Efficacy and safety of risperidone for attention deficit hyperactivity disorder and disruptive behaviour disorders: a systematic review and meta-analysis

OBJECTIVES: To quantitatively synthesise evidence from randomised controlled trials (RCTs) on the efficacy and safety of risperidone augmentation in children and adolescents with attention deficit hyperactivity disorder (ADHD) and comorbid disruptive behaviour disorders (DBDs). METHODS: PubMed, EMBASE, and Scopus were searched for studies published from inception to 14 February 2025 using combinations of the following terms: ADHD, DBD, risperidone, aggression, and RCTs. Included studies were RCTs that evaluated the efficacy and/or safety of risperidone as an adjunct to optimise stimulant therapy in individuals aged 6 to 12 years diagnosed with ADHD and comorbid DBDs. The primary outcome was change in aggression from baseline to post-intervention, measured using standardised scales, between the risperidone and placebo groups. Secondary outcomes included the tolerability of risperidone in terms of weight gain and increased serum prolactin levels. RESULTS: Three studies involving individuals aged 6 to 12 years with a dual diagnosis of ADHD and DBDs were included in the analysis. The overall sample size was 279, with 144 in the risperidone group and 135 in the placebo or active control (stimulant) group. Individuals receiving risperidone augmentation showed improvement in aggression (standardised mean difference [SMD] = -0.79, p < 0.001), greater weight gain (2.1 vs 0.5 kg, SMD = 0.22, p = 0.06), and higher serum prolactin levels (28.5 vs 2.3 ng/mL, SMD = 1.40, p < 0.001). CONCLUSION: Risperidone augmentation reduces aggression and oppositional symptoms in children and adolescents with ADHD and comorbid DBDs. Nonetheless, risperidone is associated with risks of weight gain, elevated serum prolactin, and metabolic syndrome.