Using analog baselines to assess the effects of naltrexone on self-injurious behavior1

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Research in Developmental Disabilities, Vol. 20, No. 1, pp. 1–21, 1999 Copyright © 1999 Elsevier Science Ltd Printed in the USA. All rights reserved 0891-4222/99/$–see front matter

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Using Analog Baselines to Assess the Effects of Naltrexone on Self-Injurious Behavior David Garcia and Richard G. Smith University of North Texas

Naltrexone (NLTX), an opiate receptor antagonist, has been prescribed as a pharmacological intervention for the treatment of self-injurious behavior (SIB). Previous research has investigated NLTX’s effects in the absence of information about the role of environmental events related to SIB. This study extended previous analyses by administering NLTX on analog baselines using a double-blind, placebo-controlled reversal design. Pretreatment functional analysis results showed that the SIB of the two participants occurred in more that one assessment condition. For one participant NLTX produced slight reductions in SIB across baseline conditions. The second participant’s results showed that NLTX reduced head-slapping occurring during demand sessions, but had no apparent effect on head-banging occurring during alone and demand sessions. These outcomes suggest that NLTX may have function- and/or response-specific treatment effects. The potential utility of this model as a general method for assessing pharmacological interventions, as well as other implications and limitations, are discussed. © 1999 Elsevier Science Ltd

Over the past three decades, a significant amount of research has been generated on variables related to self-injurious behaviors (SIB). An operant account of This research was supported in part by a grant from the Texas Higher Education Coordinating Board and is based on a thesis submitted by the first author in partial fulfillment of the requirement for a Master of Science degree. The authors acknowledge the support of the Denton State School and the assistance of Angela Gonzalez and Robert Churchill during the conduct of this study. Address correspondence to: Richard G. Smith, Ph.D., Department of Behavior Analysis, University of North Texas, P.O. Box 13438, Denton, TX 76203.

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self-injury (e.g., Carr, 1977) has proven useful for prescribing effective treatments that obviate the need for superimposing reinforcement or punishment contingencies over unknown and uncontrolled maintaining contingencies (Mace, 1994). Treatments that are not derived from information about the functional properties of SIB may be effective only if the reinforcing or aversive properties of the contrived contingencies are capable of overriding the reinforcement maintaining SIB. Iwata and colleagues (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982) developed an operant methodology to identify the variables maintaining SIB before treatment. The authors repeatedly exposed participants to several conditions designed to simulate those related to SIB in the natural environment (e.g., stimulus deprivation, contingent attention, and contingent escape from tasks). By examining the effects of these analog conditions on SIB, maintaining variables could be identified, allowing treatments to be matched to the function of the behavior. Knowledge of the functional properties of SIB leads to two general treatment strategies: 1) weakening the response-reinforcer relationship maintaining SIB; and 2) using the reinforcer maintaining the aberrant behavior to establish an appropriate alternative to SIB (Mace, 1994). Thus, identifying responsereinforcer contingencies increases the number of treatment options available and improves the probability that interventions will be effective in reducing SIB. As Mace pointed out, “the functional analysis of aberrant behavior has made tremendous advances since and because of the Iwata et al. (1982) publication” (1994, p. 389). In addition to examining the effects of different environmental conditions on behavior problems, analog assessment methods provide a framework for the analysis of basic behavioral processes associated with behavior disorders (Vollmer & Smith, 1996). By first identifying the reinforcer maintaining an inappropriate behavior it is possible to examine the effects of extinction, reinforcement frequency, magnitude of reinforcement, and other related variables (Vollmer & Smith, 1996). Analog baselines may also be used to assess behavioral mechanisms associated with pharmacological treatments. If relationships between pharmacological and other environmental variables can be shown by conducting functional assessments prior to and during pharmacological treatments then it may be possible to identify behavioral “markers” correlated with positive treatment response. For example, participants that exhibit particular patterns of SIB during functional analysis (e.g., persistence of SIB in the absence of social consequences) may be identified as potential responders to a given medication. In recent years, procedures used to treat SIB have frequently involved interventions that disrupt the contingencies maintaining the behavior (Day, Rea, Schussler, Larsen, & Johnson, 1988; Durand & Carr, 1991; Iwata, Pace, Kalsher, Cowdery, & Cataldo, 1990; Northup et al., 1991). Such procedures have been highly effective when matched to pretreatment functional assess-

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ments showing SIB to be maintained by environmental events such as caregiver attention, access to tangible items, and escape from aversive tasks. However, for a subgroup of individuals with SIB, preliminary functional assessments generate undifferentiated results, failing to identify one or more conditions as differentially correlated with SIB (Iwata et al., 1994; Mace & Mauk, 1995). Individuals in this subgroup often do not respond to behavioral interventions (Mace & Mauk, 1995). Recent studies suggest that particular biochemical abnormalities may play a role in the SIB of some individuals. Several investigations have implicated enhanced brain opioid activity in the maintenance of SIB (Herman, 1990; Sandman, Barron, & Coleman, 1990; Thompson, Hackenberg, Cerutti, Baker, & Axtell, 1994). Also, laboratory preparations have demonstrated animal models for particular kinds of biochemical involvement in SIB. For example, Herman (1990) induced self-injury in laboratory rats by administering high doses of an opiate agonist (Sufentanil). Several of these animals gnawed off the digits of their paws when opioids were administered. In addition, researchers have found that nonhuman primates that have a history of morphine consumption will self-administer synthetic enkephalins (i.e., biochemical substances shown to produce morphine-like analgesic effects) when morphine is no longer available (Mello & Mendelson, 1978). The results of these studies are consistent with the involvement of endogenous opioids in SIB and show that participants who are exposed to opioids (e.g., morphine) may engage in behavior that will continue to produce similar biochemical substances. Recently, the effects of the opioid antagonist naltrexone (NLTX) on SIB have been investigated (Crews, Bonaventura, & Rowe, 1993; Knabe, Schulz, & Richard, 1990; Sandman et al., 1990; Smith, Gupta, & Smith, 1995; Thompson et al., 1994). NLTX, which competes with opioid substances at receptor sites in the central nervous system, has a half-life of approximately 8 hr (Thompson et al., 1994) and a duration of action of up to 24 hr (Herman, 1990). NLTX presents an attractive treatment option because very few side effects have been reported in the literature (Casner & Weinheimer, unpublished observations; Herman, Hammock, Arthur–Smith, Kuehl, & Applegate, 1989; Thompson et al., 1994). For example, Herman et al. (1989) evaluated the physiological effects of NLTX (at doses of 0.5, 1.0, 1.5 & 2.0 mg/kg) on cardiovascular function (e.g., blood pressure and heart rate), body temperature, body weight, and serum concentrations of liver enzymes in five autistic children and found no significant side effects on any of these measures (Herman et al., 1989). Sandman et al. (1990) examined the effects of three doses (25, 50, 100 mg) of NLTX on SIB using a double-blind, Latin square, experimental design. Results indicated that NLTX reduced SIB in all four participants. Three participants showed a dose-dependent decrease in SIB, with the lowest rates occurring at the highest dose of NLTX (100 mg). In a similar study, Smith et al. (1995) administered NLTX to two participants (50 mg for Participant 1, 100 mg for Participant 2) using a within-participant withdrawal design. During baseline

