Guanfacine extended release: a novel treatment for attention-deficit/hyperactivity disorder in children and adolescents.

BACKGROUND: Guanfacine extended release (GXR) has reported efficacy for the treatment of attention-deficit/hyperactivity disorder (ADHD) as monotherapy and adjunctive therapy to psychostimulant medications. OBJECTIVE: The objective of this article was to review the efficacy, safety profile, mechanism of action, pharmacokinetics, and appropriate dosing of GXR in children and adolescents with ADHD. METHODS: Pertinent English-language literature was identified from searches of MEDLINE (1950-February 2012), BIOSIS (1969-February 2012), and EMBASE (1974-February 2012). Search terms included guanfacine, guanfacine extended release, attention deficit disorder with hyperactivity, ADHD, nonstimulant, and alpha-2 adrenergic receptor. Of the 49 publications identified, 12 are reviewed herein. Citations from identified articles were reviewed for additional references. Abstracts and posters presented at recent scientific meetings and data included in the prescribing information were also reviewed. RESULTS: Studies of GXR have demonstrated efficacy as once-daily monotherapy as well as adjunctive therapy to psychostimulants for ADHD in short-term trials. The safety profile of GXR is consistent with that of a centrally acting α2A-adrenoceptor agonist. Somnolence, sedation, and hypersomnia adverse events (AEs), although frequent, are typically mild to moderate and tend to diminish with continued treatment. However, 1 long-term, open-label study found that 22 serious treatment-emergent AEs occurred in 16 (6.2%) of 259 subjects, and another found that 26% of subjects discontinued therapy due to AEs. The cardiovascular effects, of GXR are consistent with guanfacine's known effects, and are generally modest in nature. The mechanism of action of GXR in ADHD is unknown. Because the pharmacokinetics of immediate-release guanfacine differ from GXR, dose substitution on a milligram-for-milligram basis is inappropriate. Clinical trials analyzed according to weight-adjusted doses suggest a dose-response relationship for efficacy. Doses >4 mg/d cannot be recommended due to lack of study data at those doses. CONCLUSIONS: Current evidence indicates that GXR is an effective treatment option for children and adolescents with ADHD. AEs are typically mild to moderate, although severe AEs and discontinuations due to AEs have been observed.

A review of attention-deficit/hyperactivity disorder complicated by symptoms of oppositional defiant disorder or conduct disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder with significant functional impairment. ADHD is frequently complicated by oppositional symptoms, which are difficult to separate from comorbidity with oppositional defiant disorder, conduct disorder, and aggressive symptoms. This review addresses the impact of oppositional symptoms on ADHD, disease course, functional impairment, clinical management, and treatment response. REVIEW OF CLINICAL EVIDENCE: Oppositional defiant disorder or conduct disorder may be comorbid in more than half of ADHD cases and are more common with the combined than with the inattentive ADHD subtype. Comorbid symptoms of oppositional defiant disorder and conduct disorder in patients with ADHD can have a significant impact on the course and prognosis for these patients and may lead to differential treatment response to both behavioral and pharmacologic treatments. IMPACT ON CLINICAL MANAGEMENT: Assessment of oppositional symptoms is an essential part of ADHD screening and diagnosis and should include parental, as well as educator, input. Although clinical evidence remains limited, some stimulant and nonstimulant medications have shown effectiveness in treating both core ADHD symptoms and oppositional symptoms. CONCLUSIONS: Oppositional symptoms are a key consideration in ADHD management, although the optimum approach to treating ADHD complicated by such symptoms remains unclear. Future research should focus on the efficacy and safety of various behavioral and medication regimens, as well as longitudinal studies to further clarify the relationships between ADHD, oppositional defiant disorder, and conduct disorder.