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. Author manuscript; available in PMC: 2026 Jun 6.
Published in final edited form as: Autism. 2015 Apr 16;20(2):145–152. doi: 10.1177/1362361315574889

Sensitivity of the modified Children’s Yale–Brown Obsessive Compulsive Scale to detect change: Results from two multi-site trials

Lawrence Scahill 1, Denis G Sukhodolsky 2, Emily Anderberg 3, Anastasia Dimitropoulos 4, James Dziura 2, Michael G Aman 5, James McCracken 6, Elaine Tierney 7, Victoria Hallett 8, Karol Katz 2, Benedetto Vitiello 9, Christopher McDougle 10
PMCID: PMC13238152  NIHMSID: NIHMS2175836  PMID: 25882391

Abstract

Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children’s Yale–Brown Obsessive Compulsive Scale modified for autism spectrum disorder to detect change with treatment. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. In Study 2, 49 subjects received risperidone only and 75 subjects received risperidone plus parent training. The combined sample consisted of 187 boys and 38 girls (aged 4–17 years). At the medication-free baseline, the internal consistency on the Children’s Yale–Brown Obsessive Compulsive Scale modified for autism spectrum disorder total score was excellent (Cronbach’s alpha = 0.84) and the mean scores were similar across the four groups. Compared to placebo in Study 1, all three active treatment groups showed significant improvement (effect sizes: 0.74–0.88). There were no differences between active treatment groups. These results indicate that the Children’s Yale–Brown Obsessive Compulsive Scale modified for autism spectrum disorder has acceptable test–retest as evidenced by the medium to high correlations in the placebo group and demonstrated sensitivity to change with treatment.

Keywords: autism spectrum disorder, clinical trials, outcome measurement, repetitive behavior, risperidone

Introduction

Repetitive behavior is a core feature of autism spectrum disorder (ASD) (American Psychiatric Association (APA), 2000, 2013). Current diagnostic criteria and extant phenomenological research recognize multiple forms of repetitive behavior in ASD (Honey et al., 2012; Lam et al., 2008; Scahill et al., 2013). In addition to stereotyped motor movements, children with ASD may also show more complicated rituals such as repeatedly reading the same book or watching the same video. Repetitive speech and ritualized nonverbal behaviors are also common in ASD. For some children with ASD, interruption of their repetitive behavior can trigger tantrums, aggression, or self-injury (Scahill et al., 2014). Despite psychosocial and pharmacological interventions aimed at reducing repetitive behavior, these behaviors often persist and pose a barrier to progress in multiple domains of functioning. Currently, most assessment instruments designed to quantify repetitive behavior rely on parent report. Other measurement approaches, such as clinician-based instruments, may be less susceptible to expectancy bias and especially useful for intervention studies.

Repetitive behaviors are also central to other disorders including Tourette’s syndrome (TS) and obsessive-compulsive disorder (OCD). The most effective class of pharmacological agents for the treatment of tics in children with TS are the dopamine D2 receptor subtype blocking antipsychotic drugs, although alpha agonists and anticonvulsants are also commonly used (Scahill and Guler, 2013). By contrast, selective serotonin reuptake inhibitors (SSRIs) are indicated for the treatment of OCD (Grados and Riddle, 2008) but are not effective for treating tics (Scahill and Guler, 2013). Dopamine D2 receptor blocking drugs are also effective in reducing stereotypic behavior in children and adults with intellectual disabilities (Aman, 1997). The differential response to these classes of medications suggests different underlying neurobiology. The biological model for treatment selection to target repetitive behaviors in ASD has been difficult to ascertain.

