Descriptive Longitudinal Analysis of Stereotypy and Corresponding Changes in Psychotropic Medication

Abstract

Psychotropic medication is often prescribed to individuals with intellectual and developmental disabilities who engage in challenging and other behavior (e.g., aggression and stereotypy, respectively), but there is limited understanding of the effects of these medications on behavior. Within the context of a larger study that evaluated the effects of psychotropic medication regimen changes on the presentation of challenging behavior, this study describes the presentation of stereotypic behavior of three individuals diagnosed with autism spectrum disorder. Stereotypy was measured during weekly, one-hour, direct observations and during the control and ignore conditions of functional analyses of challenging behavior (which were conducted following changes in psychotropic medication regimens). Patterns of stereotypy varied over time, but not significantly, and at times seemed to coincide with medication changes. Areas of needed research are discussed.

Individuals with autism spectrum disorder (ASD) often engage in stereotypy, or repetitive behavior, which can be restrictive in nature and may adversely impact one’s engagement in daily activities (Leekam et al., 2011). There are many topographies of stereotypy, which may include simple repetitive motor actions, such as body rocking and hand flapping, or more complex behaviors, such as fixation on specific objects or rituals (Luiselli et al., 2004). Stereotypy can also present as vocalizations, for example, repetitive sounds and echolalia (van Haaren, 2015). Research has demonstrated that stereotypic behavior may be influenced by various environmental stimuli (e.g., Lloyd et al., 2018; Petrongolo et al., 2015). Additionally, the engagement in stereotypy may serve different functions depending on the individual (e.g., Kennedy et al., 2000). For example, engagement in stereotypic behavior may produce automatic reinforcement for some (van Haaren, 2015), or be maintained by social attention for others (Roantree & Kennedy, 2006).

The use of experimental functional analysis (FA) has been successful in identifying potential variables that impact stereotypy. Within an FA, individuals experience controlled manipulations of socially-mediated antecedents and consequences (e.g., access to attention, escape from demands; Iwata et al., 1994). Additionally, there are control conditions that counter-balance the presentation and manipulation of these variables (e.g., free access to attention, lack of demands). These manipulations often serve as motivating operations, which momentarily alter the value of consequences associated with targeted behavior and impact the probability of behavior. Thus, the core objective of this analysis is to determine whether the behavior is maintained by social reinforcement (e.g., escaping demands, attaining tangible items, attention, etc.), or by some other non-social reinforcer (e.g., biological, sensory). If target behavior occurs at a significantly higher rate in an “alone” condition than in an “attention” condition, one could conclude that behavior is likely maintained by automatic reinforcement (Lancioni et al., 2012). When stereotypy is maintained by automatic reinforcement, the individual engages in stereotypy in situations that may or may not be devoid of opportunity for social consequences (Dozier et al., 2013). In other words, it is engagement in stereotypy and the stimulation produced by engagement in the behavior itself that is reinforcing, rather than external environmental consequences, which may complicate treatment (Reid et al., 2010). At present, it is unknown how much of observed stereotypic behavior is mediated and controlled by access to environmental stimuli.

Behavioral interventions have been used to decrease stereotypy presentation or limit engagement in stereotypy. Exercise has recently been explored as a possible intervention to reduce engagement in stereotypy (Schmitz et al., 2017). Other interventions may focus on interrupting the engagement in stereotypy or redirecting individuals to engage in a competing task to reduce stereotypy (e.g., vocal stereotypy redirected to answer a question; motor stereotypy redirected to engage in motor task; Boyd et al., 2010; Cassella et al., 2011). Additionally, interventions have manipulated access to reinforcing activities to produce decreases in stereotypy (e.g., Rapp et al., 2017), particularly those that provide sensory stimulation (Hill et al., 2012). The use of these interventions suggests that, although stereotypy is largely thought to be automatically reinforcing, engagement in stereotypy can also be impacted by one’s environment.

In the absence of observable stimuli controlling behavior, however, researchers have suggested that biological variables, such as neurotransmitters (e.g., dopamine), may be integral in explaining engagement in stereotypy (Guerra & Silva, 2010; Luciana et al., 2012; Singer, 2013). For example, the role of dopamine (e.g., dopamine3-receptor gene; DRD3; Staal, 2015; Staal et al., 2012) and its availability and activity within the striatum, particularly within the reward pathway (e.g., Kohls et al., 2018), has been examined in relation to stereotypic behavior. In fact, research suggests that increased levels of dopamine in the striatum are often associated with decreased levels of acetylcholine (ACh), and this imbalance of neurotransmitters often correlates with the presentation of motor stereotypies (Péter et al., 2017). There is also growing evidence to suggest that other neurotransmitter systems may affect stereotypy. For example, serotonin, ACh, histamine, glutamate, and GABA have all been linked to autism spectrum disorder (Eissa et al., 2018).

