Therapies for Children With Autism Spectrum Disorders

Serotonin Reuptake Inhibitors
SRIs have come into wide use for the treatment of depression and anxiety and are some of
the most commonly prescribed medications for children with ASDs. 41-43 Most recent clinical
trials in children with ASDs have focused on their potential to decrease repetitive behaviors. 49
Content of the literature. We identified five studies that addressed the use of serotonin reuptake
inhibitor medications in children with autism spectrum disorders; table 17 includes additional
details. Two of these studies evaluate the effects of fluoxetine, 220,221 one of citalopram, 222 one of
escitalopram, 223 and one of a variety of SRIs. 224
The literature base on the effects of fluoxetine in children with ASDs included one
retrospective case series 221 and one randomized, controlled, cross-over trial of fluoxetine
compared with placebo. Both of these studies were conducted in academic clinic settings using
institutional or grant funding. 220 The single study on the effects of citalopram in children with
ASDs was a randomized, controlled trial conducted in multiple academic centers using
institutional and grant funding. 222 The single study on the effects of escitalopram in children with
ASDs was a prospective case series 223 that analyzed outcome by serotonin transporter genotype,
and is therefore discussed in detail in the Modifiers of Treatment Effectiveness (KQ 2) section of
the report. One retrospective case series 224 reported on a number of SRIs.
The two RCTs included a total of 112 participants in treatment arms, and 115 participants in
comparison arms. Participants had an average age of 8.8 and 9.1, in the treatment and
comparison groups, respectively. 220,222 Both treatment and comparison groups had more male
subjects (83.7 percent and 81.7 percent, respectively). Both of the studies included subjects with
any pervasive development disorder (Autistic Disorder, PDD-NOS, or Asperger Disorder) and
used either the ADI-R 222 or the ADI-R and the ADOS for corroboration. 220
One of the RCTs had a minority of subjects with intellectual disability, 222 and the other had
an average IQ in the intellectual disability range. 220 The three case series included 276 subjects
with any diagnosis of PDD. 221,223,224 One study used ADI-R to corroborate DSM-IV diagnosis, 223
one used CARS plus ADOS, 221 and one used DSM-IV only. 224 Among the case series subjects,
the average age was 6.9 years old and 87.1 percent were male. Only one case series provided IQ
measures on subjects 223 and had average verbal and nonverbal IQ in the borderline to low
average range (76 and 86, respectively). Among all studies of SRIs, one was good quality, two
were fair, and two were poor.
Summary of the literature. We review citalopram and escitalopram together because
escitalopram is the active component (enantiomer) of citalopram. One 12-week randomized,
controlled trial of citalopram was identified. 222 This trial focused on repetitive behavior
outcomes with a number of secondary outcomes also measured.
The entry criteria for the study were a PDD diagnosis corroborated by both ADI-R and
ADOS, moderate illness severity on the CGI-Severity and significant repetitive behavior on the
Children’s Yale-Brown Obsessive Compulsive Scale-PDD version. 222 It had 73 subjects in the
citalopram arm and 76 in the placebo arm. 222 Subjects were begun on 2.5 mg of citalopram daily
with weekly increases of 2.5 mg per day for the first five to six weeks as clinically indicated,
followed by weekly increases of up to five mg per day thereafter, up to a maximum dose of 20
mg per day. 222 This dose is lower than the equivalent daily dose of SRIs used in obsessive
compulsive disorder in previous studies, 225,226 but it is similar to dosing used in an earlier case
series in autism. 227
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