A Trial of D-Cycloserine to Treat Stereotypies in Older Adolescents and Young Adults With Autism Spectrum Disorder

Abstract

Objectives 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.

Autism throughout genetics: Perusal of the implication of ion channels

“…In a recent clinical trial carried out on 20 patients with autism, it has been shown that D‐cycloserine treatment alleviated the stereotyped behavior of these patients (Urbano et al., 2014). To go more into details, the administration of D‐cycloserine during 8 weeks with different dosages showed to be effective on ASD manifestations in these patients without showing any side effects (Urbano et al., 2014).…”

“…To go more into details, the administration of D‐cycloserine during 8 weeks with different dosages showed to be effective on ASD manifestations in these patients without showing any side effects (Urbano et al., 2014). Additional studies will be required to determine the therapeutic effect of this drug in ASD.…”

Developing Medications Targeting Glutamatergic Dysfunction in Autism: Progress to Date

“…In a 2-week, pilot, single-blind placebo lead-in study with children, adolescent and young adults with ASD (N=10; mean age 10.0±7.7; range 5–28 years), D-cycloserine resulted in significant improvement in the social withdrawal subscale of the Aberrant Behavioral Checklist (ABC-SW) [45]. In a double-blind randomized, 10-week pilot study (N=20; age range 14–25 years), the result on improvement in ABC-SW by D-cycloserine was not replicated [46]. However, D-cycloserine was found to reduce stereotypic symptoms (as measured by stereotypy subscale of the ABC) in young adults and adolescents [46].…”

Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy

“…Buspirone [95,[201][202][203], fluoxetine [204][205][206][207][208], escitalopram [209,210], citalopram [211], sertraline [212][213][214], D cycloserine [186,[215][216][217][218], amantadine [219], and memantine [220][221][222] have already been used in clinical research into autism. Finally, naltrexone, a potent opiate antagonist tested in ASD for improving behavioral changes [223][224][225][226][227][228][229][230][231][232][233][234][235][236][237][238][239], could also possess immunomodulatory action [240].…”