Methylphenidate in severely retarded residents and the clinical significance of stereotypic behavior

Applied Research in Mental Retardation, Vol. 3, pp. 345-358, 1 9 8 2 Printed in the USA. All lights reserved.

0270-3092/82/040345-14503.00/0 Copyright O 1982 Pergamon Press Ltd

Methylphenidate in Severely Retarded Residents and the Clinical Significance of Stereotypic Behavior Michael G. Aman Department of Psychiatry, School of Medicine, University of Auckland

and

Nirbhay N. Singh Department of Psychology, University of Canterbury

An attempt was made to evaluate a model predicting stimulant drug response based on attentional characteristics of the participants. Twenty-eight severely and profoundly mentally retarded residents took part in a double blind, placebo controlled trial of methylphenidate (Ritalin). Methylphenidate was administered, for one week each, in a low dose of 0.3 mglkg and a high dose of 0.6 mglkg. The results failed to show any clinically relevant differences between placebo and active drug conditions with the exception that methylphenidate caused a significant reduction infood consumption. A variety of subject characteristics, including level of stereotypy, hyperactivity, and IQ were unrelated to drug effect. One positive finding, unrelated to drug effects, was that subdivision of the group by degree of stereotypy provided substantial clinical information about individual subjects.

Stimulant drugs, such as the amphetamines, have been extensively used over the last two decades to bring about behavioral improvements in hyperactive children of normal IQ (Cantwell & Carlson, 1978; Conners & Werry, 1979). Clinical changes include reduction in overactivity, impulsiveness; aggressiveness, and distractibility (Safer & Allen, 1976; Wender, 1971; Werry, 1976). Stimulant drugs have also been observed to cause short-term improvements on Requests for reprints may be addressed to MichaelAman, Ph.D., Departmentof Psychiatry,School of Medicine, PrivateBag, Universityof Auckland, Auckland, New Zeat~md. 345

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Michael G. Aman and Nirbhay N. Singh

a variety of structured laboratory tasks, including aspects of verbal learning, cognitive style, short term memory, and IQ performance (Aman, 1978, 1980; Sprague & Sleator, 1975, 1977; Sroufe, 1975). However, the most consistently reported changes, especially in hyperactive children, have been in attention span (Aman, 1978; Sroufe, 1975). Stimulant drugs are infrequently used for treating behavior problems in institutionalized mentally retarded persons, the prevalence of prescription being around 3% (Aman, 1982-a; Lipman, 1970). Nevertheless, there has been considerable research with these drugs in institutions for mentally retarded people. This probably reflects a belief on the part of some workers that these drugs may have beneficial effects in mentally retarded people comparable to those in hyperactive children of normal IQ. However, reviews of the literature (Aman, 1982-a, 1982-b; Lipman, DiMascio, Reatig, & Kirson, 1978; Sprague & Werry, 1971) simply do not support this expectation. Whereas a few studies of stimulant medication do show isolated areas of improvement, the majority show essentially no changes and some even indicate worsening of behavior under stimulants (see Aman, 1982-b). The reason for this overall lack of effect is uncertain, but it may be related to attentional mechanisms in mentally retarded people. The work of Zeaman and House (Zeaman, 1965, 1973; Zeaman & House, 1963) is renowned in this field. They conducted an elaborate series of studies designed to disentangle the components involved in discrimination learning problems and were able to show that there were few differences due to mental age in instrumental learning rate. Instead, the major differences could be attributed to the number of trials required to attend to the relevant stimulus dimensions. In general, children of lower mental ages tended to require much more practice before attending to the relevant cues. This work was taken further by Ullman (1974) who developed a test of "breadth of attention," which provides an index of how well subjects can attend to several stimulus dimensions, presented simultaneously. Ullman demonstrated that trainable mentally retarded children performed worse on this task than controls matched on mental age, suggesting that lower mental age is associated with a restriction in breadth of attention. There is also a sizeable literature suggesting that autistic children display a similar attentional style which can be characterized as overselective or "narrow" (see Lovaas, Koegel, & Schreibman, 1979). Thus, there is a large body of evidence indicating that attention tends to become increasingly constricted with decreasing mental age. Another issue pertinent to this discussion is that of stimulant-induced stereotypy in animals. It has been repeatedly demonstrated that moderate and high doses of stimulant drugs evoke stereotypic behavior in various species including mice, rats, cats, monkeys, and man (Randrup & Munkvad, 1965, 1966, 1967, 1974; Randrup, Munkvad & Udsen, 1963). Stimulant-induced stereotypy is widely believed to be due to dopaminergic mechanisms (e.g., Iverson, 1980) but an attentional explanation has been offered as well. Robbins and Sahakian