Prompted by evidence that alterations in serotonin neurotransmission may play a role in the pathophysiology of ASD and the success of the SSRIs in OCD, this class of medications is commonly used in children with ASD (Oswald and Sonenklar, 2007). Results from randomized clinical trials (RCTs) on the efficacy of the SSRIs for the treatment of repetitive behavior in ASD have been inconsistent. In adults with ASD, both fluvoxamine (McDougle et al.,1996) and fluoxetine (Hollander et al., 2012) were statistically superior to placebo in reducing repetitive behavior. Hollander and colleagues conducted a placebo-controlled study of fluoxetine in 39 children and reported modest but statistically greater reductions in repetitive behaviors versus placebo (Hollander et al., 2005). However, in the two largest randomized trials in children with ASD, neither liquid citalopram (King et al., 2009) nor an oral-disintegrating formulation of fluoxetine (Autism Speaks, 2009) showed superiority to placebo for the target of repetitive behaviors. These two trials used the Children’s Yale–Brown Obsessive Compulsive Scales modified for youth with ASD (CYBOCS-ASD) to measure repetitive behavior before and after treatment.

The CYBOCS-ASD is a clinician-rated scale that measures the current severity (over the past week) of repetitive behavior in children and adolescents with ASD on five severity items. It was derived from the CYBOCS developed to measure symptom severity in children with OCD (Scahill et al., 1997). The original CYBOCS contains a separate checklist for obsessions and compulsions, and five severity items for each domain. The interviewer surveys each checklist with the parent and child and then rates severity on the following: Time Spent, Interference in daily life, Distress from the symptoms, Resistance (child’s push against the symptoms), and Control (success of suppressing symptoms). Each severity item is scored from 0 (not present) to 4 (extreme), yielding a score for Obsessions (0–20), a score for Compulsions (0–20), and a Total score (0–40). The checklist is used to guide the discussion of severity, but the checklist is not separately scored.

In the absence of accepted measure for repetitive behavior in children with ASD, the CYBOCS was modified by investigators in the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network to make it more relevant to ASD (Scahill et al., 2006). For example, children with OCD describe obsessions as recurrent, unwanted thoughts or images. By contrast, the preoccupations and circumscribed interests in children with ASD often appear to be pleasurable (Baron-Cohen, 1989; Scahill et al., 2014). In addition, some children with ASD have cognitive delays, language delays, or both and may be unable to express the nature of recurring thoughts. Thus, the modified CYBOCS for ASD retains only the five compulsion items. In advance of the first RUPP study, we also added items to the compulsions checklist and made minor adjustments to the severity anchor points for use in children with ASD. The CYBOCS-ASD has demonstrated reliability and validity for measuring repetitive behavior in this population (Scahill et al., 2006). Failure to detect a treatment effect in the citalopram trial and the trial with oral-disintegrating fluoxetine formulation raises the possibility that the CYBOCS-ASD is not sensitive to change. Hollander et al. (2006, 2010) conducted placebo-controlled two trials (total sample = 40) with valproate and used a version of the CYBOCS-ASD as an outcome measure. One study showed positive effects on repetitive behavior; the other showed no difference from placebo. In an 8-week study of risperidone in a sample of 101 children with autism accompanied by serious behavior problems, the RUPP Autism Network showed that risperidone was superior to placebo for reducing repetitive behavior as measured on the CYBOCS-ASD (McDougle et al., 2005). The purpose of this study is to extend the findings of this previous report by examining the sensitivity of the CYBOCS-ASD to detect change in repetitive behavior in a larger sample of children with ASD who participated in RUPP Autism Network risperidone trials.

Methods

Subjects

Data for this set of analyses were compiled from two federally funded, multi-site, RCTs (Aman et al., 2009; RUPP Autism Network, 2002). The institutional review board at each site approved the trials, and a primary caregiver of each subject provided informed consent prior to data collection. Subjects who were intellectually able to understand the purpose and procedures for the studies provided assent. In the first trial (Study 1), subjects were randomly assigned to risperidone (n = 49) or placebo (n = 52) for 8 weeks under double-blind conditions. All 101 participants (aged 5–17 years) in Study 1 met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for autistic disorder (RUPP Autism Network, 2002). Study 2 included 124 children (aged 4.5–14 years) with autistic disorder, Asperger’s disorder, or pervasive developmental disorder not otherwise specified (PDD-NOS). In Study 2, random assignment was unbalanced such that 49 subjects were assigned to risperidone alone and 75 subjects to risperidone plus parent training (n = 75) (Aman et al., 2009). Although the treatment with risperidone was open in Study 2, the clinicians who managed the medication and the independent evaluators charged with assessing outcome were blind to treatment assignment for the first 8 weeks.

