Stewart, S., & Ambuel, J. Effects of methyl
phenidate on underachieving children. Journal of
Consulting and Clinical Psychology, 1976, 44, 250-260.
Routh, D. & Roberts, R. Minimal brain dysfunction in children:
Failure to find evidence for a behavioral syndrome.
Psychological Reports, 1972, 31, 307.
Routh, D., Schroeder, C., & O'Tuama, L. Development of
activity level in children. Developmental Psychology,
1974, 10, 163.
Safer, D. & Allen, R. Stimulant drug treatment of hyper
active adolescents. Diseases of the Nervous System,
1975, 36, 454-457.
Satterfield, J., Cantwell, D., Lesser, L., & Podosin, R.
Physiological studies of the hyperkinetic child: I.
American Journal of Psychiatry, 1972, 128, 1418-1424.
Schleifer, M., Weiss, G., Cohen, N., Elman, M., Cvejic, H.,
& Kruger, E. Hyperactivity in preschoolers and the
effect of methylphenidate. American Journal of Ortho
psychiatry , 1975, 45, 38-50 -63-
Sprague, R. , Barnes, K., & Werry, J. Methylphenidate and
thioridazine: learning, reaction time, activity, and
classroom behavior in disturbed children. American
Journal of Orthopsychiatry, 1970, 40, 615-628.
Sroufe, A., Sonies, B., West, W., & Wright, F. Anticipatory
heart rate deceleration and reaction time in children
with and without referral for learning disability.
Child Development, 1973, 44, 267-273.
Wender, P. Minimal Brain Dysfunction in Children. New York:
J. Wiley & Sons, 1971.
Werry, J. Developmental hyperactivity. Pediatric Clinics
of North America, 1968, 15, 581.
Werry, J. Some clinical and laboratory studies of psycho
tropic drugs in children: An overview. In W. L. Smith
(Ed.) Drugs and Cerebral Function. Springfield, Illinois:
Charles Thomas, 1970.
Werry, J. & Sprague, R. Methylphenidate in children: Effect
of dosage. Australian and New Zealand Journal of
Psychiatry, 1974, 8, 9-19. -64-
APPENDIX A -65-
Predicting the Response of Hyperkinetic Children
to Stimulant Drugs: A Review
Bradley (1937-38) is typically credited with being the
first to describe the effectiveness of stimulant drugs in the
treatment of children's behavior disorders. Since that time,
a plethora of research has been conducted on the effects of
central nervous system (CNS) stimulant drugs on children,
particularly those described as hyperkinetic or minimally
brain damaged (MBD). A review of this research (See Appendix
B) clearly shows that not all hyperkinetic children respond
well to stimulant drugs — indeed the symptoms of some are
exacerbated by them. It appears that approximately 75 percent
of hyperkinetic children receiving these drugs respond favor
ably, while the remaining 25 percent are unchanged or exacer
bated by them (Barcai, 1971; Bradley, 1950; Rapoport et. al.,
1974; Weiss et. al., 1971).
Given that hyperkinetic children respond differentially
to the CNS stimulants, it would seem clinically useful to
identify those variables which discriminate responders (those
who improve) from nonresponders (those who are unchanged or
worsened). If this could be done, a clinician would be better
able to decide which children should receive stimulant drugs
and which should not. Previous attempts at identifying pre
dictors have focused on a number of variables, several of which appear to have some utility. An overview of these
studies is provided in Table 1 in which 36 research reports are TABLE 1
Review of Research on Predicting Stimulant Drug Response in Hypebkinetic Children
a. Drug Authors & Number of b. Daily Dosage Use of Use of 2 Year Children c. Time on Drug Placebo Design Type3- Double Blind Drug Response Criteria
Arnold et. al. (1973) 11 a. 1-amphetamine Yes Crossed Yes Changes in ratings completed by d-amphetamine parent, teacher, & psychiatrist. b. 5-30 mg. c. 3 weeks
Barcai (1971) 53 a. d-amphetamine Yes Crossed Yes Independent staff ratings of b. 20 mg. response vs. no response based c. 6 weeks on pre-post drug changes in teacher ratings.
Barkley & 14 a. methylphenidate Yes Crossed Yes Changes in multiple measures of Jackson (1976) b. 10 mg. activity level and attention span c. 1 day from placebo to drug conditions.
Barkley, 18 a. methylphenidate Yes Crossed Yes Changes in a variety of measures Ullman, & b. 10 mg. of activity and attentiveness. Brown (1976) c. 1 day
Breitmeyer 54 a. methylphenidate Yes Crossed 7 . Changes in measures of activity. (1969) b. 1.1 & 4.5 mg/kg c. One dose
Buchsbaum Si 24 a. amphetamine No Crossed - On vs. Off No Clinical judgement of prior drug Wender (1973) b. 10-20 mg. Drugs response. c. 4-8 months
Burks (1964) 43 a. amphetamine No Pre-post drug No Changes in teacher ratings. b. ? treatment c. ?
Butter & 32 a. methylphenidate Yes Crossed Yes Improvement in test scores on the Lapierre (1C75) b. 10-30 mg. Illinois Test of Psycholinguistic c. 2 we ?ks Ability and a series of mono-, bi- and tri-sensory stimulation detec tion tests.
Conners (1971) 132 a. methylphenidate Yes Uncrossed Yes Changes in human figure drawings d-amphetamine test. b. 30 mg 15 mg c. 3 weeks 1 Ci Conners 178 a. stimulant drugs ? ? ? ? 1 (1972a) b. ? c. ? Table 1 Continued Page 2
Conrad & 31 a. amphetamine No Study of case No Based upon case records, the Insel (1967) b. ? records children were judged as improved c. ? or unimproved.
Denhoff et. al. 42 a. d-amphetamine Yes Crossed Yes Changes in teacher ratings. (1971) b. 10 mg. c. 3 weeks
Epstein et 10 a. d-amphetamine Yes Crossed Yes Changes in a variety of medical, al. (1968) " b. 10-15 mg. psychophysiological, and psycho c. 2 weeks logical dependent measures.
Hoffman et. al. 34 a. methylphenidate No Pre-Post Drug No Children were judged as "variable" (1974) b. 20-80 mg. Treatment or "consistent" responders using c. 12 weeks the variability of teacher ratings over the 12 weeks of drug therapy.
Knights & 40 a. methylphenidate Yes Uncrossed Yes Judgement of good or poor drug Hinton (1969) b. 20-40 mg. response. c. 6 weeks
Knopp et. al. 22 a. d-amphetamine No Pre-Post Drug No Changes in electropupillographic (1973) b. less than 5 mg. Treatment responses and ratings made by c. ? parents and clinicians.
Loney et. al. 50 a. methylphenidate No Pre-Post Drug No Psychologist's judgement of drug (1975) b. ? Treatment improvement using parent and c. ? teacher reports that all major problems had cleared up.
Lytton & 20 a. methylphenidate ? Pre-Post Drug ? Judged to be good or poor respon Knobel (1958) b. 80-100 mg. Treatment ders based on parental reports, c. 1 wk. to 4J mos, clinician's opinion, and teacher reports.
McConnell 57 a. d-amphetamine Yes Crossed Yes Changes in activity level as et. al. (1964) b. 7j & 15 mg. measured by ballistograph and c. 6 days ward attendants' ratings.
Porges et. al. 16 a. methylphenidate Yes Crossed ? Improvement in reaction time, (1975) b. 3mg./kg. heart rate variability, and c. 3 weeks classroom behavior ratings.
Rapoport et. 19 a. d-amphetamine Yes Crossed No Changes in a variety of tests al. (1971) b. 10 mg. and rating scales. c. 3 weeks
Rapoport et. 76 a. methylphenidate Yes Crossed Yes Psychologist's judgement of al. (1974) b. 30 mg. improvement. ( c. 6 weeks 05 <1 Rie et. al. 28 a. methylphenidate Yes Crossed Yes Changes in a variety of measures 1 (1976). b. 5-40 mg. of activity level, achievement c. 12 weeks skills, intelligence, and parent and teacher ratings. Tabic 1 Continued Page 3
Safer & Allen 84 a. methylphenidate No Pre-Post Drug No Children with greater than 50% (1974) d-amphetamine Treatment change in teacher ratings from b. 10-40 mg. pre-post drug therapy were 4-20 mg. judged to be improved. c. ?
Satterfield 31 a. methylphenidate Yes Uncrossed Yes Judgement of good vs. poor drug et. al. (1972) b. ? response using changes in c. 3 weeks teacher ratings.
Satterfield 57 a. methylphenidate Yes Uncrossed Yes Children with greater than 30% et. al. (1973) b. ? change in teacher ratings from c. 3 weeks pre-drug scores were judged as improved.
Schain & 98 a. methylphenidate Yes Uncrossed Yes Changes in parent and teacher Reynard (1975) b. 10-60 mg. ratings. c. 16 weeks
Schleifer et. 26 a. methylphenidate Yes Crossed Yes Changes on a variety of free al. (1975) , b. 2J-20 mg. play and structured playroom c. 3 weeks measures and psychological tests.
Shetty (1971) 28 a. methylphenidate Yes Crossed Yes Judgement of good vs. poor drug d-amphetamine response using changes in sub b. 20 mg. jective and objective measures 10 mg. of activity, impulsivity, per c. one intravenous formance, and coordination. injection then 3 weeks oral ingestion
Steinberg et. 46 a. d-amphetamine Yes Crossed Yes Children whose ratings had changed al. (1971) b. 10-15 mg. more than the highest change score c. 4 weeks from pre-drug to placebo condi tions were judged as improved.
Weber & 12 a. methylphenidate Yes Crossed Yes Changes in classroom behavior Sulzbacher dr-amphetamine ratings. (1975) b. .12-.62 mg/kg c. ?
Weiss et. al. 89 a. methylphenidate Yes Uncrossed Yes ? (1971) d-amphetamine b. less than 50 mg less than 20 mg c. 4-6 weeks
Weiss et. al. 40 a. d-amphetamine Yes Uncrossed Yes (1968) b. 5-20 mg. O) c. 3-5 weeks % oo I Table 1 Continued Page 4
Werry & Aman 24 a. methylphenidate Yes Crossed Yes Changes in scores on memory and (1975) b. .3 mg/kg vigilance tasks. c. 3 weeks
Werry & Sprague 37 a. methylphenidate Yes Crossed Yes Physician's judgement of good (1974) b. .1-1.0 mg/kg vs. poor drug response. c. 4 weeks
Zahn et. al. 42 a. methylphenidate No Pre-Fost Drug No Poor responders were children who (1975) d-amphetamine Treatment failed to change a certain amount b. ? from pre- to post-drug conditions c. About 2.5 months or whose on-drug ratings were worse than pre-drug ratings.
The type of experimental design employed in the study. "Crossed" refers to a complete crossover design in which children receive both drug and placebo conditions in a random fashion. "Uncrossed" refers to a design in which children were assigned to either the drug or placebo condition, or the drug or no-drug condition, in the study. "Pre-Post Drug Treatment" refers to a design in which all children were evaluated before receiving drugs and then again while receiving drugs.
This refers to the criterion used in the study to determine whether or not children were good or poor drug responders, or to determine the degree to which the children improved during drug treatment.
? This indicates that the information in this column was either not provided in the report or was so ambiguously stated so as to be uncertain. - 6 9 I -70-
summarized, covering more than 1,400 children. For each, the
authors, the number of subjects, the type of drug studied,
the daily dosage administered, and the time the child spent
on the drug during the study, as well as information relevant
to placebo conditions are reported. Also noted are the types
of experimental designs, the blindness of raters, and the
criteria adopted to define improvement. Only those results
bearing on the prediction of drug response will be reported.
The discussion will be organized according to types of predic
tor variables investigated in the studies: (1) psychophysio
logical, (2) neurological, (3) familial, (4) demographic/socio-
logical, (5) diagnostic category, (6) parent/teacher/clinician
ratings, (7) psychological, and (8) profile types. The limita
tions of these studies and of the present review also will be
briefly discussed.
Psychophysiological Predictors.
The most frequently studied psychophysiological variable
in the literature dealing with prediction of drug response has been the presence or absence of abnormalities in clinical electroencephalograms (EEG). The results of research on this variable however, appear to be equivocal. Satterfield et. al.
(1973) found that significantly more drug responders had abnor mal EEGs as compared to nonresponders. On the other hand, several investigators either have found no relationship between drug response and EEG abnormality (Knights & Hinton, 1969;
Lytton & Knobel, 1959; Rapoport et. al., 1974; Weiss et. al.,
1968; Weiss et. al., 1971) or they report that abnormal EEGs -71
predict poor drug responding (Burks, 1964; Schain et. al.,
1975). Thus, at this time, there does not appear to be any
clearcut evidence of a relationship between EEG abnormality
and responsiveness of hyperkinetic children to stimulant drugs.
While not as frequently studied, one aspect of the EEG
which has shown a consistent relationship with differential
drug responding in hyperkinetic children has been the averaged
evoked response (AER). This measure involves recording the effects on the EEG of presenting various patterns of stimuli
in one or more sensory modalities. Research with hyperkinetic children has focused on visual and auditory AERs as a neuro psychological means of studying the attentional deficits in these children (Buchsbaum & Wender, 1973). With respect to auditory AERs, research indicates that drug responders have significantly higher baseline (pre-drug) AER amplitudes, lower recovery of evoked responses, less change in latency and intensity of AERs with age, and greater variability of
AERs as compared to nonresponders (Buchsbaum & Wender, 1973;
Satterfield et. al., 1972). Furthermore, responders have been shown to have significantly lower off-drug, placebo, and on-drug AER thresholds as compared to nonresponders (Weber &
Sulzbacher, 1975). On visual sine-wave stimulation, both responders and nonresponders show greater right hemisphere occipital AERs but nonresponders and normal children show a decreased hemispheric asymmetry in responding with age.
Responders, however, continue to lag behind this developmental -72-
pattern and show an increasing right hemisphere predominance
of AER with age (Buchsbaum & Wender, 1973). The results of
this research indicate that responders appear to show psycho-
physiological evidence suggestive of an immature central nervous system (Buchsbaum & Wender, 1973; Satterfield et. al.,
1072). Further research is necessary however before such a conclusion can be drawn safely.
Satterfield et. al. (1972) also examined other aspects of the EEG and found responders to have higher baseline resting
EEG amplitudes, range of amplitudes, EEG power, and EEG move ment artifacts as compared to nonresponders. On drugs, respon ders also differed in displaying no increase in resting EEG power whereas nonresponders did show such an increase.
Shetty (1971) also studied various aspects of the clinical EEG in hyperkinetic children and found responders to show an increase in alpha rhythm while nonresponders did not during drug treatment. These results support the notion that respon ders are somehow psychophysiologically different from nonres ponders but do not clearly support any one explanation for this difference.
Another psychophysiological measure examined in this research is the skin conductance response (SCR). Only two studies used this variable and their results were contradic tory. Satterfield et. al. (1972) found responders to have
SCRs which were lower than those of normal children and much lower than those of nonresponders. These findings are consis tent with the possibility that the hyperkinetic drug responder -73- may be centrally underaroused. Zahn et. al. (1975) however, found responders to have lower SCRs as well as slower rises and recovery of SCRs, smaller and longer latency of specific
SCR to tones in a reaction time task, and greater increase in
SCR recovery while on drugs. These results suggest that the responders of Zahn et. al. (1975) are autonomically overaroused rather than underaroused as found by Satterfield et. al. (1972).
Thus, with respect to SCR, no conclusions about the level of autonomic arousal of responders or the predictive utility of this measure can be drawn at this time.
Various aspects of heart rate have also been studied for their predictive utility. Porges et. al. (1975) found that responders had significantly lower baseline heart rate levels, a significantly greater increase in heart rate while on drugs, and a significantly greater reduction in heart rate variability while on drugs as compared to nonresponders. These results suggest that responders are autonomically underaroused in comparison to nonresponders or normal children. However,
Barkley and Jackson (1976) observed just the opposite results when mean pre-drug heart rate levels were correlated with change scores representing degree of improvement on a variety of measures of activity level and attention span during drug treatment. It was found that mean pre-drug heart rate signi ficantly correlated with improvement in ankle activity in free play and wrist activity during a testing setting. That is, the higher the mean pre-drug heart rate for these hyper- -74-
kinetic children, the greater the improvement in free play
ankle activity and wrist activity during testing. As with
measures of skin conductance, these results do not permit any
clearcut conclusions to be drawn with respect to the level of
autonomic arousal of drug responders or the utility of heart
rate as a predictor of drug responsiveness.
Two studies were found which examined heart rate decelera
tion as a predictor of drug responsiveness in hyperactive chil
dren.' Zahn et. al. (1975) found no difference between good
and poor drug responders in heart rate deceleration immediately
prior to the response signal on a reaction time task. Similarly,
Porges et. al. (1975) found no relationship between heart rate
deceleration on a delayed reaction time task and response to
drug treatment. Heart rate deceleration, then, has yet to
prove itself a useful predictor of drug responding in hyper
kinetic children.
Using a different psychophysiological measure, Barkley
and Jackson (1976) attempted to correlate mean pre-drug levels
of respiration with degree of improvement on a number of I measures of activity level and attention span during drug treatment. Results indicated that mean pre-drug rate of respiration was negatively related to improvement in wrist and seat movement activity during observation of a televised school lesson and to improvement in the amount of time the child did not visually attend to that lesson. That is, the lower the child’s pre-drug rate of respiration, the more improvement he displayed during drug treatment on measures of wrist activity, seat restlessness, and time spent not attending -75- to a televised school lesson. However, mean pre-drug rate of respiration was found to positively correlate with improve ment in toy change activity during a restricted play setting.
Restricted play refers to a setting in which a child is instructed to play in only one part of a large playroom and with only one of a variety of toys available for play. Results suggested that the higher the pre-drug rate of respiration, the greater the improvement in toy change activity during the restricted play period. Thus, depending on which objective measure of activity or attentiveness one uses as a criterion of drug improvement, pre-drug rate of respiration can be found to be either positively or negatively related to such improve ment in hyperactive children.
Another promising psychophysiological measure of drug response is the electropupillogram (EPG). Knopp et. al. (1973) measured the changes in dark-adapted pupil diameter in response to light in hyperkinetic children both before and after admin istration of dextroamphetamine. Changes in EPG from pre-drug to on-drug phases were found to correlate significantly with parental (r=.59) and clinicians' (r=.41) ratings of improve ment. These children were then categorized into five groups based upon their EPG responses. These five groups differed from each other in the percentage of children showing behavioral improvement as reflected in parental and clinician ratings.
