Placebo Controlled Study of Atomoxetine in the Treatment of Mild to Moderate Cognitive Difficulties in Menopausal Women
Condition: Menopause; Cognitive Disturbances
MeSH terms: Cognitive Dysfunction
Study type: Interventional

Summary: 
      The purpose of this study is to examine the efficacy of atomoxetine (ATX) treatment for the
      mild to moderate cognitive disturbances frequently experienced by women during the menopause
      transition. In addition, we seek to determine, using the Brown Attention Deficit Disorder
      Scale (BADDS), whether and to what degree peri- and early post-menopausal women experience
      cognitive disturbances which overlap with the impairments of executive function
      characteristic of adults with attention deficit disorder (ADHD).
    

Detailed description: 
      Decline in cognitive function, and in particular memory, is a frequent complaint for which
      menopausal women seek clinical intervention. While there is a wealth of preclinical evidence
      demonstrating the neuroprotective and cognitive enhancing role of estradiol (Wise et al.,
      1999; Jezierski & Sohrabji, 2001), recent publicity from the Women's Health Initiative Study
      has made gynecologists and menopausal women concerned about using estrogen therapy (ET) to
      address their cognitive complaints as well as other symptoms of menopause (WHI Writing Group,
      2002). Decades of data suggesting that estrogen enhances cognitive function in women
      undergoing surgical or natural menopause (Sherwin et al., 1998) has been all but forgotten in
      the wake of the results of the WHI. Further, recent findings from a naturalistic study
      suggesting that having used estrogen replacement therapy for three years before the mean age
      of 70 years significantly reduced the risk of Alzheimer's Disease (AD; Zandi et al., 2002)
      did not receive sufficient attention in the lay press or in scientific circles to allay
      concerns. Most recently, conjugated equine estrogen plus medroxyprogesterone acetate
      (PremPro®) use daily is associated with a small increased risk for dementia (Schumaker et
      al., 2003).

      Now that clinicians and women have become hesitant to utilize ET, they find themselves
      between the proverbial rock and a hard place as there have been no studies demonstrating
      efficacy of any other agent in the treatment of mild to moderate cognitive difficulties in
      healthy non-demented menopausal women. Thus, it is timely and crucial to investigate other
      pharmacologic strategies aimed at improving cognitive function in this population.

      Interestingly, many of the cognitive complaints detected in menopausal women including,
      short-term memory, organization of tasks, sustaining focus and concentration, and regulating
      emotions, overlap with symptoms frequently reported by adults with ADHD (Warga, 1999; Brown,
      2000). That ATX has demonstrated efficacy in the treatment of ADHD provides a compelling
      rationale for investigating the treatment of menopause-related declines in memory and
      cognitive function. Thus, this will be the first double-blind, placebo-controlled, cross-over
      clinical trial to obtain preliminary data for the efficacy of ATX in the treatment of mild to
      moderate cognitive disturbances in menopause aged women. Women who are in the early menopause
      have been chosen for this study as clinical and preclinical data suggest that long periods of
      hypoestrogenism may be associated with poorer response to intervention with ET. Therefore, we
      believe that this population may be more likely to respond to treatment with ATX than women
      who have been postmenopausal for many years.
    

Intervention name(s): atomoxetine; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Subjects will receive ATX 40mg/d x 1 week, then 80mg/d x 5 weeks followed by a 4-week wash out period that is followed by an additional 6 weeks of treatment in the alternate condition. The 4-week washout period include a 4-day taper in the first week.; Subjects will receive placebo equivalent for 6 weeks followed by a 4-week wash out period that is followed by an additional 6 weeks of treatment in the alternate condition. The 4-week washout period include a 4-day taper in the first week.
Other intervention name(s): Strattera
Intervention MeSH terms: Atomoxetine Hydrochloride
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Menopause; Cognition