Therapies for Children With Autism Spectrum Disorders

One prospective case series of escitalopram was identified. 223 This ten-week study sought to
identify pharmacogenetic modifiers of treatment response in the challenging behavior domain as
measured by the ABC-C-Irritability. Fifty-eight subjects with a PDD corroborated by ADI-R and
a minimum ABC-C-I score of 12 underwent a forced dose titration of escitalopram from 2.5 mg
daily increasing weekly to 5 mg, 10 mg, 15 mg, and 20 mg, essentially twice the dose equivalent
of citalopram given that escitalopram is the active component of racemic citalopram. Predesignated
dose-limiting side effects included sleep disruption and an increase in ABC-C
Irritability or Hyperactivity subscales of ten points over the previous week. Average daily doses
of escitalopram were 10.8-12.4 mg and did not differ across genotype groups, which reflects the
fact that most subjects in all genotype groups could not tolerate the maximum dose.
Unfortunately, the data are presented in figures only, and raw values cannot be inferred. It is
evident, however, that the ABC-C-Irritability for all subjects was 20 or greater at baseline and
that improvements were about ten points for three of the four genotype groups. 223 Adverse
effects were not directly assessed in this study.
One randomized, controlled crossover trial of fluoxetine was identified with two eight-week
treatment periods separated by a four-week washout period. 220 Thirty-nine subjects with a PDD
corroborated with ADI-R and ADOS were included in the final analysis with no minimum
required score on a repetitive behavior scale. Five additional subjects were randomized but not
included in the analysis for various reasons. Of the randomized subjects, 19 received fluoxetine
followed by placebo and 20 received placebo followed by fluoxetine. During each phase of the
study, subjects began the first week at 2.5 mg per day of fluoxetine or placebo, followed as
clinically indicated by weekly upward titration to 0.3 mg/kg for week 2, 0.5 mg/kg/day for week
3, and 0.8 mg/kg/day for weeks four to eight. During the first eight-week treatment period of the
study, subjects randomized to fluoxetine first had baseline Children’s Yale-Brown Obsessive
Compulsive Scale scores of 12.8 and those to placebo first had baseline scores of 13.5.
Subjects in the first fluoxetine group showed an improvement of 1.2, and those in the first
placebo arm showed an improvement of 0.5. These differences were not statistically significant
when considered alone. In the second eight-week treatment period, subjects randomized to
fluoxetine second had baseline Children’s Yale-Brown Obsessive Compulsive Scale scores of
12.8 and those to placebo second had baseline scores of 12.2. Subjects in the second fluoxetine
arm showed an improvement of 1.2, and those in the second placebo arm showed a worsening of
0.1. When analyzed together with the first treatment period in a repeated measures design, the
Children’s Yale-Brown Obsessive Compulsive Scale change in the fluoxetine arms was
significantly greater than the change in the placebo arms. No adverse events were significantly
more frequent in the fluoxetine group; although more subjects on fluoxetine had their dose
reduced due to agitation. 220 The two chart reviews of SRIs 221,224 reported in the literature were of
poor quality and included general outcome measures that are difficult to compare with the RCT
data.
69