Effects of antipsychotic medication on discrimination learning for institutionalized adults who have...

Behavioral Residential Treatment, Vol. 5, No. 2, 105-120 (1990)

EFFECTS OF ANTIPSYCHOTIC MEDICATION ON DISCRIMINATION LEARNING FOR

INSTITUTIONALIZED ADULTS WHO HAVE M EN TAL R ETA R DAT I0 N

Mark Carpenter, Charles A. Cowart Ellisville State School, Ellisville, Mississippi, USA

R. Steve McCallum and Sherry Mee Bell University of Tennessee-Knoxville, 108 Claxton, Knoxville Tennessee 37996-3400 USA

Reduction in medication levels of drugs used to suppress inappropriate behavior (chlorpromazine, thioridazine and haloperidol) resulted in increases in performance on a discrimination learning task for seven residents of a state institution who are mentally retarded. After training to criterion on a matching-to-sample task, these participants experienced reductions in medication in an N of 1 AB replication paradigm. Two controls were medication free, and one remained on a stable dosage throughout. Improvement of performance on the first dependent variable (number of trials needed to meet criterion) ranged from 13.8% to 53.3% for the seven participants, while the three controls improved less than 1%. Improvement of performance on the second dependent variable (percentage of correct responses) ranged from 2.7% to 19.7% for experimental subjects; five of the seven subjects exhibited a minimum improvement of 8%. The change in percentage of correct responses for the three controls ranged from -4.9 to 1.3. Treatment implications are discussed.

Antipsychotic drugs, which have direct pharmacological effects on the central nervous system, are often used in the treatment of behaviors exhibited by persons who are mentally retarded. The most common therapeutic aim of these drugs is for the suppression of inappropriate behaviors. However, in some instances, pharmacotherapy involves little more than the use of excessive medication as a chemical strait-jacket, a restrictive ‘treatment’ devoid of any therapeutic ben- efit and incompatible with patient habilitation.

Administrators of institutions responsible for providing care and habilitative programming for the mentally retarded have become increasingly sensitive to criticisms involving inappropriate drug use. Regulating agencies have placed tighter restrictions on carte blanche drug administration. An example of this is Standard 22 of the Minimal Constitutional Standards for the Adequate Habili- tation of the Mentally Retarded, which resulted from the Wyatt versus Stickney

0084558 1/90/020 105-1 6S08.00 0 1990 by John Wiley & Sons Ltd.

106 M. Carpenter et al.

(1972) case in Alabama. It states that ‘residents shall have the right to be free from unnecessary medication. Medication shall not be used in quantities that interfere with a resident’s habilitation program’ (p. 18). Consequently, empirical comparisons of the commonly used drugs, their side-effects, and alternative treatments must be evaluated. Limitations of pharmacotherapeutic research with individuals have been identified in literature. Even when conditions are similar, the effectiveness of a particular drug in improving a given target behavior has differed across studies. Consequently, there is a need to provide carefully conducted empirical studies to contribute to the growing drug-behavior interac- tion knowledge base. The purpose of this study was to investigate the effects of modifying the medication levels of antipsychotic drugs on the performance of people who are mentally retarded.

The most common antipsychotic used to suppress undesired behaviors in persons who are mentally retarded are chlorpromazine (Thorazine) and thioridazine (Mellaril), both phenothiazine derivatives, and haloperidol (Haldol), a butyrophenone derivative. Pharmacologically, a11 three of these drugs are very similar. The antipsychotic effect of each centers around its ability to block dopaminerigic receptors in the brain. After the administration of these drugs, the turnover of dopamine receptors is blocked and central stores increase. The ability to block the receptors is related to potency of each drug (Goth, 1974). Because these drugs are administered so frequently in institutional settings there is a continuing need to determine their influence on institutionally relevant appropriate behavior.

Hollis and St. Omer (1972) employed operant techniques to study the effects of graded doses of chlorpromazine on the motor behavior of children who are mentally retarded. Using direct and precise measurement techniques of motor behavior (Lindsey, 1962), the investigators hypothesized that the rate of motor responding would be depressed, in a dose-related manner, under the influence of chlorpromazine regardless of type of motor movement. The results indicated a direct relationship between the quantity of chlorpromazine administered and the rate of responding. Higher increments of chlorpromazine resulted in decreased response rates; also latency to response times increased for all subjects. The investigators concluded that chlorpromazine depressed the types of motor behavior under study and that dosage had a linear effect on response rate. Wysocki et al. (1981) designed a study to assess the effects of thioridazine on performance of a titrating delayed matching-to-sample discrimination in adults who are mentally retarded. With one exception, all of the subjects’ performances increased in the ‘limit of delay’ only after dosage reductions had occurred. ‘Limit of delay’ was defined as the longest delay value at which the subject emitted four consecutively correct responses during a session. The final

EfSects of antipsychotic medication 107

significant finding was that the largest performance increments occurred following the reduction to 0 mg from the previous dosage. The authors concluded that thioridazine impairs delayed matching-to-sample performance of persons with mental retardation.