Psychotropic medication, specifically antipsychotics (both typical and atypical) and selective serotonin reuptake inhibitors (SSRIs), have been used to target automatically reinforced stereotypy. Antipsychotics primarily target the dopaminergic system, while SSRIs act to increase levels of serotonin (van Haaren, 2016). The antipsychotics Risperdal® (risperidone) and Abilify® (aripiprazole) are two medications that are FDA-approved to treat symptoms of ASD. Both medications have been shown to reduce motor stereotypies but are often accompanied by undesirable side effects (Martino et al., 2016). And, although research suggests SSRIs are efficacious for treating stereotypy (e.g., Hollander et al., 2012), the effects observed are marginal, and significant effects are lost when further analyses compensate for publication bias (Carrasco et al., 2012).

Despite limited research on the use of psychotropic medication for treating behavior associated with ASD symptomology, psychotropic medication use remains prevalent in this population. It is reported that an estimated 58% of persons with IDD are prescribed these medications (Tsiouris et al., 2013), and rates are higher for those with an ASD diagnosis as they age (Houghton et al., 2017). However, the prevalence of psychotropic medication in the treatment of ASD-related symptoms is somewhat variable. For example, one review found that psychotropic medication treatment was prescribed for 2.7% to 80% of individuals with ASD, with 5.4% to 54% of those individuals prescribed more than one psychotropic medication (Jobski et al., 2017). Furthermore, there does not appear to be a common medication regimen prescribed.

Due to the ritualistic nature of stereotypy, there appears to be little variation in how the behavior presents from one instance to another or over extended periods of time (Wainwright et al., 2008). In fact, stereotypy tends to persist from childhood through adulthood for most individuals (Rumsey et al., 1985). Although, some research suggests that the severity of specific motor stereotypy may decrease as an individual ages (Oakley et al., 2015). Evaluating engagement in stereotypy is important for several reasons. Although stereotypy may impact participation in daily activities, it is the relationship to challenging behavior that presents additional concerns. Access to engagement in stereotypy has been suggested to have a functional relationship to challenging behavior (Hausman et al., 2009; White et al., 2011). Additionally, research has found that engagement in stereotypy may predict long-term engagement in self-injurious behavior (Laverty et al., 2020). Developing a better understanding of the conditions under which stereotypy occurs, as well as the many factors that influence its presentation, may serve an important role in the treatment of more severe problem behavior and could be beneficial to supporting those who engage in these behaviors. Current research is limited regarding the longitudinal pattern of stereotypy in adulthood and, similarly, there is a lack of research examining the impact of psychotropic medication on the presentation of stereotypy. Given that psychotropic medications are highly prevalent among individuals diagnosed with ASD and may potentially impact engagement in stereotypic behavior via their mechanism of action, further research is warranted.

The purpose of this study was to examine patterns of stereotypy of three individuals diagnosed with ASD over an extended period of time as they experienced changes in psychotropic medication regimens. Additionally, we measured the rate or duration of stereotypy during two conditions of functional analyses (e.g., control, ignore) of challenging behavior.

Methods

Participants

The three participants in this study were chosen from a group of individuals who took part in a larger three-year research project that evaluated the impact of psychotropic medication changes on challenging behavior (see Valdovinos et al., 2016). These specific individuals were selected from the larger study to participate in the current study because they engaged in observable topographies of stereotypy. Additionally, all participants were diagnosed with ASD and intellectual disability (ID). Participants were on regimens of psychotropic medication prior to their enrollment in the study. Each participant in this study experienced changes to his medication regimens, however the number and type of change varied for each individual (see Table 1).

Table 1.

