473Genotype and Response to Methylphenidate
in Children with ADHD
Methylphenidate acts primarily by inhibiting the dopamine transporter (DAT), a
protein responsible for the reuptake of dopamine from the synapse into presynaptic
terminals. However, it is often diffi cult to predict how patients will respond to
ADHD medications.
A double-blinded, crossover trial found that children with a variant form of a
dopamine transporter gene, 9/9-repeat DAT1 3′-UTR genotype, responded poorly
to methylphenidate in contrast to those with 10/10-repeat variant who showed
excellent response (Stein et al. 2005 ). This study shows that testable genetic differ-
ences might be used to predict the effectiveness of methylphenidate in children with
ADHD. Further research is needed to determine the mechanisms related to poor
response in patients with the 9/9-repeat genotype, and to determine if this group
responds differentially to alternative treatments. A larger study is evaluating chil-
dren with ADHD on two other medications to see if their genes predict who will
respond to either or both drugs.
Pharmaco-EEG for Personalized Treatment of ADHD
The ‘impaired vigilance’ subgroup of ADHD with excess frontal theta or alpha
activity on EEG responds well to stimulant medication, whereas in depression this
subtype might be unresponsive to antidepressant treatments and respond better to
stimulant medication (Arns and Olbrich 2014 ). A slow individual alpha peak fre-
quency is an endophenotype associated with treatment resistance in ADHD. Future
studies should incorporate this endophenotype in clinical trials to investigate further
the effi cacy of new treatments in this substantial subgroup of patients.
Personalized Approach to Addiction
Pharmacogenetics of Drug Addiction
Pharmacogenetics provides the tools required to identify genetic predictors of prob-
able drug response, drug effi cacy, and drug-induced adverse events-identifi cations
that would ideally precede treatment decisions. Drug abuse and addiction genetic
data have advanced the fi eld of pharmacogenetics in general. Although major fi nd-
ings have emerged, pharmacotherapy remains hindered by issues such as adverse
events, time lag to drug effi cacy, and heterogeneity of the disorders being treated.
The sequencing of the human genome and high-throughput technologies are
enabling pharmacogenetics to have greater infl uence on treatment approaches.
Genes important in drug abuse pharmacogenetics have been identifi ed, which pro-
vide a basis for better diagnosis and treatment of drug abuse disorders.
Personalized Approach to Addiction