Antipsychotic treatment in children and adults with ADHD: a systematic review of efficacy and safety

Abstract Background The use of antipsychotics in the treatment of attention-deficit/hyperactivity disorder (ADHD) is becoming an increasingly common practice, especially if psychiatric comorbidities are present. The aim of this study was to investigate the efficacy of first, second and third generation antipsychotics across the lifespan in patients with ADHD, specifically focusing on pediatric, adolescent, and adult populations. Methods We carried out a systematic research of MedLine, PubMed, Cochrane, Embase and ScienceDirect databases according to PRISMA protocol. We included reports that examined populations of patients suffering from ADHD and treated with antipsychotics. To obtain data on the clinical outcome of the treatment we focused on studies that used clinical scales. Results A sample of 427 subjects diagnosed with ADHD was analyzed. 290 were exposed to antipsychotic treatment, while 137 were controls. The included studies were predominantly pediatric or adolescent (mean ages ranging from 3.98 to 10.2 years), with only one randomized controlled trial focusing on an adult population (mean age 34.3 years). First-generation antipsychotic resulted in a useful add-on option alongside psychostimulants. In children and adolescents, second-generation (specifically risperidone) and third-generation (aripiprazole) antipsychotics proved effective in improving both hyperactive/inattentive and affective dysregulation dimensions. Regarding the adult subgroup, brexpiprazole did not show statistically significant improvement as an add-on therapy with psychostimulants in the symptomatology of ADHD. A relevant observation from our review supports the hypothesis that early therapeutic intervention may be associated with more favorable clinical outcomes. Conclusions Among the antipsychotics considered, it would seem that risperidone and aripiprazole have the most encouraging results in reducing ADHD symptomatology, particularly in pediatric and adolescent populations. In contrast, evidence in adults remains limited and showed non-significant results for brexpiprazole. Further studies, preferably homogeneous with each other in terms of outcome assessment and time horizons, are needed to confirm these results.