The effects of intermittent drug therapy on stereotypy and collateral behaviors of mentally retarded persons

Research in Developmenrol Drznbilrlres. Vol. 8, pp. 211-227. Printed in the USA. All rights rcservtd.

1987

0891-4222/8753.00 + .OO Copyright 0 1987 Rrgamon Journals Inc.

The Effects of intermittent Drug Therapy on Stereotypy and Cgllateral Behaviors of Mentally Retarded Persons C. Jane Millichamp Nirbhay N. Singh University ofCanterbury New Zealand

A double-blind, placebo-controlled study was conducted to assess the effects of intermittent drug therapy on stereotyped and collateral behaviors of six profoundly mentally retarded, institutionalized, adult males. The subjects, all of whom had received antipsychotic medication for more than three years, had their maintenance dosages gradually reduced by almost half during the eight-month study. A multiple baseline across subjects design was utilized to assess drug effects on object and body stereotypy and a range of collateml behaviors. While there was individual variation across behaviors and subjects, the main finding was that despite the marked reduction in medication, there were no geneml changes of clinical significance in any of the behaviors. This finding is of considerable therapeutic importance since a very large number of institutionalized mentally retarded persons receive similar long-term medication for behavior problems and there is some concern regarding the adverse side effects of such treatment.

*This study was funded in part by a grant from the University of Canterbury (# 592055) to NNS. The authors thank Dr. J. Marshall, Medical Superintendent of Templeton Hospital, Dr. R. Nixon, Peter Bootsma, and Engel Scholten for their active support and encouragement. The staff members of Cedar Villa who participated in this investigation are thanked for their cooperation and assistance, with special thanks to Jane Guillen, Robin Phillips, and Trish Falconer for their practical assistance. This paper benefited from the comments of Alan Winton, Kelly D. Brownell, and R. Douglas Greer on an earlier draft. This research was approved by the Ethics Committee of the Canterbury Hospital Board and the residents’ institutional authorities. Address correspondence and reprint requests to: Nirbhay N. Singh, Department of Psychology, University of Canterbury, Christchurch, New Zealand. 213

214

C. J. Millichamp and N. N. Singh

Approximately two-thirds of institutionalized mentally retarded persons engage in one or more forms of stereotyped behavior (Berkson & Davenport, 1962; Kaufman & Levitt, 1965). These behaviors refer to repetitious, invariant motor responses that occur at a very high rate and are characterized by their rhythmicity, irrelevance, and acausality (Lewis & Baumeister, 1982). Examples of such behavior include body rocking, head weaving, complex hand movements, arm and leg movements, object spinning, and stringtwirling, Although stereotyped behaviors do not result in physical harm to the client, they are maladaptive and interfere with their learning. Research shows that stereotypy and adaptive behaviors are “functionally incompatible” (Koegel & Covert, 1972; Risley, 1968), and that stereotypy and adaptive environmental interaction may be inversely related (Whitman, Scibak, & Reid, 1983). The treatment of stereotypy has often involved the use of behavioral techniques, including differential reinforcement, removal of positive reinforcement, punishment, and several overcorrection procedures. However, with mentally retarded persons and particularly those who are severely or profoundly mentally retarded, the main form of therapy currently used in most institutions is pharmacotherapy. In general, about half the residents in institutions for the mentally retarded receive psychotropic medication for behavior problems, including stereotypy, often for extended periods of time (Aman, 1983; Sprague & Baxley, 1978). There are two major problems with pharmacotherapy for the mentally retarded. One of the problems is that although the mentally retarded are given antipsychotic maintenance medication, at present little is known of the long-term consequences of such treatment. The most serious consequence of long-term treatment appears to be tardive dyskinesia, a movement disorder characterized by involuntary, rhythmic, and repetitive movements of the face, mouth, and extremities (Gualtieri & Hawk, 1980). No effective treatment for tardive dyskinesia is currently available (Baldessarini & Tarsy, 1978). Other long-term effects may include factors which influence cognition, growth, and the endocrine system. The other major problem is that despite the widespread use of antipsychotic medication, there are few well-controlled investigations which have established the efficacy of such treatment for specific behavior problems of the mentally retarded. Indeed, there are few established indications for the use of antipsychotic medication with this population. However, stereotypy is one problem behavior which has shown a response to antipsychotic drug therapy (Singh & Aman, 1981). Current research indicates that chlorpromazine, thioridazine and haloperidol are useful in decreasing stereotypy in mentally retarded and autistic children, particularly in those who exhibit stereotypy at a high baseline rate or are severely or profoundly mentally retarded (Aman & Singh, 1986).

