Penn study shows stimulant drug may help women cope with post-menopausal memory lapses

(Press-News.org) NEW YORK – Menopausal women have long reported experiencing hot flashes, mood swings, night sweats and memory lapses, too.

A new study from researchers in the Perelman School of Medicine at the University of Pennsylvania shows preliminary evidence that the psychostimulant drug lisdexamfetamine (LDX) can aid post-menopausal women by improving attention and concentration, organization, working memory and recall. The findings will be presented by C. Neil Epperson, MD, director of the Penn Center for Women's Behavioral Wellness, on Tuesday during the American Psychiatric Association annual meeting at the Jacob K. Javits Convention Center in New York City.

Dr. Epperson's study enrolled 30 women between the ages of 48 and 60 who had experienced a diminished ability to focus and multi-task in their early post-menopausal years. The cohort was made up of successful women –none of whom were more than five years post-menopause.

"We believe estradiol, a form of estrogen, is very important in normal brain function, specifically in the pre-frontal cortex, which regulates executive function—organization, recall, memory and other cognitive functions," Epperson says. "Its decline during the menopausal years, we believe, can play a role in the simultaneous decline in executive function that many women experience during the menopause transition. More specifically, estrogen plays a role in dopamine levels and the brain's normal dopaminergic tone. "We theorize that this process can result in symptoms similar to those experienced by people with attention deficit hyperactivity disorder."

The double-blind, placebo-controlled crossover study gave participants a four week regimen of LDX (which has been approved by the FDA for the treatment of ADHD) as well as four weeks of placebo to assess the drug's effectiveness in reducing subjective, new-onset executive function difficulties, and improving performance on verbal recall, working memory and attention tasks.

A subset of women also underwent brain imaging, functional MRI and proton magnetic resonance spectroscopy to assess brain activation and dorsal lateral prefrontal cortex neurochemistry. The women were then asked to report their level of executive function across five domains: Organization and motivation for work; concentration and attention; alertness, effort and processing speed and managing affective interference, the tendency to overly focus on the emotion of a message; and working memory and recall.

Preliminary data show that all executive function domains, except managing affective interference, showed a significant reduction in severity of symptoms during active LDX treatment versus treatment with placebo. In one domain, organization and motivation for work, the severity of reported impairment predicted the degree of response to LDX treatment such that women with greater severity of symptoms in this domain found the greatest improvement with LDX treatment.

"While some individuals experienced no improvement with LDX, we were heartened by these findings and hope to examine the genetic profile of our participants in the near future to determine whether there are predictors regarding who is is most likely to experience improvement with this kind of treatment," says Epperson.

"We know that estradiol treatment is helpful in only a subset of the population of menopausal women with cognitive and mood complaints and for many women estradiol treatment is not an option due to their medical history. It is crucial that we identify treatment options for those women who experience significant changes in cognition during this transition, whether it occurs naturally or is induced by surgery or chemotherapies."

She suggests that additional research will be necessary to determine if pyschostimulants that work for very different, but related, conditions, might be an option for these menopausal women with executive function issues.

Epperson will present the abstract "Mid-life Onset of ADHD-like Cognitive Impairments in Menopausal Women," on Tuesday, May 6th in Room 1E09, Level 1 location from 2 p.m. to 5 p.m. INFORMATION: Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.