The serotonergic system is implicated in ADHD, but the impact of serotonin's precursor molecule, tryptophan, on ADHD symptomology remains unclear. Systematic searches of randomised controlled trials with an experimental tryptophan intervention in children and adults with ADHD identified 14 studies measuring core and related symptoms of the condition. Risk of bias was assessed using the Cochrane Risk of Bias tool. The 14 studies all used acute tryptophan depletion procedures, and most did not investigate core ADHD symptoms (inattention, impulsivity, hyperactivity) as primary outcome measures. Only two studies examined attention and revealed mixed effects of tryptophan. Similar effects were found for impulsivity in a small number of studies. No studies investigated hyperactivity. Most studies focused on reactive aggression, but samples were heterogenous and small, rendering potential meta-analyses inconclusive or misleading. However, the narrative analysis indicates tryptophan interventions may impact reactive aggression. More research is needed on the effect of tryptophan modulation on core ADHD symptoms, especially in adults, using more diverse samples to determine potential as an intervention. From current data, tryptophan modulation appears to alter aggressive behaviour in ADHD; however, the available studies were insufficient for the planned meta-analysis.
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