Noradrenaline reuptake inhibitors (NRIs) for attention deficit hyperactivity disorder (ADHD) in adults

RationaleAttention deficit hyperactivity disorder (ADHD) in adults is controversial. Noradrenaline reuptake inhibitors (NRIs) are used for treatment. It's unclear how helpful/harmful they are.ObjectivesThis review brings together available evidence to evaluate the benefits and harms of NRIs in adults with ADHD.MethodsWe searched for all randomised controlled trials that compared NRIs to placebo/no treatment in bibliographic databases (April 2025) and synthesised their results. We assessed the certainty of evidence applying GRADE.ResultsWe included 21 trials, 5124 participants from Europe, Americas and Asia. NRIs may have little to no effect on people's ability to function in daily life, or on improving ADHD symptoms and quality of life. NRIs increased treatment discontinuation (RR 1.16, 95% CI [1.03, 1.30]) and non-serious adverse events (AEs) (RR 1.27, 95% CI [1.09, 1.49]), both with very low certainty. Atomoxetine increased serious AEs (RR 2.31, 95% CI [1.79, 2.97]; moderate certainty).ConclusionsThere is probably more harm (compared to placebo) with atomoxetine use in adults, with over two-fold increase in the number of people with serious (life-threatening) adverse events, a higher proportion of people with any adverse event amongst patients taking atomoxetine and higher withdrawal rates of people treated with atomoxetine or reboxetine.