inrerrnitrent Drug Therapy

21.5

Given that antipsychotics may be useful in controlling the stereotypic behavior of some mentally retarded persons and that antipsychotic maintenance medication may have adverse side effects, it is useful to investigate ways by which behavioral control can be maintained within minimum levels of maintenance medication. A systematic method of decreasing maintenance medication is through intermittent drug therapy. In this procedure, the client’s daily medication is gradually decreased to medication on only some days of the week. Although such a procedure has not been employed with mentally retarded persons, studies with schizophrenic adults show that their maintenance medication can be reduced to four days per week without any clinically significant deterioration in behavior (Prien, Gillis, & Caffey, 1973). Similar results have been obtained in other investigations with psychiatric patients on antipsychotic medication (Caffey et al., 1964; Chien & DiMascio, 1971; Greenberg & Roth, 1966; Olson & Peterson, 1962). When taken in concert, the results of these investigations suggest that intermittent drug therapy is a safe, effective and economical method of reducing antipsychotic maintenance medication. The present study was designed to assess the effects of intermittent drug therapy on the behavior of mentally retarded adults. The subjects chosen for study had been on antipsychotic maintenance medication for behavior problems including stereotypic behavior. Stereotypic behavior was chosen as the target variable since any clinically significant changes due to intermittent drug therapy should be most marked for this behavior. Finally, the effects of intermittent drug therapy were tested in a setting in which no behavioral programming was occurring. METHOD

Subjects and Setting Six young men participated. All had been diagnosed as profoundly mentally retarded according to the AAMD criteria: (Grossman, 1983) and had been maintained on antipsychotic monotherapy for the management of stereotypy and other behavioral problems. No subject was observed to display dyskinetic movements. Further subject details are presented in Table 1. Informed consent and ethical approval were obtained from the residential authorities and the Ethics Committee of the Canterbury Hospital Board. The subjects lived in a residential unit with 37 other profoundly and severely mentally retarded adult males. During observations, they were in the dayroom, a large sparsely furnished room. Throughout the study, the subjects were not involved in any treatment or training programs other than the informal recreation encouraged by institutional staff.

2 o\

Profoundly mentally retarded of unknown etiology

Profoundly mentally retarded due to maternal rubella

Profoundly

Ian

Dennis

Kevin

aOn AAMD criteria (Grossman, hFairview language age.
1983).

mentally retarded

Profoundly mentally retarded due to maternal rubella

Profoundly mentally retarded and right Hemaplegia due to cerebral palsy

Richard

Craig

Profoundly mentally retarded of unknown etiology

Etiology’

Hugh

Subjects

Age

37

18

20

I7

12

22

(Yrs)

1.5

2

6

12

I2

12

Language Age (Mth+

3.4

7.9

17.6

7.5

I2

17.6

Behavioral Age (Mths)’

2.5

17.6

Chlorpromazine

Chlorpromazine

Methotrimeprazine

Methotrimeprazine

11.6 20.2

Methotrimeprazine

Methotrimeprazine

Drug

19.1

17.3

Social Age (Mths)”

