Treatment of Aggressive ADHD in Children and Adolescents: Conceptualization and Treatment of Comorbid Behavior Disorders
Department of Psychiatry, University of California, San Francisco, CA 94143, USA. Postgraduate Medicine
(Impact Factor: 1.7).
11/2009; 121(6):158-65. DOI: 10.3810/pgm.2009.11.2084
Primary care physicians who treat attention-deficit/hyperactivity disorder (ADHD) may expect to encounter oppositional defiant disorder (ODD) in about half of patients with ADHD. Up to 20% of patients with ADHD may meet criteria for conduct disorder (CD), and a higher percentage will exhibit aggressiveness or other symptoms of CD without meeting full diagnostic criteria. Primary care physicians self-report more competence in managing ADHD alone than when it is accompanied by comorbid ODD or CD, even though the diagnostic and treatment considerations are similar. The empirical literature on normal and antisocial behavioral development provides insight into understanding how patients with comorbid disruptive behavior may differ from those with uncomplicated ADHD. Primary care physicians who are competent to diagnosis and treat ADHD may develop similar competence in managing patients with ADHD plus oppositional and/or aggressive behavior and, if allied with colleagues who provide specialized psychosocial treatment, may fill an important role in the overall management of complex cases.
Available from: Ghazi Daradkeh
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ABSTRACT: Psychostimulants are first-line therapy for patients with attention-deficit/hyperactivity disorder (ADHD). However, some patients are not optimal responders to monotherapy or present as comorbid for a variety of other disorders that either preclude the use of stimulants or produce a symptom complex that is resistant to monotherapy. Unfortunately, there are few agents well studied in combination with psychostimulants for patients with ADHD. The combination of psychostimulants with alpha2-adrenergic agonists may offer a complementary approach to treating such complex patients. The rationale for combination therapy is that the primary effects of stimulants and alpha2-adrenergic agonists are mediated by different but complementary mechanisms of action, emphasizing different neurotransmitter systems, which together modulate prefrontal cortex functioning. Although immediate-release clonidine and guanfacine have long been studied in ADHD, their usage has been limited by rapid absorption and clearance, negative side effects, and reduced efficacy compared with stimulants. New controlled-release formulations of the alpha2-adrenergic agonists have overcome some of these limitations, with recent clinical trials demonstrating their enhanced tolerability and effectiveness for treatment of ADHD in children and adolescents. Studies with each of these new formulations (ie, guanfacine extended release and clonidine hydrochloride extended-release tablets) in combination with psychostimulants have demonstrated that the addition of an alpha2-adrenergic agonist to psychostimulant therapy significantly enhances efficacy without compromising safety. This review will encompass the clinical study database for novel formulations of alpha2-adrenergic agonists, enabling the reader to appreciate their place in ADHD treatment as well as the potential utility of a combination approach with psychostimulants for patients with complex ADHD.
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ABSTRACT: Guanfacine extended-release (GXR) is a non-stimulant approved in the US for treatment of attention deficit/hyperactivity disorder (ADHD). GXR is a 'first in class' α(2A)-adrenoceptor agonist reformulated to optimize efficacy. GXR enters a rapidly growing but crowded ADHD market as an alternative not only to psychostimulants but also to atomoxetine.
Pharmacodynamics, pharmacokinetics, clinical efficacy and safety of GXR are covered based on a literature review (MEDLINE and EMBASE) from 1980 to 2010. Two large pivotal controlled trials are reviewed along with companion safety studies over 24 months. Collateral studies in ADHD children with oppositional symptoms and combination use of GXR in psychostimulant partial-responders are featured.
Novel aspects of apparent GXR mechanism of action may complement existing treatments. Study evidence indicates that GXR is a well-tolerated and effective treatment for children and adolescents with ADHD, and appears efficacious to reduce oppositional symptoms in children with these complicating features. The GXR safety database reflects mild and asymptomatic decreases in both blood pressure and heart rate throughout, with most adverse events being somnolence-related and time-limited.
This review of GXR will allow the reader to determine the place for GXR in the ADHD treatment landscape.
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