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Randomized Controlled Trial
. 2014 Jun;24(5):238-44.
doi: 10.1089/cap.2013.0102. Epub 2014 May 9.

Dopamine transporter genotype and stimulant dose-response in youth with attention-deficit/hyperactivity disorder

Mark A Stein  1 , Irwin Waldman, Jeffrey Newcorn, Jeffrey Bishop, Rick Kittles, Edwin H Cook Jr
Affiliations
Randomized Controlled Trial

Dopamine transporter genotype and stimulant dose-response in youth with attention-deficit/hyperactivity disorder

Mark A Stein et al. J Child Adolesc Psychopharmacol. 2014 Jun.

Abstract

Objectives: This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD).

Methods: Fifty-six children and adolescents (mean age=11.7±2.2) participated in a double-blind, two period crossover, dose-response study with a randomized placebo week in each 4 week drug period. Each period consisted of sequential week-long exposures to three dose levels (10, 20, 25-30 mg, depending upon weight) of D-MPH or MAS.

Results: Doses of 10-20 mg of either D-MPH or MAS had little to no effect on hyperactivity-impulsivity and total ADHD symptom scores in subjects with the 9/9 genotype; this was in contrast to the dose-response curves of subjects with either the 10/10 or 10/9 genotype.

Conclusions: ADHD youth with the 9/9 genotype may require higher stimulant doses to achieve adequate symptom control.

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Figures

<b>FIG. 1.</b>
FIG. 1.
Baseline and dose response for Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) total by DAT1 3′UTR VNTR genotype for mixed amphetamine salts (MAS) and dexmethylphenidate (D-MPH). (A) represents both stimulants combined and includes baseline characteristics. (B) and (C) represent MAS and D-MPH dose-response curves separately (excludes baseline). A color figure is available in the online version of this article at www.liebertonline.com/jcap
<b>FIG. 2.</b>
FIG. 2.
Dose-response for emotionality by DAT1 3′UTR VNTR genotype for mixed amphetamine salts and dexmethylphenidate. SERS, Stimulant Side Effect Scale. A color figure is available in the online version of this article at www.liebertonline.com/jcap
<b>FIG. 3.</b>
FIG. 3.
Dose effects on somatic complaints by DAT1 3′UTR VNTR genotype for mixed amphetamine salts and dexmethylphenidate. SERS, Stimulant Side Effect Scale. A color figure is available in the online version of this article at www.liebertonline.com/jcap
<b>FIG. 4.</b>
FIG. 4.
Dose-response effects on overfocused factors by DAT1 3′UTR VNTR genotype for mixed amphetamine salts and dexmethylphenidate. SERS, Stimulant Side Effect Scale. A color figure is available in the online version of this article at www.liebertonline.com/jcap
See this image and copyright information in PMC

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