New onset executive function difficulties at menopause: a possible role for lisdexamfetamine

Abstract

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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Funding and disclosures

This project was funded in part by Shire Pharmaceuticals through an Investigator-Initiated Grant, the National Institute of Mental Health (P50 MH099910; CNE and DRK), the National Institute on Aging (R01 AG048839; CNE), and the National Institute on Drug Abuse (R01 DA030301; CNE). Dr. Epperson discloses research grant support from Shire and Novartis and stock holdings in Pfizer, Johnson and Johnson, Abbott, Abbvie and Merck. Dr. Brown discloses research grant support from Lilly and Shire and publication royalties from PsychCorp/Pearson, Yale University Press, Routledge, and Wiley. Dr. Sammel and Dr. Kim and Ms. Iannelli, Appleby, Bradley, Czarkowski and Shanmugan report no competing interests. As the lead author, Dr. Epperson can attest that the authors have had full control of all primary data and the journal Psychopharmacology may have access to the data if necessary.

Author’s contributions

As the corresponding author, CNE confirms that all authors have contributed to conceptualizing the study design, conducting some or part of the study, analyzing and interpreting findings, and preparing the manuscript.

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Corresponding author

Correspondence to C. Neill Epperson.

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Epperson, C.N., Shanmugan, S., Kim, D.R. et al. New onset executive function difficulties at menopause: a possible role for lisdexamfetamine. Psychopharmacology 232, 3091–3100 (2015). https://doi.org/10.1007/s00213-015-3953-7

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Keywords

  • Menopause
  • Cognition
  • Executive function
  • ADHD
  • Psychostimulant
  • Lisdexamfetamine
  • Brown Attention Deficit Disorder Scale
  • Verbal memory
  • Paragraph recall