Therapies for Children With Autism Spectrum Disorders

“unusual intellectual achievement” in those subjects with a good/excellent response. Subjects
with good/excellent response also showed an increased rate of verbal language before starting
fluoxetine. Finally, subjects with a good/excellent response were more likely to have hyperlexia,
an early or precocious interest in letters or numbers. They did not find a significant relationship
between history of regression and response to fluoxetine. They also did not find a relationship
between dose of fluoxetine and likelihood of response.
One additional retrospective case series described response to various serotonin reuptake
inhibitors, primarily sertraline, citalopram, paroxetine, and fluvoxamine in 89 children and
adolescents with ASDs by DSM-IV criteria. 224 The CGI-Improvement was used to gauge
medication response, with 40 subjects rated as at least “much improved.” Family history of
ASDs was significantly associated with positive treatment response. Other possible moderators
showed no association with response, including family history of depression or anxiety, subject
diagnosis, concurrent medications, specific SRI prescribed, and indication for SRI initiation,
whether for anxiety, repetitive behavior, aggression, or depression.
In the double-blind cross-over trial of MPH in 66 children with PDDs, 228-230 authors found no
effect of age, IQ, weight, or diagnosis on teacher- or parent-rated hyperactivity subscale scores /
Swanson Nolan and Pelham-Fourth edition rating scale (SNAP-IV) / Children’s Yale-Brown
Obsessive Compulsive Scale-PDD scores. Children with Asperger syndrome/PDD-NOS (n=19)
showed a trend of being more likely to be classified as responders to both placebo and MPH than
those with autism. Response to each dose of MPH was significantly superior to placebo in the
autism subgroup but not for the Asperger / PDD-NOS subgroup.
Similarly, Posey et al., in their retrospective review of 80 children with PDDs treated with
guanfacine, 232 found that subjects with PDD-NOS and Asperger syndrome showed a greater rate
of global response than those with autistic disorder. Those without intellectual disability showed
a higher rate of global response to guanfacine (37.5 percent) than those with co-morbid
intellectual disability (17.9 percent). They also identified that the responders were less aggressive
at baseline by the CGI severity item. Finally, Stigler et al., in their study on the effectiveness of
psychostimulants in 195 children with PDDs, found that children with Asperger disorder were
found to be more likely to respond to treatment than those with autistic disorder or PDD-NOS.
Those children on concomitant medication were also found to be more likely to respond to
treatment; the study did not find any association between stimulant type, gender or IQ and
response to treatment. 233
Of particular interest currently in the study of medical treatment of autism is the possibility
of genetic modifiers that might be used to target treatment choices. One prospective ten-week
case series of escitalopram sought to identify pharmacogenetic modifiers of treatment response
in the challenging behavior domain as measured by the ABC-C-Irritability. 223 Fifty-eight
subjects with ASDs corroborated by ADI-R and a minimum ABC-C-Irritability 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. Pre-designated dose-limiting side
effects included sleep disruption and an increase in ABC-C Irritability or Hyperactivity subscales
of 10 points over the previous week.
Subjects were also genotyped at several polymorphisms in the serotonin transporter gene.
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. One genotype group, designated a priori as the low-expression genotype group,
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