The Use of Clonidine in Patients With ADHD and Comorbid ODD

Background Attention-deficit/hyperactivity disorder (ADHD) co-occurs with oppositional defiant disorder (ODD), which lacks an approved treatment. Clonidine, an alpha-2 agonist approved for ADHD, is used off-label to target aggression, impulsivity, and hyperactivity, though evidence is limited to case-level observation. Methods We present three adolescent males (ages 14-15) with comorbid ADHD and ODD, stabilized on stimulant or non-stimulant therapy, who had clonidine added to target residual hyperactivity, impulsivity, and aggression. NICHQ Vanderbilt Assessment Scale scores were obtained before and after 12 weeks of treatment. Descriptive statistics were used, with percentage change calculated for ODD subscale scores. Results All three patients showed reductions in ODD subscale scores after clonidine initiation, ranging from 25% to 40% from baseline, with reductions in ADHD scores. Response varied: one patient achieved behavioral and academic stability; one showed partial improvement in classroom disruption, with persistent anger and anxiety requiring pharmacotherapy; one responded favorably after switching from a transdermal patch to oral dosing. Conclusion In this case series, clonidine added to ADHD treatment was associated with reduced oppositional and disruptive symptoms, though response varied. These findings support clonidine as adjunctive treatment for comorbid ADHD/ODD alongside behavioral interventions. Larger controlled studies with standardized measures are needed to confirm these observations.