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conditions both participants engaged in high levels (range 5 5 to 14 episodes per day) of several different topographies of SIB (e.g., face-hitting, headbanging, hand-biting, eye-gouging, biting, and picking sores). NLTX completely eliminated SIB in both participants. However, the higher dose of NLTX (100 mg) produced more rapid suppressive effects. Similarly, Crews et al. (1993) reported the effects of NLTX (75 mg) on a single participant. During a pretreatment baseline their participant engaged in continuous SIB (no mean daily frequency of SIB was provided). In the treatment condition the mean daily frequency of SIB episodes decreased to 1.57 episodes per day and remained low during a 6-month follow-up (mean of 1.29 episodes per day). Several hypotheses have been proposed to explain the effects of NLTX. First, the self-administration account suggests that SIB may be positively reinforced by the release of endogenous opioids, producing a “euphoric” effect (Aman, 1991; Sandman et al., 1990). Opioid antagonists (i.e., NLTX) compete with endogenous opioids at the receptor sites by binding to the receptors but not activating them. By blocking opioids from their receptor sites, reinforcing consequences are withheld and extinction may occur. A related account asserts that repeated self-administration of endogenous opioids results in physical dependence and that SIB may be maintained by avoidance or escape of withdrawal distress (Thompson et al., 1994). According to this account, NLTX prevents endogenous opioids from binding to their receptor sites, thus withholding the negatively reinforcing consequences maintaining SIB. A third account suggests that enhanced brain opioid activity produces excessive levels of endogenous opioids, resulting in an elevated pain threshold for certain individuals (Crews et al., 1993; Herman, 1990; Sandman et al., 1990). Such effects may allow SIB to be maintained by socially mediated consequences, without the normal experience of pain. According to this hypothesis, NLTX prevents an increase in the pain threshold allowing individuals to contact automatic aversive consequences (i.e., punishment) produced by SIB. If the aversive properties of SIB override the reinforcing effects of socially mediated consequences, then SIB decreases. Despite encouraging results of several investigations, some individuals have failed to respond favorably to NLTX as treatment for SIB. Zingarelli and colleagues (1992) examined the effects of NLTX (50 mg) on the SIB and related inappropriate behaviors of eight autistic adults. Results indicated that although one participant showed a slight decrease in the frequency of inappropriate behaviors, NLTX did not significantly reduce any participant’s SIB. Other investigators have reported similar results (Benjamin, Seek, Tresise, Price, & Gagnon, 1995; Campbell et al., 1993; Campbell et al., 1989). Such variability in treatment response suggests that different mechanisms may be involved in the maintenance of SIB for responders versus nonresponders to NLTX (Casner & Weinheimer, 1995; Schaal & Hackenberg, 1994; Thompson et al., 1994). Thompson et al. (1994) found that NLTX (50 and 100 mg) had responsespecific effects for three of eight participants. NLTX selectively decreased the

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rate of specific topographies of SIB (e.g., hand-to-head hitting, wrist-biting, hand-biting, and hand-to-chin hitting) while having little or no effect on other topographies (e.g., throat-poking and nose-poking). Based on these findings, the authors suggested that: 1) forms of SIB that were not affected by NLTX may be produced or maintained by social or other environmental events that are unrelated to the opioid receptor antagonist; and/or 2) that different topographies of SIB may selectively stimulate the release of endogenous opioids. Forms of SIB that release high levels of opioids may be most sensitive to NLTX as treatment (Thompson et al., 1994). Recently, researchers have called for an integrated approach that recognizes the role of environmental events when examining the behavioral effects of pharmacological treatments (Schaal & Hackenberg, 1994). Northup and his colleagues have begun to investigate such interactive effects. For example, this research team recently conducted a study in which antecedent and consequent conditions were systematically arranged to examine possible interaction effects between methylphenidate, a pharmacological treatment for school-related behavior problems of children diagnosed with attention deficit hyperactivity disorder (Stoner, Carey, Ikeda, & Shinn, 1994), and environmental contingencies (Northup, Jones et al., 1997). Results indicated that the problem behavior of their subject was maintained by peer attention in the absence, but not in the presence, of methylphenidate. In another study, data indicated that methylphenidate could alter the reinforcement value of common classroom consequences (Northup, Fusilier, Swanson, Roane, & Borrero, 1997). Several authors have suggested that functional-analysis procedures might be useful to increase our understanding of the influence of endogenous opioids on SIB (Casner & Weinheimer, 1995; Iwata, 1994). The present study utilized analog baselines as described by Iwata et al. (1982) to examine the effects of NLTX on SIB. Before administering NLTX, analog baselines were conducted to identify environmental conditions correlated with SIB. Subsequently, NLTX was administered while continuing to conduct baseline sessions. The goals of this study were to describe a functional-assessment methodology that may: 1) help isolate function-specific effects of NLTX on SIB; 2) contribute toward an understanding of the biobehavioral mechanisms involved in SIB and NLTX interactions; and 3) provide a preliminary model for identifying participant characteristics associated with positive outcomes to treatment with NLTX.

