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Pharmacogenetics of Methylphenidate (Ritalin) in ADHD

By March 11, 2017Provider

Methylphenidate (MPH), branded as Ritalin, Concerta, Daytrana, Methylin, and Aptensio, is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). There is, however, considerable interindividual variability exists in clinical outcomes, which may arise from underlying genetic influences coupled with environmental influences, as discussed in a January 2017 article in The Pharmacogenomics Journal “Pharmacogenetics of methylphenidate response and tolerability in ADHD.”
 
The study is the first of its kind examining multiple SNPs across genes encoding the main components of the dopaminergic system to identify genetic factors that moderate response variability in ADHD treatment, according to the authors.
 
Specifically, the study was based in the analysis of 57 single-nucleotide polymorphisms (SNPs) in nine dopamine-related candidate genes (TH, DBH, COMT, DAT1 and DRD1-5) as potential predictors of methylphenidate efficacy and tolerability, and additionally considered teratogenic and postnatal xenotoxins (specifically maternal nicotine use)  as factors.
 
In analyzing the clinical efficacy of MPH, researchers found a “[a]dverse events after MPH treatment were significantly associated with variation in DBH  and DRD2. This study suggests that the geneticallly modulated dopaminergic system together with xenobiological and teratogenic influences may moderate MPH treatment effects.
 
“[C]linical response to MPH may be the result of a much more complex matrix of factors, including both genetic and environmental risks,” the authors concluded, calling for [f]urther pharmacogenetic studies with larger samples are required to fully validate these results and to disentangle the impact of prenatal xenotoxins on clinical response to MPH in genetically susceptible individuals.”

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