Therapies for Children With Autism Spectrum Disorders

Additional assessments of challenging behavior were also performed in these two
aripiprazole RCTs. Similar improvements for a second measure of challenging behavior, the
ABC-C Hyperactivity subscale, which indexes noncompliance as well as hyperactivity, were
also seen across both trials. Baseline ratings of hyperactivity were similar across aripiprazole and
placebo arms. Decreases in ABC-C-Hyperactivity were significantly greater for aripiprazole in
which improvements of 12.7-16.3 were seen, in comparison to the placebo arms, with
improvements of 2.8-7.7. The ABC-C Inappropriate Speech subscale also showed significant
improvement in one study216 with a supportive trend in the other. 215
Secondary outcomes in the two major RCTs of aripiprazole included measures of repetitive
behavior.218 Both studies included the ABC-C Stereotypy Subscale, which showed significantly
greater response in the aripiprazole arms. Baseline ratings of stereotypy were similar across
aripiprazole and placebo arms. Decreases in ABC-C-Stereotypy were greater for aripiprazole,
with improvements of 4.2-4.8, in comparison to placebo arms, with improvements of 1.8-2.0.
Both studies 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 greater
decrease in the aripiprazole compared with placebo arms (2.4-3.8 vs. 0.8-1.7). A number of other
outcomes were measured in these two studies, but none outside of challenging behavior and
repetitive behavior yielded statistically significant findings once corrected for multiple
comparisons.
The two aripiprazole RCTs also provided data on harms (Table 19). Both studies reported on
weight gain,215, 216 which was greater in the aripiprazole arms (1.3-2.0 kg) than in the placebo
arms (0.3-0.8 kg), with a statistically significant difference reported in both of the studies. 215,216
Somnolence and sedation were the most common adverse events in both of these studies,
occurring in 66 of 210 subjects in aripiprazole arms and eight of 101 subjects in placebo
arms. 215,216 Both studies also reported more extrapyramidal symptoms, including tremor,
dyskinesia, and rigidity, occurring in 44 of 210 subjects in the aripiprazole arms in comparison
with ten of 210 subjects in the placebo arms. 215,216 Both studies found a statistically significant
decrease in prolactin levels in the aripiprazole arms in contrast with the placebo arms. 215,216
Cyproheptadine plus haloperidol. One eight-week RCT compared addition of cyproheptadine
versus placebo to haloperidol. 217 Each arm contained 20 subjects. 217 The medication doses were
titrated up from some starting point to cyproheptadine 0.05 mg/kg/day and haloperidol 0.2
mg/kg/day, but no details are provided. Two general outcome measures were used, the ABC-C
and the Childhood Autism Rating Scale. Each measure was apparently translated into Farsi,
although no details were provided on validation of the translated versions, nor is it clear whether
parents completed paper and pencil versions of these measures or were interviewed. Baseline
scores on measures were only presented in graphs.
The ABC-C scores shown are markedly lower than the total ABC-C scores obtained at
baseline in other medication trials, 206,211,215,216 suggesting that a subscale may have been
administered; although this is not stated. 217 The response to placebo plus haloperidol was
smaller 217 than the response found in previous haloperidol trials. 39,219 The improvement in ABC-
C score in the cyproheptadine plus haloperidol arm was larger (10.9) than the improvement in
the placebo plus haloperidol arm (3.7). 217 Similarly, the improvement in Childhood Autism
Rating Scale score was greater in the cyproheptadine plus haloperidol arm (1.85) than in the
placebo plus haloperidol arm (0.37).
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