Impact of nutritional factors on the pharmacokinetics of ADHD medication – a systematic review

Abstract Background Attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy relies primarily on stimulant medications such as methylphenidate and amphetamines. Pharmacokinetic variability may influence therapeutic efficacy and tolerability. Nutritional factors, including food intake and alcohol consumption, may alter drug absorption, metabolism, and systemic exposure, yet these interactions have not been systematically synthesized across ADHD medications. Main body A systematic literature search was conducted across PubMed, Web of Science, Scopus, Embase, and Cochrane CENTRAL. Clinical studies in humans investigating the pharmacokinetics of ADHD medications under defined nutritional conditions (e.g., fasting vs. fed states or alcohol co-administration) were included. 33 clinical studies met the inclusion criteria. Most included studies were small, single-dose pharmacokinetic studies conducted in healthy adults, and evidence under steady-state conditions or in patients with ADHD was limited. Modified-release formulations showed greater formulation-specific variability, including changes in t max , C max , early exposure, and the shape of the concentration–time profile despite comparatively preserved total AUC in several studies. Eligible published evidence for non-stimulant ADHD medications was sparse, with only one eligible study each for extended-release clonidine and viloxazine. Human studies investigating alcohol interactions were predominantly available for methylphenidate and demonstrated increased methylphenidate exposure and formation of ethylphenidate. Conclusions Food intake affects the pharmacokinetics of most ADHD medications primarily by affecting the rate rather than the extent of absorption. Alcohol–methylphenidate interactions are clinically significant. Consistent administration conditions and patient counselling are important to optimize therapeutic outcomes.