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(1979) have argued compellingly that a major effect of the stimulants is to produce a focusing of attention in both animals and man, and they have suggested that stimulant-induced stereotypy is a consequence of severe constriction of attention. This attentional explanation is of interest because of the generally indifferent response of mentally retarded subjects to stimulant medication. Autistic children also tend to react adversely to stimulant drugs, frequently with an exacerbation of symptoms of stereotypy (Campbell, Fish, Davis, Shapiro, Collins, & Koh, 1972; Campbell, Small, Collins, Friedman, David, & Genieser, 1976). It is well known, of course, that stereotypic behaviors, such as body rocking, head rolling, head banging, and complex hand movements are frequently observed in severely mentally retarded persons (Baumeister & Forehand, 1973). It seems reasonable that stereotypic behavior may be caused in part by the excessively narrow focus of attention which has been documented in this group. Indeed, one of the popular explanations for self stimulation is that it is due to inadequate stimulation and represents a kind of homeostatic response to inadequate arousal levels (Baumeister & Forehand, 1973). Thus, if stimulant drugs do cause a narrowing of attention as suggested by Robbins and Sahakian (1979), we might expect these drugs to have an adverse effect in those persons already characterized by narrow attention. Conversely, stimulants would be expected to have beneficial effects in people with relatively broad attentional focus (see Aman, 1982-b). The above relationships suggested that it may be possible to predict the clinical response of severely mentally retarded residents to stimulant medication. It was postulated that high levels of self stimulation would be associated with constricted attention. We then hypothesized that subjects with narrow attention, so defined, would respond adversely to medication, whereas those with relatively global breadth of attention would respond positively. In addition, the effect of dose was assessed, and IQ level and degree of hyperactivity were examined for their relationship to therapeutic response. METHOD Subjects The participants were 29 severely and profoundly mentally retarded adolescents and adults. These residents were selected for a variety of serious problem behaviors, including stereotypic behavior, severe aggressiveness, destructiveness, hyperactivity, and temper tantrums. Informed consent was obtained from the parents, and approval from institutional authorities, before subjects were admitted to the study. One girl showed a strong adverse behavioral reaction to ~ e experimental drug and was excluded from the trial. Unlike the remainder of the subjects, she was

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observed to have psychotic-like behaviors before the trial began. She reacted to a low (5 mg) dose of methylphenidate with the following behaviors: repetitive spinning of her body, screaming, hand hiting, the use of odd phrases, and compulsive rituals such as continuously lining up objects. The definitive group was comprised of 20 males and eight females. Prior to the trial, 15 of these residents were receiving antipsychotic drugs, most notably haloperidol (Haldol, Serenace), thioridazine (Mellaril), and trifluoperazine (Stelazine) in that order of frequency. The only other medication given with any frequency was benzotropine mesylate, to counteract extrapyramidal symptoms. Other characteristics of the subjects, including chronological age, behavioral age, social age, language age and IQ are presented in Table 1. Design

This was a double blind, placebo controlled, crossover experiment. Prior to the study, the subjects were phased off all previous medication and maintained in a drug-free state for four weeks. In the last week before the trial began, baseline measures were taken on all dependent variables. At the end of the baseline week, but prior to the trial itself, each subject was given a single 5 mg dose of methylphenidate to test for idiosyncratic drug reactions. Each subject then received placebo, a low dose (0.3 mg/kg) and a high dose (0.6 mg/kg) of methylphenidate for one week each. Drug orders were determined by a Latin Square design so that drug conditions were balanced with respect to time. Subjects were randomly assigned to equal numbers to the three drug orders. The low dose (0.3 mg/kg) was chosen because it corresponded to that which has been found to optimize learning in hyperactive children on a laboratory learning task (Sprague & Sleator, 1975, 1977). The high dose of 0.6 mg/kg was adopted because it fell within the range known to improve behavior in most hyperactive children (Werry & Sprague, 1974) and yet was sufficiently low that it was unlikely to provoke significant side effects. Following the three week drug comparison, a one week post-drug baseline ensued. Drug treatment was always initiated on Saturdays and medication was administered once daily with breakfast. All measurements and observations were conducted during the last five days (Monday to Friday) of each treatment week and (with the exception of Mealtime Behaviors) were carried out in the mornings. TABLE 1 Characteristics of Subjects

