Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a common childhood onset neuropsychiatric disorder with a complex and heterogeneous symptomatology. Persistence of ADHD symptoms into adulthood is common. Methylphenidate (MPH) is a widely prescribed stimulant compound that may be effective against ADHD symptoms in children and adults. However, MPH does not exert satisfactory effect in all patients. Several genetic variants have been proposed to predict either treatment response or adverse effects of stimulants. We conducted a literature search to identify previously reported variants associated with MPH response and additional variants that were biologically plausible candidates for MPH response. The response to MPH was assessed by the treating clinicians in 564 adult ADHD patients and 20 genetic variants were successfully genotyped. Logistic regression was used to test for association between these polymorphisms and treatment response. Nominal associations (p < 0.05) were meta-analysed with published data from previous comparable studies. In our analyses, rs1800544 in the ADRA2A gene was associated with MPH response at a nominal significance level (OR 0.560, 95 % CI 0.329–0.953, p = 0.033). However, this finding was not affirmed in the meta-analysis. No genetic variants revealed significant associations after correction for multiple testing (p < 0.00125). Our results suggest that none of the studied variants are strong predictors of MPH response in adult ADHD as judged by clinician ratings, potentially except for rs1800544. Consequently, pharmacogenetic testing in routine clinical care is not supported by our analyses. Further studies on the pharmacogenetics of adult ADHD are warranted.Electronic supplementary materialThe online version of this article (doi:10.1007/s00702-016-1540-7) contains supplementary material, which is available to authorized users.
Highlights
Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder characterized by developmentally inappropriate levels of impulsivity, hyperactivity and inattention (American Psychiatric Association 2013)
Knowledge about the pharmacogenetics of MPH response may increase our insights into the aetiology of ADHD and improve patient care
We assessed the genetic background of MPH response in patients with adult ADHD
Summary
Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder characterized by developmentally inappropriate levels of impulsivity, hyperactivity and inattention (American Psychiatric Association 2013). Pharmacogenetic studies conducted in ADHD children may not be directly applicable to adults Despite this lack of reliable genetic markers in the published literature and the uncertainties regarding the impact of aging, several commercial genetic tests are being marketed to patients, parents and health care providers to guide pharmacological intervention in ADHD. Discovering and affirming genetic variants involved in the response to MPH in ADHD patients could help guide treatment strategies with respect to symptom control and adverse effects, helping to secure treatment compliance and adherence (Gajria et al 2014) This may be of great importance for adult ADHD patients, who often are burdened with polypharmacy, comorbidity and socioeconomic distress (Halmoy et al 2009). We hypothesized that variants in the genes formerly linked to psychiatric or pharmacological phenotypes and which are involved in MPH metabolism or MPH pharmacodynamics, could potentially affect the response to MPH in adult ADHD patients
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