Procedures

An experienced clinical team at each site (e.g. child psychiatrist, psychologist, and nurse practitioner) evaluated potential subjects using standard methods. The prerandomization assessment verified eligibility via medical history and physical examination, developmental and psychiatric histories, and behavioral assessments. The ASD diagnosis was based on clinical interview and observation and supported by the Autism Diagnostic Interview–Revised (Lord et al., 1997). Intellectual ability was determined by one of several tests based on the child’s ability; both trials excluded subjects with IQ less than 35. A total of 12 subjects (5.3%) could not be tested due to lack of cooperation, but were deemed eligible by a case panel.

Eligible subjects were healthy and medication-free (7–28 days depending on the prior medication) without past or current psychotic disorder or bipolar disorder. Both trials required a score of 18 or higher on the parent-rated Aberrant Behavior Checklist (ABC) Irritability subscale and a clinician rating of at least Moderate on the Clinical Global Impression–Severity (CGI-S) (Aman et al., 2009; RUPP Autism Network, 2002).

In these trials, two clinicians, who were blind to treatment assignment during the first 8 weeks of the trial, followed study subjects. The treating clinician monitored adverse effects and adjusted the medication dose at Weeks 1, 2, 4, 6, and 8. The weight-based risperidone dose schedule was the same in both trials. The treating clinician could delay scheduled increases or reduce the dose to manage suspected adverse effects. An independent evaluator, who did not engage in discussion of adverse effects, rated the CGI–Improvement scale and the CYBOCS-ASD. The frequency of CYBOCS-ASD administration was slightly different across studies (e.g. baseline and every 2 weeks in Study 1; baseline and every 4 weeks in Study 2). Thus, we used data collected at baseline, Week 4, and Week 8 in this analysis.

Measures used in this report

CYBOCS-ASD.

The version of the CYBOCS-ASD used in these trials surveys 39 possible symptoms across nine categories (e.g. Washing Rituals, Checking Behaviors, Repeating Routine Behaviors, Counting, Ordering and Arranging, Hoarding, Superstitious Behavior, Rituals Involving Others, and Miscellaneous Repetitive Behaviors). Each category also permits the entry of “other” behaviors relevant to that category. The parent is the primary informant, but children are encouraged to participate to the extent that they are able. Following the review of the current repetitive behaviors, the interviewer inquires about the five severity items (Time Spent, Interference, Distress, Resistance (child’s own effort to limit the behavior), and Control (success of efforts to redirect the child)). This revised instrument has demonstrated reliability (coefficient alpha = 0.85; intraclass correlation for inter-rater reliability = 0.97) and showed sensitivity to change in Study 1 (McDougle et al., 2005; Scahill et al., 2006).

In both risperidone trials, raters were trained to reliability using didactic sessions on how to conduct the interview and video recordings to illustrate scoring. Raters then scored three videos independently. To be considered reliable, raters had to be within 15% of the total score compared to the gold standard rater.

ABC.

The ABC is a reliable and valid, 58-item, informantrated scale that includes five subscales: Irritability (agitation, aggression, and self-injurious behaviors, 15 items), Social Withdrawal (16 items), Stereotypic Behaviors (7 items), Hyperactivity (16 items; includes over-activity, impulsiveness, and noncompliance), and Inappropriate Speech (4 items) (Aman et al., 1985; Brown et al., 2002).

CGI-S.

The CGI-S is a 7-point scale ranging from non-symptomatic (score of 1) to extreme (score of 7) (Guy, 1976). Raters with at least master’s level of education were trained to reliability.

Child and Adolescent Symptom Inventory.