METHOD Participants and Setting Two adult females living in a state residential facility participated in this study. Each participant had previously received a diagnosis of profound mental retardation and was referred to a day treatment program for assessment and treatment of their SIB.

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Gilda was 29 years old and had an extensive history of head-banging and knee-hitting (knee-hitting did not occur during the assessment and so is not included in this analysis). Gilda exhibited a few manual signals to request preferred items and physical contact from caregivers and parents. She received Prozac 20 mg per day for depression, Tegretol 1200 mg per day to control for seizures, and Tranxene 7.5 mg per day to reduce her behavior problems. These medications remained constant throughout the study. Betty was 42 years old, and had an extensive history of SIB (i.e., head-banging and head-slapping). Her head-banging produced frequent swelling of her forehead and had resulted in a permanent loss of vision in her left eye. Betty had no apparent vocal verbal repertoire, but did use a few manual gestures to request preferred items or restroom breaks. She received Depakote 3000 mg per day to control for seizures and Trazadone 200 mg per day to help her sleep patterns. These medications remained constant throughout the study. This study was conducted in a building designated for assessment and treatment of SIB, located on the campus of a large residential and training facility. Couches, chairs, and tables were provided in the therapy room at all times, but toys, work and leisure materials varied according to experimental conditions. The duration of the sessions was 10 min (Betty) and 5 min (Gilda) and typically took place 5 days per week, between 1:00 p.m. and 3:30 p.m. Session durations were determined in part by the rate and severity of the participants’ SIB during initial observations at the treatment center. Typically, each participant participated in four sessions per day (range 5 two to eight sessions per day).

Response Measurement and Reliability Topographies of SIB were defined as follows: head-banging—forceful contact by the head against any furniture, wall or floor; head-slapping—forceful contact between an open hand and any part of the head or face. The primary dependent variables were responses per minute (rpm) of headbanging (Gilda and Betty) and head-slapping (Betty). During each session data were continuously recorded using hand-held computers (Newton Message Pad Model 100) onto which software designed for collecting behavioral data had been installed. Interobserver agreement was assessed by having a second observer simultaneously, but independently, collect data during 29.3% of all observations (26.1% of sessions with Gilda and 32.6% of sessions with Betty). Percentage agreement scores were calculated by dividing session time into consecutive 10-s intervals, dividing the smaller number by the larger number of responses observed during each interval, and averaging those values across the session. The mean percentage agreement for Gilda’s head-banging was 97.5% (range 5 76.0 –100%). Mean percentage agreement for Betty’s head-banging

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was 94.6% (range 5 77.1–100%) and 99.1% for head-slapping (range 5 89.2–100%). Experimental Design Each participant was exposed to four analog baseline conditions presented in a multi-element format. Pretreatment baselines were conducted for 51 sessions (Betty) and 44 sessions (Gilda). Treatment conditions were implemented using a double-blind, placebocontrolled, reversal design. The order of phases for Gilda was placebo, NLTX, placebo, and NLTX (beginning on session 303 the blind condition was removed). For Betty, the order of phases was placebo, NLTX, placebo, NLTX, baseline (no placebo administered to participant), and NLTX (blind removed). Throughout the analysis, analog baseline conditions were presented using a multi-element format. Phases were time-limited at 21 days to expedite the analysis; however, phases were extended for up to 7 additional days based on the experimenters’ determination of ongoing trends or excessive variability in the data. NLTX or placebo was administered in a capsule form at 8:00 a.m. daily by nursing staff. Only the pharmacist had knowledge of and access to the drug/placebo codes. Analog Baseline Conditions Analog baselines were conducted for each participant based on procedures described by Iwata et al. (1982). Alone The participant was observed alone in a therapy room, without access to materials that might function as external sources of stimulation. No social consequences were programmed for SIB. This condition was designed to simulate a “barren environment,” where SIB may persist in the absence of socially mediated consequences. If SIB persists in the absence of social contingencies then it is possible that it is maintained by automatically produced consequences. Attention The participant was placed in a therapy room where leisure materials (i.e., toys and games) were available. The experimenter directed the participant to “play with the toys while I do some work,” then engaged in other activities (i.e., complete paperwork, read a manuscript or book). Contingent on SIB, the experimenter approached the participant and provided brief attention in the form of concern or social disapproval (e.g., “Don’t do that; you’ll hurt yourself”) and

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brief physical contact (e.g., hand on shoulder). All other responses emitted by the participant were ignored. This condition was designed to simulate situations in which SIB produces caregiver attention, and was conducted to assess whether the participant’s SIB was sensitive to attention as a form of positive reinforcement. Demand The participant was placed in a therapy room with task materials present (tasks were selected for each participant based on informal observations conducted before the assessment indicating a low probability of compliance). During demand sessions, the participant was seated on the floor, and the experimenter initiated learning trials approximately every 30 s, using a graduated three-prompt procedure (verbal instruction, visual prompt, physical guidance) if compliance did not occur within 5 s. If compliance occurred the experimenter delivered social praise and the trial was terminated. Contingent on SIB, the experimenter terminated the trial and turned away from the participant until the next scheduled trial. SIB that occurred within 5 s of the next scheduled trial delayed that trial for an additional 5 s. This condition was designed to assess if SIB was sensitive to negative reinforcement in the form of escape from instructional demands. Control The participant was placed in a therapy room where no instructional tasks were presented and leisure materials (e.g., toys and games) were available within the participant’s reach. Approximately every 30 s the experimenter provided social attention (e.g., “you look very nice today”) and brief physical contact. There were no social consequences for SIB. This condition functioned as a control in which little SIB was expected to occur due to the availability of potentially stimulating materials, high level of noncontingent attention and the absence of instructional tasks. Treatment Conditions Placebo. In this condition each participant was administered two placebo capsules (consisting only of baking soda) daily, at 8:00 a.m. Participants continued to be exposed to analog baseline conditions while self-injurious responses were recorded. Naltrexone. In this phase, each participant received two capsules consisting of a mixture of baking soda and NLTX (2 mg/kg of participant’s body weight) daily at 8:00 a.m. As in the placebo phase, participants continued to be exposed to the analog baselines while self-injurious responses were recorded.

