Drug combination with memantine could improve executive function in ADHD.
A new placebo-controlled study reported that adding memantine (Namenda/Allergan) to treatment with a stimulant medication improved executive function deficits in adults with attention-deficit/hyperactivity disorder (ADHD).
"The positive effects of memantine over placebo...suggest that treatment with memantine may amplify the effects of methylphenidate on some aspects of the regulation of emotion known as deficient emotional self-regulation," said Joseph Biederman, MD, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, and colleagues.
The investigators studied memantine this application, because of its unique action and effect on brain function, and favorable tolerability and safety profile. The N-methyl-D-aspartate (NMDA) receptor antagonist, approved for use in Alzheimer's disease, effects glutamate and dopamine activity in the prefrontal regions that are implicated in the neurobiology of both executive function deficits and ADHD.
The study involved 34 participants between 18 and 57 years of age diagnosed with ADHD persisting from childhood, and evidencing some degree of executive function deficit on assessment with the Behavior Rating Inventory of Executive Functions-Adult (BRIEF-A).
Participants were randomized to receive 12 weeks of treatment with either memantine or placebo, in addition to a stimulant medication. Osmotic-release oral system (OROS) methylphenidate (Concerta/ Janssen) was administered to all but one participant, who had been on a stable dose of dextroamphetamine for over two years and was maintained on the regimen. Twenty-six participants were included in the final sample of the intent to treat analysis, with fourteen receiving memantine and twelve on placebo.
Assessing change from baseline, more participants receiving memantine than placebo normalized their BRIEF-A scale measures by end of treatment. On specific measures, those on memantine were more likely to normalize on the Behavioral Regulation Index, Shift, Emotional Control, Self-Monitor, and Plan Organize scales. The placebo group was more likely to normalize on the Inhibit and Organization of Materials scales.
Biederman and colleagues explained that the areas of measured improvement with memantine reflected improved regulatory control over emotions and behaviors. The improvement in the Shift scale, for example, corresponded to greater flexibility in problem solving; and improvements on the Emotional Control and Self-Monitor scales indicated improved regulation of emotional response and capacity to monitor one's actions.
Significantly more participants on memantine (50%) than on placebo (20%) showed improvement on the composite score of the patient reported BRIEF-A and the clinician rated Executive Functions Deficit-specific Clinical Global Impression scale (BRIEF-A GEC Scale). The distinction between memantine and placebo group by these measures was not affected by distribution of age, sex or race.
"Results from this pilot study suggest that in participants with ADHD and associated executive function deficits, treatment with memantine may improve behavioral manifestations of executive function deficits, particularly inhibition and emotional regulation," Biederman and colleagues conclude.
The study of memantine for executive function deficits in adults with ADHD, “Memantine in the Treatment of Executive Function Deficits in Adults with ADHD: A Pilot-Randomized Double-Blind Controlled Clinical Trial,” was published in the February issue of the Journal of Attention Disorders.