Therapies for Children With Autism Spectrum Disorders

C-Irritability 21.2-25.5) arms. Decreases in ABC-C Irritability were significantly greater for the
risperidone arms in both studies, which saw improvements of 12.1-14.9, compared with the
placebo arms, which saw improvements of 3.6-6.5.
Similar improvements for a second measure of challenging behavior, the ABC-C
Hyperactivity subscale, which indexes noncompliance as well as hyperactivity, were also seen in
both trials. Baseline ratings of hyperactivity were similar, with decreases significantly greater for
risperidone compared with placebo ( 14.8-14.9, in comparison to 4.7-7.4). The RUPP study also
reported a number of other outcomes that may correlate with challenging behavior, including the
Ritvo-Freeman Real Life Rating Scale Affectual Reactions subscale, which includes abrupt
changes in mood, temper tantrums, and crying, the VABS Maladaptive Behavior Domain, and
quantitative ratings of parent-rated target symptoms, each of which showed significant
improvements in the risperidone group. 204,207
Secondary outcomes in the two RCTs of risperidone included measures of repetitive
behavior. Both studies included the ABC-C Stereotypy Subscale, which showed greater response
in the risperidone arm. Baseline ratings of stereotypy were similar across risperidone and placebo
arms. Decreases in ABC-C-Stereotypy were significantly greater for risperidone in one RCT (4.8
vs. 1.7) 206 but would not have been significant after correction for multiple testing in the other
RCT (4.3 vs. 2.4). 211 One study 204,206 also used the Children’s Yale-Brown Obsessive
Compulsive Scale-PDD version to assess repetitive behavior, finding no baseline differences
between the groups but a significantly greater decrease in the risperidone compared with placebo
arms (3.9 vs. 1.0). A number of other outcomes were measured in these studies, but none outside
of challenging behavior and repetitive behavior would have yielded statistically significant
findings once corrected for multiple comparisons.
Two additional RCTs were identified that did not provide specific numerical ratings on either
challenging behavior or repetitive behavior. 203,212 One of these was an eight-week drug
discontinuation RCT with risperidone and placebo arms 203 after positive response during four
months of open label risperidone treatment following the RUPP risperidone RCT. 206 This
publication did not provide quantitative outcome data but instead indexed “relapse” using a
composite measure of ABC-C-Irritability and clinician ratings of CGI-I, 203 finding significantly
less “relapse” in the risperidone arm (two of 16 subjects) in comparison to the placebo arm (10
of 16 subjects).
The last RCT was a six-month RCT with risperidone and placebo arms that used a variety of
general rating scales to assess response and provided quantitative outcome data on only some of
these scales, 212 with the primary outcome measures being parent ratings on the Childhood
Autism Rating Scale and clinician ratings on the Children’s Global Assessment Scale. The study
only reports Childhood Autism Rating Scale median ratings for those participants with at least a
20 percent response. 212 Average ratings on the Children’s Global Assessment Scale were similar
in the risperidone (29.8) and placebo (32.7) arms with more improvement in the risperidone
(11.1) than placebo (2.5) arms.
All of the risperidone RCTs also provided data on adverse events or side effects (Table 19).
All studies reported on weight gain, 202,203,206,210-212 which was greater in the risperidone arms
(2.7-2.8 kg) than in the placebo arms (0.8-1.7 kg), with a statistically significant difference
reported in two of the studies. 202,206,210,211 Three of the RCTs 202,203,206,210,211 provided data on
other adverse events in both the risperidone and placebo arms. Somnolence or drowsiness was
the most common adverse event in two of these studies, occurring in 53 of 89 subjects in
risperidone arms and nine of 91 subjects in placebo arms. 202,206,210,211 These studies also reported
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