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Objectives: The purpose of this study is to examine the relationship between 5-HTTLPR polymorphism (44-bp insertion/deletion polymorphism of serotonin transporter gene) and methylphenidate (MPH) treatment response, as well as the association between the adverse events of MPH treatment and 5-HTTLPR polymorphism in children with attention-deficit/hyperactivity disorder (ADHD)., Methods: A total of 114 children with ADHD (mean age 9.08 ± 1.94 years) were recruited from the child psychiatric clinic in a hospital in South Korea. We have extracted the genomic DNA of the subjects from their blood lymphocytes and analyzed 5-HTTLPR polymorphism of the SLC6A4 gene. All children were treated with MPH for 8 weeks, with clinicians monitoring both the improvement of ADHD symptoms and the side effects. We compared the response to MPH treatment and adverse events among those with the genotype of 5-HRRLPR polymorphism., Results: There was no significant association between the 5-HTTLPR genotype and the response to MPH treatment in children with ADHD. Subjects with the S/L+L/L genotype tended to have tics and nail biting (respectively, p < 0.001, p = 0.017)., Conclusions: The results of this study do not support the association between the 5-HTTLPR polymorphism and treatment response with MPH in ADHD. However, our findings suggest the association between 5-HTTLPR polymorphism and the occurrence of tics and nail-biting as an adverse event of methylphenidate. This may aid in our understanding of the genetic contribution and genetic susceptibility of a particular allele in those ADHD patients with tics or nail biting.

Objectives: While stimulants are the recognized first-line choice of pharmacotherapy for ADHD, reports that they may induce or exacerbate tics have tended to limit their use in ADHD children who have a history of tics or a family history of Tourette's syndrome. This study analyzes the incidence of tics reported across five studies of children with ADHD who received methylphenidate (MPH)-based therapy as part of the clinical development program for once-daily OROS MPH (CONCERTA McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA)., Methods: Data were analyzed from three placebo-controlled, active-controlled studies (studies 1-3) lasting 1-4 weeks, and two open-label studies lasting 2 years (study 4) and 9 months (study 5), respectively. During the course of the studies, parents were asked at the end of each week of treatment (studies 1 and 2), biweekly (study 3), or monthly (for the first year of study 4, then at 3-month intervals thereafter) whether their child had experienced tics. Tics could also be reported as adverse events in the two open-label studies., Results: Pooled data from the three placebo-controlled studies showed that the incidence of tics was not significantly different across all three treatment groups (OROS MPH, 4.0%; MPH tid, 2.3%; placebo, 3.7%, p = 0.5249). During the first year of the 2-year open-label study, the monthly incidence of tics remained constant, at approximately 5%. Analysis of tic episodes per patient in this study found no correlation between an OROS MPH dose and the frequency of tic episodes. The risk of tic episodes was higher in patients with a history of tics than in those with no history of tics (33% versus 7%, p < 0.0001). However, only 2 children with a history of tics (4%) withdrew from therapy because of their tics., Conclusions: These data suggest that MPH-based therapy does not significantly induce or exacerbate tics in children with ADHD.