Although the results discussed above suggest that the 10-repeat allele may be associated with poor treatment response to methylphenidate, other studies have reported that therapeutic responses are poorer in patients with the 9-repeat allele. In a double-blind study, Stein et al. (2005) found that children with the 9/9 genotype showed poor response to methylphenidate treatment as measured by ARS and CGI-S when they received higher (36 and 54 mg) but not lower (placebo or 18 mg) doses of methylphenidate. These results suggest that individuals with at least one copy of the 10-repeat allele responded better when given higher doses of methylphenidate. Joober et al. (2007) also performed a double-blind, placebo-controlled fixed-dose study, in which children diagnosed with ADHD were treated with methylphenidate for two weeks (0.5 mg/kg/day) and the effect of 3′-UTR VNTR was assessed. Similar to the results of Stein et al. (2005), children with the 9/10 and 10/10 genotypes showed significant improvement in ADHD symptoms following treatment as measured by the CGI-Parents scale when compared to 9/9 children; no difference was observed between the 9/10 and 10/10 groups.