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FIGURE 1. Pretreatment assessment outcomes. Top panel shows rates of head-banging for Gilda, center panel shows rates of head-banging for Betty, and bottom panel shows rates of head-slapping for Betty.

RESULTS AND DISCUSSION Participant 1: Gilda Pretreatment Analog Assessment. Figure 1 displays the outcomes of each participant’s analog assessment. During Gilda’s assessment (top panel), rates of head-banging were variable both within and across test conditions, and were consistently low in the control condition. Mean rpm of head-banging was 4.3 in demand (range 5 1.2 to 7.2), 4.0 in alone (range 5 0.4 to 7.0), 3.7 in attention

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FIGURE 2. NLTX assessment outcomes for Gilda during alone (top panel), attention (center panel), and demand (bottom panel) sessions.

(range 5 1.0 to 7.8), and 0.1 in the control condition (range 5 0 to 0.8). The functional assessment generated undifferentiated results, failing to identify one or more test conditions as differentially correlated with SIB. Naltrexone versus Placebo Comparison. Figure 2 shows the results of Gilda’s NLTX assessment. The top panel shows rpm of head-banging during alone sessions, the center panel shows rpm of head-banging during attention sessions, and the bottom panel shows rpm of head-banging during demand sessions.

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Although control sessions continued to be conducted throughout the NLTX assessment, data from these sessions are not shown because no SIB was observed in this condition. During the first placebo phase, rates of head-banging were variable across test conditions. In general, higher rates of responding occurred in alone and demand conditions relative to the attention condition, and there was a decreasing trend in the attention condition with the exception of the 14th session, during which Gilda emitted 12.2 rpm. Mean rpm of head-banging was 3.7 in demand (range 5 1.0 to 6.8), 3.0 in alone (range 5 0 to 6.2), and 2.3 in attention (range 5 0 to 12.2). During the first NLTX phase, Gilda’s head-banging decreased to zero in the alone and attention conditions. Head-banging continued to occur at variable rates throughout the demand condition, but showed a decreasing trend overall. Mean rpm of head-banging was 2.6 in demand (range 5 0 to 6.0), 1.3 in alone (range 5 0 to 3.8), and 1.0 in attention (range 5 0 to 5.0). During the second placebo phase, Gilda’s head-banging was variable, with increasing trends in the demand, alone, and attention conditions. Mean rpm of head-banging was 3.8 in demand (range 5 0 to 7.8), 2.5 in alone (range 5 0 to 8.2), and 1.5 in attention (range 5 0 to 5.8). In the second NLTX phase, head-banging decreased to zero within 10 sessions, but then recovered in all test conditions. Finally, Gilda’s head-banging seemed to stabilize at relatively low levels in alone and attention conditions, but continued to occur at higher and more variable rates in the demand condition. Mean rpm of head-banging was 2.6 in demand (range 5 0 to 7.0), 1.5 in alone (range 5 0 to 4.2), and 1.1 in attention (range 5 0 to 4.0). Comparison of average rates of head-banging across test conditions and phases reveals two interesting findings. First, mean rates of responding within baseline conditions were always lower during NLTX phases than during placebo phases. Second, condition means were rank-ordered demand, alone, attention, and control during all phases. Outcomes of Gilda’s assessment suggest that her SIB may have been controlled by multiple contingencies. The persistence of head-banging during demand sessions supports a negative reinforcement account of her SIB (i.e., that her SIB was maintained by escape from instructional demands). Gilda also exhibited SIB during alone conditions, suggesting a nonsocial function for her head-banging. Although head-banging persisted during contingent attention conditions, it was not elevated over conditions when no attention was provided. Thus, although Gilda’s SIB may have been maintained by contingent attention, her data are also consistent with maintenance of SIB by escape and nonsocial variables only. Results of Gilda’s NLTX assessment show small but generalized decreases in SIB across test conditions, although these patterns were most apparent during alone and attention conditions. Whereas SIB decreased during demand sessions in the first NLTX phase, no such decreases occurred during the second NLTX

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phase. Thus, any possible effects of NLTX seem to have been limited to SIB maintained by nonsocially mediated consequences and/or by contingent attention. At least three accounts of decreases in Gilda’s SIB during NLTX phases are tenable. If Gilda’s SIB in alone and attention conditions was maintained by a common, nonsocial mechanism, then decreases in head-banging may have been attributable to extinction. That is, Gilda’s SIB may have been reinforced through self-administration of endogenous opioids (Aman, 1993), which was disrupted because of the inability of the endogenous opioids to occupy their receptor sites. The gradual, simultaneous decreases in head-banging during alone and attention conditions and the selective effects of NLTX on only these baselines are consistent with this account. Alternatively, it is possible that Gilda’s SIB was maintained by consequences other than endogenous opioids (e.g., by contingent attention, escape, and some unknown nonsocial mechanism) but that NLTX allowed her behavior to contact the automatic aversive consequences produced by SIB. That is, because NLTX can increase sensitivity to pain, SIB may have been more aversive during NLTX phases than during placebo phases. However, this account requires an explanation for persistence of Gilda’s SIB during demand conditions, because putative punishment effects of NLTX would be expected to be effective across conditions. Alternatively, establishing operations (EOs) present during demand sessions may have been sufficient to override the punishing effects of SIB; that Gilda’s escape behavior decreased slightly during NLTX phases is consistent with this account. Finally, it is possible that different consequences maintained SIB during alone and attention baselines and separate mechanisms were responsible for the decreases in SIB observed on those baselines. If Gilda’s SIB was maintained by both nonsocial consequences and attention, then only decreases in SIB on the alone baseline can be accounted for by extinction because SIB continued to produce reinforcement during the attention condition. In this case, the mechanism(s) responsible for the possible effects of NLTX in the attention condition may have involved punishment or an EO effect in which the reinforcing properties of attention as a consequence for SIB were reduced. Although the pharmacological effects of NLTX do not provide a strong basis for such an account, results of a recent study suggest that certain pharmacological treatments may have an EO effect on reinforcing stimuli (Northup, Fusilier et al., 1997).