TABLE 1. Subject Characteristics

I50

75

75

150

125

150

Mg/day

3

2.2

1.3

3.5

5

2.4

Mg/kg

6

6

I

3

3

5

Yrs on Medication

Intermittent

Drug Therapy

217

Response Definitions Nine categories of behavior were formulated prior to the study from daily observations of the subjects over a two-week prebaseline period. A wide range of both appropriate and inappropriate behaviors were included for observation so that specific effects of intermittent drug therapy could be monitored. The categories and their definitions aretpresented in Table 2. Data Collection and Reliability Four observers with previous experience in behavioral observation procedures received additional training prior to and throughout the study. Data were collected by one observer, randomly assigned an a daily basis. A second observer was also randomly assigned on 25% of the sessions during each phase for reliability checks. An interval recording technique was used to collect data on a daily basis in an unstructured ward setting. All observations occurred between 9 a.m. and 11 a.m., five days a week. No observations were scheduled during the weekends. Each observation session of 15 minutes was divided into 90 consecutive lo-second intervals. The end of each lo-second interval was signalled through earplugs to the primary observer. The reliability observer, when present, received the same signal. Baseline observations were undertaken only when the interobserver’agreement between randomly assigned observer pairs was above 85% on the Weighted-Agreement (W-A) index (Harris & Lahey, 1978). The W-A index was used since it provides a conservative measure of agreement and has been found to be the index of choice for behavioral drug studies (Towns, Singh, & Beale, 1984). Where both observers agreed on total occurrence or total nonoccurrence of a behavior session, the W-A index was scored as 100%. Percentage agreements were calculated by multiplying all indices by 100. The interobserver agreements summed across the six subjects ranged from 76% to 100% for the nine behaviors, with a mean of 93%. The mean (range in parentheses) for each behavior across all subjects was: object stereotypy 98% (94-loo), body stereotypy 91% (87-95), aggressive/destructive 94% (87-99), vocal sound 84% (76-92), other 89% (85-91), pica 100% (IOO), social interaction 98% (95-loo), self-injury 97% (91-lOO), walking/skipping 95% (87-98), and toy play 87% (79-94). Experimental Design A multiple baseline across subjects design (Kazdin, 1982) was used to assess the effects of intermittent drug therapy on the behavior of each subject. This study employed a double-blind, placebo-control. Before baseline observations were initiated, each subject’s medication was changed

C. J. Millichamp and N. N. Singh

218

TABLE 2. Response Definitions of Behavior Observed

Categories Stereotypy Object Body

Definitions Any repetitive manipulation of objects, e.g., spinning, rubbing, tapping, fiddling with objects. Any repetitive movements involving only body parts, e.g., body-rocking or swaying, repetitive hand, finger, limb or head movements, teeth grinding, masturbation.

Aggressive/ Destructive

Any violent or negative physical behavior directed at people or objects, e.g., biting, scratching, hitting or forceful pushing of others, and, hitting, throwing or slamming objects in the dayroom.

Vocal Sound

Repetitive or continuous vocal sounds of a noncommunicative nature, e.g., humming, inappropriate laughter, screaming without provocation, uttering meaningless syllable combinations.

Pica

Placing inedible or non-nutritive objects in mouth, chewing and/or swallowing them, e.g., string, clothing, cigarette butts.

Social Interaction

Any positive prosocial behavior directed at staff or residents, e.g., touching, patting, hand-holding, eye contact, smiling, or friendly-sounding vocalization with communicative intent.

Self-injury

Any deliberate action causing harm to resident’s own body, e.g., hand-biting, head-banging, face-scratching.

Walking/Skipping

Resident makes two or more steps in the same direction (for Craig, crawling on all fours is included in this category).

