Psychiatric News December 3, 2004
Volume 39 Number 23
© 2004 American Psychiatric Association
p. 25
Antibiotic Offers Some Hope In Autism Treatment
Joan Arehart-Treichel
A 5-year-old autistic boy became more sociable while he was taking
D-cycloserine. The antibiotic is one of the medications that looks promising
for increasing socialization in autistic children.
Researchers have identified some medications that help autistic youngsters
socialize.
For example, when autistic children were given selective serotonin reuptake
inhibitors (SSRIs) or atypical antipsychotics in open-label studies, they
became more spontaneous than before and interacted more with other people than
before. However, these medications' putative ability to increase socialization
in autistic youngsters has yet to be demonstrated in placebo-controlled
trials. Also, it is not yet known whether the purported socialization benefits
derive from a direct impact on socialization or via an indirect
effect—say, by reducing irritability and anxiety.
Still another medication that looks promising for autistic children is the
antibiotic D-cycloserine, a pilot study reported in the November American
Journal of Psychiatry suggests. The study was headed by David Posey,
M.D., an assistant professor of psychiatry at Indiana University and director
of the university's autism treatment center.
Various factors prompted Posey and his colleagues to undertake a pilot
study to determine whether D-cycloserine might increase socialization in
autistic children. In addition to being used to treat tuberculosis for 45
years, D-cycloserine enhances the activity of the neurotransmitter glutamate
in the brain. Adding low doses of D-cycloserine to antipsychotics other than
clozapine can temper social withdrawal in persons with schizophrenia, several
studies have suggested. D-cycloserine has been safely used in children at high
doses to treat tuberculosis, and the low doses of D-cycloserine used in
persons with schizophrenia have produced limited side effects.
In the pilot study by Posey and his coworkers, 10 individuals who met a
DSM-IV diagnosis of autism and who were on average 10 years old
received a placebo for two weeks, then three different, ascending doses of
D-cycloserine during each of three two-week periods. The daily doses were
about 0.7 mg/kg, 1.4 mg/kg, and 2.8 mg/kg, respectively. The subjects' social
withdrawal was measured with four yardsticks at the start of the study, at the
end of the placebo phase, and at the end of each two-week phase. The
yardsticks were the Clinical Global Impression Scale, the Social
Responsiveness Scale, a modified Children's Yale-Brown Obsessive-Compulsive
Scale, and the Aberrant Behavior Checklist.
Test results were encouraging. For example, subjects performed
significantly better on the Clinical Global Impression Scale after they had
received the medium and high doses of D-cycloserine than they had at the start
of the study. Subjects performed significantly better on the social withdrawal
subscale of the Aberrant Behavior Checklist after they had gotten the highest
dose of D-cycloserine than they had at the start of the study (see chart). In
four of 10 subjects, social improvement was clinically meaningful.
One of these four subjects was 5-year-old "Greg." Greg had been
in individual speech therapy and in group social skills training with a speech
and language therapist for two years. The therapist was not informed about
Greg's participation in the D-cycloserine study. Nonetheless, she noted marked
improvement in his attention, spontaneous use of language, and initiation of
social interaction while he was on D-cycloserine.
The pilot study was financed by the National Alliance for Research on
Schizophrenia and Depression (NARSAD), the National Institutes of Health, a
Daniel X. Freedman Psychiatric Fellowship Award, and the U.S. Department of
Housing and Urban
Development.
A randomized, double-blind, placebo-a controlled trial to further explore
D-cycloserine's impact on socialization in autistic subjects got under way
earlier this year, Posey told Psychiatric News. It is being funded by
the National Institute of Mental Health and NARSAD.
The study, "A Pilot Study of D-Cycloserine in Subjects With
Autistic Disorder," is posted online at
<http://ajp.psychiatryonline.org/cgi/content/full/161/11/2115?>.
Am J Psychiatry 2004 161 2115[Abstract/Free Full Text]
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