Approximately 23 percent of the hyperkinetic children were found to have high pre-drug electropupillary contractions suggesting underaroused EPG responses while 36 percent had low -76
electropupillary contractions indicating the possibility of
underarousal. Both of these groups changed significantly during drug treatment and both were rated as more improved than the other groups of children. Children with normal EPG responses which did not change significantly during drug treat ment also did not change significantly in behavioral ratings by parents and clinicians. A fourth group of hyperkinetic children were somewhat underaroused in EPG and changed very little with respect to on-drug EPG. These children were also rated as having worsened behaviorally during drug treatment.
The fifth category consisted of only one child whose EPG response was the smallest in deviating from the mean of normal children but whose response became very sensitive or reactive when placed on a CNS stimulant. Little behavior change was reported for this child. Thus, Knopp et. al. (1973) appear to have found a method of discriminating between groups of drug responders and nonresponders on the basis of their auto nomic arousal levels, as inferred from their EPG responses.
Yoss (personal communication, 1975) and Yoss and Moyer
(1971) also have studied the EPGs of hyperkinetic children both on and off CNS stimulant drugs and have found 25 to 35 percent of these children to have narcoleptic or underaroused
EPG responses while off drugs. When placed on stimulant drugs, the level of EPG arousal in these children is significantly increased. Coupled with the findings of Knopp et. al. (1973), these results suggest two conclusions. First, hyperkinetic children appear to be heterogeneous in their autonomic arousal -77-
level as reflected in EPG responses, with those who are either
over- or underaroused responding favorably to CNS stimulants.
Those children with EPGs approximating normal children appear
to respond poorly or not at all to stimulant medication.
Second, the EPG, as a measure of arousal and a correlate of
attention span (Hakerem, 1970), shows promise as a predictor
of good as opposed to poor drug responders.
Related to the research into psychophysiological correlates
and drug responding is a study by Epstein et. al. (1968) which
found that responders have a higher mean percentage of free
amphetamine recovery from their urine than do nonresponders.
This may account for their finding that responders were able
to tolerate higher doses of amphetamine with fewer side effects
than nonresponders. The study, however, has yet to be repli
cated.
Other psychophysiological variables investigated but
found to have no discriminative validity in this area are skin temperature, blood pressure, and pulse rate (Epstein et. al.,
1968; Zahn et. al., 1975).
In summary, in the category of psychophysiological pre dictors, EEG averaged evoked responses, other EEG parameters, heart rate, heart rate variability, EPGs, and free amphetamine recovery from urine have been reported to discriminate good from poor drug responders. Of these variables, all but urine recovery of amphetamine probably bear some relationship to
attention span. This relationship between correlates of -78-
attention span and drug response in hyperkinesis appears
repeatedly throughout this review and is perhaps due to the
fact that CNS stimulants seem to have their major effect on
the attention span or concentration of hyperkinetic children
(Appendix B; Conners, 1972b; Douglas, 1972; Werry, 1970).
Neurological Predictors.
One of the more commonly studied neurological variables
has been the number of "soft" signs found during a neurological
examination. Satterfield et. al. (1972) found that hyper
kinetic children with four or more soft signs had a more
favorable response to CNS stimulants than those with no soft
signs. As noted earlier, they also found a positive relation
ship between EEG abnormality and drug response. Ranking
the hyperkinetic children on the extent of abnormality on
both of these measures, Satterfield et. al. (1973) found an
interaction suggesting a correlation between degree of "soft" neurological and EEG abnormality and drug response. This evidence was interpreted as indicating a more favorable response to stimulants among those children with evidence suggestive of organic brain damage. Similar results with respect to neurological soft signs have been found by Stein berg et. al. (1971) and Conrad and Insel (1967). However, other investigators (Rapoport et. al., 1974; Weiss et. al.,
1968, 1971) have found no association between extent of neurological soft signs and drug response in hyperkinetic children. Thus, the predictive utility of neurological soft signs is uncertain at this time. -79-
Several investigators have categorized hyperkinetic chil dren as "organic" or "nonorganic" using evidence (developmental, neurological, cognitive, historical, etc.) suggestive of organic impairment. Epstein et. al. (1968) found that "organics showed greater improvement in Porteus Maze performance, parental evaluations, and psychiatric interview ratings while on stimu lants as compared to "nonorganics." These "organics" were the same drug responding children who had greater free amphetamine recovery from their urine and fewer side effects while tolerat ing higher drug dosages than "nonorganics." Weiss et. al.
(1968) also noted a trend for children with a history sugges tive of brain damage to have a better drug response. However,
Knights and Hinton (1969) found no differences between groups of hyperkinetic children categorized in a manner similar to the Epstein et. al. (1968) groups. Further, Rie et. al.
(1976) found cognitive measures of organicity to be negatively related to stimulant drug response. That is, children who were less "organic" showed more improvement in parental ratings of activity level, achievement, and general behavior.
It is tempting, though premature, to take these results in conjunction with those for neurological soft signs and abnormal EEGs and suggest that the greater the evidence for neurological impairment, the more likely the hyperkinetic child is to respond favorably to stimulant drugs. Further research is needed, however, to clarify the role of "organicity" in the prediction of drug responsiveness. -80-
Another potentially useful measure of drug response is
Barcai’s (1971) finger twitch test. In this test, the child
is asked to sit with his hands hung between his knees to see
how long he can maintain this posture without moving his
hands or fingers. His score is the time between test onset
and the first brisk finger movement. Coupled with the results
of a personality assessment procedure to be reviewed later,
Barcai (1971) was able to correctly predict 21 of 23 responders
and 15 of 16 nonresponders. Rapoport et. al. (1974) also t found this simple test to accurately predict response to
methylphenidate. If future research continues to replicate
this finding, a very simple test may have been discovered
which can predict differential responding of hyperkinetic
children to stimulant drugs.
At first glance, this simple test appears to be associated
with motor inhibition and extrapyramidal signs of neurological
impairment. A closer look at the instructions to the child
also suggests that it may involve that aspect of attention
known as "maintenance of set." However, whether it is the motor or the attentional aspects of this test which underly
its usefulness as a predictor is uncertain at this time.
Familial Predictors.
Several research reports have examined the relationship between familial variables and drug response. Loney et. al.
(1975) judged the parents of hyperkinetic children as either good or poor managers of their children. They found that good managers had a significantly greater number of drug responders than poor managers. The results of Schleifer et. -81-
al. (1975) appear to contradict this finding in that they
found mothers of children who were rated as extremely hyper
active used more physical punishment and were more "frustrated”
than mothers of children rated as less hyperactive. Yet, these
extreme hyperactive children showed the best response to drugs.
In agreement with the findings of Loney et. al. (1975) however,
Weiss et. al. (1971) and Conrad and Insel (1967) noted that
hyperkinetic children rated as having better mother-child
relationships also had a greater number of drug responders
than those with poor relationships. Additionally, Conrad and
Insel (1967) found that a group of children living with at
least one parent rated as "grossly deviant" or "socially
incompetent" had significantly fewer responders than a group of children without such a parent. With the exception of the data reported by Schleifer et. al. (1975), these results appear to indicate that a child is more likely to respond favorably to stimulant medication when the parents are competent, good managers, and able to maintain a positive relationship with the child. Just exactly how such variables influence drug responding is uncertain nor is the direction of causality in these relationships very clear. Do drug responders create better parent-child relationships or is the opposite the case?
Demographic/Sociological Predictors.
A number of studies have examined demographic and socio logical predictors such as age, race, sex, and socioeconomic status for their utility in determining drug responses in hyperkinetic children (Buchsbaum & Wender, 1973; Butter & -82-
Lapierre, 1975; Hoffman et. al., 1974; Safer & Allen, 1975;
Schain et. al., 1975; Werry & Sprague, 1974; Weiss et. al.,
1968, 1971). The only variables for which positive results
have been found are age at the time the child began drugs and
age at time of testing. Contradictory results have been
reported for both variables. While not tested for statistical
significance, the data reported by Schain et. al. (1975) were
interpreted as suggesting a trend for poor drug responders to be older at the time they began drug treatment. Safer and
Allen (1975), on the other hand found no support for any relationship between drug responsiveness and age at which medication was started.
As for the variable of age, itself, Butter and Lapierre
(1975) divided their hyperkinetic children into three groups on the basis of chronological age and found that older hyper actives (ages 10.4 to 12.6 years) made significantly fewer errors on a trisensory stimulation test when they were receiv ing medication than when they were on placebo. This pattern of results was not observed for younger hyperactives. Buchs baum and Wender (1973) also found an effect of age on visual
AERs for good and poor drug responders (See section on Psycho physiological Predictors). Thus, the variable of age appears to influence drug response on some measures, although its utility as a predictor is unclear.
Diagnostic Category Predictors.
Several research reports have looked for differences in responsiveness to drugs among various diagnostic categories. -83-
The vast majority of these studies examined differences among
the three diagnostic subcategories advocated by Fish (1971).
These subcategories are: "unsocialized aggressive," "hyper
kinetic," and "overanxious reactions to childhood." In an
investigation of drug response to 1-amphetamine and d-ampheta
mine, Arnold et. al. (1973) compared MBD children diagnosed
as unsocialized aggressive with a -group comprised of both
hyperkinetic and overanxious children. They found that the
unsocialized aggressive children responded as well to both
amphetamine isomers but that d-amphetamine was more effective with the hyperkinetic and overanxious children.
Knopp et. al. (1973) studied the response to drugs of children who were assigned to groups using Fish's diagnostic system. They found differences among the three groups on both pre-drug and on-drug EPGs. Unsocialized aggressives were observed to have pre-drug electropupillary contractions suggestive of underarousal which were reduced during drug treatment. Hyperkinetic children tended to have smaller than normal pre-drug electropupillary contractions indicating over arousal with these contractions being increased or "normalized" by stimulant drugs. Only 14 percent of the total subject sample were labeled overanxious and these children tended to show normal pre-drug EPGs with little change in EPG while on drugs. Werry and Aman (1975) however, compared MBD children diagnosed as unsocialized aggressive with those diagnosed hyperkinetic and pound no significant differences between them on several memory and vigilance tasks. It appears, there -84-
fore, that differences among Fish's diagnostic categories have
not been consistently found, although the data of Knopp et.
al. (1973) and Arnold et. al. (1973) are encouraging in that
they suggest possible psychophysiological differences among
these groups. Further research into the diagnostic categories may prove useful.
Using a different diagnostic system, Conrad and Insel
(1967) divided their hyperkinetic children into three groups according to the presence or absence of emotional pathology
(unspecified) and the number of neurological soft signs present
"Organics" were those children with three or more soft signs, while "organic-emotionals" were those with two or more soft signs and emotional pathology, and "emotionals" were those without soft signs but with emotional pathology. The "organic" group contained a significantly greater number of drug respon ders than the other two groups which suggested that the presence of emotional pathology might predict a poor response to stimulant drugs. This notion, however, has yet to be tested and confirmed by other investigators.
Rating Scale Predictors.
Several studies provided parents, teachers, and clinicians with the opportunity to rate hyperkinetic children on their home and classroom behavior, as well as on other dimensions, and these ratings were subsequently used to predict improve ment on CNS stimulants. With respect to parental ratings, the results are equivocal. Hoffman et. al. (1974) used the variability in teacher ratings over a 12 week drug treatment -85-
interval to divide hyperkinetic children into "variable”
and "consistent" responders. Parents completed the Werry-
Weiss-Peters Activity Rating Scale and the Conners Parent
Symptom Questionnaire (PSQ). Only the initial pre-drug scores
on five of the PSQ categories discriminated "Consistent" from
"variable" responders. "Variable" or unstable drug responders
were found to have higher scores on the scales of conduct
problems, hyperactivity-impulsivity, learning problems, and
perfectionism. Other investigators, however, have not found
parental ratings to be particularly useful in predicting
drug responsiveness (Barkley et. al., 1976; Rapoport et. al.,
1971, 1974; Rie et. al., 1976; Werry & Sprague, 1974; Zahn
et. al., 1975).
Similarly, studies using teacher rating scales have not been consistently useful in predicting drug response. Denhoff et. al. (1971) divided learning disabled children into groups of "probable" and "nonprobable" hyperkinetic children using scores from the Davids Rating Scale of Hyperkinesis as com pleted by teachers. The former group had scores of four or more on each of the six subscales of this questionnaire while the latter consisted of the remaining children. Denhoff et. al. (1971) found that "probable" hyperkinetics showed signi ficantly greater improvement in teacher ratings than "non probable" hyperkinetics. Steinberg et. al. (1971) found similar results using children classified in a similar manner.
Schleifer et. al. (1975) also used teacher ratings to divide, hyperactive children into "extreme," "moderate," or "low" groups. Extreme hyperactives tended to show greater on-drug -86-
improvement in the frequency with which they were observed to
leave their chairs during nursery school as compared to the
other two groups of children. However, other researchers
(Hoffman et. al., 1974; Rapoport et. al., 1971, 1974; Rie
et. al., 1976; Werry & Sprague, 1974) have not found teacher
ratings to be useful predictors of drug responding.
A similar state of affairs exists for clinician's ratings
of children's behavior. Butter and Lapierre (1975) assigned
children to high, medium, and low hyperactive groups on the
basis of ratings made by three psychiatrists using the Davids
Rating Scale of Hyperkinesis. "High" hyperactives were found
to improve more from drugs than the other two groups on the
Illinois Test of Psycholinguistic Ability, on an auditory
and visual monosensory stimulation test, and on a simultaneous
bisensory stimulation test.
In another study, Barcai (1971) compared good and poor
drug responders on clinician's ratings of nine personality
characteristics which were assessed during apsychiatric inter view. Differences were found between the groups on six of nine rated areas. Good responders were rated higher on
"excessive body movement," and lower on "ability to abstract and use imagination," "adjustment to societal values," "sense of perspective," "good language ability,” and "planning" than poor responders. Coupled with his finger twitch test, Barcai
(1971) was able to correctly predict 21 of 23 responders and
15 of 16 nonresponders. -87-
A study by Zahn et. al. (1975) also found clinician's
ratings to be useful in predicting differential drug respon siveness. Hyperkinetic children were rated on a scale intended to measure "acting out," "anxiety," and "inattention." Prior to medication, poor drug responders were rated as having higher anxiety and acting out scores than good responders.
This finding is consistent with the previously mentioned results of Conrad and Insel (1967), who found that children with primarily emotional pathology are poorer responders to stimulant drugs than those without such pathology. It is also in keeping with the finding that of the three diagnostic categories defined by Fish (1971), the anxious and aggressive groups tended to be the poor responders. Thus, perhaps highly aggressive and anxious children do not respond as well as inattentive or hyperkinetic children to CNS stimulant drugs.
Knopp et. al. (1973) as noted earlier, found EPG differences among these diagnostic categories suggesting that a basic physiological difference might mediate the differential response to drugs of hyperkinetic children. While clinician's ratings were found to be of some use in the above studies, other investigators (Hoffman et. al., 1974; Lytton & Knobel, 1959;
Rapoport et. al., 1974; Werry & Sprague, 1974) have not found such relationships.
An obvious flaw in many studies using rating scales is the absence of empirical proof that the scales measure the constructs they purport to assess. Since little research has been conducted to uncover the relationships between rating -88-
scales and more objective measures, it is difficult to ascer
tain what these scales do measure. For instance, while intended
to measure some aspect of children's activity level, the
Werry-Weiss-Peters Activity Rating Scale has not been found
to correlate with more objective measures of activity level
(Barkley & Ullman, 1975). Such ambiguity makes it difficult
to determine which variable(s) the parents, teachers, and
clinicians are using when they judge hyperkinetic children
to be improved on drugs. It is also difficult to compare the
results of studies which used different rating scales. Thus, the conclusions that can be drawn in this section must be
limited to noting that empirical validation of these scales is needed and that parent, teacher, and clinician ratings of behavior have so far proven inconsistent in their ability to predict response to drugs in hyperkinetic children.
Psychological Predictors.
A substantial amount of research has examined the ability of a variety of psychological measures to predict drug respon ding in hyperkinetic children. Most of these have not proven useful. These include the Wechsler Intelligence Scale for
Children (Buchsbaum & Wender, 1973; Hoffman et. al., 1974;
Knights & Hinton, 1969; Rapoport et. al., 1971, 1974; Satter field et. al., 1972; Weiss et. al., 1968; Werry & Sprague,
1974; Zahn et. al., 1975), Wide Range Achievement Test (Hoff man et. al., 1974; Rapoport et. al., 1974; Satterfield et. al.,
1972), Illinois Test of Psycholinguistic Ability (Satterfield et. al., 1972), motor inhibition and body boundary tests -89-
(Hoffman et. al., 1974), Goodenough Draw-A-Man Test (Rapoport
et. al., 1971, 1974; Satterfield et. al., 1972; Weiss et. al.
1968; Zahn et. al., 1975), playroom activity ratings and
measures (Breitmeyer, 1969; Rapoport et. al., 1971, 1974;
Schleifer et. al., 1975), self-concept tests (Rapoport et. al.
1974) , Burt Reading Test (Werry & Sprague, 1974), Witkin Rod
and Frame Test (Buchsbaum & Wender, 1973; Zahn et. al., 1975),
Child♦s Manifest Anxiety Scale (Rapoport et. al., 1971),
short-term memory tests (Werry & Aman, 1975), Loney Draw-A-
Car Test (Loney et. al., 1975), motor steadiness and fine
motor coordination tests (Knights & Hinton, 1969), Lincoln
Oseretsky Motor Development Test (Satterfield et. al., 1972;
Weiss et. al., 1968), the Primary Mental Abilities Test
(Weiss et. al., 1968), and the Bender Visual Motor Gestalt
Test (Knights & Hinton, 1969; Rapoport et. al., 1971, 1974;
Satterfield et. al., 1972; Weiss et. al., 1968; Zahn et. al.,
1975) .
Exceptions to these findings were observed in a recent study by Rie et. al. (1976) in which WISC full scale and
Performance IQs were found to be predictive of improvement in parental ratings of attention, WISC object assembly scores were predictive of improvement in teacher ratings of achieve ment, ITPA scores on auditory association were related to improvement in actometer measures of arm activity, and leg actometers were positively related to improvement in parental ratings of attention but negatively related to improvement in arm activity. These tests, then, appear to be inconsistent -90-
in their ability to predict drug responses in hyperkinetic
children.
