A prospective, open-label trial of memantine in the treatment of cognitive, behavioral, and memory dysfunction in pervasive developmental disorders.

BACKGROUND: This pilot study examined the effectiveness of memantine hydrochloride in improving cognitive functioning and behavioral symptoms in children with pervasive developmental disorders (PDDs). METHOD: Subjects aged 3-12 years inclusive were enrolled in this 8-week, open-label study. Expressive and receptive language, nonverbal IQ, and nonverbal memory measures were administered at baseline and after 8 weeks of treatment with 0.4 mg/kg of memantine hydrochloride. Throughout the study, the Aberrant Behavior Checklist (ABC) was sent in weekly by parents as a measure of behavioral change. RESULTS: Twelve of 14 subjects completed the study. Significant improvement from baseline was noted on the memory test (Children's Memory Scale Dot Learning Subtest). There were no significant differences from baseline on measures of expressive or receptive language or nonverbal IQ. There were significant improvements on a number of ABC subscales, including hyperactivity, lethargy, and irritability. There were no overall significant statistical differences from baseline on the Clinical Global Improvement-Severity (CGI-S) scale. On the Clinical Global Improvement-Improvement (CGI-I), 4 of 14 subjects showed minimal improvement, and none was deemed "much-improved" or "very much improved." CONCLUSIONS: This small, prospective, open-label study suggests that memantine may be useful in the treatment of memory functioning and some behavioral symptoms in PDDs. The investigators did not see the same degree of change as endorsed by caretakers. Controlled studies are needed to substantiate and clarify these preliminary findings.

A pharmacogenetic study of escitalopram in autism spectrum disorders.

OBJECTIVE: To determine the effect of serotonin transporter polymorphism promoter region (5-HTTPLR) genotypic variation (low, intermediate, and high expression groups) on response to escitalopram treatment of children and adolescents with autism spectrum disorders (ASDs). METHOD: The study used a forced titration, open label design, with genotype blind until study completion. Participants were children and adolescents aged 4-17 years of age with a confirmed ASD (autistic disorder, Asperger's disorder, or pervasive developmental disorder, not otherwise specified). RESULTS: There was an interaction between genotype group and time on the Aberrant Behavior Checklist (ABC) Irritability Subscale (primary outcome variable) (linear maximum marginal likelihood estimation=-4.84, Z=-2.89, SE=1.67, P=0.004). Examination of baseline to last visit revealed that a genotype grouping based on a previous study of platelet 5-HT uptake revealed less response in the genotype group that had S/S genotype for 5-HTTLPR and did not have a diplotype in intron 1 previously shown to be associated with increased platelet 5-HT uptake. CONCLUSION: This genotype-blind, prospective pharmacogenetic study found the group of subjects with associated with the lowest platelet 5-HT uptake from previous study had the smallest reduction in ABC-Irritability scores after open label treatment with escitalopram. Replication is necessary to confirm these findings.