Once-Daily Guanfacine Approved to Treat ADHD

Yael Waknine

September 03, 2009

September 3, 2009 — The US Food and Drug Administration has approved guanfacine extended-release tablets (Intuniv; Shire plc) for the once-daily treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents aged 6 to 17 years.

Guanfacine is the first selective alpha-2a adrenergic receptor agonist to be approved for treating ADHD. It is thought to exert its effects by directly engaging receptors in the prefrontal cortex to reduce susceptibility to distraction and improve working memory, attention regulation, behavioral inhibition, and impulse control.

"Everyday situations and challenges may be difficult for children and adolescents with ADHD as it is a disruptive disorder that includes symptoms and behaviors such as being easily distracted, always on the go, interrupting others, arguing with adults, or temper outbursts," noted Frank A. Lopez, MD, a neurodevelopmental pediatrician in private practice at Children's Developmental Center in Winter Park, Florida, in a company news release.

The approval was based on data from 2 similarly designed phase 3 double-blind parallel-group trials of 669 children and adolescents randomized to receive placebo or guanfacine once daily. Guanfacine was initiated at a fixed dose of 1, 2, 3, or 4 mg/day and increased in increments of 1 mg/week; the 1 mg dose was assigned only to patients weighing less than 50 kg (110 lbs).

Results of both studies showed that guanfacine therapy yielded a significant mean reduction in ADHD symptoms relative to placebo, as evaluated using the ADHD Rating Scale-IV (–16.7 vs –8.9; P < .0001 and –19.6 vs –12.2; P = .0040).

Significant improvements were also observed on the Conners' Parent Rating Scale-Revised: Short Form across a full day during home, school, and after-school activities, as measured by parents at 6 pm, 8 pm, and 6 am the next morning. Teachers also reported significant improvements at 10 am and 2 pm the next day on the Conners' Teacher Rating Scale-Revised: Short Form. Both comprehensive scales allow parents and teachers to assess improvements in ADHD behavior, such as inattentiveness/being easily distracted, running around or climbing excessively, arguing with adults, losing temper, and interrupting or intruding on others.

When improvements were rated using the standard Clinical Global Impressions-Improvement scale, the proportion of patients rated "much improved" or "very much improved" was significantly higher in the active-treatment group than in the placebo group for both studies (50% - 56% vs 26%; P < .05 and 54% - 56% vs 30%; P < .05, except for the 2 mg dose).

Adverse events most commonly reported (incidence ≥10%) in children and adolescents receiving guanfacine therapy included somnolence (32%), headache (26%), fatigue (18%), upper abdominal pain (14%), and sedation (13%). Small to modest changes in blood pressure, pulse rate, and electrocardiography parameters were observed.

Because of the potential for sedation, patients should be cautioned against using heavy machinery or driving until they know how guanfacine therapy will affect them.

Guanfacine is also linked to a risk for hypotension, bradycardia, and syncope, so heart rate and blood pressure should be measured prior to initiation of therapy, after dose increases, and periodically during treatment.

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