However, the following psychological variables were found
to have some predictive utility in discriminating good from
poor drug responders: number of toy changes in free play
(Rapoport et. al., 1971), reaction time (Porges et. al., 1975;
Zahn et. al., 1975), Porteus Mazes (Epstein et. al., 1968;
Rapoport et. al., 1971), Kagan Matching Familial Figures Test
(Rapoport et. al., 1974), and WISC Verbal IQ (Epstein et. al.,
1968). With the exception of WISC Verbal IQ, all of these measures found to predict drug response have been regarded as having some relationship to attention span (Barkley & Routh,
1974; Douglas, 1972, 1974; Pope, 1970; Routh et. al., 1973;
Sroufe et. al., 1973; Zahn et. al., 1975). Thus, it seems that those psychological measures associated with attention span have been found to be the most sensitive predictors of differential drug responses in hyperkinetic children.
Apparently, then, measures of attention span appear to be the most promising predictors of the hyperkinetic child’s response to stimulant drugs.
Profile Type Predictors.
In an attempt to identify those characteristics of hyper kinetic children which predict their favorable response to stimulant drugs, Conners (1971, 1972a) correlated and factor analyzed the results for a substantial number of psychological tests, rating scales, physiological measures, and objective laboratory measures of behavior. This analysis yielded seven -91-
distinct profile patterns that accounted for a significant
amount of drug treatment effects among the large number of
hyperkinetic children sampled (See Conners, 1971, 1972a).
In general, profiles containing measures of inattentiveness or
the inability to concentrate, or the psychophysiological
correlates of these abilities, were the best predictors of
drug treatment. However, further research is needed to cross
validate these profile patterns before their utility as drug
response predictors can be established.
Limitations of this Review.
Before attempting to draw conclusions from the results of
research in this area, it is important to briefly mention
certain limitations placed upon such conclusions as a result
of differences across the studies being reviewed. These
limitations appear to be: (1) differences in the definitions used to' select hyperkinetic children, (2) differences in the
drug types, dosages, and time on drug, (3) differences in the
type of experimental designs and control procedures, (4)
differences in the measuring techniques used to assess the
same construct, and most importantly (5) differences in the
criteria used to define improvement in hyperkinetic children
during drug treatment. Obviously, the likelihood of finding
a child "improved" on stimulant drugs depends, to some extent,
on the manner in which these investigators chose to deal with
these limitations. To the extent that differences in their procedures resulted in discrepancies in the results of these
studies, the conclusions drawn from these findings are also
limited. -92-
Conclusions.
Taking these limitations into consideration, the results
of this review indicate that a number of variables are related
to drug responsiveness of hyperkinetic children. In general,
those variables which have been consistently found to predict
improvement during stimulant drug treatment appear to be those
related to attention span or concentration. This is particularly
apparent in those research reports utilizing psychophysiological
or psychological measures as drug response predictors. The
former have found such measures as averaged evoked responses
in the EEG, other EEG parameters, heart rate, heart rate varia bility, rate of respiration, and electropupilligram responses to be useful predictors of drug responding. Most of these measures have also been noted to have some relationship to attentional processes in children (Buchsbaum & Wender, 1973;
Hakerem, 1970; Knopp et. al., 1973; Porges et. al., 1975;
Satterfield et. al., 1972; Sroufe et. al., 1973; Yoss & Moyers,
1971). As for psychological predictors, measures of toy change activity, reaction time, maze coordination, Porteus
Mazes, and the Matching Familiar Figures Test appear to have some utility in predicting drug responsiveness. Here, too, such measures have been regarded as related to attention span or concentration in hyperkinetic children (Barkley & Ullman,
1975; Conners, 1972b; Douglas, 1972, 1974; Pope, 1970; Sroufe et. al., 1973). Thus, measures of attention span and its correlates seem to be the most promising predictors of drug responding in hyperactive children. -93- This conclusion is not surprising given that research on the effects of stimulant drugs and hyperkinesis finds attention span or concentration to be the variable most affected by these drugs (Appendix B; Conners, 1972b; Douglas, 1972, 1974)
The results of this review have also suggested other avenues which future research might wish to pursue. Further study of the extent to which the presence or absence of organic impairment or emotional pathology contributes to drug responding is needed. The determination of the empirical correlates of the commonly used parental, teacher, and clinician rating scales would be another direction for future research.
An additional one would be the cross-validation of the profile types of Conners (1972a) or the diagnostic categories of Fish
(1971). Certainly, further research on the ability of measures of attention span to predict the response of hyperactive children to stimulant drugs is also required. -94-
References
Arnold, E., Kirilcuk, V., Corson, S., & Corson, E. Levo-
amphetamine and dextroamphetamine: differential effect
on aggression and hyperkinesis in children and dogs.
American Journal of Psychiatry, 1973, 130, 165-170.
Barcai, A. Predicting the response of children with learning
disabilities and behavior problems to dextroamphetamine
j sulfate. Pediatrics, 1971, 47, 73-80.
Barkley, R. & Jackson, T. L. Jr. The relationship of auto
nomic arousal to the effects of methylphenidate on the
activity level and attention of hyperkinetic children.
Unpublished Manuscript, Bowling Green State University,
1976.
Barkley, R. & Routh, D. Reduction of children's locomotor
activity by modeling and the promise of contingent reward.
Journal of Abnormal Child Psychology, 1974, 2, 117-131.
Barkley, R. & Ullman, D. A comparison of objective measures
of activity and distractibility in hyperkinetic and
nonhyperkinetic children. Journal of Abnormal Child
Psychology, 1975, 231-244.
Buchsbaum, M. & Wender, P. Averaged evoked responses in normal
and minimally brain dysfunctioned children treated with
amphetamine. Archives of General Psychiatry, 1973, 29,
764-770.
Bradley, C. Benzedrine and Dexedrine in the treatment of
•children's behavior disorders. Pediatrics, 1950, 5, 24-37 -95-
Breitmeyer, J. Effects of thioridazine and methylphenidate
on learning and retention in retardates. Unpublished
Masters Thesis, University of Illinois, 1969. Cited in
Werry, J. Some clinical and laboratory studies of psycho
tropic drugs in children: an overview. In W. L. Smith
(Ed.) Drugs and Cerebral Function. Springfield, Illinois:
C. Thomas, 1970.
Burks, H. Effects of amphetamine therapy on hyperkinetic
children. Archives of General Psychiatry, 1964, 11,
604-609.
Butter, H. & Lapierre, Y. The effect of methylphenidate on
sensory perception in varying degrees of hyperkinetic
behavior. Diseases of the Nervous System, 1975, 36, 286-288
Cohen, N., Douglas, V., & Morgenstern, G. The effect of
methylphenidate on attentive behavior and autonomic
activity in hyperactive children. Psychopharmacologia,
1971, 22, 282-294.
Conrad, W. & Insel, J. Anticipating the response to amphetamine
therapy in the treatment of hyperkinetic children.
Pediatrics, 1967, 40, 96-98.
Conners, C. A teacher rating scale for use in drug studies in
children. American Journal of Psychiatry, 1969, 126,
884-888.
Conners, C. The effect of stimulant drugs on human figure
drawings in children with minimal brain dysfunction.
Psychopharmacologia, 1971, 19, 329-333.
Conners, C. Psychological effects of stimulant drugs in -96-
children with minimal brain dysfunction. Pediatrics, 1972a,
49, 702-708.
Conners, C. Pharmacotherapy of psychopathology in children.
In H. Quay & J. Werry (Eds.) PsychopathoTogical Disorders
of Childhood. New York: J. Wiley & Sons, 1972b.
Conners, C. & Rothschild, G. Drugs and learning in children.
In Learning Disorders, Volume 3. Washington, D. C.:
Special Child Publications, 1968.
Denhoff, E., Davids, A., & Hawkins, R. Effects of dextro
amphetamine on hyperkinetic children: a controlled
double-blind study. Journal of Learning Disabilities,
1971, 4, 259-282.
Douglas, V. Stop, look, and listen: the problem of sustained
attention and impulse control in hyperactive and normal
children. Canadian Journal of Behavioral Science, 1972,
4, 259-282.
Douglas, V. Sustained attention and impulse control: Impli
cations for the handicapped child. In Psychology and
the Handicapped Child. Washington, D. C.: Department
of Health, Education, and Welfare, Office of Education, 1974
Epstein, L., Lasagna, L., Conners, C., & Rodriguez, A.
Correlation of dextroamphetamine excretion and drug
response in hyperkinetic children. Journal of Nervous
and Mental Diseases, 1968, 146, 136-146.
Fish, B. The "one child, one drug" myth of stimulants in
hyperkinesis. Archives of General Psychology, 1971, 25,
193-203. -97-
Hakerem, G. Pupillography as a tool in the assessment of
CNS functions and drug effects. In W. L. Smith (Ed.)
Drugs and Cerebral Function. Springfield, Illinois:
C. Thomas, 1970.
Hoffman, S., Engelhardt, D., Margolis, R., Polizos, A., Waizer,
J., & Rosenfeld, R. Response to methylphenidate in
low socioeconomic hyperactive children. Archives of
General Psychiatry, 1974, 30, 354-359.
Knights, R. & Hinton, G. The effects of methylphenidate
(Ritalin) on the motor skills and behavior of children
with learning problems. The Journal of Nervous and
Mental Diseases, 1969, 148, 643-653.
Knopp, W. , Arnold, L., Andras, R., & Smeltzer, D. Predicting
amphetamine response in hyperkinetic children by electronic
pupilography. Pharmakopsychiatry, 1973, 6, 158-166.
Loney, J., Comly, H., & Simon, B. Parental management, self-
concept, and drug response in minimal brain dysfunction.
Journal of Learning Disabilities, 1975, 8, 187-190.
Lytton, G. & Knobel, M. Diagnosis and treatment of behavior
disorders in children. Diseases of the Nervous System,
1958, 20, 1-7.
McConnell, T., Cromwell, R., Bialer, I., & Son, C. Studies
in activity level: VII. Effects of amphetamine drug
administration on the activity level of retarded children.
American Journal of Mental Deficiency, 1964, 68, 647-651.
Millichap, J. & Boldrey, E. Studies in hyperkinetic behavior:
II. Laboratory and clinical evaluations of drug treatments -98-
Neurology, 1967, 17, 467-471.
Pope, L. Motor activity in brain injured children. American
Journal of Orthopsychiatry, 1970, 40, 783.
Porges, S., Walter, G., Korb, R., Sprague, R. The influences
of methylphenidate on heart rate and behavioral measures
of attention in hyperactive children. Child Development,
1975, 46, 727-733.
Rapoport, J., Quinn, P., Bradbard, G., Riddle, D., & Brooks,
E. Imipramine and methylphenidate: treatments of
hyperactive boys. Archives of General Psychiatry, 1974,
30, 789-793.
Rapoport, J., Abramson, A., Alexander, D., & Lott, I. Play
room observations of hyperactive children on medication.
Journal of the American Academy of Child Psychiatry,
1971, 10, 524-534.
Rie, H., Rie, E., Stewart, S., & Ambuel, J. Effects of methyl
phenidate on underachieving children. Journal of Con
sulting and Clinical Psychology, 1976, 44, 250-260.
Routh, D., Schroeder, C., & O'Tuama, L. Development of
activity level in children. Developmental Psychology,
1974, 10, 163-168.
Safer, D., & Allen, R. Stimulant drug treatment of hyperactive
adolescents. Diseases of the Nervous System, 1975, 3,
454-457.
Satterfield, J., Cantwell, D., Lesser, L., & Podosin, R.
Physiological studies of the hyperkinetic child: I.
American Journal of Psychiatry, 1972, 128, 1418-1424. -99-
Satterfield, J., Cantwell, D. , Saul, R., Lesser, L., & Podosin,
R. Response to stimulant drug treatment in hyperactive
children: Prediction from EEG and neurological findings.
Journal of Autism and Childhood Schizophrenia, 1973, 3,
36-48.
Schain, R., & Reynard, C. Observations of effects of a central
stimulant drug (methylphenidate) in children with hyper
active behavior. Pediatrics, 1975, 55, 709-716.
Schleifer, M., Weiss, G., Cohen, N., Elman, M., Cvejic, H.,
& Kruger, E. Hyperactivity in preschoolers and the effect
of methylphenidate. American Journal of Orthopsychiatry,
1975, 45, 38-49.
Shetty, T. Alpha rhythms in the hyperkinetic child. Nature,
1971, 234, 476.
Sroufe, A., Sonies, B., West, W., & Wright, F. Anticipatory
heart rate deceleration and reaction time in children
with and without referral for learning disability.
Child Development, 1973, 44, 267-273.
Steinberg, G., Troshinsky, C., & Steinberg, H. Dextroampheta
mine responsive behavior disorder in school children.
American Journal of Psychiatry, 1971, 128, 174-179. z Weber, B. & Sulzbacher, S. Use of CNS stimulant medication in
averaged electroencephalic audiometry with children with
MBD. Journal of Learning Disabilities, 1975, 8, 300-303.
Weiss, G., Minde, K., Douglas, V., Werry, J., & Sykes, D.
Comparison of the effects of chlorpromazine, dextro
amphetamine, and methylphenidate on the behavior and -100-
intellectual functioning of hyperactive children.
Canadian Medical Association Journal, 1971, 104, 20-25.
Weiss, G., Werry, J., Minde, K., Douglas, V., & Sykes, D.
Studies on the hyperactive child - V. The effects
of dextroamphetamine and chlorpromazine on behavior and
intellectual functioning. Journal of Child Psychology
and Psychiatry, 1968, 9, 145-156.
Werry, J. Some clinical and laboratory studies of psychotropic
drugs in children: an overview. In W. L. Smith (Ed.)
Drugs and Cerebral Function. Springfield, Illinois:
C. Thomas, 1970.
Werry, J. & Aman, M. Methylphenidate and haloperidol in
children. Archives of General Psychiatry, 1975, 32,
790-795.
Werry, J. &, Sprague, R. Methylphenidate in children - effect
of dosage. Australian and New Zealand Journal of
Psychiatry, 1974, 8, 9-19.
Yoss, R. Personal communication, December 18, 1975.
Yoss, R. & Moyers, N. The pupillogram of the hyperkinetic
child and the underachiever. Abstracts for 7th Colloquium
on the Pupil. The Mayo Clinic, Rochester, Minnesota, 1971.
Zahn, T., Abate, F., Little, B., & Wender, P. Minimal brain
dysfunction, stimulant drugs, and autonomic nervous
system activity. Archives of General Psychiatry, 1975,
32, 381-387. -101
APPENDIX B -102-
Abstract
The present paper reviews over 100 studies utilizing over
4,000 hyperactive children in an attempt to determine the effects
of stimulant drug treatment with this population. The results
indicate that, in general, an average of 75 percent of the hyper
active children treated with these drugs improve while 25 percent
remain unchanged or are exacerbated by them. The most frequently
reported side effects are insomnia, loss of appetite, and sup
pressed weight gain, followed in frequency by irritability, abdom
inal pains, and headaches. Most side effects appear to diminish
after a short period of treatment. However, some follow-up studies
suggest that suppressed weight and height gain are likely to remain
throughout the course of treatment with these drugs. These
results also indicate that stimulant drugs appear to have an ener
gizing rather than sedative or paradoxical effect on the central
nervous system of hyperactive children. The primary behavioral or
cognitive impact of the drugs seems to be increased concentration
or attention span, with changes in other variables, such as intel
ligence, achievement skills, and other abilities being an indirect,
occasional result of this effect on attentional processes. Changes
in activity level appear to be less predictable and clearcut,
suggesting that the setting in which the evaluation occurs, the * types of measures used, and the type of activity assessed strongly
influence whether or not changes in activity level are observed.
Despite these short-term findings, results of follow-up studies
lead to the inescapable conclusion that long term adjustment or outcome is not substantially influenced by stimulant drug treatment -103-
The results of this review, taken in their entirety, suggest that the stimulant drugs, by themselves, only serve to facilitate the short-term manageability of hyperactive children while having little impact on later social and psychological adjustment. Clearly, then, these drugs are not a panacea for the treatment of hyperkinesis in children and should be combined with alternative forms of treatment if they are to be used effectively. -104-
A Review of Stimulant Drug Research
with Hyperactive Children
Stimulant drugs have, for some time now, been the drug of
choice for the treatment of hyperkinesis in children. Although
some (Eisenberg, 1966; Fish, 1971) have warned that the stimulants
are not appropriate for all hyperactive children, they are certain
ly the most popular drugs in use with this population (Krager &
Safer, 1975). This is also the case with psychopharmacological
research in hyperkinesis in that the stimulant compounds appear
to be by far the most studied of the drug treatment agents for
hyperkinesis. It would, therefore, seem useful to attempt to bring
this vast body of literature together for the purposes of drawing
conclusions on the effects of stimulant drugs on hyperkinesis.
While others have reviewed various portions of this literature,
(See Cantwell, 1975; Connors, 1970, 1972b; Douglas, 1972; Fish,
1975; Freeman, 1966; Greenspoon & Singer, 1973; Kornetsky, 1970;
Millichap, 1973; Millichap & Fowler, 1967; Sprague & Werry, 1971;
Werry, 1970), the present review differs from most of these in having a greater breadth of coverage, especially of the more recent research, in addition to providing summaries of the research designs of these studies as well. Furthermore, the present study also examines the long-term follow-up effects of these drugs by summarizing the findings of recent studies in this area.
In reviewing this large body of literature, then, this review has two general purposes. First, to present the results of a vast number of research reports on stimulant drugs and hyperkinesis.
And second, to attempt to formulate conclusions and generaliza- -105-
tions regarding a number of specific questions, such as (1) How effective are these drugs in treating hyperkinesis? (2) What side effects are generally found to accompany stimulant drug therapy with hyperactive children? (3) What effects do these drugs have on various biochemical and psychophysiological charac teristics of these children? (4) What effects to the drugs have on the behavior and test performance of hyperactive children?
And (5) what are the results of maintaining hyperactive children on stimulant drugs for a prolonged period of time? These and other questions relating to drug treatment of hyperkinesis will be the focal points of this paper.
Drug Response Rates
A number of studies were found which reported the percentage of hyperactive children responding or not responding to stimulant drug treatment as judged by various social agents, such as parents, teachers, clinicians, etc. The studies and their response rates are listed in Table 1 according to the type of stimulant drug evaluated (amphteamines, methylphenidate, or magnesium pemoline).
Where a study had two different social agents judge the treatment outcome, both sets of response rates are reported. As Table 1 shows, on the average, 74 percent of the hyperkinetic children given amphetamines improved while 26 percent did not change or were exacerbated by the drugs. This compares favorably with the
60 to 75 percent improvement rate reported by Bradley (1950) for the amphetamines. Similar improvement rates are seen for methylpheni- -106-
TABLE 1
Drug Response Rates
Percentage No. of Percentage Unchanged Author(s) Subjects Judge Improved or Worsened Amphetamines
Comly, 1971 40 Teacher 78 22
Connors, 1972a 81 Clinician 96 4
Connors et. al. , 1967 37 Teacher 81 19
Connors et. al. , 1972 27 Clinician 96.3 3.7
22 Teacher 77.3 22.7
Epstein et. al. , 1968 10 Parent 70 30 10 Clinician 70 30
Knopp et. al • i 1973 22 Clinician 64 36 22 Parent 67 33
Rapoport et. al ., 1971 16 Teacher 69 31
Steinberg et . al., 1971 46 Teacher 79 21
Weiss et. al • ) 1968 26 Parent 85 15 Winsberg et. al ., 1972 32 Parent 44 56
Winsberg et. al ., 1974 18 Teacher 78 22
Zrull et. al 1963 91 Clinician 57 43
12 Studies Total-500 15 Judges 74 (Mean) 26 (Mean)
Methylphenidate
Comly, 1971 134 Parent 88 22
Hoffman et. al., 1974 34 Physician 84 16 34 Parent 77 23
Knights &. Hinton, 1969 40 Teacher 88 12
40 Parent 73 27
Knobel, 1962 150 Clinician 90 10
Lytton & Knobel, 1958 20 Clinician 75 25
Rapoport et. al., 1974 27 Psychologist 69 31
• 29 Physician 94 6 Satterfield et. al., 1973 57 Teacher 68 32
Schain et. al., 1975 98 Parents & 79 21 Teachers
Schanckenberg et. al., 1971 10 Parent 60 40
Seger et. al., 1974 29 Parent 86 14 -107 TABLE 1 (Continued) Page 2
Seger et. al., 1974 29 Teacher 90 10
Weiss et. al., 1971 26 Parent 94 6
Werry & Sprague, 1974 37 Physician 51 49
Winsberg et. al., 1974 18 Teacher 61 39
Zimmerman et. al., 1958 54 Clinician 65 35
14 Studies Total- 866 18 Judges 77 (Mean) 33 (Mean)
Magnesium Pemoline
Connors, 1972a 81 Clinician 77 23
Connors et. al. , 1972 26 Clinician 77.2 22.2
22 Teacher 63.6 36.4
2 Studies Total:=105 3 Judges 73 (Mean) 23 (Mean)
Placebo
Connors, 1972a 81 Clinician 30 70
Connors et. al. , 1972 27 Clinician 29.6 80 4
23 Teacher 30.4 69.6
Knights & Hinton, 1969 40 Teacher 67 33
40 Parent 54 46
Rapoport et. al ., 1971 18 Psychologist 38 61
18 Physician 33 66
Schain et. al., 1975 48 Parents & Teachers 8 92
Weiss et. al., 1968 12 Parent 50 50
Weiss et. al., 1971 26 Parent 50 50
Zrull et. al., 1963 84 Clinician 37 63
8 Studies 417 11 Judges 39 (Mean) 61 (Mean) -108
date and magnesium pemoline in that 77 and 73 percent, respectively, of the children taking these drugs improved. Collapsing across
drug type, it can be concluded that an average of 75 percent of the children treated with stimulants improve while 25 percent remain unchanged or are exacerbated by them.
These figures certainly exceed the 39 percent improvement rate observed for placebo treatments. Yet, it is interesting that an average of almost 40 percent of the hyperkinetic children given placebos were perceived to improve. Such a result underscores the conclusion reached by Molitch and Eccles (1937) almost 40 years ago that this rate of improvement from placebo alone necessitates the inclusion of a placebo condition in drug research in this area.
Studies not doing so will be sorely limited in interpreting their results given that other studies have found improvement rates for placebos to range from 8 to 67 percent.
An obvious problem with the data reported in Table 1 is that of defining what is meant by "improvement." This problem has been addressed elsewhere (Barkley, 1976; Loney & Ordona, 1975) and it need only be said here that judges probably disagree to some extent on just what is "improvement" in a drug study (Zrull et. al., 1966).
Thus, it is no longer adequate, as in early studies, for investiga tors to report merely the percentage of various degrees of improve ment observed in response to drugs. Such an approach will not advance our knowledge to any degree on just which behavior(s) change in the hyperactive child (or observer) as a function of drug treatment. It is necessary to objectively measure a variety -109-
of specific individual variables to ascertain how the child is and
is not altered by stimulant drugs. Indeed, a number of studies have already done so and their results will be reported shortly.
However, it is important to keep these positive findings in perspective by first reviewing the side effects or negative aspects which are known to accompany treatment with these drugs.
Stimulant Drug Side Effects
Besides the occasional exacerbation of symptoms observed for some hyperkinetic children given stimulant drugs, other side effects were noted by the early investigators in this area. Some children were observed to be more prone to crying, wearing worried expressions, mildly disturbed sleep, anorexia, nausea, malaise, dizziness, and epigastric distress during stimulant drug therapy.
Additionally, facial palor, coldness of the extremities, and fine hand tremor, as well as temporary weight loss were also noted.
These investigators also reported increased tic-like behavior, such as nail biting, hair pulling, and nose picking (Bradley,
1937, 1950; Molitch & Eccles, 1937). These side effects occurred in less than 15 percent of the children and not all side effects occurred in any one child. Most appeared to dissipate within a matter of a few days to few weeks following thé start of drug treatment.
The side effects observed in these early reports have been borne out by later research on stimulant drugs. The studies which reported side effects and the types of side effects cited are shown in Table 2. The total number of studies finding each -110-
TABLE 2
Stimulant Drug Side Effects 1 1
e ÍSide Effects t i t e n p i p a y P s A t s s i
l l s o s d _ i a e e L a e
. i n n b h s
i w
i
. n c t
a w a s
m a h e
t 0 m _ o w d i g r c _ i o a c d o _ r TJ s e _ r e e b r _ rt n _
I Other I D A H
D W CO
Author(s) L Arnold et. al., X X X 1072
Claghorn et. al., X 1971
Comly, 1971 X X
Connors, 1972a X X Dazed, nail biting, facial tics.
Connors et. al., X X 1963
Connors et. al., X X X X 1972
Epstein et. al., X X X X X X Proneness to crying. 1968
Garfinkel et. al., X X 1975
Greenberg et. al., X X X X X Depression, 1 case of induced 1972 psychosis.
Hoffman et. al., X X X X X 1974
Knights & Hinton, X X X X Bed wetting. 1 case of induced 1969 psychosis. Knobel, 1962 X X X X
Mackay et. al., Euphoria. 1973 McConnell et. al., X X X Excessive clinging. 1964
Millichap & Bol- X X X X drey, 1967
Montagu & Swarbrick X 1975
Rapoport et. al., X X 1971
Rapoport et. al., X X X X X X X Nausea, dizziness, constipation, and 1974 dry mouth.
Schain et. al., X X Lethargy 1975 -Ill-
Table 2 Continued.
0 Side Effects •H P 0 c ft •H ft >> w p ft w •H w 0 rH rH w w 0 t-J •H rt 0 0 W & c X cs w C ctf P rt •H o •H w £ 0 XJ p F rt ifl 0 0 be •H o TJ G O •H XJ rt 0 TJ c 0 0 x> 0 p ctf Author(s) M Q »-( < W Q W Other
Schliefer et. al., X X Increased solitary play. 1975
Schnackenberg et. X X al., 1971
Schnackenberg et. al., 1973 X X X
Seger et. al., 1974 X X
Steinberg et. al. , X X 1971
Weiss et. al., 1971 X X X X X X V Werry & Sprague, X X X X Nausea, and many others — See 1974 article. Number and severity of symptoms increased with dosage.
Winsberg et. al. , X Anxiousness, and 1 case of induced 1972 psychosis.
Winsberg et. al., X X X Dizziness, nightmares, tremor. 1974 X Zimmerman et. al., X ■ 1958
Total:
29 Studies 21 20 11 11 9 7 4 4 3 cases of stimulant-induced psychosis. -112-
side effect is provided at the end of the table. If the number of
studies observing various side effects can be taken as a guage of
their frequency, the most frequently noted ones are insomnia, or
sleep disturbances, and anorexia, or loss of appetite. The next
most frequent are weight loss, irritability, and abdominal pains.
Other side effects of lesser frequency are headaches, drowsiness,
sadness, dizziness, nausea, proneness to crying, euphoria, night
mares, tremor, dry mouth, constipation, lethargy, depression,
dazed appearance, nervous tics, anxiousness, and others. Many
investigators reported these side effects to be temporary and
easily modified by adjusting dosages downward (Werry & Sprague,
1974).
However, one side effect which has not been observed to dissi
pate has been suppressed weight gain. Safer, Allen, & Barr (1972)
reported that d-amphetamine inhibited weight gain significantly more than methylphenidate. Children taken off medication during
the summer months displayed an abnormally high weight gain sugges tive of a "rebound" effect. However, it did not entirely compen sate for the suppressed weight gain experienced over the previous nine months of drug therapy. No tolerance to weight suppression was observed over the two or more years of drug treatment. The results were replicated at a later time using 49 additional hyper active children. The authors concluded that weight and height gain suppression were secondary to the appetite suppressant effects of these drugs and that children on stimulants should be removed from medication during the summer months to permit partial com pensation for these suppressant effects. 113-
Several reports of stimulant induced psychosis were noted
in this review and are deserving of further attention. Three reports occurred during amphetamine treatment (Millichap &
Boldrey, 1967; Ney, 1967; Winsberg et. al., 1972) and one under methylphenidate (Knights & Hinton, 1969). All reports included symptoms of visual and tactile hallucinations with the psychotic episodes subsiding once drug treatment was discontinued.
Needless to say, these side effects strongly argue for caution and conservativeness in the prescribing of these medica tions for hyperactive children. Once prescribed, close monitor ing of the child's drug response over the course of treatment is needed in view of those studies finding some side effects to
"spring up" after prolonged drug treatment (Levy, 1959).
Stimulant Drug Effects
At this point, there have been a sufficient number of studies to indicate that stimulants "improve" the behavior of most hyper active children. Just what behavioral changes occur in the child when given stimulants are not precisely understood. While most investigators agree that attention span is enhanced (Conners, 1972b;
Douglas, 1972; Werry, 1970), data on other variables such as activity level are less conclusive. A review of the research on physiological and behavioral changes in hyperactive children taking stimulants will now be presented. The research to be cited has been set forth in Table 3. The reader is referred to this table for TABLE 3
Stimulant Drug Research with Hyperactive Children
Authors No. of Daily Time1on Use of Double & Year Children Drug Type Dosage Drug1 Placebo Design Type^ Blind
Alexandris & Lundell, 1968 21 amphetamine 7.5 to 75 mg. 6 months Yes Uncrossed Yes
Aman & Sprague, 1974 18 d-amphetamine . 2mg./kg. 75 min. Yes Uncrossed Yes methylphenidate .5-1.0 mg./kg. before testing
Anderson et. al., 1974 18 amphetamines 9 ? No On - Off Drug No methylphenidate Counterbalanced
Arnold et. al., 1973 11 1-amphetamine 5 mg.-30 mg. 3 weeks Yes Crossed Yes d-amphetamine
Bradley, 1937 30 amphetamine 10-30 mg. 1 week No On - Off Drug No
Bradley, 1950 275 amphetamine 10-40 mg. 1 week No On - Off Drug No to several months
Bradley & Bowen, 1940 19 amphetamine 20-30 mg. At least 1 No On - Off Drug No month
Bradley Si Greet, 1940-41 21 amphetamine 10-20 mg. 1-3 hours No On - Off Drug No before testing
Buchsbaum & Wender, 1973 24 amphetamine 10-20 mg. 4-8 mos. No On - Off Drug No Counterbalanced
Burks, 1964 43 amohetamine ? ? No On - Off Drug No
Butter Si Lapierre, 1974 32 methylphenidate 10-30 mg. 2 weeks Yes Crossed Yes
Butter & Lapierre, 1975 32 methylphenidate 10-30 mg. 2 weeks Yes Crossed Yes
Campbell et. al., 1971 22 methylphenidate 10-100 mg. 2 weeks Yes Crossed Yes
Carpenter & Sells, 1974 1 d-amphetamine 2.5-5 mg. 6 days Yes Crossed Yes
Christensen & Sprague, 1973 12 methylphenidate .3 mg./kg. 1.5 hours Yes Uncrossed Yes before - testing 1 1 4
Claghorn et. al., 1971 27 amphetamine 1 5 mg. 1 week Yes Crossed 7 -
Cohen et. al., 1971 22 methylphenidate 10-100 mg. 2 we-.ks Yes Crossed Yes Table 3 Continued. Page 2
Authors No. of Daily Time on Use of Double & Year Children Drug Type Dosage Drug Placebo Design Type Blind
Comly, 1971 48 d-amphetamine 5, 10, & 15 mg. 1 week Yes Crossed Yes
Conners, 1966 32 d-amphetamine Mean: 20 mg. 8 weeks Yes Uncrossed Yes
Conners, 1969 97 d-amphetamine 5-25 mg. 4 weeks Yes Uncrossed Yes
Conners, 1971 69 d-amphetamine < 15 mg. 3 weeks Yes Uncrossed Yes methylphenidate < 30 mg. .
Conners, 1972a 75 d-amphetamine <15 mg. 8 weeks Yes Uncrossed Yes methylphenidate <30 mg.
Conners & Eisenberg, 1963 81 methylphenidate 20-60 mg. 10 days Yes Uncrossed Yes See Also Conners et. al;, 1964
Conners et. al., 1967 52 d-amphetamine 10 mg. 1 month Yes Crossed Yes
Conners & Rothschild, 1968 31 amphetamine 15-25 mg. 1 month Yes Uncrossed Yes
Conners et. al., 1969 42 d-amphetamine 5-25 mg. 4 weeks Yes Uncrossed ?
Conners et. al., 1972 81 d-amphetamine 5-40 mg. 8 weeks Yes Uncrossed Yes magnesium pemo 25-125 mg. line
Conrad et. al., 1971 68 d-amphetamine 10-20 mg. 4-6 mos. Yes Uncrossed Yes
Conrad & Insel, 1967 31 amphetamine o ? No Review of No records and follow-up
Creager & Van Riper, 1967 30 methylphenidate 20 mg. 3 days Yes Crossed Yes
Cutts & Jasper, 1939 12 amphetamine 20 mg. : 6 days No On - Off Drug No
Denhoff et. al., 1971 42 d-amphetamine 10 mg. 3 weeks Yes Crossed Yes
Ellis et. al., 1974 9 methylphenidate .1, .3, 1.0 1 month Yes Crossed Yes mg. / kg.
Epstein et. al., 196S 10 d-amphetamine 10-15 mg. 2 weeks Yes Crossed Yes
Finnerty et. al., 1971 20 d-amphetamine 5-15 mg. 3 weeks Yes Uncrossed Yes -
Garfinkel et. al., 1975 8 methylphenidate 20 mg. 10 days Yes Crossed Yes 1 1 5
Greenberg et. al., 1972 76 d-amphetamine Mean: 25 mg. 8 weeks Yes Uncrossed Yes - Table 3 Continued. Page 3
Authors No. of Daily Time on Use of . Double Si Year Children Drug Type Dosage Drug Placebo Design Type Blind
Huestis et. al., 1975 18 d-amphetamine 5-25 mg. , 3 weeks Yes Crossfed Yes methylphenidate 30-60 mg. •
Hoffman et. al., 1974 31 methylphenidate 20-80 mg. 12 weeks No On - Off Drug No
Knights & Hinton, 1968 40 methylphenidate 20-40 mg. 6 weeks Yes Uncrossed Yes
Knobel, 1962 150 methylphenidate 20-40 mg. 8 months No On - Off Drug No
Knopp et. al., 1973 22 d-amphetamine At least 5 tog. ? No On - Off Drug No
Läufer et. al., 1958 13 amphetamine 5-15 mg. ? No On - Off Drug No Counterbalanced
Levy, 1959 100 amphetamine 10-40 mg. ? No On - Off Drug No
Lindsley & Henry, 1942 13 amphetamine 20 mg. 7 days No On - Off Drug No
Loney et. al., 1975 50 methylphenidate ? ? No On - Off Drug No
Lytton Si Knobel, 1958 20 methylphenidate 15-200 mg. 8-20 weeks No On - Off Drug No
Mackay et. al., 1973 10 methylphenidate 10-60 mg. ? No Case studies No
McC•onnell et. al., 1964 57 d-amphetamine 7.5-15 mg. 6 days Yes Crossed Yes Millichap et. al., 1968 30 methylphenidate .3-2.3 mg./kg. 3 weeks Yes Uncrossed Yes
Millichap Si Boldrey, 1967 13 methylphenidate ? ' 24 hours Yes Uncrossed 9
Molitch St Eccles, 1937 93 amphetamine 10, 20, Si 30 40 dn^s Yes Uncrossed Yes mg.
Montagu Si Swarbrick, 1975 6 1-amphetamine 10 mg. /n>2 1 day Yes Crossed ? d-amphetamine
Porges et. al., 1975 16 methylphenidate .3 mg./kg. 3 weeks Yes Crossed ?
Rapoport et. al., 1970 19 d-amphetamine 10 mg. 2 weeks Yes Crossed ?
Rapoport et. al., 1971 19 d-amphetamine 10 mg. 3 weeks Yes Crossed No Rapoport et. al., 1974a 76 methylphenidate 30 mg. 6 weeks Yes Uncrossed Yes See Also Rapoport et. al.,
Rie et. al., 1976 28 methylphenidate 5-40 mg. 12 weeks Yes Crossed ‘ Yes 1 1
Safer St Allen, 1975 84 d-amphetamine 5-20 mg. years No On - Off Drug No 6 methylphenidate 10-40 mg. Table 3 Continued Page 4
Author No. of Daily Time on Use of Double & Year Children Drug Type Dosage Drug Placebo Design Type Blind
Saletu et. al. , 1973 12 d-amphetamine Mean: 18.6 mg. 4 weeks Yes On - Off Drug ?
Satterfield & Dawson, 1971 24 d-amphetamine 5-10 mg. 1 hour No Uncrossed No methylphenidate 10 mg.
Satterfield et . al., 1973a 57 methylphenidate ? 3 weeks No On - Off Drug Yes See Also Satterfield et. al., 1973b.
Satterfield et . al., 1972 31 methylphenidate ? 90 minutes Yes On - Off Drug Yes
Schain et. al. , 1975 98 methylphenidate 10-60 mg. 16 weeks Yes Uncrossed Yes
Schliefer et. al., 1975 26 methylphenidate 2.5-20 mg. 3 weeks Yes Crossed Yes
Schnackenberg, 1973 11 methylphenidate ? 4 months' No On - Off Drug No
Schnackenberg Sc Bender, 1971 13 methylphenidate 20 mg. 2 weeks Yes Crossed Yes
Seger &, Hallum, 1974 29 methylphenidate 10-60 mg. 8 weeks No On - Off Drug No
Shetty, 1971 28 d-amphetamine 10 mg. 15 min. Yes Crossed Yes methylphenidate 20 mg.
Sprague et. al ., 1970 12 methylphenidate .25-.35 mg./kg. 6 days Yes Crossed Yes
Sprague Sc Slea lor, 1973 23 methylphenidate .1, .3, Sc .7 4 weeks Yes Crossed Yes mg./kg.
Spring et. al. , 1973 39 methylphenidate Mean: 14.5 mg. 1.5 hours No Uncrossed No
Spring et. al. , 1974 38 methylphenidate Mean: 13 mg. 1.25 hours No Uncrossed No
Sroufe et. al. , 1973 21 methylphenidate 1 mg./kg. 6 weeks Yes Uncrossed Yes
Sykes et. al., 1972 23- methylphenidate 10-100 mg. 2 weeks Yes Crossed Yes
Sykes et. al., 1971 40 methylphenidate 30-40 mg. 5-7 weeks Yes Uncrossed Yes
Steinberg et. al., 1971 46 d-amphetamine 10-15 mg. 4 weeks Yes Crossed Yes
Weber Sc Sulzbacher, 1975 12 d-amphetamine .12-,62 mg./kg. 7 Yes Crossed Yes methylphenidate
Weiss et. al.,, 1971 51 methylphenidate up to 50 mg. 4-6 weeks Yes Uncrossed Yes
Weiss et. al.,, 1968 40 d-amphetamine 5-20 mg. 3-5 weeks Yes Uncrossed Yes I Table 3 Continued______Page 5
Author No. of Daily Time on Use of Double & Year Children Drug Type Dosage Drug Placebo Design Type Blind
Werry & Aman., 1975 24 methylphenidate .3 mg./kg. 3 weeks Yes Crossed Yes
Werry & Sprague, 1974 37 methylphenidate .1, .3, 1.0 4 weeks Yes Crossed Yes mg./kg.
Winsberg et. al., 1972 41 d-amphetamine 15-30 mg. 7-10 days Yes Crossed Yes
Winsberg et. al., 1974 18 d-amphetamine 20 mg. 9-10 days Yes Crossed Yes methylphenidate 30 mg.
Zahn et. al. , 1975 42 d-amphetamine ? 2.5 Months No On - Off Drug No methylphenidate
Zimmerman & ] Burgemeister, 108 methylphenidate 20-40 mg. 6 months No On - Off Drug No 1958
Zrull et. al . , 1963 16 d-amphetamine .5 mg. b.i.d 2 weeks Yes Crossed Yes
1Tnis column indicates the total length o f time the child spent on each type of drug, or placebo if one was used, during each of the drug conditions. Where such a time was not reported, the time after oral ingestion or injection of the drug until testing is reported instead.
2 In this column are listed the types of methodological designs employed in each study. On - Off Drug means a design m which all children received the drug and were evaluated both on and off the drug. Where "counterbalanced” follows this design, it indicates that approximately half of the children were evaluated off-drug first while the other half were evaluated on-drug first. Uncrossed means a design in which children were assigned to either a drug or placebo group, or to a drug or no drug group if no placebo was used. Crossed means a complete crossover design in which each subject served as his own control, receiving all of the possible drug and placebo conditions in a randomized order. The other designs indicated are self-explanatory.
00 119- more specific information on the studies to be mentioned. The
results of these studies are presented under the general types of
dependent measures which have been utilized. These are: (1) bio
chemical, (2) psychophysiological, (3) behavior rating scales, and
(4) objective psychological tests and measures. A number of these
studies attempted to examine predictors of drug responding in hyper
active children. These have been reviewed elsewhere (Barkley,
1976) and little attention will be given to those findings in this
paper.
In reviewing these studies, it is necessary to remember that
some are less methodologically rigorous than others thereby limit
ing the comparison of their results. A well controlled drug study
should conform to the guidelines set forth by Sprague & Werry (1971)
although the majority of those reviewed in this paper do not.
Where the results of several studies on a particular variable are
equivocal, they are interpreted in favor of the studies having the
greater methodological control.
Biochemical Effects.
Rapoport et. al. (1974b) studied changes in plasma dopamine-
beta-hydroxylase (DBH) levels in hyperkinetic children in response
to methylphenidate administration. Results revealed that methyl
phenidate significantly increased DBH levels but that this did not
correlate with changes in behavior ratings of hyperactivity or
conduct problems. The lack of association between DBH levels and
activity ratings does not mean such a relationship may not exist but perhaps means that the ratings are too insensitive to the subtle
variations in activity level that may be occurring with changes in -120- DBH levels. In any event, biochemical studies of this type are
encouraged as a means of revealing a possible biochemical basis
for hyperkinesis in some children. Currently, this area is receiving
considerable attention in animal research which may hopefully shed
more light on the mechanisms involved in stimulant drug action in
children.
In other studies, Knights and Hinton (1969) found no change in
urine ph values as a result of 6 weeks of stimulant drug treatment.
Rapoport et. al. (1974a) did not find any changes in liver func
tioning due to methylphenidate nor were changes in blood count
noted to occur. Similarly, Bradley (1950) also failed to find
changes in blood count during treatment with amphetamines. Certain
ly, more biochemical studies are needed before any conclusive statements can be made about the physiological effects of stimulant drugs on hyperactive children.
Psychophysiological Effects.
Several studies have examined various measures of psychophysio logical functioning in hyperactive children for changes due to stimulant drug manipulations. These will now be examined.
Two studies were found which measured changes in respiration during drug and no-drug periods and neither found an effect for stimulants on this variable (Epstein et. al., 1968; Zahn et. al.,
1975). As for skin temperature, only one report monitored this variable with significant decreases being observed during drug treatment (Zahn et. al., 1975). Several studies reported trends for pulse and/or blood pressure to increase during drug therapy
(Arnold et. al., 1972; Epstein et. al., 1966; Knights & Hinton, 1969;
Rapoport et. al., 1974a; Rie et. al., 1976) although several other investigators have failed to find such results (Bradley, 1950; 121-
Conners et. al., 1972).
As for heart rate, while Rapoport et. al. (1974a) did not
find methylphenidate to change the electrocardiograms of hyper
active children, changes in heart rate have been frequently reported
in the literature as a result of stimulant drug treatment (Cohen et. al., 1971; Knights & Hinton, 1969; Porges et. al., 1975;
Zahn et. al., 1975). While this suggests an energizing effect on the autonomic nervous system of hyperactive children, the effect may actually be occurring directly on the cardiovascular system itself. In addition to these findings, Porges et. al. (1975) reported a significant reduction in heart rate variability due to methylphenidate while Sroufe et. al. (1973) and Zahn et. al.
(1975) observed the stimulants to significantly change heart rate deceleration during a reaction time task. Heart rate deceleration has been considered to be a psychophysiological correlate of attentional processes (Sroufe et. al., 1973) suggesting that the stimulants are, indeed, altering these processes in hyperactive children — a conclusion strongly supported by studies using psychological measures of attention span as well (Douglas, 1972).
Turning to measures of electrodermal parameters, several studies using measures of basal skin conductance have found them to be significantly increased by stimulant drugs (Cohen et. al.,
1971; Satterfield & Dawson, 1971; Zahn et. al., 1975). Spring et. al. (1974), however, did not find such an increase while
Montagu & Swarbrick (1975) actually found a significant decrease in palmar skin admittance in hyperactive children on amphetamines.
This is contrary to the significant increases noted above and -122-
indicate that some hyperactive children respond paradoxically to the
stimulant compounds. Yet, it is possible that such findings for
skin conductance have been confounded by peripheral changes in
skin temperature (Zahn et. al., 1975) thereby questioning whether
such results reflect paradoxical changes in central processes.
In any event, further study of this phenomenon is in order.
Other parameters of skin conductance to be studied include
nonspecific and specific skin conductance responses. The findings
to date seem equivocal as to the effects of stimulant drugs on these variables. Satterfield & Dawson (1971) found significantly more nonspecific GSRs (galvanic skin responses) in hyperactive children on stimulants as compared to those not receiving drugs.
Spring et. al. (1974) found a similar tendency in their results while Cohen et. al. (1971) and Zahn et. al. (1975) did not. How ever, Zahn et. al. (1975) did find the stimulants to significantly decrease the amplitude of nonspecific GSRs in hyperactive children.
Both Spring et. al. (1972) and Zahn et. al. (1975) also found the stimulants to significantly increase the amplitude of specific, or evoked, skin conductance responses while Zahn et. al. (1975) also observed significant increases in the latency and rise rate of these skin conductance responses. These findings suggest that the stimulants energize or increase the arousal levels of hyper kinetic children. Although some studies did not observe such changes, none found a sedative action for the stimulants.
Another variable which has been studied for drug effects in hyperactive children has been the electroencephalogram (EEG).
Cutts and Jasper (1939) did not find benzedrine to have any effect on the alpha activity in the EEG of hyperactive children. However,
Lindsley and Henry (1942) later reported that benzedrine signifi -123-
cantly increased alpha frequency in the parietal and occipital areas
with significant decreases in amplitude of both alpha rhythms and
two abnormal EEG patterns. Shetty (1971) also observed significant
increases in EEG alpha wave activity following stimulant drug
administration. These findings suggest that the stimulants are
increasing the cortical inhibitory mechanisms of the central nervous
system and probably result in a filtering out of the impact of
irrelevant stimuli (Shetty, 1971). Stimulants have also been noted
under some circumstances to reduce the abnormality of EEG patterns
in hyperactive children (Mackay et. al., 1973) but this finding
requires more controlled investigation.
Another aspect of the EEG to be examined for drug effects has been the averaged evoked response (AER). Buchsbaum and Wender (1973)
found differences in AER responses to drugs between hyperactives defined as drug responders and those found to be nonresponders.
Responders had increased AER latencies and decreased AER slopes due to drug treatment thus "normalizing" their AER patterns. The nonresponders, however, showed just the opposite AER pattern while on drugs suggesting an exacerbation of their already abnormal pat terns. Thus, AERs in responders were reduced by stimulant drugs while those in nonresponders were augmented. Similar results were reported by Saletu et. al. (1973) and Satterfield et. al. (1972) indicating, again, that perhaps the stimulants arouse CNS inhibitory systems to screen out irrelevant sensory input to the cortex.
The results of a study by Weber & Sulzbacher (1975), however, seem difficult at first to reconcile with this conclusion. These -124- invest igators found the stimulant drugs to lower the thresholds
of AERs, thereby suggesting a sensitizing or augmenting effect on
auditory AERs. This would indicate an increase in the excitatory
systems of the central nervous system responsible for auditory AERs.
Yet, these results are not so difficult to comprehend in that the ( stimulants are quite likely increasing the level of functioning of both excitatory and inhibitory systems. This is, however, a matter of speculation at the moment.
Several studies have examined the influence of stimulants on the electropuplllograms (EPGs) of hyperkinetic children (Knopp et. al., 1973; Yoss, 1975; Yoss & Moyer, 1971). The most elaborate of these was conducted by Knopp et. al. (1973) who measured the changes in dark adapted pupil diameter in response to light in hyperactive children both before and after stimulant drug adminis tration. Changes in EPG from baseline to on-drug phases were found to correlate significantly with parental and clinician's ratings of improvement. These children were able to be subcate gorized into five distinct groups based upon their baseline EPG patterns and response to drugs. Thus, Knopp et. al. (1973) find hyperactive children to be heterogeneous in their EPG responses both on and off stimulant drugs. Additionally, they appear to have found a promising way of categorizing hyperactive children into more homogeneous subgroups and are thereby better able to predict their response to stimulant drugs. Similar results have been reported by Yoss (1975) who finds many of the children to be underaroused in EPG responses with the stimulants serving to increase these levels of EPG arousal. -125-
On a quite different type of measure, Laufer, Denhoff, and
Solomons (1957) studied changes in the photo-metrazol thresholds
of hyperactive children receiving stimulant drugs. This technique
involves the measurement of the number of milligrams of Metrazol per kilogram of body weight needed to evoke a specified type of
clinical and EEG response to a flickering stroboscope light.
These investigators found that hyperactive children have photo-metra- zol thresholds which are significantly lower than normal children and that stimulants serve to increase the thresholds up to that characteristic of normal children. They concluded that amphetamines may, in some way, be raising the level of diencephalic inhibition of the cortex thus preventing the cortex from being bombarded by a stream of impulses from irrelevant stimuli. Unfortunately, these results must be viewed with skepticism as they have yet to be replicated and little or no attention has been paid to the issue in the recent literature.
In summarizing the results for psychophysiological research with stimulant drugs and hyperkinesis, the following conclusion seems warranted: In most cases, hyperkinetic children are stimu lated or energized in CNS reactivity by the stimulant drugs, rather than being sedated. Relatively few studies have documented any "paradoxical" or sedative action on CNS activity in hyper active children. Interestingly, these results also suggest that
CNS inhibitory systems may be stimulated to a great extent by these drugs thereby enhancing the ability of the cortex to screen out distracting stimuli. Excitatory systems may also be increased in level of functioning by these drugs and thus augment the effect of stimuli upon which the child is concentrating. As a result, the hyperactive child is better able to focus attention upon the -126- relevant aspects of a situation while screening out unimportant
considerations.
Behavioral Rating Scales.
By far, the vast majority of drug research with hyperactive children has utilized some type of rating scale completed by parents, teachers, clinicians, nurses, ward attendants, etc.
Virtually all of this research has found such ratings to be sensitive to stimulant drug manipulations. This research will now be reviewed under the type of rater used in judging the child's response to stimulant drugs -— that is, parents, teachers, and other social agents.
Parental Rating Scales. Two of the most frequently used rating scales for parents are the Conners Parent Symptom Question naire (Conners et. al., 1969) and the Werry-Weiss-Peters Activity
Rating Scale (Werry, 1968). Research on the 96 item Parent Symptom
Questionnaire indicates that two factors account for most of the variance in the parental ratings of hyperactive children and these are hyperkinetic and neurotic symptoms (Conners et. al., 1969).
Conners et. al. (1969) found a significant reduction in ratings of hyperkinetic symptoms in response to stimulant drug treatment as have other reports (Arnold et. al., 1972; Conners et. al., 1972;
Hoffman et. al., 1974; Rapoport et. al., 1974). Several, however, have not (Finnerty et. al., 1971; Werry & Sprague, 1974).
All of the research conducted on the Werry-Weiss-Peters
Activity Rating Scale to date have found significant improvement in scores due to stimulant drug treatment (Conners & Rothschild,
1968; Conners et. al., 1969; Hoffman et. al., 1974; Knights &
Hinton, 1969; Rapoport et. al., 1971; Schleifer et. al., 1975; -127-
Weiss et. al., 1971; Zahn et. al., 1975). Thus, the scale appears
to be sensitive to changes in parental opinions of hyperactive chil
dren receiving stimulant drugs.
A less frequently used scale has been the Davids Rating Scale
of Hyperkinesis (Davids, 1971) which has also proven sensitive
to stimulant drug effects in hyperactive children (Huestis et. al.,
1975). Other studies have also found parental opinion to be
significantly altered by stimulant drug treatment of their hyper
active children (Greenberg et. al., 1972; Knopp et. al., 1973;
Rie et. al., 1976). However, one scale, the Peterson-Quay Symptom
Checklist, has not proven to be particularly sensitive to stimulant drug manipulations when used with parents (Knights & Hinton, 1969;
Millichap et. al., 1968).
These findings suggest that parents are attuned to changes in their children's behavior during stimulant drug treatment. A question to be raised later is whether or riot the parental ratings are accurately reflecting actual changes in the child's behavior and precisely what are those changes.
Teacher Rating Scales. A similar state of affairs exists for rating scales completed by teachers in drug studies. The most frequently used scale for teachers appears to be the Conners'
Teacher Rating Scale (Conners, 1969), composed of five factors for which separate scores can be determined. These are: (1) aggres siveness, (2) inattentiveness, (3) anxiety, (4) hyperactivity, and
(5) sociability. While Conners has reported in some instances that all five factors are sensitive to stimulant drug treatment
(Conners et. al., 1967; Conners & Rothschild, 1968; Conners, 1969), 128-
the most reliable factor to be observed to improve has been the
hyperactivity scale, while the other factors are less consistently
altered by these drugs (Arnold et. al., 1972; Conners, 1972a;
Conners et. al., 1972; Huestis et. al., 1975; Garfinkel et. al.,
1975; Rapoport et. al., 1971, 1974; Safer & Allen, 1975; Werry &
Sprague, 1974; Winsberg et. al., 1974).
Some research suggests that the hyperactivity factor, although
believed to assess activity level, is probably assessing attentional
processes instead. Schleifer et. al. (1975) found stimulant drug
effects only on the hyperactivity factor of the scale and found
this factor to correlate significantly only with the measure of
number of toy changes made in a free play situation — not with
measures of open field activity level. Thus, what has been labeled
as a hyperactivity factor may actually be regarded by teachers in
their behavioral ratings as items assessing attention span. While
this may explain why the hyperactivity factor is the most frequently
changed scale of this inventory, it still does not explain what the
inattentiveness and other factors are measuring.