Characteristic Mean Range Age 18.16 13.6-26.4 Vineland social age 2.18 0.8- 8.8 Fairview behavioral age 1.46 0.7- 4.4 Fairview language age 1.39 0.4- 5:6 Slosson IQ 11.96 4 -34 Note: All units except IQ are expressed in years.

S.D. 3.71 1.61 0.82 1.34 8.09

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PROCEDURE

Predictors of Drug Response During baseline, the subjects were assessed on three variables which were later to be used as predictors of drug response. We had intended to test the subjects on Ullman's (1974) breadth of attention task so that this aspect of attention could be directly evaluated as a predictor of therapeutic response. However, we were unable to quantify breadth of attention in these severely mentally retarded subjects despite persistent efforts with operant shaping techniques. Therefore, we had to forego this measure and we were reluctantly forced to rely upon level of stereotypy (discussed below) as a clinical manifestation of breadth of attention. The subjects were also assessed for IQ, using the Slosson (1963) Intelligence Test. Finally, the subjects were rated on Conners Abbreviated Teacher Rating Scale (Conners, 1976) which was modified for use in this group.

Dependent Variables The following measures of drug effect were selected because of their drug sensitivity and were based in part upon a previous study of thioridazine (Singh & Aman, 1981).

Physiological measures. Heart rate and blood pressure were recorded using a standardized procedure (Aman & Werry, 1975) while the subject lay supine. Body weight was recorded in kg. to the nearest 0. I kg. Instruction following.* This task was comprised of a standard set of 30 instructions ranging from very simple ("sit down") to much more complex (e.g., subject instructed to imitate examiner performing complex actions). The criteria for each item were carefully specified to enhance the objectivity and reliability of the instrument. AAMD Adaptive Behavior Scale. All subjects were rated by ward nurses on specific items selected from Part II of the AAMD Adaptive Behavior Scale (Nihira, Foster, Shellhaas, & Leland, 1974). Only 18 of the 44 categories were suitable to these subjects and they came largely from the dimensions labelled Destructive Behavior (5 categories), Withdrawal (2 categories), Stereotyped Behavior (2 categories), and Unacceptable Habits (3 categories). Behavior Rating Scale. The subjects were also rated by ward nurses on a preliminary version of a rating scale of problem behavior which was under development at the time (Aman, Singh, & Stewart, Note 1). The scale has subsequently *Available upon request.

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Michael G. Aman and Nirbhay N. Singh

been factor analyzed to render five dimensions comprising 66 items. The factors have been labelled as follows: I Aggression/Disruption, II Lethargy/Withdrawal, III Stereotypic Behavior, IV Abnormal Speech, V Emotionality/Crying. Ward behavior. Trained observers evaluated the residents for seven major cat-

egories of behavior: stereotypic behavior, destructive/aggressive, other inappropriate behavior, isolate play, solitude/inactivity, work, appropriate social behavior, and inappropriate social behavior. Because we were interested in methylphenidate's effects on stereotypic behavior, this category was further broken down into body rocking, self-injury, and other self-stimulation. An interval-recording technique was utilized in which each 15-min session was divided into 90, 10-sec observational intervals. Data were collected daily for each subject by one of six observers, all behaviorally trained ward nurses. All had practised recording the target behaviors for several weeks prior to the study, with baseline observations being initiated only when their interobserver agreement with a randomly assigned partner was above 85%. Interobserver agreement was assessed twice during each phase of the study and percent agreement was computed by the Harris and Lahey (1978) formula. The mean interobserver agreement across all behaviors was 86.5%, with a range from 81 to 93%. Mealtime behavior. Using a standardized observational technique (Singh & Beale,

1978), each subject was observed at lunch-time for a variety of mealtime behaviors: appropriate eating, messy eating, eating with fingers, pigging, disruptive behavior, and inappropriate posture. All except the first category reflect negative behaviors. Observations were carried out during the last five days of each treatment phase by behaviorally trained nurses, who had received additional practice in the mealtime observation procedures. Interobserver reliability training and assessment procedures were identical to those for the ward behavior observations. The mean interobserver agreement across all behaviors was 92% with a range of 86 to 94%. In addition to the behaviors noted above, the observers estimated the percentage of the meal actually consumed by the resident.