The Child and Adolescent Symptom Inventory (CASI) is a 132-item, parent-rated, DSM-IV-referenced scale that is a reliable and valid screening instrument for psychiatric disorders in youth (Gadow et al., 2008). Items are scored from 0 (never) to 3 (very often) yielding dimensional subscales for each disorder category. In this study, we included a 20-item anxiety scale covering separation anxiety, generalized anxiety, and social phobia (Hallett et al., 2013) and a 12-item ASD scale that quantifies core features of ASD (Gadow et al., 2008).

Intellectual functioning.

Several standard tests including the Wechsler Intelligence Scale for Children-III, Leiter International Performance Scale–Revised, Mullen Scales of Early Learning, or Stanford-Binet Version 5 were used to

ES=8week change in active−8week change in placebopooled standard deviation at baseline

measure intellectual functioning based on the child’s ability. Because several different tests were employed, we classified subjects categorically (e.g. average intelligence (⩾70) or intellectually disabled (<70)).

Survey Edition of the Vineland Adaptive Behavior Scales (Vineland).

The Vineland is a semi-structured, parent interview that is commonly used to measure adaptive functioning across domains including communication, daily living skills, and socialization. The scale is standardized for age and gender with a population mean of 100 ± 15 (Sparrow et al., 1984).

Analytic plan

First, we examined baseline values on the CYBOCS-ASD, ABC subscales, CASI PDD and Anxiety scales, Vineland scores, age, proportion of males, and proportion of subjects in the intellectually disabled range (IQ < 70) to assess for differences across the four groups (placebo and double-blind risperidone in Study 1, and risperidone alone and risperidone plus parent training in Study 2).

Using clinician-rated CYBOCS-ASD scores at baseline, Week 4, and Week 8, we compared the change in the CYBOCS across the four treatment groups with a linear repeated measures mixed model. This model included fixed effects for group (four levels), time (4 and 8 weeks), and their interaction. A random effect for subject was used to account for within-subject correlation on the repeated CYBOCS-ASD assessments. The model was adjusted for IQ (<70 versus ⩾70) and baseline CYBOCS-ASD score. In the absence of site differences in prior analyses, we did not include site in the model (Aman et al., 2009; RUPP Autism Network, 2002). The mixed model allows for the use of all available data and is valid under the missing at random (MAR) assumption.

Additional analyses included calculation of the correlation (Pearson r) of CYBOCS-ASD scores in the placebo group to estimate test–retest reliability. We also examined the change in individual dimensions of the CYBOCS to explore whether each dimension was sensitive to change with time using the Mann–Whitney U test. Effect sizes for the individual dimensions were estimated using the U statistic as described by Grissom and Kim (2012).

Results

The combined sample of 225 (187 boys and 38 girls) included 182 subjects with autistic disorder, 35 subjects with PDD-NOS, and 8 subjects with Asperger’s disorder. Among them, 160 were White, 27 were Black, 18 were Hispanic, 11 were Asian, and parents listed 8 subjects as “other” on the racial/ethnicity question. Of the subjects, 53 were in full-time regular education, 146 were in some type of a special education program, and 1 was in a residential school; 23 subjects were not in school or were in home school. Educational placement data were missing on two subjects.

Sample characteristics at baseline were similar across the two trials. By design, the Study 2 sample was slightly younger (4.5–14 years in Study 2 compared to 5–17 years in Study 1). The mean scores on the ABC Irritability and Hyperactivity subscales were slightly higher in Study 2 compared to Study 1. However, 81.3% (74 of 91 with IQ data) of subjects in Study 1 had IQ below 70 compared to 35.2% (43 of 122 with IQ data) in Study 2 (Chi square = 48.85; p < 0.0001). Vineland scores (higher scores reflect better adaptive functioning) were also higher in Study 2. In Study 2, 31.4% (39 of 124) were rated as Moderate on the CGI-S compared to 18.4% (18 of 98) in Study 1 (Chi square for Moderate vs > Moderate = 4.25; p = 0.03). Taken together, subjects in Study 1 were more severe (Table 1).

Table 1.