Medication Regimens, Mean Rate or Duration of Stereotypy, and Percentage Change across Corresponding, Grouped Direct Observations

Participant	Stereotypic Behavior	Medication Regimen	Direct Observations	Stereotypy (Rate or Duration)	Effect on Stereotypy	Percentage Change
ROB	Body rocking	(Initial Regimen) Divalproex 1000 mg Thioridazine 200 mg Escitalopram 5 mg	Observations 1–12	2284.51 s	-	-
		Divalproex 1000 mg Thioridazine D/C Escitalopram D/C Lurasidone 80 mg	Observations 13–17	2205.55 s	↓ duration	↓ 3.46%
		Divalproex 1000 mg Lurasidone 160 mg	Observations 18–25	2838.05 s	↑ duration	↑ 28.68%
THOMAS	Air holding	(Initial Regimen) Risperidone 3 mg Hydroxyzine 50 mg	Observations 1–21	0.48 rpm	-	-
		Risperidone 3 mg Hydroxyzine 75 mg	Observations 22–33	1.04 rpm	↑ rate	↑ 116.67%
		Risperidone 3 mg Hydroxyzine 75 mg Trazodone 75 mg	Observations 34–42	0.55 rpm	↓ rate	↓ 47.12%
		Risperidone 4 mg Hydroxyzine 50 mg Trazodone 75 mg	Observations 43–55	0.80 rpm	↑ rate	↑ 45.45%
		Risperidone 4.25 mg Hydroxyzine 50 mg Trazodone 75 mg	Observations 56–83	0.47 rpm	↓ rate	↓ 41.25%
MIKE	Grunting	(Initial Regimen) Trazodone 300 mg Carbamazepine 800 mg Hydroxyzine 50 mg Risperidone 4 mg	Observations 1–15	0.097 rpm	-	-
		Trazodone 250 mg Carbamazepine 800 mg Hydroxyzine 50 mg Risperidone 4 mg	Observations 16–28	0.033 rpm	↓ rate	↓ 65.98%
		Trazodone 200 mg Carbamazepine 800 mg Hydroxyzine 50 mg Risperidone 4 mg	Observations 29–40	0.028 rpm	↓ rate	↓ 15.15%
		Trazodone 200 mg Carbamazepine 800 mg Hydroxyzine 50 mg Risperidone 3.5 mg	Observations 41–50	0.189 rpm	↑ rate	↑ 575.00%
		Trazodone 200 mg Carbamazepine 800 mg Hydroxyzine 50 mg Risperidone 3.25 mg	Observations 51–79	0.034 rpm	↓ rate	↓ 82.01%

Note. A given set of observations corresponds to each medication regimen for the respective participants. Effects of medication changes are to be compared to the most previous medication regimen respective to each participant. Average percent change values were calculated by comparing data from a given set of observations with those that were most previously conducted. Changes to medication regimens are indicated in bold.

Rob, a 28-year-old Caucasian male, was diagnosed with ASD, bipolar disorder type I, and severe ID. His stereotypic behavior was body rocking, defined as movement of the body back and forth while sitting down, or movement of the body side to side while standing. Rob also engaged in self-injurious behavior (SIB) and problem vocalizations. SIB was defined as forceful contact to the head or body using an open or closed fist or forceful contact with his head to objects or surfaces, while problem vocalizations were defined as screaming (i.e., vocalizations above normal conversational volume) for 3 s or longer. The results of his functional analyses suggested that his problem vocalizations were maintained by access to tangible items. However, the function of SIB was undifferentiated due to the low and variable rates of the behavior observed across sessions.

Over the course of the study, Rob experienced a total of three medication regimens, 25 direct observations, and three functional analyses. While on his initial medication regimen, we conducted 12 direct observations (observations 1–12) and a single FA (FA 1). On his second regimen, five additional observations (observations 13–17) and another FA (FA 2) were completed. With the third and final medication regimen, we completed nine observations (observations 18–25) and an additional FA (FA 3).

Thomas, a 38-year-old Caucasian male, was diagnosed with ASD and profound ID. His stereotypic behavior was air holding, which was defined as holding his breath for longer than 3 s and exhaling audibly. His also engaged in SIB, which was defined as forceful contact to the head using an open or closed fist or forceful contact with his head to objects or surfaces. The results of his FAs were variable across different medication regimens but suggested that his SIB was maintained, in part, by escape from demands and access to attention.

Thomas experienced five different medication regimens, 83 direct observations, and four FAs of challenging behavior over the course of the study. A total of 21 observations (observations 1–21) were collected while on his initial medication regimen. With the change to his second regimen, we conducted an additional 12 direct observations (observations 22–33) and completed the first FA of challenging behavior (FA 1). During the third medication regimen, nine observations (observations 34–42) and a second FA (FA 2) were conducted. For the fourth medication regimen, there were 13 observations (observations 43–55) and a third FA (FA 3) conducted. Finally, on the fifth medication regimen, we completed 28 observations (observations 56–83) and the final FA (FA 4).

