Safety and efficacy of clonidine and clonidine extended-release in the treatment of children and adolescents with attention deficit and hyperactivity disorders.

Clonidine has been used off-label in children and adolescents with attention deficit and hyperactivity disorders (ADHD) with or without comorbidities. Clonidine extended-release was recently approved by the US Food and Drug Administration for ADHD in children. This review evaluates the efficacy and safety of clonidine extended-release and clonidine in children and adolescents with ADHD. A search of the Medline database and clinical trials register from 1996-2011 yielded ten clinical trials for critical evaluation of efficacy and safety. Eight of the ten trials reviewed were double-blinded and placebo-controlled. Nine of the ten trials utilized multiple outcome measures. Both clonidine extended-release and clonidine, as monotherapy or adjunctive therapy, were reported to be efficacious in treating ADHD symptoms in children and adolescents with or without comorbid disorders in nine of the ten clinical trials. One study showed clonidine to be ineffective in improving performance of a single task, at a specific point in time, in a small number of subjects. All of the studies that evaluated safety reported clonidine and clonidine extended-release to be well tolerated. The side effects of clonidine included somnolence, fatigue, headache, bradycardia, hypotension, and clinically insignificant electrocardiographic changes. However, there are historical anecdotal reports of serious cardiac side effects, including death in cases with other risk factors. None of the studies compared clonidine extended-release with clonidine in subjects with ADHD. Therefore, it is not clear whether clonidine extended-release is advantageous over clonidine, with regard to either efficacy or safety. It is equally unclear whether clonidine or clonidine extended-release is more efficacious in treating ADHD in subjects with comorbid disorders than in those without comorbidities. All the studies reviewed had limitations in their designs and methods. Clonidine and clonidine extended-release could be efficacious and safe for the treatment of ADHD both as monotherapy and as adjunctive therapy with stimulant medications in selected patients. There is a need for clinical trials to determine the long-term efficacy and safety of treatment with clonidine and clonidine extended-release in patients with ADHD.