A trial of D-cycloserine to treat stereotypies in older adolescents and young adults with autism spectrum disorder.
OBJECTIVE
Autism spectrum disorders (ASDs) have core impairments in social communication as well as the presence of repetitive, stereotypic behaviors and restricted interests. Older adolescents and young adults are particularly impacted by these deficits. Preclinical data implicate glutamatergic dysfunction in the pathophysiology of ASDs. D-Cycloserine (DCS), a partial glycineB agonist at the N-methyl-D-aspartic acid receptor site, has been shown to improve sociability in mouse models and a small human study. The sensitivity of the obligatory glycineB co-agonist binding site may change with daily administration of DCS as a result of agonist-induced desensitization. The efficacy of a "pulsed" once-weekly administration versus "daily" administration of DCS was compared.


METHODS
Males and females, ages 14 to 25 years, with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision diagnosis of an ASD were enrolled in a double-blind, randomized 10-week trial consisting of 8 weeks of active drug with either weekly or daily administration of 50 mg of DCS followed by a 2-week follow-up visit.


RESULTS
For the purposes of this study, no statistical or clinical differences existed between the 2 dosage groups on the Aberrant Behavior Checklist subscale 3, which measures stereotypies/repetitive movements. When combining groups, a statistically significant decrease of 37% was found from baseline to week 8 when study drug was completed using a linear mixed effects model (P = 0.003).


CONCLUSIONS
D-Cycloserine was shown to be effective in improving stereotypic symptoms in older adolescents and young adults with ASDs measured by the Aberrant Behavior Checklist subscale 3. In addition, DCS was safe and well tolerated.
*Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk; and †Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia.
Maria
M
Urbano
Leonore
L
Okwara
Paul
P
Manser
Kathrin
K
Hartmann
Amy
A
Herndon
Stephen I
SI
Deutsch
D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects; D000328:Adult; D000963:Antimetabolites / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy* / Q000503:physiopathology; D003523:Cycloserine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012920:Social Behavior Disorders / Q000209:etiology / Q000517:prevention & control*; D013239:Stereotyped Behavior / Q000187:drug effects; D019956:Stereotypic Movement Disorder / Q000209:etiology / Q000517:prevention & control*; D055815:Young Adult
D000963:Antimetabolites; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine