CNS Drugs

, Volume 24, Issue 2, pp 99–117 | Cite as

Progress and Promise of Attention-Deficit Hyperactivity Disorder Pharmacogenetics

  • Tanya E. Froehlich
  • James J. McGough
  • Mark A. Stein
Review Article


One strategy for understanding variability in attention-deficit hyperactivity disorder (ADHD) medication response, and therefore redressing the current trial-and-error approach to ADHD medication management, is to identify genetic moderators of treatment. This article summarizes ADHD pharmacogenetic investigative efforts to date, which have primarily focused on short-term response to methylphenidate and largely been limited by modest sample sizes. The most well studied genes include the dopamine transporter and dopamine D4 receptor, with additional genes that have been significantly associated with stimulant medication response including the adrenergic α2A-receptor, catechol-O-methyltransferase, D5 receptor, noradrenaline (norepinephrine) transporter protein 1 and synaptosomal-associated protein 25 kDa.

Unfortunately, results of current ADHD pharmacogenetic studies have not been entirely consistent, possibly due to differences in study design, medication dosing regimens and outcome measures. Future directions for ADHD pharmacogenetics investigations may include examination of drug-metabolizing enzymes and a wider range of stimulant and non-stimulant medications. In addition, researchers are increasingly interested in going beyond the individual candidate gene approach to investigate gene-gene interactions or pathways, effect modification by additional environmental exposures and whole genome approaches. Advancements in ADHD pharmacogenetics will be facilitated by multi-site collaborations to obtain larger sample sizes using standardized protocols. Although ADHD pharmacogenetic efforts are still in a relatively early stage, their potential clinical applications may include the development of treatment efficacy and adverse effect prediction algorithms that incorporate the interplay of genetic and environmental factors, as well as the development of novel ADHD treatments.


Methylphenidate ADHD Symptom Atomoxetine Stimulant Medication Pharmacogenetic Study 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Dr Stein has received research support from McNeil, Novartis, Eli Lilly & Co., Cortex Pharmaceuticals, Organon and Pfizer Pharmaceuticals, and serves as a consultant for Novartis Pharmaceuticals and Shire Pharmaceuticals. Dr McGough has served as a consultant to or received research support from Eli Lilly & Co., Janssen Pharmaceuticals and Shire Pharmaceuticals. Dr Froehlich has no conflicts of interest that are directly relevant to the contents of this review. No funding organizations had any role in the preparation, review or approval of this manuscript.


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© Adis Data Information BV 2010

Authors and Affiliations

  • Tanya E. Froehlich
    • 1
  • James J. McGough
    • 2
    • 3
  • Mark A. Stein
    • 4
    • 5
  1. 1.Division of Developmental and Behavioral Pediatrics, Department of PediatricsCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Division of Child and Adolescent PsychiatryUniversity of California, Los Angeles Semel Institute for Neuroscience and Human BehaviorLos AngelesUSA
  3. 3.UCLA Child and Adolescent Psychopharmacology Program and ADHD ClinicLos AngelesUSA
  4. 4.Department of PsychiatryUniversity of Illinois at ChicagoChicagoUSA
  5. 5.Hyperactivity, Attention, and Learning Problems (HALP) Clinic and ADHD Research CenterUniversity of Illinois at ChicagoChicagoUSA

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