A comparative evaluation of the efficacy and safety of clonidine and atomoxetine combined with behavioural interventions in children with autism spectrum disorder and comorbid attention-deficit/hyperactivity disorder

Abstract

Objective: To compare the clinical efficacy and safety of atomoxetine versus clonidine, each combined with structured behavioural interventions, in children aged 6–12 years with autism spectrum disorder (ASD) and comorbid attention-deficit/hyperactivity disorder (ADHD).

Methods: A retrospective observational cohort study was conducted at the Imam Al-Hussein Institute for Children with Autism in Najaf, Iraq, between October 2025 and March 2026. Sixty-two children were allocated to two equal groups: atomoxetine plus behavioural intervention (n=31) or clonidine plus behavioural intervention (n=31). Outcomes were measured using DSM‑5 criteria and Conners’ Rating Scales at baseline and three follow‑up intervals (1–3, 3–6, and 6–12 months). Data were analysed using two‑way repeated‑measures ANOVA, Bonferroni post‑hoc tests, and chi‑square tests.

Results: The atomoxetine group showed significantly greater mean symptom improvement than the clonidine group (mean improvement score –13.4 vs. –9.5; p=0.0011), with effects emerging after 3 months and increasing over time. Adverse effects were more frequent in the clonidine group, notably sedation (70.9% vs. 9.6%), irritability (45% vs. 12.9%), and fatigue (61.2% vs. 16.4%). Atomoxetine was associated with mild appetite loss (35%) and gastrointestinal symptoms (29%).

Conclusion: Atomoxetine combined with behavioural intervention demonstrated superior and more sustained clinical improvement and a more favourable safety profile than clonidine in this observational cohort. However, owing to the non‑randomised design and baseline imbalances, these findings should be viewed as hypothesis‑generating. Randomised controlled trials are needed to confirm superiority.