Toy Play

The manipulation of toys in an appropriate manner, e.g., throwing ball to another person, block-building.

from tablets to capsule form. Throughout the study, each subject received one capsule three times a day at meal times. Following baseline, placebo capsules were substituted for active medication capsules on specified days. The placebo capsules were individually prepared to taste, look and smell exactly like the active medication for each subject. Each dose, active or placebo, was individually packaged and had each subject’s name, date and time of administration written on it. Throughout the study, the subjects continued to receive their pre-study dosages on the days when medication was administered. Double-blind conditions were maintained during the first three phases, and a single-blind condition was maintained during the fourth phase. Placebos were withdrawn in the final phase during which the subjects

Intermittent

Drug Therapy

219

received their regular medication (in tablet form) on four days and no medication on the other three days of each week. The study consisted of the following five phases: Phase I: Baseline. During baseline all subjects received their usual drug dosage (see Table 1). For Hugh, Richard, Craig, Ian, Dennis, and Kevin the baseline period lasted 10, 15, 20, 25, 30, and 35 days, respectively. Phase 2: Reduction. Following baseline, all subjects participated in the 3week drug reduction phase. During the first week, all subjects ceased to receive active medication for one day of the week (Monday). Active medication was still administered on six days, with placebo on the seventh. During the second week, active medication was replaced by a placebo on two days (Monday, Wednesday) and the subjects received their usual medication on the other five days. During the third week, active medication was replaced by placebo on three days (Monday, Wednesday, Friday) with active medication being administered on the other four days. Phase 3: Intermittent drug phase. Following the reduction phase, the days on which the placebos were administered were changed to make the procedure more practical from a nursing point of view. In the first week, the drug-free day on Friday was changed to Saturday and in the second week, the drug-free day on Monday was changed to Sunday. Thus, from the third week of this phase all subjects received placebos on Saturday, Sunday, and Wednesday, and active medication on Monday, Tuesday, Thursday, and Friday. They continued to receive the active medication in the same dosages as they did prior to the study. The length of this phase was six weeks. Phase 4: Open phase. In this 3-week phase, placebos continued to be administered as described above, but the nursing staff were informed that all subjects were on active medication only on four days of each week and on placebos the other three days. However, they were not informed on which days placebos were administered. Phase 5: Maintenance. This condition lasted between 80 days (Kevin) and 104 days (Hugh). No placebos were administered on the three drug-free days. The subjects received their usual medication, in tablet form, on the other four days. The observers were naive to the experimental conditions and operated under blind conditions throughout the study.

220

C. J. Millichamp and N. N. Singh

RESULTS The daily rate of stereotypic behavior across all experimental phases is presented in Figure 1. The phase means of all behaviors observed for all subjects are presented in Table 3.

Stereotypy Overall, four subjects (Hugh, Craig, Dennis, Kevin) showed little change in the total frequency of their stereotypic behavior (i.e., object plus body stereotypy). When compared to baseline, their stereotypic behavior in the maintenance phase changed only by a maximum of f 6.4%. Three subjects (Hugh, Craig, Kevin) showed a minimal, clinically insignificant, decrease in stereotypy. The other three subjects showed an increase, one (Dennis) minimally and the other two (Richard, Ian) by 15% and 19%, respectively. However, some notable changes in the occurrence of stereotypy were observed when the two types (object and body) were analyzed separately. Although Hugh’s object stereotypy decreased by 40’70, his body stereotypy increased by 30%. Craig’s object stereotypy increased slightly and Dennis’s object stereotypy increased dramatically during the reduction phase. Richard’s body stereotypy increased by 20% and Ian’s object stereotypy increased by 24% while his body stereotypy increased by about 13‘70.

Collateral Behaviors Aggressive/destructive behaviors. Two subjects (Ian, Kevin) did not exhibit these behaviors and two others (Craig, Dennis) exhibited them a few times only during the drug reduction phase. Of the two subjects who exhibited these behaviors during baseline, the frequency decreased for one (Hugh) and remained at about the same level for the other (Richard). Vocal sound. Vocal sound generally altered little although there was some variability between phases for some subjects (e.g., Richard). The only major change was noted with Craig whose vocal behavior increased dramatically from baseline to maintenance. Pica. Pica was not exhibited to any significant degree by four subjects (Hugh, Craig, Dennis, Kevin) across the five phases. Ian showed a minor decrease when his drugs were reduced and Richard showed a small decrease. In addition, there was some variability in the frequency of Richard’s pica between phases.