Last, Mike was a 37-year-old Caucasian male, diagnosed with ASD and profound ID. His stereotypic behavior was grunting, a vocal stereotypy which was defined as filling his cheeks with air and emitting sound as he exhaled the air back out. His challenging behaviors were SIB, defined as forceful contact to the head using an open or closed fist, self-biting, or self-scratching; as well as aggression, which was defined as pinching, grabbing, biting, or kicking others. The results of his FA were variable but suggested that his SIB was attention and escape-maintained, while his aggression was tangible and escape-maintained.

Over the course of the study, Mike experienced a total of five medication regimens, 79 direct observations, and four functional analyses. While on his initial regimen, we collected 15 total direct observations (observations 1–15). With the change to his second regimen, we completed one FA (FA 1) and 18 direct observations (observations 16–28). A total of 12 observations (observations 29–40) and the second FA (FA 2) were conducted during the third medication regimen, while 10 total observations (observations 41–50) and the third FA (FA 3) were completed during the fourth medication regimen. Finally, while on his last medication regimen, we conducted 29 total direct observations (observations 51–79) and the final FA of challenging behavior (FA 4).

All procedures performed in this study complied with the American Psychological Association’s ethical standards in the treatment of the participants and were in accordance with the ethical standards of the University’s Institutional Review Board.

Study Design

As part of the larger study, the treatment team for each participant independently made decisions related to medications, and participation in this study did not influence any decisions made by the team. Given that medication changes were uninfluenced by research activity, an ABC, AA′A′′, or combination, parametric design was used to make comparisons across medication regimens. Therefore, “A” represented the starting dose of the medication regimen, while “ABC” indicated changes in medication kind and “AA′A′′” indicated changes in doses. Further, “ABB′” denoted changes in both medication kind and dose. Additionally, this study applied longitudinal methodology to examine the presentation of stereotypy over time. This specific design allowed for clearer comparisons of stereotypy as medication changes occurred week to week. Further, stereotypy rate or duration were also examined within the control and ignore conditions of the FAs conducted throughout the study. Changes in rate or duration of stereotypy were compared within these conditions across medication changes.

Data Collection and Response Measurement

Researchers collected data on either the frequency or duration of stereotypy contingent on the topography of each behavior. Frequency data were then converted to rate (RPM) by dividing the total number of occurrences by the total duration of session in minutes. Then, mean rate or duration was calculated for each behavior for each participant by dividing the sum of either rate or duration by the total number of sessions per condition.

Interobserver Agreement

All observers received extensive training in data collection and were considered reliable in data collection after obtaining at least 80% agreement with the primary data collector for a minimum of three consecutive sessions. Interobserver agreement (IOA) was calculated for a minimum of 33% of the total direct observations for each participant. Point-by-point agreement for the direct observations was calculated using a 3 s window of tolerance, meaning that agreement occurred if the secondary data collector recorded the same behavior in the 3 s either preceding or following the time in which the primary data collector scored the behavior. Additionally, IOA percentages were calculated by dividing the number of agreements by the total sum of agreements and disagreements and then multiplying by 100. For Rob, average IOA of body rocking was 100%. For Thomas, average IOA for air holding was 94.37% (range, 87.50 – 100%). Last, for Mike, average IOA of grunting was 91.85% (range, 49.09 – 100%).

For the FAs, IOA was calculated between two independent observers by dividing all sessions into 10 s intervals. For each session, the smaller number of responses was divided by the larger number of responses and multiplied by 100 in order to obtain a percentage score. A second coder individually recorded data at the same time as the primary data collector for approximately 45% of all FA sessions. Agreement was scored using a 5 s window of tolerance, meaning that agreement occurred if the secondary data collector recorded the same behavior 5 s prior to or after the time in which the primary data collector scored the behavior. Across all participants, IOA averaged 97.78% (range, 66.67% to 100%) for stereotypic behavior.

Procedures

Direct observations were recorded weekly with the time of day and day of the week held constant. The direct observations were recorded in the participants’ homes for approximately one hour each week (excluding weeks of holidays or university breaks). During these sessions, the participants were observed in a variety of tasks (e.g., leisure, meals, etc.). Throughout their enrollment, Rob, Thomas, and Mike were observed in their homes for overall time periods of 25 weeks, 83 weeks, and 79 weeks, respectively.

