Dementia Drug May Help Improve ADHD Symptoms

Pam Harrison

June 17, 2015

ATHENS, Greece — A drug approved for the treatment of dementia appears to improve executive function in adults with attention-deficient/hyperactivity disorder (ADHD) when administered with standard stimulant therapy, preliminary research suggests.

Initial results from the small, randomized controlled trial indicate that adjunctive memantine (Namenda, Forest Laboratories, Inc) with osmotic release oral system-methylphenidate (OROS-MPH) was associated with improvement in ADHD patients with executive function deficits (EFDs).

"Most of the benefits that memantine produces in dementia are improvements in cognition, so we reasoned that if memantine can improve cognition in the context of dementia, it could improve cognition outside the context of dementia," study investigator Joseph Biederman, MD, chief of pediatric psychopharmacology and adult ADHD at the Massachusetts General Hospital, in Boston, told Medscape Medical News.

"What we saw was a trend towards normalization on several measures of executive function, as reflected by changes on the BRIEF scale with memantine compared with placebo," he added.

The study was presented here at the 12th World Congress of Biological Psychiatry.

Wide Range of Difficulties

According to investigators, EFDs produce a wide range of difficulties that affect scholastic achievement in particular as well as the ability to work, plan, organize, and manage time well.

"People can have a very clear response to ADHD treatment in terms of improvement in ADHD symptoms but can still be massively affected with EFD," Dr Biederman said.

"We recently showed that the effect size on executive function is very limited with OROS methylphenidate compared with its very large effect size on ADHD symptoms. So we wanted to see if there was any possibility that a medicine with a different mechanism of action like memantine could have some benefit," he added.

A total of 26 men and women between aged 18 to 57 years with at least moderately severe ADHD and EFDs, defined as two or more abnormal test results out of nine subscales included in the BRIEF- A, were included in the study.

All participants received open-label OROS methylphenidate and were then randomly assigned to receive either memantine 10 mg twice a day or placebo. Patients were evaluated weekly for 6 weeks and then biweekly for up to 12 weeks.

"We used a wide range of ADHD rating scales to assess the effect of augmentation memantine, including the Adult ADHD Investigator Symptom Report, Clinical Global Impression, and the CANTAB cognitive battery," said Dr Biederman, "and there were no significant clinical or demographic differences between the two groups."

Because of the small sample size, investigators considered a standardized mean difference (equivalent to effect size) of ≥0.5 and odds ratios ≥2 as indicators of trend improvements.

Twelve participants received memantine and 14 received placebo.

Memantine had a standardized mean difference >0.5 on both the Behavior Rating Inventory of Executive Functions–Adult Inhibition (P = .27) and the Self-Monitor subscales (P = .40) when compared with patients receiving placebo.

On the other hand, for patients receiving placebo, with regard to organization of materials, the standardized mean difference was >0.5 (P = .66). No significant changes were noted on the Cambridge Neuropsychological Test Automated Battery in either treatment group.

"While nothing was strikingly significant, there was a trend towards more normalization of several measures of executive function with memantine than with placebo," said Dr Biederman.

Cautious Optimism

Commenting on the findings for Medscape Medical News, Jeffrey Newcorn, MD, associate professor of psychiatry and pediatrics, Icahn School of Medicine at Mount Sinai, in New York City, noted that EFDs are a major problem for a subgroup of adults with ADHD.

"These deficits have often been resistant to treatment, so any improvement that can be realized using a different approach than the current standard ADHD treatments would be very good news," he added.

However, Dr Newcorn observed that these are preliminary results obtained in a small sample, so one needs to be cautious in drawing conclusions. Nevertheless, the data seem very promising and certainly should be followed up, he added.

Dr Biederman currently receives research support from the following sources: the Department of Defense, the US Food and Drug Administration, Ironshore, Lundbeck, Magceutics Inc, Merck, PamLab, Pfizer, Shire Pharmaceuticals Inc, SPRITES, Sunovion, Vaya Pharma/Enzymotec, and the National Institutes of Health. He also has a US patent application pending through Massachusetts General Hospital corporate licensing on a method to prevent stimulant abuse. Dr Newcorn has disclosed no relevant financial relationships.

World Congress of Biological Psychiatry. Presented June 15, 2015.

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