RESULTS In general, a two-way Analysis of Variance model was used to analyze the data (Winer, 1971). Factor A was a between subjects factor and, depending upon the type of analysis, referred to the following: drug order (3 levels), level of stereotypy (3 levels), degree of hyperactivity (3 levels), and IQ (2 levels). Factor B was a within subject factor and referred to the three drug conditions (placebo, low dose, high dose).

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Overall Drug Effects The results for the Drug Order by Drug analysis are summarized in Table 2 for the Drug factor only. The only therapeutically relevant changes were on Factor I (Aggression/Disruption) of the rating scale. Post hoc tests indicated that the source of significance was between the low and high drug levels (NewmanKeuls test). Placebo did not differ significantly from either drug condition. Methylphenidate resulted in a significant reduction in food consumption, a predictable finding since the drug is known to depress appetite. However, post hoc tests revealed this effect was confined to the high dose which differed from both placebo and the low dose. TABLE 2 Summary for the Effect of Drug Variable Instruction following,

Placebo

MethLow

MethHigh

F

9.33

7.78

7.85

2.49

14.78 2.58 49.53 0.52 4.78 4.48 12.09 4.21 5.26 0.75

12.08 2.44 51.86 1.19 5.93 6.54 9.73 3.93 4.60 1.08

14.08 1.69 51.39 1.37 6.52 3.66 8.70 4.14 5.68 0.70

0.81 0.67 0.20 1.58 0.52 1.67 0.66 0.02 0.44 1.10

87.46 43.99 18.90 7.33 11.03 4.25 6.44 8.07

87.89 41.04 19.17 7.15 11.86 4.36 7.10 9.32

78.75 38.73 16.95 5.77 12.19 5.99 6.97 13.39

3.60* 1.51 0.35 0.97 0.18 1.60 0.07 1.70

30.64 8.21 15.82 11.36 1.14 15.43

29.07 6.75 16.32 11.12 1.04 14.21

30.96 9.86 17.36 10.68 1.29 18.00

0.11 3.91" 0.79 0.15 0.57 1.06

86.72 119.78 75.61 46.14

93.88 122.83 77.96 45.98

88.96 119.56 77.83 45.76

1.72 1.08 0.54 1.14

Ward Behavior Body rocking ( - ) Self-injury ( - ) Other self-stimulation( - ) Destructive/aggressive ( - ) Other inappropriate ( - ) Isolate play Solitary inactive ( - ) Work Appropriate social Inappropriate social ( - )

Mealtime Behavior % Food consumption Appropriate eating Messy eating ( - ) Fingers ( - ) Pigging ( - ) Disruptive ( - ) Inappropriate posture ( - ) Refusal ( - )

Rating Scales AAMD ( - ) I Disruptive ( - ) II Lethargy ( - ) III Stereotypy ( - ) IV Abnormal speech ( - ) V Emotionality ( - )

Physiological Heart rateb Systolic B.P.c Diastolic B.P. c Body weight

Note: Degrees of freedom = 2,50 for all variables with the following exceptions: ,2,48; b2,44; °2,40. Reduced degrees of freedom resulted from loss of subjects due to noncompliance with test procedures. On variables tagged ( - ) , higher scores indicate worsening of behavior. *p < .05

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Michael G. Aman and Nirbhay N. Singh

Because many of the behavioral categories did not occur in individual cases or occurred with very low frequency, a square root transformation was applied (Winer, 1971) and the data were reanalyzed. This had no effect on outcome, and indeed Factor I of the rating scale ceased to show any effect due to the drug. We then wondered whether the drug was causing individual but inconsistent changes in behavior and cancelling out across subjects. To resolve this issue, absolute change scores were computed for each of the three drug conditions with respect to the baseline scores. Analysis of variance (Drug Order X Drug, square root transformation) indicated that the drug did influence the following variables: inappropriate social behavior on the ward, food consumption and inappropriate posture during meals, and Aggression/Disruption and Emotionality/Crying (Behavior Rating Scale), Post hoc tests showed that all changes were restricted to the high dose of methylphenidate. With the exception of Emotionality/Crying, the high dose also differed significantly from the low dose, indicating that the low dose was relatively inert in this group. However, the majority of behaviors appeared to be unaffected even by the high dose.