IrzrermittentDrug Therapy

FIGURE 1. Percent occurrence of stereotyped behaviors (object and body) across all experimental conditions. For the reduction and intermittent phases, the small letters with arrows beside them indicate the days on which placebos were given each week. Where these letters end, placebos continue to be administered as indicated by the last set of letters (i.e., SWS). Gaps in the data occur where the subject was asleep, sick, or away from the institution during the observation period.

Social interaction. Minimal or no social interaction occurred with five subjects. Richard showed a minimal, clinically insignificant, decrease although there was some interphase variability in his behavior. Self-injury. Self-injury occurred at very low levels or not at all in five subjects. The sixth subject’s (Richard) self-injury increased slightly during

222

C. J. Millichamp and N. N. Singh

the drug reduction phase but decreased during each successive phase to just below baseline level in the maintenance phase. Walking/skipping. The frequency of walking/skipping decreased in two subjects (Hugh, Richard). No clinically significant changes were noted with the other four subjects. Toy play. Toy play varied little across all phases for five subjects. Richard’s toy play increased during the drug reduction phase but decreased thereafter to about half of the baseline level.

DISCUSSION The data from this study show that, overall, there was little deterioration in the subjects’ behavior despite a major reduction in their weekly maintenance dosage. Some changes were noted in the occurrence of both body and object stereotypy but these were not of a magnitude to suggest that the overall results are not still clinically significant. Generally, no clinically significant changes were observed in the collateral behaviors of all subjects. Thus, the major conclusion that can be drawn from this study is that intermittent drug therapy offers a viable method of reducing maintenance medication in the mentally retarded without a concomitant loss of behavioral control. The overall results were the same for all subjects regardless of the dosage of their maintenance medication prior to intermittent drug therapy. The subjects’ dosages were neither excessively high nor low and appeared to be typical for residents at the subjects’ institution. Thus, the findings can usefully be generalized to the broader population of mentally retarded persons at this institution. In addition, the subjects in the present study showed similar responses to drug reduction regardless of the particular antipsychotic medication (i.e., chlorpromazine or methotrimeprazine) they were on. This suggests that residents on other antipsychotics (e.g., thioridazine, haloperidol) may also respond to intermittent drug therapy in a similar manner. There are other implications of the current research. Recent studies on the effects of ,antipsychotic medication with mentally retarded adults suggest that high maintenance dosages may impair their rehabilitation and learning performance (see Aman, 1984). Intermittent drug therapy may provide one method for reducing such effects by decreasing the weekly drug dosage of mentally retarded persons. Although no formal testing was instituted in the present study, nursing and medical staff did not report observing any withdrawal dyskinesia in any of the subjects. This was probably due to the fact that the dosages were typically not very high. In addition, since

Intermittent

223

Drug Therapy

TABLE 3. Percentage Occurrence of BehaviorsAcrossExperimentalConditions

Pica

Social Interaction

Self Injury

Walking/ Skipping

Toy Play

Stereotypy Experimental Condition 1. Hugh Baseline Reduction Intermittent Drug Therapy Open Maintenance 2. Richard Baseline Reduction Intermittent Drug Therapy Open Maintenance 3. Craig Baseline Reduction Intermittent Drug Therapy Open Maintenance 4. Ian Baseline Reduction Intermittent Drug Therapy Open Maintenance 5. Dennis Baseline Reduction Intermittent Drue Therapy Open Maintenance 6. Kevin Baseline Reduction Intermittent Drug Therapy Open Maintenance

