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Meta-analysis of the association between dopamine transporter genotype and response to methylphenidate treatment in ADHD

The Pharmacogenomics Journal volume 14, pages 77–84 (2014)Cite this article

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Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent childhood-onset neuropsychiatric disorder. Treatment with methylphenidate, which blocks dopamine and noradrenaline transporters, is clinically efficacious in reducing the symptoms of ADHD. However, a considerable proportion of patients show no or only insufficient response to methylphenidate. Following a pharmacogenetic approach, a number of studies have suggested that heterogeneity in treatment response across subjects might to some extent be due to genetic factors. In particular, a variable number tandem repeat (VNTR) polymorphism in the 3′ untranslated region of the SLC6A3 gene, which codes for the dopamine transporter, has been considered as a predictor of treatment success. However, the literature has so far been inconsistent. Here we present results of a meta-analysis of studies investigating the moderating effect of the SLC6A3 VNTR on response to methylphenidate treatment in subjects with ADHD. Outcome measures from 16 studies including data from 1572 subjects were entered into a random-effects model. There was no significant summary effect for the SLC6A3 VNTR on the response to methylphenidate treatment (P>0.5) and no effect on specific symptom dimensions of hyperactivity/impulsivity and inattention (all P>0.2). However, in a subanalysis of naturalistic trials, we observed a significant effect of d=−0.36 (P=0.03), indicating that 10R homozygotes show less improvement in symptoms following treatment than the non-10/10 carriers. This meta-analysis indicates that SLC6A3 VNTR is not a reliable predictor of methylphenidate treatment success in ADHD. Our study leaves unanswered the question of whether other genetic polymorphisms or nongenetic factors may contribute to the observed heterogeneity in treatment response across ADHD subjects.

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Acknowledgements

Joseph Kambeitz is supported by a doctoral fellowship of BayEFG. Ulrich Ettinger is supported by the DFG Emmy Noether programme (ET 31/2-1). We thank Cristian Patrick Zeni, Veronica Contini, Aiveen Kirley, Diane Purper-Ouakil, Sandra K Loo, Harriet de Wit and Sandra Kooij for providing us with data necessary for the meta-analysis.

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  1. Department of Psychiatry, University of Munich, Munich, Germany

    J Kambeitz

  2. Department of Child and Adolescent Psychiatry, University Hospital of Würzburg, Würzburg, Germany

    M Romanos

  3. Department of Psychology, University of Bonn, Bonn, Germany

    U Ettinger

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Kambeitz, J., Romanos, M. & Ettinger, U. Meta-analysis of the association between dopamine transporter genotype and response to methylphenidate treatment in ADHD. Pharmacogenomics J 14, 77–84 (2014). https://doi.org/10.1038/tpj.2013.9

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