As a part of the larger study, FAs (Iwata et al., 1994) of challenging behavior (e.g., aggression, self-injury) were conducted for each participant in their homes upon enrollment in the study, with the exception of Mike whose assessments were completed in a small clinic room. FAs were conducted again at least two weeks following a reported medication change. There are a number of factors that influence how long medications take to reach therapeutic levels, such as genetics, medication half-life, and health status. Based on these factors, the effects of a medication, both intended and adverse, can be experienced within a window of two weeks or longer (Stahl, 2013). Therefore, for this study, a period of two weeks was chosen as the minimum duration between medication changes and repeat FAs. The functional analyses were conducted at the same location; the time of day and day of the week were held constant. Behavioral programming was provided by the organizations caring for the individuals. We were unaware of any changes in support services (i.e., behavioral programming) for any of the participants during the study period.

Sessions within the FAs lasted 5 min with a 1 min break between sessions. The order of sessions was randomized, and each condition was presented three times, with the exception of Rob who was exposed to the ignore condition once in the first two FAs and three times in the final FA. Stimuli used during these sessions were selected based on caregiver responses obtained during the study intake process and were designed to mirror participant daily activities. During these sessions, programmed consequences were delivered for challenging behaviors (e.g., aggression, self-injury). Engagement in stereotypy did not produce consequences.

The conditions used in this study to evaluate challenging behavior included control, ignore, attention, tangible, and demand. Typically, within the FA conditions, consequences were delivered following challenging behavior. Given that programmed consequences were not delivered contingent upon stereotypy, this study evaluated the motivating operations created within these conditions and their subsequent impact on the presentation of stereotypy. That is to say, the antecedent condition manipulations within the FA served to make stimuli more reinforcing or aversive. In the control condition, access to attention and preferred stimuli were provided and demands were withheld. In the ignore condition, the researcher withheld attention in all forms (e.g., verbal or visual) and there were no programmed consequences for challenging behavior. Only the videographer remained in the room (except for Mike, in which the researcher remained in the room with their back turned). The attention condition mirrored the ignore condition, however, if the participant engaged in challenging behavior, attention was then delivered as a consequence immediately following. Additionally, both the researcher and videographer remained in the room during the attention condition. In the tangible condition, desired objects (e.g., items, activities, food, drink) were in the room, but the participant was not given access to the items unless challenging behavior occurred. Finally, in the escape condition, participants were presented with multiple demands using a three-step, least-to-most guided compliance procedure and were provided with a 30 s break if they engaged in challenging behavior.

The weekly direct observations were initiated prior to the functional analyses, meaning that for some participants, there was one less comparison between FAs than there was between groups of observations. For example, both Thomas and Mike experienced four comparisons between direct observations and three comparisons between FAs. However, Rob experienced two comparisons between both groups of direct observations and FAs (see Table 1).

Data Analysis

Stereotypic behaviors for each participant were scored using a continuous, timed-event sampling procedure via Noldus Observer ® XT program. Across all sessions, researchers collected duration data for body rocking, while rate (converted from frequency data using procedures described earlier) was used to report air holding and grunting. For the direct observations, we conducted two-sample, one-tailed, t-tests assuming unequal variances in an attempt to determine whether or not there were any significant differences (p<0.05) in mean rate or duration between the groups of observations given a medication regimen for each participant as changes were made to medication regimens.

Comparisons were made between the values obtained in given FAs (i.e., the FA conducted during one medication regimen and the FA conducted during the next medication regimen). Percentage change was then calculated by comparing the results from a given FA with the FA that immediately preceded it for each participant (i.e., FA2 compared to FA1, FA3 compared to FA2, etc.). Comparisons were also made between specific groups of direct observations, with each group correlating to the weeks a participant was on a given medication regimen. These observations were compared in a similar manner to the way in which the FAs were compared, where a given set of observations was compared to the temporally closest of observations. For example, the group of observations that occurred during the second medication regimen was compared to the group of observations during the initial regimen.

Results

Each participant in this study experienced changes to his medication regimens, although the number and type of change varied. Table 1 depicts the mean rate or duration of stereotypy for each topography during the group of observations that correspond with a particular medication regimen. The table also shows the average percentage change across medication regimens of each participant. In the direct observations, we observed variable patterns of engagement in stereotypy across observations (Figures 1–3). Although there was variability from one observation to the next, as a whole there were no significant increases or decreases. For example, for Rob the mean duration of engagement in body rocking across all observations was 2445.85 s (5.57 s to 3589.15 s, range), the median duration was 3085.76 s, and no significant change was observed as a function of time (F(1, 22) = 1.14, p = 0.29, R2 = 0.05; Figure 1, top panel). There also appeared to be variability in Thomas’s stereotypy with a mean rate of air holding across all observations at 0.61 rpm (0.01 rpm to 2.19 rpm, range) and a median rate of 0.55 rpm; and, significant change as a function of time was also not apparent (F(1, 80) = 1.44, p = 0.23, R2 = 0.02; Figure 2, top panel). Finally, variability was observed for Mike’s grunting (Figure 3, top panel). The mean rate of grunting was 0.06 rpm (0 to 0.7 rpm, range) and the median was zero with no significant changes as a function of time (F(1, 76) = 0.92, p = 0.34, R2 = 0.01).

