Could ADHD Medications Improve Memory, Focus & Organization in Menopausal Women? The Research Says Yes
An overview of the first studies providing evidence that a stimulant medication can be well-tolerated and improve executive functions in healthy menopausal women without ADHD who report subjective decline in working memory, organization, focus and attention that were unprecedented for them prior to menopause.
A surprising thing happened when I was evaluating teenagers for ADHD. One by one, the mothers of my patients approached me regarding the age-normed rating scale I had developed to gauge their adolescents’ symptoms. The questionnaire, which asked about a variety of problems in daily life associated with ADHD and asked both the patients and their caregivers to rate each problem on a scale of 0 to 3. It was hitting a nerve — but not in the way I expected.
“I never had those problems when I was growing up or when I was in school, but over the past few years I’ve had increasing trouble with many of the items on that list,” the mothers told me regarding problems with working memory, organization, focus and attention. “That scares me! It makes me wonder if I had ADHD all this time and didn’t know it. But more than that, I worry that those changes could be early signs of Alzheimer’s Disorder.”
Most of those mothers were well-educated and successful in various businesses or professions. They were also roughly 45 to 55 years old, the typical age of menopause.
Research the Interplay Between Menopause and Dopamine
As I began researching this phenomenon, I was reminded that estrogen is one of the primary modulators for dopamine in the female brain. I began to wonder if the natural reduction of estrogen that comes during menopause might be related to some of the ADHD-like problems that some of those mothers were reporting.
I consulted with Dr. C. Neill Epperson, a colleague of mine when we were both teaching at Yale; she is a psychiatrist specializing in research related to women’s issues. She advised me that several studies had reported that many women report mid-life onset of decline in cognitive functions, particularly short-term memory, sustaining attention, and activating/organizing for work tasks.
Those discussions led to our collaboration on three research studies about mid-life cognitive problems of menopausal women who did not have ADHD but did have cognitive problems with ADHD-like symptoms that appeared at the time of menopause. We were curious about whether medications used to treat ADHD might be helpful for menopausal women who suffer with mid-life onset of ADHD-like symptoms. Results of those studies were published in peer-reviewed medical journals in medical journals in 20111, 20152, and 20173, but results of that research have not yet been widely recognized.
All of those three studies utilized the adult version of my normed Brown Attention-Deficit Disorder Scale (BADDS), which had been tested not only for evaluating persons for ADHD, but also for testing the effectiveness of several different medications developed and approved for treatment of ADHD.
A Foundation in Executive Functions
Below is a diagram that illustrates the model on which the Brown Attention-Deficit Rating Scale and its more recent successor, the Brown Executive Function/Attention Rating Scale (BEFARS) are based.
The BADDS and BEFARS scales are based on a model that sees ADHD not as a simple behavior problem, but as a complex problem in the development and functioning of the brain’s self-management system, its executive functions. This model sees ADHD as a problem that usually is inherited and generally develops during childhood, though, for some, it is not recognized until the person enters teen years or later. More details explaining this model are available on my website.
Menopause Research Protocol
The first study done by Dr. Epperson’s team involved 15 healthy women who were evaluated to confirm that they did not have ADHD. All were complaining of problems with memory and attention that had started in mid-life after their monthly menstrual periods had stopped. After baseline administration of the BADDS scale, each woman participated in a crossover trial in which they were treated for six weeks with the non-stimulant medication atomoxetine (ATX) or with placebo, followed by a four-week washout period and a six-week trial of whichever of those two treatments they had not previously been given.
After each treatment phase, the BADDS was readministered. Neither the women nor the researchers knew who was on medication or on placebo until the study ended.
Results from the BADDS showed that treatment with ATX significantly improved scores for working memory; focus scores showed improvement in the BADDS when the women were on ATX as well. No such improvements were found when the women were taking placebo.
The second study in this series involved 32 healthy women aged 45 to 60 who reported mid-life onset of executive function symptoms as measured by the BADDS. All of the women were required to have had irregular menstrual cycles for at least the previous 12 months and no menstrual period for at least 3 months. None had a history of ADHD. Those women were treated for 4 weeks with the stimulant medication lisdexamphetamine (LDX) (i.e. Vyvanse), a washout period, and four weeks with placebo; medication and placebo treatments were in randomized sequence.