A less frequently used scale with teachers has been the already mentioned Davids Rating Scale of Hyperkinesis which has been found to be sensitive to changes during drug treatment (Denhoff et. al.,
1971; Hoffman et. al., 1975; Schnackenberg, 1973). Comly (1971) reports finding significant improvement in the Fels Rating Scale of
Classroom Behavior and Adjustment during drug treatment with similar results being reported by other investigators using other scales
(Greenberg et. al., 1972; Lindsley & Henry, 1942; Rie et. al., 1976;
Satterfield et. al., 1972). However, as with the findings for -129-
parental ratings, the Peterson-Quay Behavior Checklist as completed
by teachers has not revealed significant drug changes over those
noted on the scale during placebo conditions (Knights & Hinton, 1969).
Rating Scales for Other Agents. A number of research reports
have used rating scales completed by clinicians, ward attendants,
nurses, etc. In general, these studies have found such ratings
to improve significantly during drug manipulations, especially if
the scales appear to be assessing activity level, inattentiveness,
or aggressiveness (Alexandris & Lundell, 1968; Burks, 1964; Clag-
horn et. al., 1971; Conrad et. al., 1971; Greenberg et. al., 1972;
Weiss et. al., 1971).
Problems with Rating Scales. Although the rating scale has
been the most frequently used measure in drug research with hyper
active children, there are serious problems which exist with this measure that cannot go overlooked. First of all, there are simply
too many rating scales in use with little regard being given to their construction and how they relate to others already in use.
Second, there is little or no information available on most scales as to their reliability, either test-retest or inter-rater. But the third and most serious issue involves their validity. That is, do the scales actually measure what they purport to measure.
Most of these scales are said to assess activity level, attention span, or aggression and they are interpreted as if they did so.
Yet, for most of them, there is virtually no information on the relationship of the scale to more objective measures of the same construct. For instance, as already mentioned, one factor of the Conners Teachers Rating Scale has been said to assess hyper- -130-
activity yet it has failed to correlate significantly with more
objective measures of activity level. Instead, it seems to cor
relate with playroom measures of attention span (Rapoport et. al.,
1971). Similarly, the Werry-Weiss-Peters Activity Rating Scale
has been said to measure activity level yet it too does not correlate
significantly with objective measures of this construct (Barkley &
Ullman, 1975; Routh, Schroeder, & O'Tuama, 1974). While it is possible that this simply means that playroom measures of activity do not relate to activity in the home or classroom, another inter pretation is conceivable. It is equally as plausible to assume that these scales are not measuring what they claim to measure.
That is, parents or teachers may actually be assessing the child's attention span or concentration rather than activity level in com pleting these rating scales.
Considering these difficulties, future studies should use more objective measures of the constructs under study than just rating scales alone. It has been known for some time that drug therapy with hyperactive children results in an improvement in parental or teacher opinions of those children. The more impor tant question is which aspects of the child's behavior are changing in response to drug treatment. More attention and effort, therefore, need to be given to the use of objective measures of behavior change in drug research with hyperactive children.
Some research has already done so and the findings of these reports will now be discussed.
Objective Psychological Tests and Measures.
A number of tests and measures have been used to assess a -131-
variety of behavioral and psychological constructs in drug research
with hyperactive children. The results for these studies are
discussed under the particular type of construct evaluated. These
are: (1) intelligence tests, (2) achievement tests, (3) tests and
measures of attention span, (4) measures of drawing and copying
ability, (5) measures of activity level, and (6) other tests and
measures.
Intelligence Tests. Studies attempting to examine the effects
of stimulant drugs on the intelligence test scores of hyperactive
children have generally found equivocal results. The test most
frequently used has been the Wechsler Intelligence Scale for
Children (WISC). This permitted many studies to analyze the effects
of drugs on various subtest scores in addition to verbal, perfor mance, and full scale IQs. Several studies have found significant
improvement in full scale IQ (Conners, 1972a; Hoffman et. al., 1974;
Weiss et. al., 1971), while others have found changes in either
verbal (Epstein et. al., 1968; Conners, 1972a; Weiss et. al., 1968;
Weiss et. al., 1971) or performance IQs (Epstein et. al., 1968;
Finnerty et. al., 1971; Greenberg et. al., 1972; Hoffman et. al.,
1974; Knights & Hinton, 1969). In some instances, only one or a
limited number of subtest scores were affected by the drugs (Conners,
1972a; Conrad et. al., 1971; Seger & Hallum, 1974; Weiss et. al.,
1968; Weiss et. al., 1971). However, others have found no signifi cant changes in WISC IQ for hyperactive children on stimulant drugs
(Alexandris & Lundell, 1968; Conners & Rothschild, 1968; Conners et. al., 1969; Conners et. al., 1972; Conrad et. al., 1971; Rapo port et. al., 1974; Rie et. al., 1976; Werry & Sprague, 1974).
Similarly, some investigators have found no significant drug effects -132-
on other tests of intelligence, such as the Stanford-Binet, with
hyperactive children (Bradley & Green, 1940; Molitch & Eccles,
1937; Weiss et. al., 1968).
Given the inconsistency of findings in this area, it is likely
that these changes in IQ or subtest scores probably do not reflect
significant changes in basic intellectual or cognitive skills.
Instead, it seems that they are due to a significant improvement
in the concentration or attention span of the hyperactive child
(Conners, 1972b; Douglas, 1972; Weiss et. al. , 1971).
Achievement Tests. The most frequently used test of achieve
ment skills in this area is the Wide Range Achievement Test (WRAT).
Several investigators report finding significant improvement in
one or more of the WRAT subtests (Conners et. al., 1969; Conners
et. al., 1972) although most have not (Conners, 1972a; Conrad et.
al., 1971; Finnerty et. al., 1971; Hoffman et. al . , 1974; Rapoport
et. al., 1974). Regarding less frequently used tests, Weiss et.
al. (1971) found significant improvement on the oral reading part
of the Durrell Test. Werry & Sprague (1974) did not find any
drug effects on the Burt Reading Test nor did Conners et. al.
(1969) on the Gray Oral Reading Test, although in a later report
(Conners et. al., 1972) such improvement was found to reach signi
ficance. In a recent study of stimulant drug effects on the achievement scores of hyperactive children, Rie et. al. (1976) found significant improvement only on the word analysis subtest of the Iowa Test of Basic Skills.
As with the findings for intelligence tests, these equivocal results for achievement tests also suggest that the few reports of positive findings are due to increased concentration or atten -133-
tion span in response to stimulant drug treatment (Weiss et. al.,
1971).
Measures of Attention Span. A number of various tests and
measures have been employed to assess attention span in drug research
with hyperactive children. These have included reaction time,
continuous performance tests, the Porteus Mazes, Kagan's Matching
Familiar Figures Test, and such playroom measures as the number
of toy changes made by a child during free play. While it is obvious
that these tests measure a number of other variables besides atten tion span, some research (Douglas, 1972) suggests that they have a common source of variance which can be labeled as concentration or the ability to inhibit impulsive responding. For ease and brevity, then, these tests will be reviewed with respect to this attentional component. In examining the results of this research, it must be concluded that the greatest influence of the stimulant drugs on hyperactive children is increased concentration, or attention span, and decreased impulsiveness in responding (Conners,
1972b; Douglas, 1972).
If reaction time is considered as a measure of attention span, the above conclusion is supported by the fact that virtually every study which has employed a measure of reaction time has found the time to be significantly decreased, or improved, by the stimulant drugs (Cohen et. al., 1971; Conners et. al., 1967;
Conners & Rothschild, 1968; Sprague et. al., 1970; Spring et. al.,
1973; Sroufe et. al., 1973; Sykes et. al., 1972; Zahn et. al., 1975) or find trends in that direction (Porges et. al., 1975). Only
Bradley and Bowen (1940) found no significant changes in reaction time while Campbell et. al. (1971) observed reaction times to -134-
significantly increase, or become slower, while the children were
on stimulants.
Another type of test believed to measure attention span is
the continuous performance or vigilance test (See Anderson et. al.,
1974). Most studies using this type of task have observed signi
ficant reductions in error scores as a function of stimulant drug
treatment (Anderson et. al., 1974; Conners, 1966, 1972a; Conners
& Rothschild, 1968; Sykes et. al., 1972; Sykes et. al., 1971;
Weiss et. al., 1971; Werry & Aman, 1975). Only a few studies have
not found such improvement (Conners et. al., 1972; Sprague &
Sleator, 1973). In a recognition task similar to the continuous performance task, both Werry and Aman (1975) and Sprague et. al.
(1970) found stimulant drugs to significantly improve scores for correct responding.
Performance on the Porteus Mazes has also been considered as a measure of attention span (Douglas, 1972), as well as of the ability to plan, reason, and control impulsive responding (Conners
& Rothschild, 1968). Almost every study using this test found it to be sensitive to stimulant drug effects (Conners, 1972a;
Conners & Eisenberg, 1963; Conners & Rothschild, 1968; Conners et. al., 1969; Conners et. al., 1972; Epstein et. al., 1968; Greenberg et. al., 1972; Hoffman et. al., 1974; Rapoport et. al., 1974).
Only one study did not (Winsberg et. al., 1972).
Using a maze coordination test, Knights and Hinton (1969) and Garfinkel et. al. (1975) found that stimulant drugs did not significantly reduce the number of contacts made with the sides of the maze but did significantly reduce the time spent in contact with the sides. This has been interpreted (Sroufe et. al., 1973) -135-
as reflecting improvement in concentration rather than in motor
coordination in response to drug treatment.
Other tests believed to assess attention span are the Kagan
Matching Familiar Figures Test (Douglas, 1972) and the Early
Childhood Familiar Figures Test (Schleifer et. al., 1975). Scores
on both tests have been found to improve significantly after
stimulant drug administration (Campbell et. al., 1971; Garfinkel
et. al., 1975; Rapoport et. al., 1974; Schleifer et. al., 1975).
Besides these measures of attention span, others (Barkley &
Routh, 1974; Barkley & Ullman, 1975) have used the number of toy
changes made by a child during free play as a measure of attention
span. Rapoport et. al. (1971) reported significant reductions in
toy change activity following stimulant drug treatment in hyper
active children. Similarly, on a measure of attention to classroom
tasks, Sprague et. al. (1970) also found improvement resulting
from stimulant drugs.
In summarizing this section, it is apparent that these results add strong empirical support to the conclusions reached by others
(Conners, 1972b; Werry, 1970) that the major influence of the stimulant drugs on hyperactive children is improved attention span or the ability to "stop, look, and listen" (Douglas, 1972).
While the tests reviewed above assess a number of different abilities, they appear to have in common the fact that each is strongly influenced by the child's ability to concentrate on the task and to inhibit impulsive responding. It is improvement in these abili ties by the stimulant drugs that probably accounts for the equi vocal findings on other tests, such as those of intelligence or achievement skills. Hence, improved test performance is likely -136-
to occur in some situations using some tests while not in others
using different tests depending upon the extent to which the setting
and test are sensitive to changes in attentional processes.
Tests of Drawing or Copying Ability. In drug research with
hyperactive children, a wide variety of drawing and copying tests
have been utilized. In general, these tests are not typically I affected by the stimulant drugs. The most frequently used of these
tests are the Bender-Gestalt Visual Motor Test and the Goodenough-
Harris Draw-A-Man Test.
For the Bender-Gestalt, most studies, especially the more
rigorously controlled ones, do not find this test to be improved
by stimulant drugs (Alexandris & Lundell, 1968; Conners & Roth
schild, 1968; Conners et. al., 1969; Conners et. al., 1972; Conrad
et. al., 1971; Epstein et. al., 1968; Garfinkel et. al., 1975;
Greenberg et. al., 1972; Knights & Hinton, 1969; Rapoport et. al.,
2974; Rie et. al., 1976; Schnackenberg & Bender, 1971; Weiss et.
al., 1968; Weiss et. al., 1971; Winsberg et. al., 1971). Only
a relatively few studies of a less well controlled nature found
improvement in test scores by hyperactive children receiving
stimulant drugs (Conners, 1972a; Millichap et. al., 1968; Seger
& Hallum, 1974).
Similarly, only a few studies have found improved performance by hyperactive children on the Goodenough-Harris Draw-A-Man Test
during stimulant drug treatment (Conners, 1971, 1972a; Millichap
et. al., 1968) while most have not (Alexandris & Lundell, 1968;
Conners & Rothschild, 1968; Conners et. al., 1969; Conners et. al.,
1972; Rapoport et. al., 1974; Schnackenberg et. al., 1971; Weiss
et. al., 1968; Weiss et. al., 1971). 137-
Additionally, Schleifer et. al. (1975) did not find any signi
ficant drug effects on a draw-a-line test nor did Schnackenberg
& Bender (1971) on the Benton Visual Retention Test. Thus, once
again, where a few positive effects of stimulant drugs on drawing
tests have been found, they are probably due to improved concen
tration or attention span rather than to changes in other cognitive
or intellectual abilities (Conners, 1971).
Measures of Activity Level. The results of drug studies using
rating scales of activity level with hyperactive children strongly suggest that the major impact of these drugs is the reduction of
activity level across all situations. As will be seen below, the results of studies using more objective measures of activity level have revealed a far more complex picture. It seems that drug effects on activity level are due to several possible factors:
(1) the situation in which the measures are taken (free play or structured situations), (2) the type of activity measured (wrist, ankle, full body, torso, or locmotor), and (3) the type of instru ment used to assess that type of activity (i.e. actometers, pedo meters, ultrasonic generators, grid-marked playrooms, etc.).
One measure frequently used to assess activity level in structured situations is the stabilimetric cushion. This device yields a score for seat movements made by the child while completing a given task. All of the studies which have used the device reported significant reductions in seat movement activity during stimulant drug treatment (Christensen & Sprague, 1973; Sprague et. al., 1970; Sprague & Sleator, 1973; Sroufe et. al., 1973; Werry
& Aman, 1975). However, in a study in which hyperactive children were required to sit in a ballistograph chair (McConnell et. al., -138-
1964), no drug effects on ballistograph activity were observed.
Millichap et. al. (1968) used the actometer to measure the
activity of the dominant hand or arm of hyperactive children.
This device is a modified self-winding wrist watch which measures motion in the plane parallel to the face of the watch. Although the reliability of the device has been questioned (Johnson, 1971),
Millichap et. al. (1968) did observe a trend for reduced wrist activity during stimulant drug conditions. This was probably due to the fact that the measure was taken while the child was perform ing a number of tests. Since some dominant wrist activity would be needed to perform these tasks, it is not likely that the drugs would have resulted in the complete reduction of this relevant type of activity. Thus, in structured situations, significant reductions in irrelevant activity, such as seat movements, appear to occur in response to drug treatment while more task-relevant activity, such as dominant wrist movement, only tends to do so.
In free play activity where no demands are placed on the child to channel his activity in any direction, the results are much less clearcut. Montagu and Swarbrick (1975) used the ultra sonic generator to measure full body movement during free play and observed significant reductions in this type of activity.
However, using a similar device, Claghorn et. al. (1971) did not.
Montagu and Swarbrick (1975) also used electric pressure floor mats to measure locomotor activity in free play and found a signi ficant reduction in this measure during the drug conditions.
Another measure of locomotor activity involves dividing a play room floor up into several parts using tape or electric eye beams and then counting the number of grid-lines the child crosses during a certain period of time. Here, too, significant reductions -139-
in scores have been found in response to drug treatment (Rapoport
et. al., 1971).
Millichap and Boldrey (1967) measured dominant wrist activity
using the actometer over a 24 hour period and observed significant
decreases in this activity score as a function of stimulant drug
treatment. While Rie et. al. (1976) do not indicate the type of
setting in which their measures were taken, they too found signi
ficant reductions in wrist, as well as ankle, activity scores
using the actometer. Rapoport et. al. (1971) placed actometers
on the backs of hyperactive children in free play and found a trend
(p<.10) for this type of torso activity to be reduced during drug
treatment. To complicate the picture still further, Ellis et.
al. (1974) derived nine measures of free play activity from video
taped play sessions of hyperactive children and found none of
these to be significantly influenced by stimulant drugs. They
concluded that in informal settings, stimulant drugs are not
likely to alter the activity level of hyperactive children.
These results for free play activity suggest that wrist and
ankle, or locomotor, activity may be significantly reduced by
stimulant drugs while changes in total body activity, such as
that measured by the ultrasonic generator or by torso actometers,
are less predictable. Additionally, under some circumstances,
different measures of free play activity, such as those used by
Ellis et. al. (1974) may not show alterations during drug therapy.
In general then it appears that stimulant drugs are most
likely to reduce irrelevant activity during structured situations while having less of an impact on goal-directed, relevant activity.
In free play, however, some types of activity, such as wrist or -140-
ankle movement, may be reduced by the drugs while changes in other
types, such as torso movement, may not. It is possible, as
Werry (1970) has suggested, that if total activity level could
be assessed, increases in such activity due to stimulant drugs
might be observed. This is, however, a matter of speculation at
the moment.
Two studies have observed the classroom activity of hyperactive
children during drug treatments (Schleifer et. al., 1975; Sprague
et. al., 1970). Neither found stimulant drugs to significantly
reduce activity as measured by the number of times the child got up from his seat. Schleifer et. al. (1975) also found no reduction
in the number of times the child was away from his desk during drug treatment. Thus, in this type of situation, which is probably a mixture of both free play and structured settings, changes in some forms of activity do not occur in response to drug treatment.
In summarizing these results, it seems that in comparison to measures of attention span, changes in activity level in response to stimulant drugs are less predictable. Such changes appear to depend to a great extent on a number of factors, such as type of setting, type of activity being measured, and type of measuring instrument being used.
Other Tests and Measures. Research on stimulant drug effects with hyperactive children has also utilized numerous other tests and measures. Improved test performance has been observed during drug treatment on tests of quickness and decisiveness (Conners et. al., 1967), paired associate learning (Conners, 1972a; Conners &
Eisenberg, 1963; Conners & Rothschild, 1968; Conners et. al., 1969), and measures of verbal productivity (Conners, 1972a; Creager & Van -141-
Riper, 1967).
A number of tests showed equivocal results during drug treat ment with the stimulants. These were: the Frostig Test of Visual
Perception (Conners, 1972a; Conners et. al., 1969; Conners et. al.