Baseline characteristics across four groups in RUPP Autism Network risperidone trials.

Placebo (1) (N = 52)
 Risperidone (1) (N = 49) Risperidone (2) (N = 49) Risperidone + PT (2) (N = 75)
N (%)
Males 43 (82.7) 39 (79.6) 40 (81.6) 65 (86.7)
ASD diagnosis
 Autistic disorder 52 (100) 49 (100) 32 (65.3) 49 (65.3)
 PDD-NOS  0 (0)  0 (0) 13 (26.5) 22 (29.3)
 Asperger’s  0 (0)  0 (0)  4 (8.2)  4 (5.3)
IQa
 ⩾70  6 (13.3) 11 (23.9) 23 (46.9) 46 (63.0)
 <70 39 (86.7) 35 (76.1)
CGI-Sb
 Moderate  9 (18.4)  9 (18.4) 14 (28.6) 25 (33.3)
 Marked 28 (57.1) 27 (55.1) 19 (38.8) 33 (44.0)
 Severe 12 (24.5) 12 (24.5) 15 (30.6) 17 (22.7)
 Extreme  0 (0)  1 (2.0)  1 (2.0)  0 (0)
Mean (SD)c
 Mean age (SD)  9.1 (2.58)  8.6 (2.97)  7.5 (2.80)  7.4 (2.21)
CYBOCS baselined 14.8 (4.27) 15.25 (3.25) 16.2 (2.47) 14.7 (2.85)
Vineland (standard scores)
 Communication 42.0 (14.28) 45.2 (16.79) 53.2 (19.94) 61.1 (20.95)
 Daily Living 47.4 (10.07) 49.1 (16.78) 41.1 (19.81) 50.8 (18.49)
 Socialization 34.0(15.59) 40.8 (21.04) 53.5 (14.41) 59.5 (15.01))
ABC
 Irritability 25.5 (6.82) 26.2 (7.9) 29.7 (6.10) 29.3 (6.97)
 Social withdrawal 16.1 (8.7) 16.4 (8.24) 17.1 (8.37) 15.2 (9.01)
 Stereotypy  9.0 (4.4) 10.6 (4.83) 10.6 (5.46)  7.6 (5.20)
 Hyperactivity 32.3 (8.5) 31.8 (9.58) 36.1 (6.86) 35.3 (9.30)
 Inappropriate speech  6.5 (3.64)  4.8 (408)  6.4 (4.03)  5.7 (3.43)
CASI
 PDD 23.2 (7.7) 24.3 (6.9) 23.2 (7.0) 22.0 (7.7)
 Anxiety 13.8 (7.6) 14.5 (9.7) 14.6 (9.5) 17.2 (10.3)
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RUPP: Research Units on Pediatric Psychopharmacology; ASD: autism spectrum disorder; PDD-NOS: pervasive developmental disorder not otherwise specified; CGI-S: Clinical Global Impression–Severity; CYBOCS: Children’s Yale–Brown Obsessive Compulsive Scales; ABC: Aberrant Behavior Checklist; CASI: Child and Adolescent Symptom Inventory; PT: parent training; SD: standard deviation.

a

IQ data missing on 12 subjects (10 in Study 1 and 2 in Study 2).

b

CGI missing on three subjects on placebo in Study 1.

c

Raw means; CYBOCS missing on one subject in Study 1.

The baseline CYBOCS was missing for one subject. After 8 weeks of treatment, CYBOCS-ASD total scores declined in the three active treatment groups, but showed little change with placebo (Table 2). In the placebo group, the correlation of the CYBOCS-ASD total score from baseline to Week 4 was 0.54 (p = 0.0001) and from Week 4 to Week 8 was 0.79 (p < 0.0001). Compared to placebo, all active treatment groups (risperidone in Study 1, risperidone only in Study 2, risperidone plus parent training in Study 2) showed significantly greater change from baseline with effect sizes ranging from 0.74 to 0.88 (see Table 2). There were no significant differences between any of the active treatment groups.

Table 2.