Figure 1. Duration of Body Rocking Observed during One-Hour, Direct Observations and Mean Duration of Body Rocking Observed during Functional Analyses for Rob.

Note. The top panel represents the duration of body rocking in seconds across one-hour, direct observations over the course of 25 weeks. The bottom panel represents the mean duration of body rocking across FA conditions.

Figure 3. Rate of Grunting Observed during One-Hour, Direct Observations and Mean Rate of Grunting Observed during Functional Analyses for Mike.

Note. The top panel represents the rate of grunting across one-hour, direct observations over the course of 79 weeks. The bottom panel represents the mean rate of grunting across FA conditions.

Figure 2. Rate of Air Holding Observed during One-Hour, Direct Observations and Mean Rate of Air Holding Observed during Functional Analyses for Thomas.

Note. The top panel represents the rate of air holding across one-hour, direct observations over the course of 83 weeks. The bottom panel represents the mean rate of air holding across FA conditions.

When examining stereotypy data during direct observations on a particular medication regimen for Rob (Figure 1, top panel), there was no significant difference in duration of body rocking between the first medication regimen (M = 2,284.51 s, SD = 1,523,195.8 s) and the second medication regimen (M = 2,205.55 s, SD = 1,110,523.7 s) when Latuda® (lurasidone; affecting primarily dopaminergic and serotonergic systems) was initiated and Lexapro® (escitalopram; serotonin) and Mellaril® (thioridazine; dopamine) were discontinued, although there was an overall decrease in the duration of body rocking observed (2284.51 s to 2205.55 s). There was also no significant difference found in duration of body rocking, t(8) = −1.07, p = 0.32, between the second and third medication regimens (M = 2,838.05, SD = 1,039,753) where the dosage of lurasidone was increased, even though an increase in body rocking (2205.55 s to 2838.05 s) was observed.

Regarding data from the FAs, following the first medication change, the mean duration of body rocking increased in the ignore (0.0 s to 43.35 s) condition but body rocking was not observed in the control condition of either of the first two FAs (see Figure 1, bottom panel). After the second medication change, we observed an increase in the duration of body rocking in the control (0.0 to 12.97 s) and ignore (43.35 s to 164.24 s) conditions. Thus, the changes in both the control and ignore conditions across medication changes appeared to track with what was observed during the direct observations.

When we looked at stereotypy during the direct observations for a given medication regimen for Thomas, there was a different pattern observed. There was no significant difference in the rate of air holding between the first medication regimen (M = 0.48, SD = 0.07) and the second medication regimen (M = 1.04, SD = 0.08) where the dosage of Vistaril® (hydroxyzine; affects histamine, primarily, and lesser effects on serotonin and dopamine) was increased. However, between the second medication regimen and the third (M = 0.55, SD = 0.17) where trazodone (antidepressant; primarily affects serotonin) was initiated, the differences were significant, t(13) = 3.12, p = 0.0041. The differences in rate between the third regimen and fourth regimen (M = 0.80, SD = 0.29) when the dosages of risperidone increased and hydroxyzine decreased was not significant; however the difference in rate of air holding between the fourth and fifth medication regimens (M = 0.47, SD = 0.060), when the dosage of risperidone was increased further, was found to be significant, t(14) = 2.13, p = 0.026.

When we compare the direct observations (Figure 2, top panel) to the four FAs (Figure 2, bottom panel) conducted for Thomas, following the second medication change, we observed a decrease in the rate of air holding in the control (2.93 rpm to 2.12 rpm) and ignore (3.27 rpm to 3.19 rpm) conditions, and the rate also decreased in the direct observations (1.04 rpm to 0.55 rpm). After the third medication change, there was a further decrease in rate of air holding across the control (2.12 rpm to 0.8 rpm) and ignore (3.19 rpm to 1.46 rpm) conditions. Conversely, there was an increase in rate of air holding in the direct observations (0.55 rpm to 0.8 rpm). With the final medication change, mean rate of air holding increased in the control (0.8 rpm to 1.3 rpm) condition, but decreased in the ignore condition (1.46 rpm to 0.91 rpm), and this decrease was observed in the direct observations (0.80 rpm to 0.47 rpm). Thus, for Thomas, the changes in the control and ignore conditions across medication changes did not always coincide with the pattern of change noted in the direct observations.

Finally, comparing mean rates of stereotypy during direct observations for a particular medication regimen for Mike, there were no significant differences found in the rate of grunting between the first medication regimen (M = 0.10, SD = 0.016) and the second medication regimen (M = 0.033, SD = 0.014) when the dosage of trazodone was decreased. Results were also not significant between the second medication regimen and the third medication regimen (M = 0.028, SD = 0.0046) when the dosage of trazodone was further decreased. Nor between the third and fourth (M = 0.19, SD = 0.051) which involved a decrease in the dosage of risperidone, and fourth and fifth medication regimens when risperidone was decreased further (t(10) = −2.18, p = 0.027 and M = 0.033, SD = 0.010); t(10) = 2.11, p = 0.03, respectively).

After the initial medication change, we observed a decrease in mean rate of grunting in the direct observations (0.097 rpm to 0.033 rpm; see Figure 3, top panel). Following the second medication change, we observed that the mean rate of grunting decreased in the control (1.52 rpm to 0.80 rpm) and ignore (1.79 rpm to 0.0 rpm) conditions (Figure 3, bottom panel), and the rate of grunting also decreased across the direct observations (0.033 rpm to 0.028 rpm). With the next medication change, we observed an increase in rate of grunting in the control (0.80 rpm to 1.60 rpm) and ignore (0.0 rpm to 1.19 rpm) conditions, and an increase was also observed in the direct observations (0.028 rpm to 0.189 rpm). With the final medication change, the mean rate of grunting decreased during the control (1.60 rpm to 0.60 rpm) and ignore (1.19 rpm to 0.86 rpm) conditions, as well as with the direct observations (0.189 rpm to 0.034 rpm). Thus for Mike, rate of grunting during ignore and control conditions of the FA corresponded with overall changes observed during the direct observations.

Discussion

The literature regarding longer-term patterns of stereotypy (i.e., does it remain stable or variable?) is limited. Given that stereotypy can sometimes interfere with skill acquisition and may contribute to the presentation of challenging behavior, the purpose of this study was to observe the occurrence of stereotypy over an extended period of time as individuals experienced changes to their psychotropic medication regimen. To accomplish this, we measured the rate or duration of stereotypy that occurred during weekly, one-hour, direct observations and we measured rate or duration of stereotypy during the ignore and control conditions of FAs of challenging behavior (which were conducted at least two weeks after changes were made to psychotropic medications). Topographies measured involved both gross motor activity (i.e., body rocking) and more subtle movements (i.e., air holding, grunting). We observed some variability in the presentation of stereotypy over time, although few of the changes were significant. Based on the results of this study, we posit that engagement in stereotypy persists throughout adulthood with slight variability but what accounts for this variability is unknown. Further, although it is likely that medications have some effect on the presentation of stereotypy, this influence is not predictable or consistent in nature.

Admittedly, participants experienced multiple medication changes over time. Thus, it is possible that the variability observed in stereotypy could be attributed to the impact of medication changes. As mentioned previously, several neurotransmitters (e.g., dopamine, serotonin, acetylcholine, histamine, glutamine, and GABA) have been linked to the onset and progression of ASD (Eissa et al., 2018). Different types of medications can affect these neurotransmitters in varying ways. For example, typical antipsychotics like chlorpromazine or thioridazine are dopamine receptor agonists that work to both prevent neurotransmission and decrease levels of dopamine by blocking D2 dopamine receptors in the brain. Atypical antipsychotics, such as lurasidone or risperidone, affect levels of dopamine and serotonin, as they block both D2 dopamine receptors and serotonin receptor antagonists (Chokhawala & Stevens, 2020). SSRIs and antidepressants, such as trazodone or escitalopram, are the most commonly prescribed medications for ASD, and they work to regulate dysfunctional activity of serotonin in the brain (Nadeau et al., 2011).

