Attention-Deficit/Hyperactivity Disorder Pharmacogenomics

Abstract

Although the efficacy of medications for attention-deficit/hyperactivity disorder (ADHD) is well demonstrated in clinical trials, substantial numbers of patients fail to remain on therapy, and there is tremendous variability in tolerability and treatment acceptance. The emerging science of pharmacogenomics seeks to identify patterns of genetic variation that will direct individually tailored treatment regimens and enhance long-term adherence. For this review, existing studies in ADHD pharmacogenomics were reviewed to assess current knowledge and provide a basis for planning future research. Twelve studies were identified. The majority investigated the role of candidate genes in predicting clinical response to methylphenidate. The most frequently studied is DAT1, although findings are inconsistent, with the 10-repeat polymorphism predicting both increased and decreased symptom reduction in various reports. Other candidates include DRD4, DRD5, DBH, 5HTT, SNAP-25, and COMT. One study was based on quantitative trait analyses in a genome-wide scan. Although interest in ADHD pharmacogenomics is encouraging, preliminary studies have been limited by small sample sizes, inconsistent research designs, retrospective reports, and a focus on symptom response. Future studies should emphasize large, prospective trials, assess multiple medications in individual subjects, and consider a full range of pharmacodynamic and pharmacokinetic outcomes.