Overall, the literature suggests that antipsychotic drug use with individuals who are mentally retarded can impair performance in a variety of ways. The effects of antipsychotics have been well documented on intelligence scores (Ison, 1957); on motor ability (Aman et al., 1984, Davis et al., 1969; Hollis and St. Omer, 1972); and on general behavioral and cognitive aspects (Alexandris and Lundell, 1968; Heistad et al., 1982; Singh and Aman, 1982, Wysocki et al., 198 1). Impairments associated with antipsychotic drug use can be detrimental to habilitative programming. The goal of residential retardation centers is to place residents in the least restrictive environment possible. Antipsychotic drug use may interfere with this goal as optimal discrimination and performance cannot be gained from residents while on these drugs, as demonstrated by Wysocki et. al. (1981). The present study extended the findings of Wysocki et al. by examining the effects of three psychopharmacological agents, chlorpromazine, thioridazine, and haloperidol, upon performance of a similar discrimination task. In assessing the effects of these antipsychotic drugs on performance of a delayed matching-to-sample task, the following research question was posed: Will task performance be functionally related to reduction in medication levels?

METHOD Subjects Experimental

Seven residents of a State institution for persons who are mentally retarded served as experimental subjects. Each subject had received a particular daily dosage of chlorpromazine, thioridazine, or haloperidol for at least 90 days prior to the study. An interdisciplinary habilitation team of professionals, including a physician, a psychiatrist, a clinical pharmacologist, and a psychol- ogist, identified each of the subjects as candidates for gradual reduction of medication. No subjects were receiving other psychotropics or anticonvulsant medications.

Con t r 01 Three residents of the same State institution for persons who are mentally

retarded served as control subjects. Two of the subjects were medication-free,

108 M. Carpenter et nl.

while the third subject remained on a stable dosage level of haloperidol for the duration of the study. Further descriptive data regarding experimental and control subject characteristics are presented in Table 1.

Setting and apparatus All testing was conducted in a room measuring 8 feet wide x 12 feet long.

The room contained a table, chair, and a Commodore 64 computer equipped with a joystick and a 19 in CRT. Depression of the fire button on the joystick triggered the projection of one of three 3% cm x 3% cm illuminated squares on the screen. Colors used in the task were red, green, and blue against a white background. Subjects could accurately identify these colors prior to the experiment.

Procedure The subjects received chlorpromazine, thioridazine, and haloperidol orally

in suspension to ensure its ingestion. The nurses in the dormitory administered the medication in equal daily dosages. Base-line dosage levels ranged from 50 mg to 2250 mg. Haloperidol (mg) units were converted to chlorpromazine equivalents. Direct-care workers were not informed of medication changes for any of the subjects. All medication changes were ordered and monitored by the assigned physicians. Directions for the training consisted of the following oral presentation.

‘You are being asked to play a game where you will match colors. When you press the fire button, a color will appear in the center of the screen. This color will then disappear and two more colors will appear. One will be the same color as the first, while the other color will be a non-matching one. You are to move the stick in the direction of the matching color. If you are correct, you will hear a tone. If you are incorrect, the screen will black-out for 10 seconds. When the screen lights up again you can push the fire button and start over. This game takes about 30 minutes. There are not risks involved and you may stop and return to your dorm at any time. You may ask me any questions about the game. No one other than myself will know how well you played this game. Do you have any questions?’

Pre-experimental phase The pre-experimental phase involved training subjects to perform the match-

ing-to-sample task until a criterion of 70% correct responding across two conse-

EfSects of antipsychotic medication 109

cutive sessions was reached. The training and subsequent testing sessions for any given subject were scheduled at the same hour each day and each subject was alone in the testing room during all training and testing sessions. At the start of each trial, depression of the fire button on the joystick illuminated a 3% cm x 3% cm square sample stimulus in the center of the 48 cm screen with one of three colors. The sample stimulus remained visible for a 5 s period, after which the illumination was terminated and two comparison stimuli on either side of the sample were illuminated. One of the comparison colors was identical to the sample, while the other was a non-matching color. Position of the matching comparison stimulus varied randomly. All three colors appeared equally as the sample, matching, or non-matching comparison stimulus. Moving the joystick in the direction of the matching color terminated the comparison stimuli. A screen display consisting of flashing % in block letter spelled the word ‘correct’, and was followed immediately by a 3 s 10 Hz tone. Moving the joystick in the non-matching direction terminated the comparison stimuli for a 10 s time-out period and was accompanied by a 3 s aversive 10 Hz tone. Failure to move the joystick to either side within 30 s of the appearance of the comparison stimuli caused a 10 s time-out period. Trials where no response was made within 30 s were recorded as errors. At the conclusion of a trial, depression of the fire button again illuminated the sample stimulus and the next trial began. When an incorrect response was made, the trial was repeated until the subject responded correctly. Each session lasted for 30 min.