SSRIs increase levels of serotonin in the brain by inhibiting the reuptake of serotonin into neurons. Antidepressants generally increase both the reuptake and release of serotonin (Andrade & Rao, 2010). While these medications primarily target serotonin, they may also have an effect on other important neurotransmitters, such as dopamine and norepinephrine (Harmer et al., 2017). Several studies have hypothesized that dysfunctional levels of dopamine in specific brain regions may be linked to ASD and its related symptoms and behaviors (Marotta et al., 2020). Medications prescribed to the participants in this study may have had a significant influence on the intracellular levels of those neurotransmitters commonly linked to ASD. Therefore, it is possible that the changes we observed in rate or duration of stereotyped behavior were a result of specific medication changes and their subsequent effects on neurotransmitter levels. Given that psychotropic medications are prevalent among individuals diagnosed with ASD and may potentially impact engagement in stereotypic behavior via their mechanism of action, further research in this area is warranted.

Another observation is that although participants experienced the same type of medication change more than once (e.g., decrease in dosage of the same medication class), the results of the change were different each time, thereby suggesting that some other factors might be influencing the presentation of stereotypy aside from psychotropic medication changes. For example, Mike experienced two successive medication changes in which the dose of risperidone was decreased (i.e., regimens 4 and 5). Following the change to the fourth medication regimen, the mean rate of grunting increased in ignore and control conditions and the rate increased across the direct observations. However, for the fifth medication regimen, we observed decreases in the rate of grunting in the FA conditions and direct observations. Consistent changes in stereotypy were not always observed even when similar medication changes were made for a given participant. These findings suggest that some other factor or factors may likely have an influence on the presentation of stereotypy, however further research is necessary to identify these factors. It is possible that medication changes created potential MOs within the FA beyond those manipulated by researchers; however, given that the reinforcement rate varied from session to session and FA to FA contingent upon the rate of challenging behavior, it would be difficult to determine the impact on stereotypy.

There are limitations to this study that make it difficult to draw any conclusions regarding psychotropic medication effects on stereotypy presentation. First, the topography of stereotypic behavior varied across each of our participants. Although all forms of stereotypy were observable, only one involved gross motor movements, and the others involved more subtle movements or actions (e.g., holding air or oral movements involved in grunting). It is possible that topography may influence engagement in stereotypy over time. For example, gross motor movements that involve activation of the basal ganglia and the neurotransmission of dopamine may be more impacted as one ages given maturational changes. In this study, Rob experienced an increase in stereotypy across the control and ignore conditions of the FA and during the one hour observations once his dosage of lurasidone, an atypical antipsychotic, was increased. Given the literature regarding the neurotransmitters involved in stereotypic behavior, an evaluation of specific medication, topography, and function is merited.

Additionally, although some participants experienced single medication manipulations, multiple medications were prescribed simultaneously for all of the participants in the study. Therefore, it is nearly impossible to tell if the presentation of stereotypy was influenced by the manipulation of medications or if any observed changes in stereotypy were attributed to environmental conditions, availability of reinforcement, natural variation over time, etc. Unfortunately, the literature regarding the stability or variability of stereotypy over time is limited. Furthermore, for some individuals, stereotypy is an automatically maintained behavior (Lovaas et al., 1987). In our study, we generally observed that stereotypy did occur in both the control and ignore conditions of the FA, as well as in a naturalistic setting during the direct observations, thereby suggesting that these behaviors were maintained by automatic reinforcement. However, stereotypy across these conditions, and across direct observations, varied with medication regimen. Given the nature of medication combinations and changes, we were unable to determine if medications impacted the potential automatic nature of reinforcement for stereotypic behavior.

Finally, the conditions used in this study to evaluate challenging behavior included control, ignore, attention, tangible, and demand. In the larger study, consequences were delivered for challenging behavior rather than stereotypic behavior, which may have had an impact on the overall presentation of stereotypy across all the conditions tested, including the control and ignore conditions. Therefore, it is difficult to interpret the data from the test conditions of the functional analyses.

Future research on specific topographies of stereotypy and aging should be conducted. For example, determining if there is a relationship between the changes often observed in activities of daily living as one ages and with changes in engagement in stereotypy could be important, as changes in stereotypy could then serve as an indication of decline. Research should also address the limitations of this work and include a focus on the impact psychotropic medication may have on stereotypy. For example, FAs could be conducted to specifically target stereotypy and then subsequently assess any potential changes in stereotypy that might occur as a result of a medication or medication change. This approach could more accurately assess if psychotropic medication differentially impacts stereotypy maintained by automatic versus socially mediated stimuli. Finally, research should be conducted to determine if medications that target specific neurotransmitter systems are more or less likely to impact stereotypy presentation.