Participant 2: Betty Because casual observations and anecdotal reports suggested that Betty’s head-banging and head-slapping occurred in different contexts, her headbanging and head-slapping data are displayed separately. This facilitated an

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assessment of function- and response-specific effects of NLTX on different topographies of her SIB. Pretreatment Analog Assessment. The outcomes of Betty’s initial analog assessment are displayed in the center and bottom panels of Figure 1. The center panel shows rpm of head-banging across conditions and the bottom panel shows rpm of head-slapping across conditions. Rates of head-banging initially were variable both within and across alone, demand and control conditions, and were generally low in attention sessions. After the 24th session, rates of head-banging typically were higher during alone than other conditions. Mean rpm of headbanging was 10.5 in alone (range 5 0 to 27.8), 1.8 in demand (range 5 0 to 7.4), 0.9 in attention (range 5 0 to 3.5), and 3.0 in play (range 5 0 to 14.3). These results suggest a nonsocial function for her head-banging. Rates of head-slapping were higher in the demand than in other test conditions. Mean rpm of head-slapping was 2.1 in demand (range 5 0.1 to 9.0), 0.6 in alone (range 5 0 to 4.9), 0.1 in attention (range 5 0 to 0.7), and 0 in play. These results suggest that head-slapping was sensitive to escape from tasks as a form of negative reinforcement. Naltrexone versus Placebo Comparison. The results of Betty’s NLTX assessment are displayed in Figure 3. The top panel shows rpm of head-banging during alone sessions, the center panel shows rpm of head-banging during demand sessions, and the bottom panel shows rpm of head-slapping during demand sessions. Because head-banging rarely occurred during attention and play sessions, and head-slapping rarely occurred during alone, attention, and play sessions, these results are omitted from the display (these data are available from the second author upon request). The top and center panels of Figure 3 show high and variable rates of head-banging during the first placebo phase. Mean rpm of head-banging was 16.5 in alone (range 5 0 to 31.1) and 11.0 in demand (range 5 0 to 23.0). When NLTX was introduced, high and variable rates of head-banging continued during the alone condition; however, a decreasing trend was observed in the demand condition, from 13.5 rpm in the first session to 2.8 rpm in the last session. Mean rpm of head-banging was 12.0 in alone (range 5 0 to 24.1) and 7.9 in demand (range 5 0.7 to 13.5). During the second placebo phase, head-banging occurred at high and variable rates in both alone and demand conditions. Mean rpm of head-banging was 13.9 in alone (range 5 0 to 26.6) and 7.6 in demand (range 5 0.3 to 17.1). During the second NLTX phase, head-banging continued to occur at high and variable rates throughout the alone condition. In the demand condition headbanging occurred at rates similar to those in the previous placebo phase. Mean rpm of head-banging was 14.7 in alone (range 5 3.0 to 22.5) and 8.3 in demand (range 5 0.4 to 17.8). After the second NLTX phase, there was a brief return to baseline (because

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FIGURE 3. NLTX assessment outcomes for Betty’s head-banging during alone (top panel) and demand (center panel) sessions, and for Betty’s head-slapping during demand sessions (bottom panel).

of an inability to obtain NLTX for several days) that produced higher rates of head-banging in the alone condition relative to the previous phase. In the demand condition, head-banging continued to occur at rates similar to those in the previous phase. Mean rpm of head-banging was 28.7 in alone (range 5 28.1 to 29.4) and 10.8 in demand (range 5 3.8 to 14.5). During the third NLTX phase, high rates of responding continued to occur in the alone condition. In the demand condition, rates of head-banging remained similar to those observed in

