New onset executive function difficulties at menopause: a possible role for lisdexamfetamine
Open accessAbstract
Rationale Reports of cognitive decline, particularly in the domains of executive functions (EFs), are common among menopausal women. Objective This study aims to determine the impact of the psychostimulant lisdexamfetamine (LDX) on subjective and objective cognitive function among menopausal women who report new-onset EF complaints. Methods Thirty-two healthy perimenopausal and early postmenopausal women experiencing mid-life-onset executive function difficulties as measured using the Brown Attention Deficit Disorder Scale (BADDS) were administered LDX 40-60 mg/day for 4 weeks in this double-blind, placebo-controlled, cross-over study. Diagnosis of lifetime ADHD was exclusionary. BADDS total and subscale scores and performance on verbal memory and working memory tasks were outcomes of interest. Results Analyses revealed a significant effect of LDX treatment over placebo for total BADDS scores (p = 0.0001) and for four out of the five BADDS subscales (all p < 0.004). LDX treatment also resulted in significant improvement in delayed paragraph recall (p = 0.018), but there was no significant effect of treatment on other cognitive measures. Systolic blood pressure (p = 0.017) and heart rate increased significantly (p = 0.006) when women were on LDX but remained, on average, within the normal range. Conclusions LDX 40-60 mg/day was well tolerated and improved the subjective measures of executive function as well as objective measures of delayed verbal recall in this sample of healthy menopausal women.
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Although self-report is subject to various challenges including social desirability, recall, and response-shift biases, the BADDS has demonstrated predictive validity and utility in treatment trials, supporting its value in assessing subjective experience of executive functioning.
“Although self-report is subject to various challenges including social desirability, recall, and response-shift biases [35], the BADDS has demonstrated predictive validity and utility in treatment trials [15], supporting its value in assessing subjective experience of executive functioning.”
From Treating new-onset cognitive complaints after risk-reducing salpingo-oophorectomy: A randomized controlled crossover trial of lisdexamfetamine (2024) · cites this paper as [15]
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Experimental — accuracy not yet measuredAmong women experiencing cognitive difficulties associated with natural menopause, LDX improves executive function.
“Among women experiencing cognitive difficulties associated with natural menopause, LDX improves executive function, including in one double-blind, placebo-controlled, crossover study [14,15].”
From Treating new-onset cognitive complaints after risk-reducing salpingo-oophorectomy: A randomized controlled crossover trial of lisdexamfetamine (2024) · cites this paper as [15]
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“Although the tolerability and safety profile of short-term LDX treatment was observed in this study, long-term studies of menopausal women receiving LDX would be required to confirm a positive risk–benefit profile like that observed for the drug among adults with ADHD (Maneeton et al. 2014).”
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Self-citation
- Authors
- Epperson, 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.
- Affiliations
- University of Pennsylvania (US)
- Yale University (US)
- Corresponding author
- Epperson, C. Neill
- Venue
- Psychopharmacology
- Published
- 2015-06-11
- Volume
- 232
- Issue
- 16
- Pages
- 3091-3100
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC4631394
- OpenAlex
- W621126837
- Cited by
- 90
- References
- 4
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 10 · 2023: 5 · 2022: 5 · 2021: 32 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 3
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG048839)
- National Institute of Mental Health (P50MH099910)
- National Institute on Drug Abuse (R01DA037289, R01 DA030301, K24DA030301)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- lisdexamfetamine, menopause, executive function, perimenopausal women, psychostimulants, cognitive decline, verbal memory, working memory, delayed recall, blood pressure, heart rate, drug tolerability
- MeSH terms
- Lisdexamfetamine Dimesylate, Central Nervous System Stimulants, Attention, Cognition, Cognition Disorders, Double-Blind Method, Female, Humans, Memory, Short-Term, Menopause, Middle Aged, Mental Recall, Treatment Outcome, Cross-Over Studies, Executive Function
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