ADHD Drug May Boost Cognitive Function in Menopause

Fran Lowry

June 22, 2015

Menopausal women experiencing a decline in executive functions, including difficulty with time management, attention, organization, memory, and problem solving, may be helped with a drug already approved to treat attention-deficit/hyperactivity disorder (ADHD), new research suggests.

The double-blind, placebo-controlled study showed that menopausal women who took lisdexamfetamine (Vyvanse, Shire) showed improvement in both subjective and objective measures of cognitive decline that are often experienced at menopause.

"Cognitive changes during the menopause are common, and what women frequently complain of are difficulties in the executive functioning domain," lead author C. Neill Epperson, PhD, from the Perelman School of Medicine, at the University of Pennsylvania, in Philadelphia, told Medscape Medical News.

"Women will tell me they used to be able to do three or four different projects at the same time but now can only do one, or they will get a phone call and then forget what they had been doing before the call. So it's not that they cannot remember information they learned from high school or what they saw on TV last night; rather, it is difficulty keeping information readily available and usable. It's more a problem of focusing and executive functioning," Dr Epperson said.

The study was published online June 11 in Psychopharmacology.

Effective Treatment Needed

There are some 45 million postmenopausal women in the United States alone, and most will live a third of their lives in the postmenopausal state.

"Not all of these women will experience executive functioning difficulties, but the ones who do shouldn't suffer. Some women can experience these symptoms for up to 11 years, and that, for some women, is very problematic. Promoting healthy cognitive aging among menopausal women should be a major public health goal," said Dr Epperson.

Because the women's complaints of executive dysfunction was consistent with those observed in adults diagnosed with ADHD, Dr Epperson and her group decided to see whether a psychostimulant would improve their symptoms.

They enrolled 32 healthy perimenopausal and early postmenopausal women between the ages of 45 and 60 years who reported onset of executive function difficulties during the menopause transition. All were within 5 years of their final menstrual period.

The women were assessed with the Brown Attention Deficit Disorder Scale (BADDS) to determine the severity of their subjective symptoms of executive functioning difficulties. They were excluded from the study if they had a lifetime diagnosis of ADHD.

In this double-blind, placebo-controlled study, the women received lisdexamfetamine 40-60 mg/day for 4 weeks. The women served as their own controls by being randomly assigned to cross over to a placebo for an additional 4 weeks.

The researchers found a 41% overall improvement in executive functions for women receiving lisdexamfetamine, compared with a 17% improvement when taking placebo.

At baseline, the mean BADDS score was 35.7.

There was a significant effect of lisdexamfetamine treatment in comparison with placebo for total BADDS scores, with participants having a mean total score of 21.2 while on the active drug vs a mean of 29.8 while on placebo (P = .0001).

Similarly, scores on four of the five BADDS subscales (attention and concentration, alertness, effort and processing speed, managing affective interference, and working memory and accessing recall) also showed significant treatment effects (for all, P < .004).

Lisdexamfetamine treatment also resulted in significant improvement in delayed paragraph recall (P = .018), but there was no significant effect of treatment on other cognitive measures.

Systolic blood pressure (P = .017) and heart rate (P = .006) increased significantly with lisdexamfetamine treatment but remained, on average, within the normal range.

Dr C. Neill Epperson

"This is something that you would expect with psychostimulants, but this was short-term use, and for most women, it stayed within the normal range," Dr Epperson said.

"Still, you want to know you have a good heart and that your blood pressure is under control, and then talk to your doctor if you feel that use of a psychostimulant might be helpful to improve executive functions," she said.

Dr Epperson emphasized that the study was short term and needs to be replicated in larger studies.

"We need to have ways to help these women as they are going through this transition. We've gone far past the time where we just tell women who are having difficulties in the menopause transition not to worry and that this too shall pass. If the transition lasts a decade, that is really a long time to suffer," she said.

Informs Understanding

Commenting on the findings for Medscape Medical News, Pauline M. Maki, PhD, professor of psychiatry and psychology at the University of Illinois, in Chicago, and president of the North American Menopause Society, noted that although the drug was effective in improving memory in this population, "it would be wrong to conclude from this study that women get ADHD when they transition through the menopause."

Dr Pauline Maki

"The entry criteria for this trial were not focused solely on memory complaints per se. Instead, they focused on aspects of executive functions that are disturbed in ADHD, such as organizing work activities and paying attention. The level of cognitive complaints at study entry was elevated and disturbing to the women, but only a very small minority of them, just 5.5%, had cognitive complaints that were as severe as those seen in ADHD," said Dr Maki.

The study "informs our understanding of the neurobiological basis of memory complaints in midlife women and suggests there is a strong prefrontal component to those changes," Dr Maki said.

"It is interesting that the stimulant improved subjective aspects of executive function but not objective performance on executive function tests. Psychostimulants improve prefrontal function in other populations, such as ADHD. It might be that more complex tests of executive function would have shown improvements with treatment. The finding that story recall improved with treatment contributes to the growing body of evidence that memory complaints in midlife women reflect changes in prefrontal function," she said.

The study was supported by Shire, the National Institute of Mental Health, the National Institute on Aging, and the National Institute on Drug Abuse. Dr Epperson reports financial relationships with Shire, Novartis, Pfizer, Johnson & Johnson, Abbott, Abbvie, and Merck. Dr Maki reports financial relationships with Abbott, Noven, and Pfizer.

Psychopharmacology. Published online June 11, 2015. Abstract

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