Prediction of Drug Effect Previous studies of stimulants have generally been unable to document therapeutic changes in mentally retarded persons, particularly in severely mentally retarded subjects. For this reason, an emphasis was placed on prediction of differential response by compelling subject variables. For brevity the individual data are not presented here but are available upon request from the authors. Stereotypy was examined because of its possible relationship to breadth of attention as discussed earlier (see also Aman, 1982-b) and because of its recent emergence as an important clinical variable. The subjects were divided on the basis of stereotypy exhibited during baseline: 0%--66% of observations (moderate), 72%-84% (high), 87%-100% (very high). It was predicted that residents exhibiting lower levels of stereotypy would respond favorably to the stimulant, whereas those exhibiting higher levels would respond adversely. The results were analyzed by a 2-way ANOVA using both the original and transformed scores. Two significant Stereotypy-Drug interactions did emerge but the pattern was not consistent with prediction or readily interpretable by any theoretical scheme. Degree of hyperactivity was also assessed with respect to drug response because of the demonstrated effectiveness of stimulants in treating childhood hyperactivity. The subjects were allocated as follows on the basis of their Abbreviated Hyperactivity Scale score: 0 - 1 2 (low), 13-18 (moderate), 2 0 - 3 0 (high). It was predicted that the subjects rated as most hyperactive would respond favorably to methylphenidate. Only one significant interaction emerged from this set of analyses, and this failed to support the prediction. Finally, the subjects were allocated to low IQ (<9, X = 7.07) or high IQ

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353

( > 1 4 , X = 25.17) groups on the basis of their Slosson IQ scores. As stimulants often have therapeutic effects in children of normal IQ, we predicted the high IQ group would show a more beneficial response to the drug. Only one interaction reached statistically significant levels and it failed to support our prediction.

Clinical Significance of Stereotypy Examination of stereotypy, hyperactivity, and IQ as predictors of drug response also afforded the opportunity to assess each of these variables for its clinical significance. When the subjects were subdivided in this manner, it was found that all three dimensions contributed to the outcome in other variables. However, classification by degree of stereotypy was distinctly the most useful in this respect. The result of subclassifying the group by level of stereotypy is shown in Table 3. It appears that stereotypy may be quite useful in accounting for differences in several ward behaviors including isolate play, work, and appropriate and inappropriate social behavior. This finding is not surprising since stereotypy was measured in the same setting and at the same time of day. It appears less

TABLE 3 Summary for the Effect of Degree of Stereotypy (Square Root Transformations)

Variable Instruction following

Moderate

H i g h VeryHigh

F

3.79

2.61

1.91

9.98***

1.94 0.40 4.68 0.72 1.97 2.58 2.52 2.17 3.22 0.94

2.15 1.43 7.27 0.50 1.91 !.20 3.04 1.21 1.24 0.18

3.14 0.54 7.66 0.42 0.88 0.86 1.71 0.71 0.68 0.46

0.51 2.47 6.82** 0.46 1.68 5.13" 1.54 3.48* 11.36*** 3.55*

5.30 2.68 2.44 2.50 0.44 4.03

5.03 2.39 4.22 3.00 0.66 3.23

5.26 2.43 4.50 3.53 0.45 3.73

0.09 0.12 14.55"** 2.71t 0.15 0.79

Ward Behavior Body rocking ( - ) Self-injury ( - ) Other self-stimulation( - ) Destructive/aggressive( - ) Other inappropriate ( - ) Isolate play Solitary/inactive( - ) Work Appropriate social Inappropriate social ( - )

Rating Scales

AAMD ( - ) I Disruptive ( - ) II Lethargy ( - ) III Stereotypy ( - ) IV Abnormal speech ( - ) V Emotionality ( - )

Note: Degrees of freedom = 2,25 for all variablesexcept InstructionFollowing where df = 2,24. On variables tagged ( - ) , higher scores indicate worseningof behavior. *p < .05 **p < .01 ***p < .001 tp < .lO