Experimental phase After each subject had performed the discrimination task at 70% accuracy

for two consecutive sessions the experimental phase began. Subjects were tested at their initial dosage levels for two sessions. Following physicians’ recommenda- tions, medication was reduced and subjects performed the delayed matching-to- sample discrimination task biweekly. The procedures during the initial testing trials were identical to those of the pre-experimental phase. After four consecutively correct responses, a 1 s delay between termination of the sample stimulus and illumination for the comparison stimuli was introduced. Each sequence of four consecutively correct responses by a subject resulted in an increase in the delay interval for the subsequent trials following the progression: 0, 1, 2, 3, 4, 5 , 6, 9, 12, 15, 18, 21, 24, 27, 30, 35, 40, 45, 50, 55, and 60 s. The first error following 30 min of testing terminated the session. For subjects who failed to progress through the delay intervals, testing was terminated following 30 min at any given interval.

The dependent variables in the experiment were trials needed to meet the

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criterion of four consecutively correct responses and percentage of correct responses across delay intervals. Data from the study were analyzed by examining trends in performance following medication reductions.

RESULTS

Summative results are reported in Figures 1 through 10 (mean trials to criterion) and 11 through 20 (percentage of correct responses across comparative delay intervals). As is apparent, performance improved for all of the experimental participants on both of the criteria: performance of the control participants reflected no change.

Tables 2 and 3 present overall mean trials to criterion across comparative delay intervals, and percentage of correct responses across comparative delay intervals, respectively.

If a subject completed four delay intervals during base-line, but completed eight delay intervals during the final sessions, only the first four intervals are compared in Table 2. All seven experimental subjects improved in the number of trials required to meet criterion following medication reductions. The percentage improvement ranged from 14.1 to 53.3. The three control subjects improved less than 1%. The percentage of correct responses across comparative delay intervals is presented in Table 3. Five of the seven experimental subjects had a minimum improvement of 8%. The remaining two experimental subjects (Sub- jects 5 and 6) improved 2.9% and 2.7%, respectively. The small improvement for Subjects 5 may be due to a ceiling effect. That is, his performance during base-line was over 87% accurate, creating a leveling effect. The three control subjects’ change in percentage of correct responses ranged from -4.9 to 1.3.

DISCUSSION

The focus of this project was to examine the effects of reduced dosage levels of chlorpromazine, thioridazine, and haloperidol on performances of a discrimination learning task by mentally retarded individuals. The results indicate a relationship between dosage of antipsychotic medication and performance on a delayed matching-to-sample task.

Decreasing dosage levels of antipsychotic medications resulted in improved performance on the matching-to-sample task. Improvement in performance, as measured by trials-to-criterion and accuracy-of-responding, was observed following medication reductions. The conclusion that performance improve-

Effects of antipsychotic medication 113

ments were related to decreased levels of medication was further substantiated by the finding that no improvement was observed for the control subjects across six testing sessions. These robust findings are noteworthy because of their con- sistency across subjects of varying characteristics and across different drugs and drug levels. That is, regardless of varying subject characteristics, such as age, gender, race and institutionalization history, and regardless of drug and drug level, performance improved concomitantly with reductions in drug doses.

However, the design of the study is limited in some ways and generalizability is reduced. For example, only three antipsychotics were used. Chlorpromazine is generally being prescribed less frequently because it appears to have the highest potential for causing adverse side-effects (i.e. extrapyramidal symptoms and tardive dyskinesia). Other commonly prescribed antipsychotics from the phenothiazine group include thiothixene, fluphenazine, and esoridazine, as well as more butyrophenones.

Another limitation occurred as a function of the limited number of subjects. The small number of subjects in each specific drug group precluded a comparison of effects across drugs. Third, the medication levels of subjects participating in this project ranged from 0 mg to 2250 mg in chlorpromazine units. Unequal medication levels, as well as unequal reductions, make between-subject comparisons questionable. Finally, standard doses have not been clearly specified. Researchers have suggested that different doses should be separated by nondrug periods (no drug or placebo), which are long enough to allow the effects of prior doses to disappear (Sprague and Werry, 1971). Using a standard dose, based on units of the drug per unit of body weight (mg/kg/day), would yield a more accurate assessment of the drug’s effects (Sprague and Werry, 1971).