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the previous three phases. Mean rpm of head-banging was 23.6 in alone (range 5 11.1 to 33.3) and 9.1 in demand (range 5 2.1 to 19.0). The bottom panel of Figure 3 shows the results of Betty’s NLTX assessment on head-slapping during demand sessions. During the first placebo phase rates of head-slapping were variable during demand sessions, but showed a decreasing trend overall. Mean rpm of head-slapping in demand was 5.0 (range 5 0 to 10.0). Head-slapping continued to show a decreasing trend during the first NLTX phase (mean 5 2.1; range 5 0 to 4.7 rpm). During the second placebo phase, head-slapping occurred at variable rates in the demand condition, with an increasing trend overall (mean 5 3.6; range 5 0 to 10.3 rpm). Upon reintroduction of NLTX, head-slapping initially continued to occur at variable rates, but then decreased sharply to near zero (mean 5 3.5; range 5 0.1 to 10.5 rpm). During the brief return to baseline, rates of head-slapping were variable and showed a general increase relative to the previous NLTX phase (mean 5 4.9; range 5 0 to 9.2 rpm), and in the final NLTX phase (blind-removed), headslapping again decreased to near zero (mean 5 1.1; range 5 0 to 5.2 rpm). Overall outcomes of Betty’s assessment suggest that her SIB may have been controlled by multiple contingencies. The persistence of head-banging during alone sessions supports a nonsocial function for this behavior. However, Betty also exhibited head-banging throughout demand sessions, suggesting that it also may have been maintained by escape from instructional demands. To investigate whether head-banging was maintained only by nonsocial variables or was multiply controlled by both nonsocial reinforcement and social-negative reinforcement, within-session patterns of head-banging and of head-slapping were examined. Ten demand sessions were quasi-randomly selected for inspection based on the following criteria: 1) both head-banging and head-slapping occurred during the session; and 2) at least one demand session from each phase of the experiment was selected. The total number of responses of each topography emitted, the proportion of responses within each topography that were functional escape responses (i.e., the first response occurring within 15 s of the initiation of a task trial, given that no compliance had been recorded), and the proportion of all escape responses by topography were calculated. Results showed that 251 head-slaps and 887 head-bangs were recorded; 35.1% of head-slaps were functional escape responses, whereas only 0.7% of head-bangs produced escape. Of all escape responses, 93.6% were head-slaps and only 6.4% were head-bangs. Thus, head-slaps often occurred during task trials, producing trial termination, whereas head-banging rarely produced escape and occurred most frequently during intertrial intervals. These findings are consistent with an account that head-slapping was maintained by escape, and that head-banging was maintained by other (apparently nonsocial) variables. Results of Betty’s NLTX assessment showed that although there was a generalized decrease in head-banging during the first NLTX phase, no decreases were observed during the second and third NLTX phases. Thus, the decreasing trend in head-banging during the first treatment phase seems not to have been

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a function of NLTX. Results of the assessment of Betty’s head-slapping showed that NLTX decreased head-slapping during demand conditions to zero or near-zero levels of head-slapping. At least two accounts of NLTX’s effects on Betty’s head-slapping are tenable. Betty may have had enhanced brain-opioid activity, producing levels of endogenous opioids resulting in an elevated pain-threshold (Crews et al., 1993; Herman, 1990; Sandman et al., 1990). Such effects may have allowed headslapping to be maintained by socially mediated consequences (i.e., escape from instructional demands) without the normal experience of pain. During NLTX phases, head-slapping may have been more painful than during placebo phases. However, the persistence of Betty’s head-banging seems inconsistent with this account, because punishment effects should generalize across topographies (i.e., head-banging and head-slapping) and behavioral functions (i.e., social and nonsocial functions) of SIB. A second account suggests that the mechanism responsible for the effects of NLTX may have involved an EO effect in which the reinforcing properties of escape as a consequence for head-slapping were reduced. Some studies have shown that NLTX can facilitate learning, promote prosocial behavior, and increase tolerance of touch (Smith et al., 1995; Taylor, Sandman, Touchette, Hetrick, & Barron, 1993); thus, it is possible that NLTX increased Betty’s tolerance of instructional trials, reducing aversive aspects of the demand situation that previously occasioned head-slapping. GENERAL DISCUSSION The current study represents the first evaluation of NLTX using experimentally controlled baselines. By using controlled baselines, effects of NLTX were investigated while eliminating or holding constant extraneous variables that may have an effect on dependent measures. Previous studies investigating NLTX’s effects have typically, conducted observations in natural settings and have not controlled for changes in the environment that may have contaminated results. Further, many studies have used rating scale outcomes that may not represent actual changes in behaviors as primary data (e.g., Leboyer et al., 1992). By using experimentally controlled baselines and conducting direct observations, the current study limited the effects of potential confounds and increased the confidence with which measured changes in responding may be attributed to NLTX. Whereas merely exercising control over baseline conditions can reduce the influence of extraneous variables on behavior, systematic arrangement of baseline conditions can produce additional benefits. Using analog baselines that simulate environmental conditions under which SIB may occur permits analysis of NLTX’s effects on behavior maintained by various contingencies and may help identify function-specific treatment effects. Other arrangements may obscure treatment effects if: 1) conditions under which SIB occurs are not

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presented; or 2) conditions that are correlated with SIB are presented among other, uncorrelated, conditions. For example, if an individual’s SIB is maintained by escape, but task trials are not presented consistently, results of NLTX assessment may be unclear. Similarly, if the individual is exposed to demand trials but sometimes receives attention as a consequence for SIB during the same observational periods, then it would be difficult to identify function-specific effects of NLTX on escape maintained SIB. It is possible that limited control may account for results showing that NLTX had little or no effect on the SIB of some individuals (Benjamin et al., 1995; Campbell et al., 1993; Campbell et al., 1989; Zingarelli et al., 1992). Alternatively, it is equally plausible that endogenous opioids were unrelated to the SIB of “nonresponders” in these studies. Evaluating NLTX’s effects across a set of independent baselines, each of which is designed to simulate a reinforcement contingency for SIB, may help to clarify function-specific effects. The current data suggest that NLTX may have produced function-specific effects both between- and within-participants. That is, NLTX decreased Gilda’s nonsocially mediated SIB and Betty’s escape maintained head-slapping. However, although NLTX reduced Betty’s negatively reinforced head-slapping, it had no apparent effect on her nonsocially maintained head-banging. These results are interesting for two reasons. First, they provide preliminary evidence that specific variables associated with nonsocial SIB may be different across individuals. For example, data suggesting that NLTX primarily affected Gilda’s nonsocially maintained SIB suggest that endogenous opioids may have been involved in the maintenance of her SIB. In contrast, NLTX did not have an effect on Betty’s nonsocially mediated head-banging, suggesting that endogenous opioids were not related to this behavior. Although both participants displayed nonsocial SIB, these outcomes provide preliminary evidence that specific mechanisms of control may have been idiosyncratic (it must be noted that this account is limited to the extent that NLTX may have reduced Gilda’s SIB via punishment, rather than extinction). Second, isolating function-specific effects of NLTX on SIB may help to provide a basis for identifying participant characteristics associated with positive outcomes to treatment with NLTX. If differences in assessment results can be related to differences in treatment with NLTX, then empiric criteria for prescribing NLTX can be developed. Analog baselines could be used as an initial screening procedure to indicate whether individuals might be responders or nonresponders to treatment with NLTX. Of course, current results are preliminary, and the utility of functional-analysis outcomes for predicting NLTX outcomes would require replication of the current procedures across a large number of participants. This model may also contribute toward an understanding of behavioral mechanisms associated with NLTX’s effects on SIB because inferences about exactly how NLTX affects SIB may be drawn based on differential outcomes. For example, if SIB is maintained by nonsocially mediated mechanisms and NLTX decreases responding, then it may be inferred that extinction has oc-