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useful in accounting for behavior ratings by ward staff, since it was significantly associated only with Lethargy/Withdrawal and (marginally) Stereotypic Behavior of the Behavior Rating Scale. These subjects were remarkably high on degree of stereotypy, with all except one subject observed to engage in stereotypy more than 34% of the time. Given the homogeneity of the group, the power of this measure in predicting other variables is impressive. DISCUSSION

Overall Drug Changes Over the group as a whole, drug changes were minimal and confined to the high dose. Anorexic side effects, as attested to by the 10% reduction in food consumption, indicates that methylphenidate was indeed active. However, from the viewpoint of clinically relevant changes, the findings were essentially negative. Only Aggression/Disruption of the rating scale was sensitive to the drug conditions, and this finding suggested the low dose of methylphenidate improved behavior whereas the high dose caused deterioration. The analysis of absolute change scores produced a surprising result because only five of the variables showed increased variation under medication. This lack of effect cannot be attributed to inadequate reliability levels, since interrater reliability was very high on all the observational categories both at mealtime and in the ward. Furthermore, a number of studies have shown these to be sensitive indices of behavioral intervention (Singh & Beale, 1978; Singh, Dawson, & Manning, 1981). Therefore, the inevitable conclusion is that methylphenidate produced little in the way of clinically relevant change. Although this negative finding is discouraging from an empirical and theoretical stance, it is consistent with the majority of foregoing studies in this area.

Prediction of Drug Response Breadth of attention and stereotypy. In planning this study, we werewell aware that most previous investigations of stimulant drugs in mentally retarded persons had obtained negative findings. The failure of mentally retarded (and autistic) subjects to respond to such medication posed the intriguing question of what differentiated them from other groups, including normal children and adults, who generally show a positive response to these drugs (Aman, 1982-b). We speculated that the explanation may be related to altered attentional styles which appeared to characterize both of these diagnostic groups. We expected the outcome of no overall drug effect to reflect an underlying process of cancellation in which some subjects responded adversely and others beneficially to the drug.

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Unfortunately, it proved to be impossible to assess any of the subjects directly for breadth of attention and we were forced reluctantly to infer that level of stereotypy may reflect underlying differences in attentional focus. Statistical analysis failed to indicate that stereotypic behavior interacted with drug outcome. Although this does not support the proposed model, the negative findings do not convincingly refute the theory either. We have no assurance that breadth of attention is causally related to stereotypy, although the two are certainly associated clinically. Equally important is the fact that these subjects were very extreme in terms of stereotypy and IQ level. For example, all except three subjects were observed to engage in stereotypic behavior more than 50% of the time during baseline. The mean IQ for the group was 11.96. Such extreme measures suggest that the group may have been very homogeneous, in which case any attempt at prediction may have been doomed at the outset. Other Predictors

There is a massive literature on the effectiveness of stimulant drugs in altering the behavior of hyperactive children of normal IQ. Although the large majority of our subjects were post-pubertal, it appeared reasonable that the most hyperactive and inattentive might respond well to methylphenidate. However, the data failed to support any such relationship. In a similar vein, most of the investigations of stimulant drugs in hyperactive children utilize mental retardation as an exclusion criterion (Gadow & Kalachnik, 1981). Given the demonstrated usefulness of the stimulants in such children (Conners & Werry, 1979), this suggested that IQ or its concomitants may be useful predictors of treatment outcome. However, IQ in the narrow range studied here was unassociated with drug outcome. CONCLUSIONS The desire of investigators to employ a drug which (unlike the neuroleptics) often has beneficial effects on cognitive performance is commendable. However, there simply is no compelling evidence thus far that the stimulants have consistent effects, either beneficial or adverse, on the behavior of severely mentally retarded persons. If such effects do occur, the present study suggests that they are observed only at high doses. Therefore, we believe that further investigations of these drugs in severely mentally retarded people should be discouraged unless they are instigated by a theoretical model which may deal with this apparent lack of effect. Thus far, most investigations of the stimulants in this field have utilized institutionalized subjects who would typically be of very low IQ. This suggests, if further studies of the stimulants are to be undertaken, that it may be most reasonable to include mildly and moderately mentally retarded, non-institutionalized subjects. In this regard it is noteworthy that stimulants represent the most

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c o m m o n l y p r e s c r i b e d p s y c h o t r o p h i c drugs in non-institutionalized m e n t a l l y retarded c h i l d r e n attending special classes ( G a d o w & K a l a c h n i k , 1981). I f greater d i v e r s i t y o f r e s p o n s e is o b t a i n e d in such a sample, then a search for reasofial~le correlates o f therapeutic o u t c o m e m a y be m o r e profitable.