Other designs were considered and abandoned, for various reasons. For example, the use of a withdrawal design (ABA) has been recommended by Sprague and Werry (1971). The ABA design allows each subject to alternately receive the drug and a placebo and is tested under each condition, yielding a more powerful design than the single case AB design implemented for the present 10 subjects. However, the implementation of medication solely for the purpose of a reversal would raise ethical, as well as practical, questions.

The possibility that improved performance on the task for reasons other than the reduction of medication was considered. For example, the possibility of practice effects is rejected for a number of reasons. First, results are certainly consistent with those of previous studies, which show that antipsychotics impair performance in many areas including: intelligence test performance (Ison, 1957), motor ability (Aman et al., 1984, Davis et al., 1969; Hollis and St. Omer, 1972), and general behavioral and cognitive functioning (Alexandris and Lundell, 1968; Heisted, et al., 1982; Singh and Aman, 1981). The present results also support

114 M . Carpenter et al.

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Figures 6-10. Accuracy of performance across delay intervals.


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Efects of antipsychotic medication 117

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TABLE 2. Mean trials to criterion.

Medication YO % Trial Subject Dosage range" reduction Base-line Final reduction

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44.1 35.9 21.8 13.8 14.1 17.9 53.3 0.3 0.3 0.7

All medication converted to chlorpromazine equivalents. a = chlorpromazine equivalents. b = thioridazine. c = chlorpromazine. d = haloperidol. *No drug modifications made for these subjects.

TABLE 3. Percentage of correct responses across comparative delay intervals.

Medication % % Increase of Subject Dosage range" reduction Base-line Final correct responses

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All medication converted to chlorpromazine equivalents. a = chlorpromazine equivalents. b = thioridazine. c = chlorpromazine. d = haloperidol. *No drug modifications made for these subjects.

previous research findings by Wysocki et al., (1981) using a similar delayed matching-to-sample task, which con trolled for practice effects by using a reversal design with one of their subjects. In addition, the finding that three subjects on stable medication not undergoing any drug modifications evidenced no prac-

Effects of antipsychotic medication 119

tice effect lends further strength to the conclusion that improvement in performance of the experimental subjects was medication related. In comparison to the experimental group, the control subjects demonstrated minimal changes in performance. Of the three control subjects, none improved more than 1.3% across testing sessions on the two dependent variables (trials to criterion and accuracy of performance). The improvement for the experimental subjects ranged from 13.8% to 53.3% on trials to criterion, while improvement in accuracy of performance ranged from 2.7% to 19.7%.

The findings reported here present a dilemma for the health care professional who serves extremely aggressive residents. In the absence of a primary psychi- atric disorder, the primary value of antipsychotics appears to be their ability to produce a relatively nonselective sedation. Sedated persons may be less likely to engage in any behaviors, desirable or undesirable. For example, Subject 1 received thioridazine in conjunction with behavioral therapy to assist in con- trolling his aggressive outbursts. Following a reduction to no medication, trials to criterion on the matching-to-sample task improved 44.1% from base-line to the final session. Accuracy of performance also improved (19.7%) from base- line to a medication-free state, suggesting that learning is enhanced when medication is decreased. On the other hand, after Subject 1 became medication-free, his aggressive acts increased, complicating treatment. Obviously not all retarded individuals can be taken off antipsychotic medication without undesirable behaviors emerging, and this results in a complicated decision-making process for administrative personnel.

In summary, performance in situations requiring stimulus discrimination may be impaired when residents receive antipsychotic medication. Habilitation programming places mentally retarded individuals in planned learning situations in which stimulus discrimination with delayed response is required. Examples of such situations include instructional procedures that require a specific response to occur at some delay following verbal instruction or the presentation of models or prompts (Burgio et al., 1985; O’Brien and Azrin, 1972; Wunderlich, 1972). Primary care-givers should be made aware of the impairment, and make appropriate modifications of their expectations. When possible, drug levels should be reduced. However, the successful management of residents who fail to respond to behavioral interventions will continue to be a serious problem for health care providers. There is evidence that antipsychotic medication impairs performance in a number of areas, but decreasing the dosage, or discon- tinuing the medication, appears to produce an increase in maladaptive behaviors. Future research examining antipsychotic medication effects should focus on identifying a minimal effective dosage level, that, in conjunction with behavioral therapy, produces an optimal performance in learning situations.


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