Risperidone for children with attention-deficit/hyperactivity disorder and severe behavioral dysregulation: a randomized placebo-controlled assessor-blinded trial

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, and treatment of children with severe behavioral dysregulation remains challenging. This study evaluated the efficacy and safety of adjunctive risperidone specifically in children with ADHD and clinically significant behavioral dysregulation — including irritability, impulsive aggression, and oppositional symptoms — refractory to behavioral intervention alone. In this 48-week randomized, placebo-controlled, assessor-blinded trial, children aged 3–12 years with moderate-to-severe ADHD and significant behavioral dysregulation refractory to behavioral intervention alone were allocated to risperidone ( n = 48) or matched placebo ( n = 46), both in addition to ongoing structured behavioral intervention and parental psychoeducation. The primary outcome was change in clinician-rated ADHD-RS-IV score from baseline to week 48. Secondary outcomes included parent-rated Conners’ scores, Children’s Global Assessment Scale (CGAS), treatment response, adverse events, and metabolic parameters. Risperidone produced a significantly greater reduction in ADHD-RS-IV scores than placebo over time (baseline: 28.85 ± 2.62 vs. 28.70 ± 2.50; week 48: 15.63 ± 1.82 vs. 26.47 ± 2.92; p < 0.001). Parent-rated Conners’ scores also improved more in the risperidone group (week 48: 16.94 ± 1.81 vs. 28.42 ± 3.04; p < 0.001). Functional improvement was greater with risperidone, with higher CGAS scores and a higher clinical response rate (70.8% vs. 21.7%; p < 0.001). The most common adverse effects were somnolence and increased appetite. Risperidone was associated with greater weight gain and prolactin elevation than placebo, but no serious adverse events occurred. In this study, risperidone was associated with improvement in ADHD symptom severity and global functioning in carefully selected children with ADHD and prominent behavioral dysregulation. However, treatment was also associated with clinically relevant metabolic and endocrine adverse effects. These findings support selective use as a pharmacological adjunct to behavioral intervention in closely monitored patients with significant behavioral comorbidity, and do not justify routine use for uncomplicated ADHD.