RERERENCE NOTE I. Aman, M. G., Singh, N. N., & Stewart, A. W. A behavior rating scale for the assessment of severely retarded residents. Manuscript in preparation, 1982.

REFERENCES Aman, M. G. Drugs, learning, and the psychotherapies. In J. S. Werry (Ed.), Pediatric psychopharmacology: The use of behavior modifying drugs in children. New York: Brunner/Mazel, 1978. Aman, M. G. Psychotropic drugs and learning problems--A selective review. Journal of Learning Disabilities, 1980, 13, 87-96. Aman, M. G. Psychoactive drugs in mental retardation. In J. L. Matson and F. Andrasik (Eds.), Treatment issues and innovations in mental retardation. New York: Plenum Press, 1982. (a) Aman, M. G. Stimulant drug effects in developmental disorders and hyperactivity--Toward a resolution of disparate f'mdings. Journal of Autism and Developmental Disorders, 1982. (b), 12, 385-398. Aman, M. G., & Werry, J. S. The effects of methylphenidate and haloperidol on the heart rate and blood pressure of hyperactive children with special reference to time of action. Psychopharmacologia, 1975, 43, 163-168. Baumeister, A. A. & Forehand, R. Stereotyped acts. In N. R. Ellis (Ed.), International review of research in mental retardation (Vol. 6). New York: Academic Press, 1973. Campbell, M., Fish, B., David, R., Shapiro, T., Collins, P., & Koh, C. Response to triiodothyronine and dextroamphetamine: A study of preschool schizophrenic children. Journal of Autism and Childhood Schizophrenia, 1972, 2, 343-358. Campbell, M., Small, A. M., Collins, P. J., Friedman, E., David, R., & Genieser, N. Levodopa and levoamphetamine: A crossover study in young schizophrenic children. Current Therapeutic Research, 1976, 19, 70-86. Cantwell, D. P., & Carlson, G. A. Stimulants. In J. S. Werry (Ed.), Pediatric psychopharmacology: The use of behavior modifying drugs in children. New York: Brunner/Mazel, 1978. Conners, C. Rating scales for use in drug studies with children. In Assessment Manual. Rockville, Md.: Early Clinical Drug Evaluation Unit, National Institute of Mental Health, 1976. Conners, C. K., & Werry, J. S. Pharmacotherapy of psychopathology in children. In H. C. Quay & J. S. Went (Eds.), Psychopathological disorders of childhood. New York: John Wiley & Sons, 1979. Gadow, K. D., & Kalachnik, J. Prevalence and pattern of drug treatment for behavior and seizure disorders of TMR students. American Journal of Mental Deficiency, 1981, 85, 588-595. Harris, F. C. & Lahey, B. B. A method for combining occurrence and nonoccurrence interobserver agreement scores. Journal of Applied Behavior Analysis, 1978, 11,523-527. Iversen, S. D. Brain chemistry and behaviour. Psychological Medicine, 1980, 10, 527-539. Lipman, R. S. The use of psychopharmacological agents in residential facilities for the retarded. In F. J. Menolascino (Ed.), Psychiatric approaches to mental retardation. New York: Basic Books, 1970. Lipman, R. S., DiMascio, A., Reatig, N., & Kirson, T. Psychotropic drugs and mentally retarded children. In M. A. Lipton, A. DiMascio, and K. F. Killam (Eds.), Psychopharmacology: A generation of progress. New York: Raven Press, 1978.

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Michael G. Aman and Nirbhay N. Singh

Acknowledgement--This study was funded in part by a grant from the Medical Research Council of New Zealand. The authors wish to thank Dr. D. J. Woods, Medical Superintendent of Mangere Hospital and Training School, Dr. C. Vaithianathan, Dr. A. B. Tompkins, and Mr. A. Chapman for their active support and encouragement. We thank nursing supervisors R. Bovey and J. Gradey for assistance with staff rosters. The following staff are thanked for their cooperation and practical assistance: Maryanne Angell, Nelly Applehoff, Maryan Dawson, Carol Denis, Sue Melvin, Mary Mueller, and Denise Reynolds.