Object

Body

Aggressive/ Destructive

Vocal Sound

53.3 40.5 29.4

63.6 87.8 89.9

4.7 1.7 0.5

19.1 11.5 8.9

0.1 0.9 0.0

0.0 0.6 0.1

0.1 0.5 0.0

11.6 5.1 1.8

0.0 0.1 0.0

50.5 13

67.5 93.3

0.5 0.1

13.5 18.3

0.0 0.1

0.0 0.3

0.0 0.0

4.9 2.1

1.4 0.4

16.5 19.5 24.9

23.5 51.1 68.7

0.2 0.0 0.2

38.5 46.5 37

8.5 4.9 24.4

7.9 11.5 9.2

5.3 9.5 7.2

74.1 43.9 41.1

4.4 13.4 1.9

31.1 22.5

49.5 46.4

0.5 0.2

43 33.1

13.9 13.6

8.6 6.9

5.4 5.0

57.7 51.4

2.0 2.3

0.1 7.7 4.9

97.6 81.7 81.7

0.0 0.0 0.0

1.5 0.0 0.1

0.1 0.0 0.0

0.1 0.0 0.0

0.0 0.0 0.4

1.1 0.0 0.0

0.0 0.0 0.0

7.3 6.3

92.7 78.6

0.2 0.0

3.7 13.6

0.0 0.0

0.0 0.1

0.1 1.9

2.3 1.1

0.0 0.0

39.5 51 75.1

50.8 41.8 69

0.0 0.0 0.0

2.8 1.3 0.8

6.0 0.5 2.1

1.8 2.1 0.4

0.0 0.0 0.0

32.2 19.5 37.6

0.0 0.1 0.0

55.3 63.8

53.7 63.7

0.0 0.0

0.1 4.8

3.8 4.9

0.0 0.4

0.0 0.0

18.7 34.8

0.0 0.1

57.6 80.2 63.8

98.2 88.8 98

0.0 0.0 0.1

5.3 0.1 5

0.0 0.0 0.0

0.3 0.1 0.2

0.3 0.1 0.5

1.5 1.2 2.8

0.0 0.0 0.3

66.3 67.5

95.9 94.5

0.0 0.0

8.3 6.5

0.0 0.1

0.0 0.1

0.3 0.3

3 3.6

0.0 0.0

9.2 13 11.4

86.3 88.9 96.1

0.0 0.0 0.0

0.0 0.1 0.6

0.0 0.0 0.1

0.0 0.0 0.0

0.0 0.0 0.0

0.0 0.0 0.0

0.0 0.0 3.1

7.3 10.5

89 84

0.0 0.0

0.4 I.7

0.0 0.0

0.0 0.0

0.0 0.1

0.0 0.0

0.0 0.0

224

C. J. Millichamp and N. N. Singh

no measures of learning were incorporated in the present study, nothing can be said about the effects of intermittent drug therapy on learning. Future research must include formal measurement of changes in these two important variables. A finding pertinent here is that of Singh and Aman (1981) who reported that stereotypy was best controlled by thioridazine at a 2.5 mg/kg dose rather than by higher, individually titrated doses. This study suggests that dosage may be an important parameter of drug response and that lower dosages may produce equivalent or better control of behavior than higher dosages. The present study supports these findings by showing that an intermittent drug schedule produces similar behavioral control as a daily drug schedule. However, the present study did not investigate whether there would have been a significant loss of behavioral control if the subjects’ drugs had been completely withdrawn. If it is established that drug therapy is indeed necessary then it must be determined whether an effective minimum daily dose (as established via a dose-response curve) is more effective than intermittent drug therapy of the client’s individuahy titrated dose. Indeed, pharmacologically it might make more sense to provide a minimum daily dose rather than a higher intermittent dose. However, this is an empirical question which only future research can answer. Intermittent drug therapy provides a viable method for assessing the current medication requirements of individual clients. It may be useful to build-in a three- to four-week drug holiday period every few months so that the necessity for medication can be behaviorally assessed. Indeed, drug holidays are not only desirable but established in case law in the United States (see Coldbrook decision). The present study provides an objective methodology for assessing the effects of such a procedure. In addition the effects of medication on other variables can be assessed during this period, including drug-withdrawal symptoms (Gualtieri, Quade, Hicks, Mayo, & Schroeder, 1984), tardive dyskinesia (Gualtieri & Hawk, 1980), and learning (Aman & Singh, 1983). Further, as suggested by Lipman (1982), it may be found that the original reason for medication may no longer operate for the subject and can be withdrawn completely. Given that the results were generally positive, it would have been interesting to see how far the drugs could have been reduced in the present study. This could have been accomplished either by continuing to administer drugs on a progressively more intermittent schedule, or by titrating the daily dosages. Behavioral programming has been widely shown to be effective in controlling maladaptive behaviors of mentally retarded persons (Whitman et al., 1983). Therefore, the use of drugs without any attempts at controlling these behaviors by behavioral means is questionable. The present study points to the appropriateness of reducing drugs to discover the underlying

