PMC:3926778 / 2478-5739 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3926778","sourcedb":"PMC","sourceid":"3926778","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3926778","text":"Introduction\nAttention deficit hyperactivity disorder (ADHD) is reported to be one of the most commonly diagnosed childhood behavioral disorders, which can often continue through adolescence and adulthood, according to the National Institutes of Health.1 Previous research reports the prevalence rate of this disorder to be 1.7%–16%.2 ADHD is reported to be diagnosed much more frequently in males than in females and the symptoms of ADHD are frequently seen with comorbid disorders (eg, oppositional defiant disorders, conduct disorder, tic disorder, anxiety).2,3\nCommonly known core symptoms for ADHD include inattention, hyperactivity, and impulsivity.1,4 Behavioral criteria provided by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) serves as one of the most widely used tools for diagnosis.1,4,5 Treatment for ADHD has included the use of psychostimulants, centrally acting alpha-2 adrenergic agonists, tricyclic antidepressants, and antipsychotics.1 Many clinicians use medications to control the symptoms of ADHD and its comorbidity. Psychostimulants alone have not been effective in controlling sympathetic hyperarousable states of ADHD and comorbidities. Clonidine, as an adjunct to a psychostimulant, significantly enhances effectiveness in optimizing daily function and performance in patients with ADHD.6\nMost pharmacological treatments for ADHD facilitate catecholaminergic transmission,7 especially in the prefrontal cortex.8 Alpha-2 adrenergic agonists, such as clonidine, modulate sympathetic tone by increasing noradrenergic outflow from the locus ceruleus to the prefrontal cortex and by direct stimulation of presynaptic alpha-2A receptors in the cortex. The resulting increase in noradrenergic sympathetic transmission potentiates dorsolateral prefrontal cortical function, and leads to the increased regulation of attention and behavior.9 The hypothalamic-pituitary-adrenal axis works in concert with the catecholamine system in regulating attention and memory in animals.10–12 Coactivation of the noradrenergic sympathetic system with stress hormones enhances spatial memory function and provides positive feedback to the hypothalamic-pituitary-adrenal axis.13\nAdditionally, clonidine stimulates alpha-2A adrenergic receptors in the brain stem. As a result, sympathetic outflow from the central nervous system is reduced, leading to a decrease in peripheral resistance, renal vascular resistance, heart rate, and blood pressure.14 In clinical practice, clonidine has been used off-label for the treatment of ADHD and comorbidities. The use of clonidine extended-release for the treatment of ADHD as monotherapy or a therapy adjunctive to stimulant medications was approved by the US Food and Drug Administration in 2010.14 Clonidine extended-release has been approved for children aged 6–17 years with ADHD, given twice per day at a dose of 0.1–0.4 mg/day.\nClonidine has been used to treat ADHD for many years. The efficacy and safety of clonidine extended-release has not been extensively evaluated. This review aims to identify and evaluate the efficacy and safety of clonidine extended-release in ADHD and its comorbidities. Efforts were made to discover studies comparing clonidine with clonidine 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