Adjunctive extended-release molindone effective for impulsive aggression in ADHD

Data presented at the American Academy of Neurology Annual Meeting indicated certain dosages of extended-release molindone were effective for impulsive aggression in children with attention-deficit/hyperactivity disorder already receiving optimized stimulant monotherapy and behavioral therapy.

“Impulsive aggression markedly amplifies negative outcomes in children with ADHD [and is] often refractory to primary ADHD therapy. Currently, there is no medication specifically approved for adjunctive use in children with ADHD and impulsive aggression,” Scott T. Brittain, PhD, of Supernus Pharmaceuticals, Rockville, Maryland, and colleagues wrote. “In a pilot study, immediate-release molindone improved serious conduct problems in children with ADHD. [Extended-release molindone (SPN-810, Supernus)] delivers more constant drug concentrations with longer dosing interval vs. immediate-release molindone.”

To assess efficacy and tolerability of SPN-810 for impulsive aggression when added to optimized stimulant monotherapy and behavioral therapy, researchers conducted a multicenter, double-blind, placebo-controlled study among 118 children aged 6 to 12 years with ADHD and Retrospective-Modified Overt Aggression Scale scores of 20 and higher despite optimized stimulant and behavioral therapy. Participants were assigned to placebo or SPN-810 for 39 days. SPN-810 dosages were based on weight. Children who weighed less than 30 kg received 12 mg, 24 mg or 36 mg/day, while those who weighed 30 kg or more received 18 mg, 36 mg or 54 mg/day.

Participants who received 12 mg or 18 mg/day (P = .031) and 24 mg or 36 mg/day (P = .024) had greater reductions in impulsive aggression scores, compared with placebo.

Impulsive aggression remission was more common among participants who received 12 mg or 18 mg per day (52%) and 24 mg or 36 mg per day (40%), compared with placebo (20%; P < .05).

Sedation and increased appetite were the most common adverse events.

“SPN-810 (12 to 36 mg per day, depending on weight) added to optimized stimulant and behavioral therapy in children with ADHD reduced impulsive aggressive behaviors, with a low incidence of [adverse events] and no unexpected life-threatening or dose-limiting safety issues. Data suggest potential for improved tolerability with SPN-810 vs. [immediate-release] molindone,” the researchers concluded. – by Amanda Oldt

Reference:

Brittain ST, et al. Adjunctive extended-release molindone (SPN-810) to manage impulsive aggression in children with attention-deficit/hyperactivity disorder receiving optimized stimulant monotherapy and behavioral therapy. Presented at: American Academy of Neurology Annual Meeting; April 15-21, 2016; Vancouver, British Columbia.

Disclosure: Brittain reports being an employee of Supernus Pharmaceuticals and receiving royalties from Harvard University. Please see the study for a full list of relevant financial disclosures.