CYBOCS-ASD least square means by at baseline and Week 8.

Group Baseline Mean (SD) Week 8 Mean (SD) Effect size (ES) p value (compared to placebo)
Placebo (Study 1) 15.3 (3.89) n = 52 14.1 (4.43) n = 38 – –
RIS (Study 1) 15.5 (2.7) n = 48 11.3 (3.77) n = 43 0.74  0.0005
RIS only (Study 2) 16.2 (2.5) n = 49 11.0 (3.73) n = 47 0.88  0.0001
RIS + PT (Study 2) 14.7 (2.8) n = 75 11.1 (3.45) n = 70 0.86 <0.0001
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CYBOCS-ASD: Children’s Yale–Brown Obsessive Compulsive Scale modified for autism spectrum disorder; SD: standard deviation; RIS: risperidone; PT: parent training.

For the entire available sample (N = 224), Cronbach’s alpha for the CYBOCS-ASD total score was 0.84. When each dimension was removed and the remaining four items were correlated with the CYBOCS-ASD total score, correlations ranged from 0.79 to 0.81. As shown in Table 3, the Resistance item had the highest mean score at baseline and the lowest correlation to the CYBOCS-ASD total score compared to the other four dimensions. The Resistance item also showed the least amount of change over time. To explore the sensitivity to change for each dimension, we combined data from all three active treatment groups and compared change in active treatment to placebo using the Mann–Whitney U test. There was a significant improvement for all five dimensions from baseline to Week 8 in the combined active treatment groups compared to placebo.

Table 3.

CYBOCS-ASD dimensional scores at baseline, correlations between each dimension and total score at baseline, 8-week change in placebo group, and 8-week change in the three active treatments combined.

Baseline Mean (SD) N = 224 Correlation of each item with total score Alpha of 4-item scale with deleted variable Change from baseline to Week 8 for placebo (n = 38)a Change from baseline to Week 8 for active treatment (n = 160)b p value
Time spent 2.93 (0.90) 0.67 0.79 0.07 0.85 <0.0001
Interference 2.55 (0.91) 0.63 0.81 0.14 1.00 <0.0001
Distress 2.87 (0.80) 0.69 0.79 0.11 0.99 <0.0001
Resistance 3.45 (0.86) 0.60 0.81 −012 0.61 <0.01
Control 3.37 (0.72) 0.62 0.81 0.28 0.66 <0.01
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CYBOCS-ASD: Children’s Yale–Brown Obsessive Compulsive Scale modified for autism spectrum disorder; SD: standard deviation.

a

Missing data on 14 subjects at Week 8.

b

Missing data on 12 subjects at Week 8.

Discussion

Since the US Food and Drug Administration (FDS) approved risperidone and aripiprazole for the treatment of irritability in children and adolescents with autism, there has been increased interest in forging a regulatory path toward approval for other compounds (Hampson et al., 2012; Oberman, 2012). Interest is especially keen for evaluating treatments focused on core features of ASD such as social disability and repetitive behavior (Interagency Autism Coordinating Committee (IACC), 2012; Scahill et al., 2013; State and Sestan, 2012). Successful clinical trials require relevant, reliable, and valid outcome measures that are sensitive to change and not burdensome to subjects (FDA, 2009). The CYBOCS-ASD was used to measure repetitive behavior in the registration trial of oral-disintegrating fluoxetine (N = 158) and a federally funded trial of citalopram (N = 149) (Autism Speaks, 2009; King et al., 2009). The active drug was no better than placebo in either trial suggesting lack of efficacy or inadequacy of the CYBOCS-ASD as an outcome measure. To extend findings from a prior report (McDougle et al., 2005), we combined data from two risperidone trials to examine the sensitivity to change of the CYBOCS-ASD in a larger sample.

The CYBOCS-ASD includes a symptom checklist and five severity dimensions (Time Spent, Interference, Distress (when the behavior is interrupted), Resistance, and Degree of Control) each rated from 0 to 4. This architecture permits the clinician to document child-specific combinations of repetitive behavior and derive a total score from 0 to 20. If reliable and valid, a measure with a single score has statistical advantages over measures with multiple subscales that cannot be analyzed as a single outcome score.

