Antibiotic Offers Some Hope In Autism Treatment

Psychiatric News December 3, 2004 Volume 39 Number 23, Clinical & Research News

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.

See Graphic here: http://www.sarnet.org/img/3chart.gif