Pharmacogenetics of response to methylphenidate in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD): a systematic review.
Methylphenidate (MPH) is a first line option in the psychopharmacologic treatment of adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, there is a considerable proportion of adult patients who do not respond to treatment with MPH or discontinue drug therapy. Since effects of genetic variants in the response to MPH treatment might explain these negative outcomes, we conducted an electronic systematic search of MEDLINE-indexed literature looking for articles containing information about pharmacogenetics of ADHD in adults published until January, 2012. The keywords used were 'ADHD', 'Attention-Deficit/Hyperactivity Disorder' and 'gene' in combination with methylphenidate, amphetamine or atomoxetine. Only 5 pharmacogenetic studies on adult ADHD met inclusion criteria. The results evidenced that most findings obtained so far are negative, and all studies focused on MPH response. There is only one positive result, for a polymorphism at the dopamine transporter gene (DAT1) gene. The current state of the art in adult ADHD implies that pharmacogenetic tests are far from routine clinical practice. However, the integration of these studies with neuroimaging and neuropsychological tests may help to understand mechanisms of drug action and the pathophysiology of ADHD.
ADHD Outpatient Clinic, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
Verônica
V
Contini
Diego L
DL
Rovaris
Marcelo M
MM
Victor
Eugenio H
EH
Grevet
Luis A
LA
Rohde
Claiton H D
CH
Bau
D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D004351:Drug Resistance; D006801:Humans; D008774:Methylphenidate / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D008774:Methylphenidate