The combined sample from two RUPP Autism Network risperidone trials provided a sample of 224 subjects (baseline CYBOCS-ASD missing for one subject) treated for 8 weeks in protocols that used identical dosing and similar outcome measurement strategies (Aman et al., 2009; RUPP Autism Network, 2002). All three active treatment groups (blinded risperidone in Study 1, and risperidone alone and risperidone plus parent training in Study 2) showed significant improvement in the CYBOCS-ASD scores compared to the placebo group in Study 1. Indeed, the placebo group showed little change over the course of the 8-week trial, suggesting that the CYBOCS-ASD has acceptable test–retest reliability in untreated subjects. The effect sizes for the CYBOCS-ASD total score in the three risperidone-treated groups corrected for placebo ranged from 0.74 to 0.88. There were no differences between active treatment groups. These findings suggest that the total score of the CYBOCS-ASD is a reasonably precise and useful endpoint in acute treatment trials focused on repetitive behavior in children with ASD.

To examine properties of the individual severity dimensions, we looked at baseline values and sensitivity to change for each dimension. The Resistance item had the highest mean score at baseline, the lowest correlation to the CYBOCS-ASD total score, and the least absolute change over the 8-week period. When all three active treatment groups were combined and compared to placebo, however, there was significant improvement for all five dimensions from baseline to Week 8.

Although the SSRIs have been shown to be safe and effective for the treatment of children with OCD (Geller et al., 2001; March et al., 1998; Riddle et al., 2001), they do not appear effective for reducing repetitive behavior in children with ASD (Autism Speaks, 2009; King et al., 2009). This suggests that repetitive behavior in ASD may not be the same as repetitive behavior in OCD. Risperidone is a potent D2 receptor blocker. The success of a D2 blocking drug fits with animal models of stereotypy—but D2 antagonism may not be the sole mechanism for the observed changes in repetitive behavior with risperidone. The additional potent serotonin 2 receptor antagonism of risperidone may also contribute to the beneficial effects on repetitive behaviors. Finally, CYBOCS-ASD scores incorporate the child’s reaction to interruption of repetitive behavior; a reduction in the over-reaction may be closely aligned with the observed reduction in tantrums, aggression, and self-injury (RUPP Autism Network, 2002).

Repetitive behaviors in ASD have often been classified as higher order (more complicated behaviors and circumscribed interests) and lower order (motor stereotypies and object manipulation) (Honey et al., 2012; Lam et al., 2008). Self-injurious behavior may reflect a separate category of repetitive behavior (Bishop et al., 2013). In a previous study, we used principal component analysis on the CYBOCS-ASD symptom checklist in a sample of 272 children with ASD (aged 4–17 years) and identified five factors of repetitive behavior (Scahill et al., 2014). This analysis resulted in elimination of common OCD compulsions such as washing and checking rituals (revised checklist available on request of first author). Consistent with other reports, we observed that children with intellectual disability were more likely to exhibit motor stereotypy and self-injurious behavior. Children in the normal IQ range were more likely to exhibit complex ritualistic behavior. However, many children exhibited behaviors from more than one category. Thus, looking for subjects with homogeneous profiles of repetitive behavior may not be a viable drug development strategy.

The findings of this secondary analysis should be interpreted with due consideration of the limitations. First, although these two trials used similar entry criteria, outcome measurement, and dosing strategies, this was not a four-group randomized trial. Thus, the placebo control group in Study 1 may be different in unknown ways from the participants in Study 2. Second, although independent evaluators were blind to treatment assignment in Study 2, parents and subjects were not. Third, the large effects of risperidone on the primary outcome (a measure of irritability) may have enhanced the impression of positive effects in other domains.

Funding

This research received grant funding from the US National Institute of Mental Health contract N01MH70009, grants U10MH66764, R01MH099021 (L. Scahill, Principal Investigator)

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