Selective Serotonin Reuptake Inhibitors in Autism: A Review of Efficacy and Tolerability.
Alexander Kolevzon, MD; Karen A. Mathewson, MD; and Eric Hollander, MD
Background: Awareness of the impact and
prevalence of autism spectrum disorders has
significantly increased in recent years. Given the dearth of
reliable interventions, there is great interest in
demonstrating efficacy of the various treatment options. A
growing body of evidence links autism spectrum disorders
to abnormalities in serotonin function, and the
selective serotonin reuptake inhibitors (SSRIs) have been
utilized to target various symptoms of the
disorders. This article reviews the available data on the
efficacy and tolerability of SSRIs in individuals with
autism spectrum disorders. Objectives for future research
in this area will also be suggested.
Data Sources and Study
Selection: The entire PubMed database including MEDLINE
(1966-July 2005) was searched for English-language
biomedical articles. Search terms included
autism, autism spectrum disorder,
citalopram, escitalopram,
fluoxetine, fluvoxamine,
paroxetine, pervasive developmental
disorder, selective serotonin reuptake
inhibitors, and sertraline. All clinical trials evaluating
treatment outcomes associated with the use of SSRIs in
managing symptoms of autism that were identified in
the search were reviewed. All randomized
controlled trials and open-label trials were included in this
review. Case reports and case series were excluded.
Data Synthesis: We identified 3 randomized
controlled trials and 10 open-label trials or
retrospective chart reviews on the use of SSRIs in autism and
autism spectrum disorders. The SSRIs that have
been studied in autism spectrum disorders are
citalopram, escitalopram, fluoxetine, fluvoxamine, and
sertraline. Most studies demonstrate significant improvement
in global functioning and in symptoms associated
with anxiety and repetitive behaviors. While side
effects were generally considered to be mild, increased
activation and agitation occurred in some subjects.
Conclusions: Although SSRIs may
demonstrate therapeutic benefit in autism spectrum
disorders, methodological weaknesses of many of the
clinical trials suggest the need for additional
randomized controlled trials. Furthermore, given the
increased awareness of the dangers associated with
SSRI-induced activation and agitation, the presence of
these side effects in the autistic population warrants
closer attention to dosage, titration, and subject
selection issues.
J Clin Psychiatry 2006;67(3):407-414
© Copyright 2006 Physicians Postgraduate Press, Inc.