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curred or that pain associated with SIB was able to override the nonsocial mechanism(s) maintaining this behavior. Specific patterns of responding might suggest the particular process associated with the decrease. For example, an immediate and dramatic decrease in responding would suggest a punishment effect, where as an initial increase followed by a slow decrease in responding, would suggest extinction. If NLTX produced decreases in SIB maintained by social consequences (i.e., escape from instructional demands or contingent attention), then it may be inferred that the mechanisms responsible for the effects of NLTX involved punishment, or an EO effect in which NLTX reduced the reinforcing properties of SIB’s maintaining consequence. It is unlikely that decreases in SIB could be accounted for by extinction in such cases, because SIB would continue to produce reinforcement (i.e., escape from task trials or attention) during demand or attention baselines. Although the present study suggests that assessing the effects of NLTX within the context of functional-analysis baselines may provide a better understanding of the relationship between NLTX and SIB, the results should be interpreted with caution. For instance, although NLTX seemed to decrease Gilda’s SIB across conditions, these effects were neither unequivocal nor clinically significant. Similarly, Betty’s evaluation showed that NLTX reduced one topography of SIB, but did not appear to have a treatment effect on a second topography. Thus, neither participant in the current study showed the dramatic effects reported by some other investigators (e.g., Crews et al., 1993), and each required subsequent behavioral interventions to produce acceptable treatment outcomes. In addition, the current study evaluated the effects of NLTX on the SIB of only two participants. Future research using functional-analysis baselines before and during NLTX assessments with a large number of participants will be necessary to determine whether pretreatment response patterns can be used to predict who will be responders versus nonresponders to NLTX. Future studies also should conduct longer phases than those used in this investigation. It is possible that extending the length of phases in the current study would have helped clarify any possible function-specific effects of NLTX on SIB. For example, in Gilda’s NLTX assessment, a general decreasing trend in alone and attention conditions occurred during the final NLTX phase; it is possible that SIB would have reduced to zero (as in the first NLTX phase) if the phase duration would have been extended. In fact, previous research (Casner & Weinheimer, 1995) suggests that some responders to NLTX may continue to show gradual reductions in SIB for several months during follow-up periods. The use of analog baselines to examine the effects of different doses of NLTX also may be a topic of future investigation. Based on a review of current literature on NLTX, it is difficult to determine which doses are likely to be most effective in reducing SIB. Using controlled baselines may permit more sensitive comparisons of the effects of different doses, as well as identifying doses that

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most rapidly and completely suppress SIB. Also, it is possible that different doses of NLTX may be required based on different functions of SIB. For example, the dose of NLTX that is sufficient to extinguish SIB maintained by the release of endogenous opioids may be different from that necessary to produce a punishment effect for socially maintained SIB. Systematic analyses of potential dose effects and interactions will require the use of well controlled and specifically designed baselines. More generally, it may be possible to extend the use of analog baselines to examine other pharmacological interventions. Although the effects of pharmacological treatments are typically viewed as outside the purview of behavior analysis, Northup et al. (1997) have shown that methylphenidate can mediate environmental contingencies. Extending this work by using analog baselines could help identify environmental correlates of the behavior problems, isolate potential function-specific effects of these medications, identify potential responders and nonresponders to methylphenidate, and help to clarify diagnostic criteria for prescribing methylphenidate and related medications. Thus, it may be that functional-analysis baselines can contribute toward our understanding of the functional properties of a wide range of behavior problems, as well as how psychotropic medications affect those problems. Although the current study is preliminary and requires cautious interpretation, results demonstrate the potential utility of controlled baselines for examining the effects of NLTX on SIB. With further refinement and replication, this general method may contribute toward revealing the behavioral mechanisms underlying the effects of NLTX on SIB, and may provide a basis for identifying participant characteristics associated with positive outcomes to treatment. Similar models may help contribute toward the development of objective measures for determining who is likely to benefit from other pharmacological interventions. More fundamentally, procedures such as those described in the current study may improve our basic understanding of mechanisms associated with behavior disorders and the effects of pharmacological interventions. Such information could reduce the number of persons receiving ineffective pharmacological interventions and eventually enhance the quality of life of many individuals receiving treatment for behavior disorders. REFERENCES Aman, M. G. (1991). Pharmacotherapy in the developmental disabilities: New developments. Australia and New Zealand Journal of Developmental Disabilities, 17, 183–199. Aman, M. G. (1993). Efficacy of psychotropic drugs for reducing self-injurious behavior in the developmental disabilities. Annals of Clinical Psychology, 5, 171–188. Benjamin, S. B., Seek, A., Tresise, L., Price, E., & Gagnon, M. (1995). Case study: Paradoxical response to naltrexone treatment of self-injurious behavior. Journal of the American Academy of Child and Adolescent Psychiatry, 34, 238 –242. Campbell, M., Anderson, L. T., Small, A. M., Adams, P., Gonzalez N. M., & Ernst, M. (1993). Naltrexone in autistic children: Behavioral symptoms and attentional learning. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 1283–1291.

