Pharmacogenetics of methylphenidate response in attention deficit/hyperactivity disorder: Association with the dopamine transporter gene (SLC6A3)

Abstract

Pharmacogenetic studies investigating the 40‐bp VNTR polymorphism at SLC6A3 and methylphenidate response have shown conflicting results and large differences in study design and efficacy endpoints. Our objective was to investigate the relation between the 3′‐VNTR at SLC6A3 and variability in methylphenidate response in a sample of 141 ADHD children and adolescents, assessed before and after methylphenidate treatment with both clinical and neuropsychological outcome measures. 10‐R homozygotes were significantly overrepresented in the low response group, but no genotype effect was shown in cognitive variables improvement. A meta‐analysis of pharmacogenetic studies with comparable data (responders vs. non‐responders) on a total of 475 subjects showed a significant association between the 10‐10 genotype and low rates of methylphenidate response (mean Odds Ratio = 0.46; 95% CI [0.28–0.76]). Heterogeneity between these studies did not reach a significant level but, as publications with different endpoints were excluded from this meta‐analysis, our results do not rule out a possible influence of study design.