1972; Conners & Rothschild, 1968; Conrad et. al., 1971; Garfinkel et. al., 1975; Hoffman et. al., 1974; Millichap et. al., 1968;
Weiss et. al., 1971), the Lincoln-Oseretsky Test of Motor Develop ment (Conners et. al., 1972; Weiss et. al., 1968; Weiss et. al.,
1971), tests of visual or auditory perception and discrimination
(Butter & Lapierre, 1974, 1975; Conners, 1972a; Conners et. al.,
1969; Millichap et. al., 1968; Weiss et. al., 1971), tests of short-term memory (Carpenter & Sells, 1974; Conners & Rothschild,
1968; Sprague & Sleator, 1973; Werry & Aman, 1975), the Illinois
Test of Psycholinguistic Ability (Butter & Lapierre, 1974, 1975;
Rie et. al., 1976; Weiss et. al., 1971; Conners et. al., 1972), the Reitan holes test of steadiness (Garfinkel et. al., 1975;
Knights & Hinton, 1969), and embedded figures types of tests
(Campbell et. al., 1971; Conners, 1972a; Conners et. al., 1967;
Schleifer et. al., 1975; Winsberg et. al., 1972).
Negative findings in drug research with hyperactive children have been reported for the following tests and measures: tests of left-right orientation (Conrad et. al., 1971; Weiss et. al., 1971), anxiety (Conners & Eisenberg, 1963), motor inhibition (Bradley &
Green, 1940; Conners, 1966; Conners et. al., 1969; Conners &
Rothschild, 1968; Conners et. al., 1972; Hoffman et. al., 1974), body boundaries tests (Hoffman et. al., 1974), tapping speed and accuracy (Bradley & Green, 1940), repeating a motor pattern and -142-
pegboard tests (Knights & Hinton, 1969; Winsberg et. al., 1972),
behavioral measures of aggression (Schleifer et. al., 1975), the
Witkin Rod and Frame Test (Zhan et. al., 1975), and the Leiter « International Performance Scale (Carpenter & Sells, 1974).
As noted earlier, these scattered reports of positive findings
on some tests and equivocal results on others are probably due to
increased concentration or attention span rather than to any
dramatic change in cognitive, intellectual, sensory, or motor skills.
Follow-up Studies of Hyperkinetic Children on Stimulants
Besides attempting to understand the more immediate effects
of stimulant drugs on hyperactive children, it is also important
to determine what the long term effects are for prolonged treatment
with these drugs. In a follow-up study of 67 children with learning
problems, Hinton and Knights (1971) reported observing 19 of these
children on stimulant drugs over an average interval of 3 years.
About two-thirds of thesp children were reported as "improved" at
follow-up. Just exactly what constituted improvement was not
specified by the authors.
A similar result was reported by Mendelson et. al. (1971) in
a 2 to 5 year follow-up of 83 hyperactive children, 92 percent of whom had received stimulant drug therapy sometime during the follow-up interval. Of these children, 60 percent were said to have "improved" for at least 6 months while receiving drugs, 12 percent worsened, and 28 percent had "doubtful" results. Again, the criteria of "improvement" was not specified in the report.
Despite the large percentage of children receiving stimulant drug therapy, at follow-up the vast majority of children were still described as more active, inattentive, impulsive, defiant, rebel- -143-
Iious, difficult to discipline, incorrigible, and failing one or
more grades in school as compared to peers. In view of these
results, the extent to which stimulant drugs may have helped these
children seems relatively minimal.
In a later study, Minde et. al. (1972) reported the results
of a 5 year follow-up of 91 hyperactive children. All of the
children had received phenothiazines or d-amphetamine at one time
or another during the 5 years. At the end of the follow-up, only
12 of the children remained on medication with the remainder
ceasing the drug treatment for reasons such as ineffectiveness,
side effects, sufficient improvement, or inability to come for
supervision. The authors concluded that at follow-up, "psychologi
cal adjustment did not appear to be dependent on the duration of
drug taking" (pg. 602). Although a significant reduction in
symptoms was observed over the 5 year period, these hyperactive
children still scored significantly higher than normal children on ratings of hyperactivity, distractibility, and aggressiveness.
In another follow-up study, Huessy et. al. (1974) reported their findings of an 8 to,10 year follow-up of 84 hyperactive children who had been placed on pharmacotherapy when first seen by the authors. Many of the children were receiving stimulants.-
Results indicated that of the 75 who could be traced, 18 had been institutionalized in various correctional or mental health facili ties, only 25 had satisfactory academic levels, 37 had satisfactory family relations, and only 24 had a satisfactory work record. The authors were unable to relate length of treatment with final outcome and concluded that "this study gives little encouragement to the hope that temporary symptom control with medication alters prognosis -144-
(pg. 234).
Quinn and Rapoport (1975) conducted a one-year follow-up of
76 hyperactive children who had been placed on methylphenidate,
imipramine, or placebo in a drug study one year earlier. "The
striking clinical impression at one-year follow-up Was that the
boys in all three groups continued to have difficulties” (pg. 242).
More children discontinued imipramine than methylphenidate and
those who discontinued drug treatment were still described as
hyperactive and distractible by parents and teachers at follow-up. It was concluded that the children who remained on drug therapy
continued to show improvement at the end of one-year.
Contrary to this somewhat optimistic conclusion, Weiss et.
al. (1975) reported a 5 year follow-up of 24 hyperactive children treated with methylphenidate. While the drug was helpful in making the children more manageable at home and school, it did not significantly affect their outcome at the end of drug treatment.
Compared to children not receiving medication, children on drugs did not differ significantly at the 5 year follow-up in emotional adjustment, delinquency, academic performance, quality of mother- child relations, ratings of hyperactivity, or ratings of family diagnosis.
In summarizing these few follow-up studies, the results are indeed surprising. All but one of these studies reported little change in outcome at time of follow-up as a function of stimulant drug therapy. Yet, a dramatic improvement in attention span and activity level has been observed as the short-term effect of these drugs in enumerable studies. As Weiss et. al. (1975) have noted, these differences in short-term and long-term drug studies are -145-
difficult to reconcile. While it is possible that tolerance to
the medication may have developed, this seems inadequate in account
ing for these differences as parents and teachers have been able
to recognize a worsening of symptoms as soon as medication was
discontinued even if the child had been on drugs for up to 5 years
(Weiss et. al., 1971). Rie et. al. (1976) have advanced the notion
that these discrepant findings may be due to the fact that some
children lose the spontanaeity and interest in their surroundings
necessary to adequate learning experiences while they are on drugs.
Thus, while concentration may be improved, active interest and
affective reaction to the environment may be lessened to the extent that long-term gain from the stimulants is virtually nil (Rie et.
al., 1976).
It seems then that the stimulant drugs offer an effective treatment for the short-term management of hyperkinesis but that, in and of themselves, they are not the answer to long-term treatment of these children. This review suggests that they are unlikely to alter the prognosis of the disorder and strongly indicate that a treatment "package" of stimulant drugs and some other form of intervention is needed. Stimulant drugs appear to facilitate the ease of management of the hyperkinetic child but fail to provide the necessary factors that are likely to alter later social adjustment.
Limitations of This Review
Before proceeding to draw some general conclusions, several factors must be noted as limiting, to some degree, the extent to which the results of the studies reviewed herein are comparable.
While these have been reviewed in more detail elsewhere (Barkley, -146-
1976), they are briefly mentioned here. These limitations appear to be: (1) the variety of definitions used by investigators to define hyperkinesis, (2) differences in the methodology of the studies being reviewed, (3) differences in the types of stimulant drugs being studied, (4) variations in the criteria of "improvement" used by those studies citing drug response rates, (5) differences in the measures used to assess the same construct when such measures may not be comparable, (6) and others.
Despite these limitations, however, the subjects and drugs involved in these studies were felt to be sufficiently similar within themselves so as to permit their joint review. In doing so, it is believed that some useful generalizations can be made regard ing the field of stimulant drug research with hyperactive children.
Conclusions
Based upon the more than 100 studies reviewed above, the following conclusions regarding the effects of stimulant drugs on hyperactive children seem warranted:
1. On the average, 75 percent of the hyperactive children placed on stimulant medication appear to be improved while about
25 percent remain unchanged or are worsened by the drugs. There is some evidence (Barkley, 1976) to suggest that those who respond well to these drugs are more inattentive than those who do not.
2. The primary side effects noted for the stimulants appear to be insomnia, anorexia, or loss of appetite, weight loss, and irritability. These and other side effects are reported to be mild and to dissipate within a short period of time or with a reduction in drug dosage. However, some research suggests that -147-
suppression of weight and height gain occur over the course of
treatment with these drugs.
3. The psychophysiological research on stimulant drug effects
indicates that they are generally not acting paradoxically or
sedatively on the CNS of hyperactive children but are indeed having
their typical energizing effect on CNS responsivity. These results
further suggest that the stimulants are arousing the CNS inhibitory systems thereby permitting the hyperactive child to screen out distracting stimuli and to concentrate more fully on important dimensions of relevant incoming stimuli.
4. The primary behavioral impact of the stimulant drugs in hyperactive children is in the realm of increased concentration or attention span and decreased impulsiveness in responding. It is not unusual, then, for these drugs to be the drug of choice for most hyperactive children since inattentiveness, or the inability to "stop, look, and listen" (Douglas, 1972) appears to be the major symptom in most hyperactive children. Secondary to these effects on attentional processes, the stimulant drugs seem to reduce some types of activity in some situations while not in others. It appears that non-task related activity in structured settings is reduced while task-oriented or goal directed activity is less affected. In free play, wrist and locomotor activity may be reduced while torso activity may go unchanged. Certainly, in free play situations, the effects of stimulant drugs on activity level are much less clearcut and predictable than effects on concentration.
It may be that changes in activity level are simply an indirect result of the changes observed in attentional processes (Conners,
1972b; Douglas, 1972; Sroufe et. al., 1975). Effects on other -148-
tests and measures of cognitive, intellectual, achievement, sensory,
or motor abilities, when observed, are likely to be due to this
increased attentiveness rather than to dramatic changes in these
various abilities (Weiss et. al., 1971; Werry, 1970).
5. Those few follow-up studies which have been done suggest
that stimulant drug therapy is not a panacea for treating hyper
kinesis. While the drugs seem to facilitate the short-term manage
ability of hyperactive children, they appear to have little impact
on the long-term social and psychological adjustment of these chil
dren. Obviously, more research on the long-term effects of pro
longed stimulant drug therapy is needed. Nevertheless, the results
of these follow-up studies are disappointing and lead to the ines
capable conclusion that the stimulant drugs are simply not enough
for the treatment of hyperkinesis (Eisenberg, 1966; Werry, 1970).
Further, they call into question the practice of wantonly prescrib
ing these drugs to most hyperactive children without due considera
tion being given to other modes of treatment that might be used
in conjunction with or as alternatives to drugs (Greenspoon St
Singer, 1973). Physicians should not allow themselves to be
pressured into prescribing these drugs and, when prescribed, should
take adequate steps to see that the drugs are properly monitored and administered. Parents should not be permitted to "juggle" the dosage as they see fit (Solomons, 1973).
In view of these results, the conclusion reached by Werry (1970) appears to be an excellent starting point for future clinical research in this area: ". . . clinical studies which regard drugs as a treatment in themselves rather than a way of altering the 149-
state of the organism within a social learning context are likely
to underestimate thè value of pharmacotherapy in children. At best, a drug can probably only make certain behaviors more or less probable, their firm establishment or extinction requires a deliber ate structuring of crucial environment variables within some adequate theory of social learning" (pg. 143). -150-
References
Alexandris, A. & Lundell, F. Effect of thioridazine, amphetamine,
and placebo on the hyperkinetic syndrome and cognitive area
in mentally deficient children. Canadian Medical Association
Journal, 1968, 98, 92-96.
Aman, M. & Sprague, R. The state-dependent effects of methyl
phenidate and dextroamphetamine. Journal of Nervous and
Mental Diseases, 1974, 158, 268-279.
Anderson, R., Halcomb, C., Gordon, W., Jr., & Ozolins, D. Measure
ment of attention distractibility in LD children. Academic
Therapy, 1974, 9, 261-266.
Arnold, E., Kirilcuk, V., Corson, S., & Corson, E. Levoamphetamine
and dextroamphetamine: differential effect on aggression and
hyperkinesis in children and dogs. American Journal of
Psychiatry, 1973, 130, 165-170.
Arnold, E., Wender, P., McCloskey, K., & Snyder, S. Levoampheta-
mine and dextroamphetamine: Comparative efficacy in the
hyperkinetic syndrome. Archives of General Psychiatry, 1972,
27, 816-822.
Barkley, R. Predicting the response of hyperkinetic children to
stimulant drugs: A review. Unpublished paper, Bowling Green
State University, Ohio, 1976.
Barkley, R. & Routh, D. Reduction of children's locomotor activity
by modeling and the promise of contingent reward. Journal
of Abnormal Child Psychology, 1974, 2, 117-131. -151
Barkley, R. & Ullman, D. A comparison of objective measures of
activity and distractibility in hyperactive and nonhyper-
active children. Journal of Abnormal Child Psychology, 1975,
3, 231-244.
Bradley, C. The behavior of children receiving benzedrine.
American Journal of Psychiatry, 1937, 94, 577-585.
Bradley, C. Benzedrine and dexedrine in the treatment of children's
behavior disorders. Pediatrics, 1950, 5, 24-37.
Bradley, C. & Bowen, M. School performance of children receiving
amphetamine (benzedrine) sulfate. American Journal of Ortho
psychiatry, 1940, 10, 782-788.
Bradley, C. & Green, E. Psychometric performance of children
receiving amphetamine (benzedrine) sulfate. American Journal
of Psychiatry, 1940-41, 97, 388-394.
Buchsbaum, M. & Wender, P. Average evoked responses in normal and
minimally brain dysfunctioned children treated with ampheta
mine: A preliminary report. Archives of General Psychiatry,
1973, 29, 764-770.
Burks, H. Effects of amphetamine therapy on hyperkinetic children.
Archives of General Psychiatry, 1964, 11, 604.
Butter, H. & Lapierre, Y. The effect of methylphenidate on sensory
perception and integration in hyperactive children. Interna
tional Pharmopsychiatry, 1974, 9, 235-244.
Butter, H. & Lapierre, Y. The effects of methylphenidate on
sensory perception in varying degrees of hyperkinetic behavior.
Diseases of the Nervous System, 1975, 36, 286-288. -152-
Campbell, S., Douglas, V., & Morgenstern, G. Cognitive styles in
hyperactive children and the effect of methylphenidate.
Journal of Child Psychology and Psychiatry, 1971, 12, 55-67.
Cantwell, D. (Ed.) The Hyperactive Child. New York: Spectrum
Publications, Inc., 1975.
Carpenter, R. & Sells, C. Measuring effects of psychoactive medi
cation in a child with a learning disability. Journal of
Learning Disabilities, 1974, 7, 545-550.
Christensen, D. & Sprague, R. Reduction of hyperactive behavior
by conditioning procedures alone and combined with methyl
phenidate. Behavior Research and Therapy, 1973, 11, 331-334.
Claghorn, J., Neblett, G., Sutter, E., Farrell, G., & Kraft, I.
The effect of drugs on hyperactivity in children with some
observations of changes in mineral metabolism. Journal of
Nervous and Mental Disease, 1971, 153, 118-125.
Cohen, N., Douglas, V., & Morgenstern, G. The effect of methyl
phenidate on attentive behavior and autonomic activity in
hyperactive children. Psychopharmacologia, 1971, 22, 282-294.
Comly, H.- Cerebral stimulants for children with learning disorders.
Journal of Learning Disabilities, 1971, 4, 484-490.
Conners, C. The effect of dexedrine on rapid discrimination and
motor control of hyperkinetic children under mild stress.
Journal of Nervous and Mental Disease, 1966, 142, 429-433.
Conners, C. A teacher rating scale for use with drug studies with
children. American Journal of Psychiatry, 1969, 126, 884-888.
Conners, C. The use of stimulant drugs in enhancing performance
and learning. In W. L. Smith (Ed.) Drugs and Cerebral Function.
Springfield, Illinois: Charles C. Thomas, 1970. -153-
Conners, C. The effect of stimulant drugs on human figure drawings
in children with minimal brain dysfunction. Psychopharmaco-
logia, 1971, 19, 329-333.
Conners, C. Psychological effects of stimulant drugs in children
with minimal brain dysfunction. Pediatrics, 1972a, 49, 702-708.
Conners, C. Pharmacotherapy of psychopathology in children. In
H. Quay & J. Werry (Eds.) Psychopathological Disorders of
Childhood. New York: J. Wiley & Sons, 1972b.
Conners, C. & Eisenberg, L. The effects of methylphenidate on the
symptomatology and learning in disturbed children. American
Journal of Psychiatry, 1963, 120, 458-464.
Conners, C., Eisenberg, L., & Sharpe, L. Effects of methylphenidate
(Ritalin) on paired-associate learning and Porteus Maze
performance in emotionally disturbed children. Journal of
Consulting Psychology, 1964, 28, 14-22.
Conners, C., Eisenberg, L., & Barcai, A. Effect of dextroampheta
mine on children. Archives of General Psychiatry, 1967, 17,
478-485.
Conners, C. & Rothschild, G. Drugs and learning in children. In
Learning Disorders Volume 3. Seattle, Washington: Special
Child Publications, 1968.
Conners, C., Rothschild, G., Eisenberg, L., Stone, L., & Robinson,
E. Dextroamphetamine sulfate in children with learning
disorders. Archives of General Psychiatry, 1969, 21, 182-190.
Conners, C., Taylor, E., Meo, G., Kurtz, M., & Fournier, M.
Magnesium pemoline and dextroamphetamine: A controlled study
in children with minimal brain dysfunction. Psychopharmaco
logia, 1972, 26, 321-336. -154-
Conrad, W. Anticipating the response to amphetamine therapy in
the treatment of hyperkinetic children. Pediatrics, 1967,
40, 96-98.
Conrad, W., Dworkin, E., Shai, A., & Tobiessen, J. Effects of
amphetamine therapy and prescriptive tutoring on the behavior
and achievement of lower class hyperactive children. Journal
of Learning Disabilities, 1971, 4, 509-517.
Creager, R. & Van Riper, C. The effect of methylphenidate on the
verbal productivity of children with cerebral dysfunction.
Journal of Speech and Hearing Research, 1967, 10, 623-628.
-Cutts, K., & Jasper, H. Effects of benzedrine sulfate and pheno
barbital on behavior problem children with abnormal electro
encephalograms. Archives of Neurology and Psychiatry, 1939,
41, 1138-1145.
Davids, A. An objective instrument for assessing hyperactivity
in children. Journal of Learning Disabilities, 1971, 4, 499.
Denhoff, E., Davids, A., & Hawkins, R. Effects of dextroamphetamine
on hyperkinetic children: A controlled double-blind study.
Journal of Learning Disabilities, 1971, 4, 491-498.
Douglas, V. Stop, look, and listen: The problem of sustained
attention and impulse control in hyperactive and normal
children. Canadian Journal of Behavioural Science, 1972, 4,
259-282.
Eisenberg, L. The management of the hyperkinetic child. Develop
mental Medicine and Child Neurology, 1966, 8, 593-598.
Ellis, M., Witt, P., Reynolds, R., & Sprague, R. Methylphenidate -155-
and the activity of hyperactive in the informal setting.
Child Development, 1974, 45, 217-220.
Epstein, L., Lasagna, L., Conners, C., & Rodriguez, A. Correlation
of dextroamphetamine excretion and drug response in hyper
kinetic children. Journal of Nervous and Mental Disease,
1968, 146, 136-146.
Fish, B. The "one child, one drug" myth of stimulants in hyper
kinesis. Archives of General Psychiatry, 1971, 25, 193-203.
Fish, B. Stimulant drug treatment of hyperactive children. In
D. Cantwell (Ed.) The Hyperactive Child. New York: Spectrum
Publications, Inc., 1975.
Finnerty, R., Soltys, J., & Cole, J. The use of dextroamphetamine
with hyperkinetic children. Psychopharmacologia, 1971, 21,
302-308.
Freeman, R. Drug effects on learning in children. A selective
review of the past thirty years. Journal of Special Educa
tion, 1966, 1, 17-33.
Garfinkel, B., Webster, C., & Sloman, L. Methylphenidate and
caffeine in the treatment of children with minimal brain
dysfunction. American Journal of Psychiatry, 1975, 132, 723-727
Greenberg, L., Deem, M., & McMahon, S. Effects of dextroamphetamine
chlorpromazine, and hydroxyzine on the behavior and performance
of hyperactive children. American Journal of Psychiatry,
1972, 129, 532-539.
Greenspoon, S. & Singer, S. Amphetamines in the treatment of
hyperkinetic children. Harvard Educational Review, 1973,
43, 515-555. -156-
Hinton, G. & Knights, R. Children with learning problems: academic
history, academic prediction, and adjustment 3 years alter
assessment. Exceptional Children, 1971, 37, 513-519.
Huessy, H., Metoyer, M. , & Townsend, M. 8-10 year follow-up of
84 children treated for behavioral disorder in rural Vermont.
Acta Paedopsychiatrica, 1974, 40, 230-235.
Huestis, R., Arnold, E., & Smeltzer, D. Caffeine versus methyl-
x phenidate and d-amphetamine in minimal brain dysfunction:
A double-blind comparison. American Journal of Psychiatry,
1975, 132, 868-870.
Hoffman, S., Engelhardt, D., Margolis, R., Polizos, P., Waizer,
J., & Rosenfeld, R. Response to methylphenidate in low
socioeconomic hyperactive children. Archives of General
Psychiatry, 1974, 30, 354-359.
Johnson, C. Hyperactivity and the machine: The actometer.
Child Development, 1971, 42, 2105.
Knights, R. & Hinton, G. The effects of methylphenidate on the
motor skills and behavior of children with learning problems.
Journal of Nervous and Mental Disease, 1969, 148, 643-653.
Knobel, M. Psychopharmacology for the hyperkinetic child - dynamic
considerations. Archives of General Psychiatry, 1962, 6,
198-202.
Knopp, W., Arnold, E., Andras, R., & Smeltzer, D. Predicting
amphetamine response in hyperkinetic children electronic
pupillography. Pharmakopsychiatry, 1973, 6, 158-166.
Kornetsky, C. Psychoactive drugs and the immature organism. -157-
Psychopharmacologia, 1970, 17, 105-136.
Krager, J. & Safer, D. Type and prevalence of medication used in
treating hyperactive children. New England Journal of Medicine,
1974, 291, 1118-1120.
Laufer, M., Denhoff, E., & Solomans, G. Hyperkinetic impulse
disorder in children's behavior problems. Psychosomatic
Medicine, 1957, 19, 38-49.
Levy, S. Post-encephalitic behavior disorder - A forgotten entity.
A report of 100 cases. American Journal of Psychiatry, 1959,
115, 1062-1067.
Lindsley, D., & Henry, C. The effect of drugs on behavior and the
electroencephalogram of children with behavior disorders.
Psychbsomatic Medicine, 1942, 4, 140-149.
Loney, J., Comly, H., Hunter, H., & Simon, B. Parental management,
self-concept, and drug response in minimal brain dysfunction.
Journal of Learning Disabilities, 1975, J3, 187-190.
Loney, J. & Ordona, T. Using cerebral stimulants to treat minimal
brain dysfunction. American Journal of Orthopsychiatry, 1975,
45, 564-572.
Lytton, G. & Knobel, M. Diagnosis and treatment of behavior disor
ders in children. As cited in Knobel, M., Wolman, M., &
Mason, E. Hyperkinesis and organicity in children. Archives
of General Psychiatry, 1959, 3., 310-321.
Mackay, M., Beck, L., & Taylor, R. Methylphenidate for adolescents
with minimal brain dysfunction. New York State Journal of
Medicine, 1973, 73, 550-554.
McConnell, T., Cromwell, R., Bialer, I., & Son, C. Studies in -158-
activity level: VII. Effects of amphetamine drug administra
tion on the activity level of retarded children. American
Journal of Mental Deficiency, 1964, 68, 647-651.
Mendelson, W., Johnson, N., & Stewart, M. Hyperactive children as
teenagers: A follow-up study. Journal of Nervous and Mental
Disease, 1971, 153, 273-279.
Millichap, J. Drugs in the management of minimal brain dysfunction.
Annals of the New York Academy of Sciences, 1973, 205, 321-334.
Millichap, J., Aymat, F., Sturgis, L., Larsen, K., & Egan, R.
Hyperkinetic behavior and learning disorders. American Journal
of Diseases of Children, 1968, 116, 235-244.
Millichap, J. & Boldrey, E. Studies in hyperkinetic behavior.
Neurology, 1967, 17, 467-471.
Millichap, J. & Fowler, G. Treatment of "minimal brain dysfunction"
syndromes. Pediatric Clinics of North America, 1967, 14,
767-777.
Minde, K., Weiss, G., & Mendelson, N. A 5-year follow-up study
of 91 hyperactive school children. Journal of the American
Academy of Child Psychiatry, 1972, 11, 595-610.
Molitch, M. & Eccles, A. The effect of benzedrine sulfate on the
intelligence scores of children. American Journal of Psychia
try, 1937, 94, 587-590.
Montagu, J. & Swarbrick, L. Effect of amphetamines in hyperkinetic
children: Stimulant or sedative? A pilot study. Develop
mental Medicine and Child Neurology, 1975, 17, 293-298.
Ney, P. Psychosis in a child associated with amphetamine adminis
tration. Canadian Medical Association Journal, 1967, 97, 1026-
1029. -159-
Porges, S., Walter, G., Korb, R., & Sprague, R. The influence of
methylphenidate on heart rate and behavioral measures of
attention in hyperactive children. Child Development, 1975,
46, 727-733.
Quinn, P. & Rapoport, J. One-year follow-up of hyperactive boys
treated with imipramine or methylphenidate. American Journal
of Psychiatry, 1975, 132, 241-245.
Rapoport, J., Lott, I., Alexander, D., & Abramson, A. Urinary
noradrenaline and playroom behavior in hyperactive boys.
Lancet, 1970, 2, 1141.
Rapoport, J., Abramson, A., Alexander, D., & Lott, I. Playroom
observations of hyperactive children on medication. Journal
of the American Academy of Child Psychiatry, 1971, 10, 524-534.
Rapoport, J., Quinn, P., Bradbard, G., Riddle, D., & Brooks, E.
, Imipramine and methylphenidate treatments of hyperactive boys.
Archives of General Psychiatry, 1974, 30, 789-793.
Rapoport, J., Quinn, P., & Lamprecht, F. Minor physical anomalies
and plasma dopamine-beta-hydroxylase activity in hyperactive
boys. American Journal of Psychiatry, 1974, 131, 386-390.
Rie, H., Rie, E., Stewart, S., & Ambuel, J. Effects of methyl
phenidate on underachieving children. Journal of Consulting
and Clinical Psychology, 1976, 44, 250-260.
Routh, D., Schroeder, C., & O'Tuama, L. Development of activity
level in children. Developmental Psychology, 1974, 10, 163.
Safer, D., & Allen, R. Stimulant drug treatment of hyperactive
adolescents. Diseases of the Nervous System, 1975, 36, 454-457.
Safer, D., Allen, R., & Barr, E. Depression of growth in hyperactive -160-
children on stimulant drugs. New England Journal of Medicine,
1972, 287, 217-220.
Saletu, B., Saletu, M., & Itil T. The relationship between psycho
pathology and evoked responses before, during, and after
psychotropic drug treatment. Biological Psychiatry, 1973,
6, 45-74.
Satterfield, J., Cantwell, D., Lesser, L., & Podosin, R. Physio
logical studies of the hyperkinetic child: I. American
Journal of Psychiatry, 1972, 128, 1418-1424.
Satterfield, J., Cantwell, D., Saul, R., Lesser, L., & Podosin, R.
Response to stimulant drug treatment in hyperactive children:
prediction from EEG and neurological findings. Journal of
Autism and Childhood Schizophrenia, 1973, 3, 36-48.
Satterfield, J. & Dawson, M. Electrodermal correlates of hyper
activity in children. Psychophysiology, 1971, 8, 191-197.
Satterfield, J., Lesser, I., Saul, R., & Cantwell, D. EEG aspects
in the diagnosis and treatment of minimal brain dysfunction.
Annals of the New York Academy of Sciences, 1973, 205, 274-282.
Schain, R., & Reynard, C. Observations on effects of a central
stimulant drug (methylphenidate) in children with hyperactive
behavior. Pediatrics, 1975, 55, 709-716.
Schliefer, M., Weiss, G., Cohen, N., Elman, M., Cvejic, H., &
Kruger, E. Hyperactivity in preschoolers and the effect of
methylphenidate. American Journal of Orthopsychiatry, 1975,
45, 38-50.
Schnackenberg, R. Caffeine as a substitute for schedule II
stimulants in hyperkinetic children. American Journal of
Psychiatry, 1973, 130, 796-798. -161-
Schnackenberg, R. & Bender, E. The effect of methylphenidate
hypochloride on children with minimal brain dysfunction
syndrome and subsequent hyperkinetic syndrome. Psychiatric
Forum, 1971, 2, 32-36.
Seger, E. & Hallum, G. Methylphenidate in children with minimal
brain dysfunction: Effects on attention span, visual-motor
skills, and behavior. Current Therapeutic Research, 1974,
16, 635-641.
Shetty, T. Alpha rhythms in the hyperkinetic child. Nature,
1971, 234, 476.
Solomans, G. Drug therapy: Initiation and follow-up. Annals
of the New York Academy of Sciences, 1973, 205, 335-344.
Sprague, R., Barnes, K., & Werry, J. Methylphenidate and thiori
dazine: learning, reaction time, activity, and classroom
behavior in disturbed children. American Journal of Qrtho-
psychiatry, 1970, 40, 615-628.
Sprague, R. & Sleator, E. Effects of psychopharmacological agents
on learning disabilities. Pediatric Clinics of North America,
1973, 20, 719-735.
Sprague, R. & Werry, J. Methodology of psychopharmacological
studies with the retarded. International Review of Research
in Mental Retardation, 1971, 5, 147-219.
Spring, C., Greenberg, L., Scott, J., & Hopwood, J. Reaction time
and the effect of'Ritalin on children with learning problems.
Perceptual and Motor Skills, 1973, 36, 75-82.
Spring, C., Greenberg, L., Scott, J., & Hopwood, J. Electrodermal
activity in hyperactive boys who are methylphenidate respon
ders. Psychophysiology, 1974, 11, 436-442. -162-
Sroufe, A., Sonies, B., West, W. , & Wright, F. Anticipatory heart
rate deceleration and reaction time in children with and
without referral for, learning disability. Child Development,
1973, 44, 267-273.
Steinberg, G., Troshinsky, C., & Steinberg, H. Dextroamphetamine
responsive behavior disorder in school children. American
Journal of Psychiatry, 1971, 128, 174-179.
Sykes, D., Douglas, V., & Morgenstern, G. The effect of methyl
phenidate (Ritalin) on sustained attention in hyperactive
children. Psychopharmacologia, 1972, 25, 262-274.
Sykes, D., Douglas, V., Weiss, G., & Minde, K. Attention in hyper
active children and the effect of methylphenidate (Ritalin).
Journal of Child Psychology and Psychiatry, 1971, 12, 129-139.
Weber, B., & Sulzbacher, S. Use of CNS stimulant medication in
averaged electroencephalic audiometry with children with MBD.
Journal of Learning Disabilities, 1975, 8, 300-303.
Weiss, G., Kruger, E. , Danielson, U., & Elman, M. Effect of long
term treatment of hyperactive children with methylphenidate.
Canadian Medical Association Journal, 1975, 112, 159-165.
Weiss, G., Minde, K., Douglas, V., Werry, J., & Sykes, D. Compari
son of the effects of chlorpromazine, dextroamphetamine, and
methylphenidate on the behaviour and intellectual functioning
of hyperactive children. Canadian Medical Association Journal,
1971, 104, 20-25.
Weiss, G. , Werry, J., Minde, K. , Douglas-, V., & Sykes, D. Studies
on the hyperactive child: V. The effects of dextroampheta
mine and chlorpromazine on behavior and intellectual func
tioning. Journal of Child Psychology and Psychiatry, 1968,
9, 145-156. -163-
Werry, J. Developmental hyperactivity. Pediatric Clinics of North
America, 1968, 15, 581.
Werry, J. Some clinical and laboratory studies of psychotropic
drugs in children: An overview. In W. L. Smith (Ed.) Drugs
and Cerebral Functioning. Springfield, Illinois: Charles
C. Thomas, 1970.
Werry, J., & Aman, M. Methylphenidate and haloperidol in children.
Effects on attention, memory, and activity. Archives of
General Psychiatry, 1975, 32, 790-795.
Werry, J. & Sprague, R. Methylphenidate in children: Effect of
dosage. Australian and New Zealand Journal of Psychiatry,
1974, 8, 9-19.
Winsberg, B., Bialer, I., Kupietz, S., & Tobias, J.. Effects of
imipramine and dextroamphetamine on behavior of neuropsychia-
trically impaired children. American Journal of Psychiatry,
1972, 128, 1425-1431.
Winsberg, B., Press, M., Bialer, I., & Kupietz, S. Dextroampheta-
i mine and methylphenidate in the treatment of hyperactive/
aggressive children. Pediatrics, 1974, 53, 236-241.
Yoss, R. Personal communication, December 18, 1975, Mayo Clinic.
Yoss, R. & Moyers, N. The pupillogram of the hyperkinetic child
and the underachiever. Abstracts for 7th Colluquium on the
Pupil. The Mayo Clinic, Rochester, Minnesota, 1971.
//Zahn, T., Abate, F., Little, B., & Wender, P. Minimal brain
dysfunction, stimulant drugs, and autonomic nervous system
activity. Archives of General Psychiatry, 1975, 32, 381-387.
Zimmerman, F. & Burgemeister, B. Action of methylphenidate
(Ritalin) and reserpine in behavior disorders in children 164-
and adults. American Journal of Psychiatry, 1958, 115, 323-
328.
Zrull, J., Westman, J., Arthur, B., & Bell, W. A comparison of
chlordiazepoxide, d-amphetamine, and placebo in the treatment
of the hyperkinetic syndrome in children. American Journal
of Psychiatry, 1963, 120, 590-591.
Zrull, J., Westman, J., Arthur, B., & Rice, D. An evaluation of
methodology used in the study of psychoactive drugs for
children. Journal of the American Academy of Child Psychiatry,
1966, 5, 284-291. -165
APPENDIX C -166-
WERRY-WEISS-PETERS ACTIVITY RATING SCALE
Child's Name______Date______
Parent's Name______
Instructions:
Please answer each of the questions below by circling the word NO if the child does not do this behavior or almost never does it, SOME if he does it some of the time, MUCH if he does it quite a bit, and NA if the item does not apply to your child.
1. During meals, is the child up and down at the table?
NO SOME MUCH NA
2. During meals, does the child interrupt others without regard for what they are trying to say?
NO SOME MUCH NA
3. During meals, does the child fiddle with things?
NO SOME MUCH NA
4. During meals, does the child wriggle?
NO SOME MUCH NA
5. During meals, does the child talk too much?
NO SOME MUCH NA
6. When watching television, does the child get up and down during the program?
NO SOME MUCH NA
7. When watching television, does the child wriggle?
NO SOME MUCH NA
8. When watching television, does the child play with objects or his own body?
NO SOME MUCH NA
9. When watching television, does the child talk too much?
NO SOME MUCH NA -167-
10. When watching television, does the child do things which interrupt others’ ability to watch the program?
NO SOME MUCH NA
11. Is the child unable to play quietly?
NO SOME MUCH NA
12. When at play, does the child keep going from one toy to another?
NO SOME MUCH NA
13. When at play, does the child seek the attention of an adult?
NO SOME MUCH NA
14. When at play, does the child talk too much?
NO SOME MUCH NA
15. When at play, does the child disrupt the play of other children?
NO SOME MUCH NA
16. Does the child having difficulty settling down to sleep?
NO SOME MUCH NA
17. Does the child get too littleì sleep?
NO SOME MUCH NA
18. Is the child restless during sleep?
NO SOME MUCH NA
19. Is the child restless during travel?
NO SOME MUCH NA
20. Is the child restless during shopping (including touching everything)?
- NO SOME MUCH NA
21. Is the child restless during church or at the movies?
NO SOME MUCH NA 22. Is the child restless while vi Lting relatives?
NO SOME MUCH NA