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Campbell, M., Overall, J. E., Small, A. M., Sokol, M. S., Spencer, E. K., Adams, P., Foltz, R. L., Monti, K. M., Perry, R., Nobler, M., & Roberts, E. (1989). Naltrexone in autistic children: An acute open dose range tolerance trial. Journal of the American Academy of Child and Adolescent Psychiatry, 28, 200 –206. Carr, E. G. (1977). The motivation of self-injurious behavior: A review of some hypotheses. Psychological Bulletin, 84, 800 – 816. Crews, W. D., Bonaventura, S., & Rowe, F. B. (1993). Cessation of long-term naltrexone therapy and self-injury: A case study. Research in Developmental Disabilities, 14, 331–340. Day, R. M., Rea, J. A., Schussler, N. G., Larsen, S. E., & Johnson, W. L. (1988). A functionally based approach to the treatment of self-injurious behavior. Behavior Modification, 12, 565–589. Durand, V. M., & Carr E. G. (1991). Functional communication training to reduce challenging behavior: Maintenance and application in new settings. Journal of Applied Behavior Analysis, 24, 251–264. Herman, B. H. (1990). A possible role of proopiomelanocortin peptides in self-injurious behavior. Progress in Neuro-Psychopharmacological and Biological Psychiatry, 14(Suppl), S109 –S139. Herman, B. H., Hammock, M. K., Arthur–Smith, A., Kuehl, K., & Applegate, K. (1989). Effects of acute administration of naltrexone on cardiovascular function, body temperature, body weight and serum concentrations of liver enzymes in autistic children. Developmental Pharmacology and Therapeutics, 12, 81– 89. Iwata, B. A., Dorsey, M. F., Slifer, K. J., Bauman, K. E., & Richman G. S. (1982). Toward a functional analysis of self-injury. Analysis and Intervention in Developmental Disabilities, 2, 3–20. Iwata, B. A. (1994). Functional analysis methodology: Some closing comments. Journal of Applied Behavior Analysis, 27, 413– 418. Iwata, B. A., Pace, G. M., Dorsey, M. F., Zarcone, J. R., Vollmer, T. R., Smith, R. G., Rodgers, T. A., Lerman, D. C., Shore, B. A., Mazaleski, J. L., Goh, H., Cowdery, G. E., Kalsher, M. J., McCosh, K. C., & Willis K. D. (1994). The functions of self-injurious behavior: An experimental-epidemiological analysis. Journal of Applied Behavior Analysis, 27, 215–240. Iwata, B. A., Pace, G. M., Kalsher, M. J., Cowdery, G. E., & Cataldo, M. F. (1990). Experimental analysis and extinction of self-injurious escape behavior. Journal of Applied Behavior Analysis, 23, 11–27. Knabe, R., Shulz, P., & Richard, J. (1990). Initial aggravation of self-injurious behavior in autistic patients receiving naltrexone treatment. Journal of Autism and Developmental Disorders, 20, 591–593. Mace, F. C. (1994). The significance and future of functional analysis methodologies. Journal of Applied Behavior Analysis, 27, 385–392. Mace, F. C., & Mauk, J. E. (1995). Bio-behavioral diagnosis and treatment of self-injury. Mental Retardation and Developmental Disabilities Research Reviews, 1, 104 –110. Mello, N. K., & Mendelson, H. H. (1978). Self-administration of an enkephalin analog by rhesus monkey. Pharmacology, Biochemistry and Behavior, 9, 579 –586. Northup, J., Fusilier, I., Swanson, V., Roane, H., & Borrero, J. (1997). An evaluation of methylphenidate as a potential establishing operation for some common classroom reinforcers. Journal of Applied Behavior Analysis, 30, 615– 624. Northup, J., Jones, K., Broussard, C., DiGiovanni, G., Herring, M., Fusilier, I., & Hanchey, A. (1997). A preliminary analysis of interactive effects between common classroom contingencies and methylphenidate. Journal of Applied Behavior Analysis, 30, 121–125. Northup, J., Wacker, D., Sasso, G., Steege, M., Cigrand, K., Cook, J., & DeRaad, A. (1991). A brief functional analysis of aggressive and alternative behavior in an outclinic setting. Journal of Applied Behavior Analysis, 24, 509 –522. Sandman, C. A., Barron, J. L., & Colman, H. (1990). An orally administered opiate blocker, naltrexone, attenuates self-injurious behavior. American Journal on Mental Retardation, 95, 93–102.

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Schaal, D. W., & Hackenberg, T. (1994). Toward a functional analysis of drug treatment for behavior problems of people with developmental disabilities. American Journal on Mental Retardation, 99, 123–140. Smith, S. G., Gupta, K. K., & Smith, S. H. (1995). Effects of naltrexone on self-injury, stereotypy, and social behavior of adults with developmental disabilities. Journal of Developmental and Physical Disabilities, 7, 137–146. Stoner, G., Carey, S. P., Ikeda, M. J., & Shinn, M. R. (1994). The utility of curriculum- based measurement for evaluating the effects of Methylphenidate on academic performance. Journal of Applied Behavior Analysis, 27, 101–113. Taylor, D. V., Sandman, C. A., Touchette, P., Hetrick, W. P., & Barron, J. L. (1993). Naltrexone improves learning and attention in self-injurious individuals with developmental disabilities. Journal of Developmental and Physical Disabilities, 5, 29 – 42. Thompson, T., Hackenberg, T., Cerutti, D., Baker, D., & Axtell, S. (1994). Opioid antagonist effects on self-injury in adults with mental retardation: Response form and location as determinants of medication effects. American Journal on Mental Retardation, 99, 85–102. Vollmer, T. R., & Smith, R. G. (1996). Some current themes in functional analysis research. Research in Developmental Disabilities, 17, 229 –249. Zingarelli, G., Ellman, G., Hom, A., Wymore, M., Heldorn, S., & Chicz–DeMet, A. (1992). Clinical effects of naltrexone on autistic behavior. American Journal on Mental Retardation, 97, 57– 63.