Results showed that LDX in doses from 20 to 60 mg daily significantly improved total scores on the BADDS, and subscale scores related to organization and motivation to work, focus and attention, effort and processing speed, and working memory and accessing recall. LDX also improved an objective measure of short-term working memory in that sample of healthy menopausal women. Women taking LDX reported improved sleep quality much more than did women taking the placebo.
Using Neuroimaging to Confirm Findings
This was the first study to provide evidence that a stimulant medication can be well-tolerated and improve executive functions in healthy menopausal women without ADHD who report subjective decline in executive functions that were unprecedented for them prior to their menopause.
Encouraged by these results, the team undertook a third study, which used neuroimaging to study the effects of LDX on brain functioning of 14 women who had no history of ADHD, but did report cognitive difficulties with working memory, organization, focus, and attention that had begun during their menopause transition.
The study used multimodal neuroimaging to test the hypothesis that LDX would be associated with increased activation of dopaminergic circuits and would reduce glutamate in regions of the brain often impaired in ADHD. Researchers predicted that LDX would increase brain activation during a working memory task and decrease glutamate and glutamine levels in specific portions of the prefrontal cortex at rest.
Participants in that third study were 14 women aged 45 to 60 who reported executive function difficulty that had started during menopause. All were within 5 years of their last menstrual period. Each was tested with the BADDS scale at starting point and after a 4-week trial of LDX and a 4-week trial of placebo, during which researchers and the women were all blinded as to who was on medication or placebo.
Results showed that LDX significantly improved total BADDS scores and the subscales for focus, effort, emotion, and memory. As predicted, neuroimaging data showed that LDX activated executive networks in specific areas of the brain. Those data also showed that LDX’s effect on specific brain regions was associated with improved BADDS scores overall, and with BADDS scores for activation and alertness/effort. Imaging data indicated that improvements in brain activation were significantly larger when women were on LDX than when they were on placebo.
Implications of Menopause Research
It should be noted that these studies do not claim that the women involved had ADHD or developed ADHD during menopause. All participants were carefully studied to make certain that they had not met ADHD diagnostic criteria prior to the study and did not meet those criteria during or after menopause.
What these studies showed is that some women report mid-life onset of some executive functions similar to ADHD symptoms during menopause and/or in their post-menopausal functioning and that those symptoms may respond to treatment with medications approved for treatment of ADHD, specifically ATX and LDX. Treatment response in these studies was stronger after treatment with LDX than after treatment with ATX.
These three studies do not provide information about why some women experience the onset of these cognitive impairments during menopause while other women do not experience such difficulties. However, the studies do provide evidence that, for some women who are impacted by the cognitive impairments described in these studies, there is evidence that medications used to treat ADHD may be helpful.
More detailed information about selecting, prescribing, and monitoring medications approved for treatment of ADHD is available in my book, Outside the Box: Rethinking ADHD in Children and Adults-A Practical Guide, published by American Psychiatric Publishing.
Menopause, Memory, and ADHD Medication: Next Steps
- Free Download: 6 Ways to Retain Focus (When Your Brain Says ‘No!’)
- Read: Is it ADHD or Menopause?
- Read: Inside the Aging ADHD Brain
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View Article Sources
1Epperson, C. N., Pittman, B., Czarkowski, K. A., Bradley, J., Quinlan, D. M., & Brown, T. E. (2011). Impact of atomoxetine on subjective attention and memory difficulties in perimenopausal and postmenopausal women. Menopause (New York, N.Y.), 18(5), 542–548. https://doi.org/10.1097/gme.0b013e3181fcafd6
2Epperson, C. N., Shanmugan, S., Kim, D. R., Mathews, S., Czarkowski, K. A., Bradley, J., Appleby, D. H., Iannelli, C., Sammel, M. D., & Brown, T. E. (2015). New onset executive function difficulties at menopause: a possible role for lisdexamfetamine. Psychopharmacology, 232(16), 3091–3100. https://doi.org/10.1007/s00213-015-3953-7
3Shanmugan, S., Loughead, J., Nanga, R. P., Elliott, M., Hariharan, H., Appleby, D., Kim, D., Ruparel, K., Reddy, R., Brown, T. E., & Epperson, C. N. (2017). Lisdexamfetamine Effects on Executive Activation and Neurochemistry in Menopausal Women with Executive Function Difficulties. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 42(2), 437–445. https://doi.org/10.1038/npp.2016.162