Intermittent

Drug Therapy

22s

rates of behavior which can then be subjected to appropriate behavioral/ educational interventions. It must be emphasized that the present study was conducted in a setting where no behavioral programming was occurring and that medication was the treatment of choice for controlling maladaptive behavior. Thus, our results should best be interpreted as applying only to nonprogrammed settings. In an interesting study, Saxe (1984) found that stereotypy actually decreased with the gradual removal of drugs (thioridazine) in a highly controlled environment which used extensive behavioral programming. Future research could assess the effects of intermittent drug therapy in such environments or in environments where reinforcement could be provided for the nonoccurrence of stereotypy (or other maladaptive behaviors). In addition, observations could be undertaken in several settings so that the subject’s behavior could be sampled in settings which differed only in terms of the degree of structure provided by the caregivers. One of the problems of the present study was in the choice of subjects. While all the subjects responded in a similar way, the data show that three of six subjects engaged in stereotypy at very high levels during baseline, thereby leaving little possibility of showing deterioration during intermittent drug therapy. It could be argued that these subjects were non-responders (i.e., not showing a reduction in stereotypy by about 25%) and therefore medication was inappropriate for them anyway. This is certainly possible. Future studies should select subjects who can be shown to be drug responders before initiating intervention. In sum, the present study showed that it is possible to use intermittent drug therapy with profoundly mentally retarded persons without a clinically significant loss in behavioral control. In this respect, the study extends the research initially carried out with schizophrenic patients (e.g., Caffey et al., 1964; Chien & DiMascio, 1971; Greenberg & Roth, 1966; Olson & Peterson, 1962; Prien et al., 1973) to institutionalized mentally retarded persons. However, because of some of the limitations discussed above it should be seen as an initial attempt to assess the effects of intermittent drug therapy with mentally retarded persons.

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Aman, M. Cl., & Singh, N. N. (1983). Pharmacological intervention. In J. L. Matson & J. A. Mulick (Eds.), Handbook of mental retardation (pp. 317-337). New York: Pergamon. Aman, M. G., & Singh, N. N. (1986). A critical appraisal of recent drug research in mental retardation: The Coldwater studies. Journal of Mental Deficiency Research, 30, 203-216. Baldessarini, R. A., & Thrsy, D. (1978). Tardive dyskinesia. In M. A. Lipton, A. DiMascio, & K. Killiam (Eds.), Psychopharmacology: A generation of progress (pp. 993-1004). New York: Raven. Berkson, G., & Davenport, R. K. (1962). Stereotyped movements of mental defectives, I: Initial survey. American Journal of Mental Deficiency, 66, 849-852. Caffey, E. M., Diamond, L. S., Frank, T. V., Grassberger, J. C., Herman, L., Klett, C. J., & Rothstein, C. (1964). Discontinuation or reduction of chemotherapy in chronic schizophrenics. Journal of Chronic Diseases, 17, 347-358. Chien, C., & DiMascio, A. (1971). Clinical effects of various schedules of medication. Behavioral Neuropsychiatry,

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