SOURCE: Eli Lilly & Company

May 26, 2005 10:03 ET

New Analysis Highlights Gender Differences in ADHD Patients Treated With Atomoxetine

A Sub-Analysis Showed Women Surpassed Men on Emotional Symptom Improvement After Treatment With Atomoxetine

ATLANTA, GA -- (MARKET WIRE) -- May 26, 2005 -- Females with Attention-Deficit/Hyperactivity Disorder (ADHD) and treated with atomoxetine HCl showed no difference in core ADHD symptom improvement compared to men, yet women displayed greater emotional symptom improvement when treated. The data is according to a retrospective analysis of two studies presented today at the 158th Annual Meeting of the American Psychiatric Association. Atomoxetine is approved for the treatment of adult ADHD.

At the start of the study, females displayed greater core ADHD symptoms (e.g., disorganization, inattention, and impulsivity) than males and showed no difference in symptom improvement over males at the end of the study using the Conner's Adult ADHD Rating Scale Investigator Total ADHD Symptom Score (CAARS-INV). Similar results were seen using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), a secondary analysis, in the overall symptom improvement, as well as the hyperactivity/impulsivity and the attention/disorganization subscales. In the WRAADDS emotional impairment subscale (measuring elements like: irritability, brief periods of depression, mood fluctuation, inability to handle stress), females exhibited greater emotional symptom improvement compared to their male counterparts by study's end. Both male and female participants showed improvement with treatment with atomoxetine compared to placebo.

"ADHD is often believed to be a male disorder yet epidemiological studies demonstrate that there are many more women living with the condition than generally believed. Unfortunately, as symptoms of ADHD often manifest themselves differently, many women are undiagnosed," said Fred W. Reimherr, M.D., University of Utah, Department of Psychiatry, Salt Lake City, UT. "We are encouraged by the results of this analysis as it highlights atomoxetine's ability to significantly reduce all symptoms of ADHD in women, who are typically more difficult to assess, as they are more likely to have been diagnosed with other conditions including depression or anxiety."

Data Highlights:

-  At baseline, women were rated more impaired on every measure of ADHD
   symptoms compared to men (18.2+/-4.4 female vs. 16.7+/-5.2 male,
   p=0.001) when using the WRAADDS Total score which measures the
   severity of the target symptoms of adults with ADHD.
   -  At the end of the study, on the WRAADDS Total score, both genders
      demonstrated significant symptom improvement with atomoxetine
      (improvement of 5.6 on WRAADDS or 30 percent overall symptom
      improvement among females vs. 2.8 on placebo or 16 percent;
      improvement of 4.6 on WRAADDS or 27 percent among males vs.
      2.9 on placebo or 18 percent). There were no significant
      differences between genders in benefit of treatment with
      atomoxetine over placebo.
   -  Emotional symptoms improved significantly more in females
      (improvement of  2.1 on WRAADDS or 35 percent vs. placebo .4 or
      7 percent) after receiving atomoxetine than in males (improvement
      of 1.3 on WRAADDS or 25 percent vs. placebo 1.0 or 20 percent).
      The benefit of atomoxetine over placebo was greater in females than
      in males, p=0.011.
   -  Additional sub-scales on the WRAADDS included: attention/
      disorganization and hyperactivity/impulsivity. Scores on these
      sub-scales showed no difference between males and females.
-  At baseline, females showed more impairment than males (35.4+/-7.6
   female vs. 33.2+/-7.1 male, p=0.001) on every measure of ADHD
   symptoms when using the CAARS-INV, which is designed to help assess,
   diagnose, and monitor treatment of ADHD in adults.
   -  On the CAARS Total ADHD Symptom Score, both genders demonstrated
      significant symptom improvement with atomoxetine (improvement of
      14.1 on CAARS or 36 percent overall symptom improvement among
      females vs. 25 percent placebo; 12.8 on CAARS or 35 percent
      among males vs. 26 percent placebo). There were no significant
      differences between genders.
"Not only does ADHD affect adults differently than children, there are studies in children that show ADHD presents itself differently in boys and girls, and we wanted to extend that research into adults to improve patient care," said Dr. Reimherr. "We hope that this analysis will help physicians better diagnose and treat women who may not present the typical childhood symptoms of ADHD. It's clear that proper treatment can have a substantial positive impact on patients' lives. We hope that future studies will clarify our knowledge regarding these particular gender differences."

Methods:

--  Combined data from two identical placebo-controlled 10-week double-
    blind studies of atomoxetine in adults with ADHD (536 participants at 31
    sites) were examined.
--  The primary analysis of baseline measures and change from baseline
    measures was a comparison of gender-defined groups.
--  Of the 188 females and 348 males in the analysis, 75 percent of
    females were diagnosed with a combined ADHD subtype (hyperactive/impulsive,
    inattentive), a significantly higher rate than males.
--  Patients with depression, anxiety or other psychiatric diagnosis were
    excluded from the study.
    
About ADHD

ADHD affects three-seven percent of school-age children and manifests itself in levels of attention, concentration, activity, distractibility and impulsivity that are inappropriate to the child's age.(1) In addition, 60 percent of children with the disorder carry their symptoms into adulthood.(2) Experts estimate four percent of adults in the United States, more than eight million people, have ADHD. (3,4)

About Atomoxetine

Atomoxetine, a selective norepinephrine reuptake inhibitor, is approved to treat ADHD in children aged six and over, adolescents, and adults. It is not known precisely how atomoxetine reduces ADHD symptoms, but scientists believe it works by blocking or slowing reabsorption of norepinephrine, a chemical in the brain considered important in regulating attention, impulsivity and activity levels. This keeps more norepinephrine at work in the spaces between neurons in the brain. Improved efficiency in the norepinephrine system is associated with improvement in symptoms of ADHD (Pliska, 1996).

Atomoxetine should not be taken at the same time as, or within two weeks of taking, a monoamine oxidase inhibitor (MAOI) or by patients with narrow angle glaucoma. Patients with a history of high or low blood pressure, increased heart rate, or any heart or blood vessel disease should tell their doctor before taking atomoxetine. Atomoxetine has not been tested in children less than 6 years of age or in geriatric patients. Some children may lose weight when starting treatment with atomoxetine. As with all ADHD medications, growth should be monitored during treatment. Atomoxetine can cause liver damage in rare cases. Patients should tell their doctor right away if they have itching, dark urine, yellow skin/eyes, upper right-sided abdominal tenderness, or unexplained "flu-like" symptoms.

Most people in clinical studies who experienced side effects were not bothered enough to stop using atomoxetine. The most common side effects in children and adolescents in medical studies were upset stomach, decreased appetite, nausea and vomiting, dizziness, tiredness and mood swings. In adults, the most common side effects were constipation, dry mouth, nausea, decreased appetite, dizziness, problems sleeping, sexual side effects, problems urinating and menstrual cramps.

About Lilly

Lilly (NYSE: LLY), a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers -- through medicines and information -- for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

For full prescribing information visit www.lilly.com.

1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, Washington, DC, American Psychiatric Association, 2000.

2. Schweitzer JB, et al. Attention-deficit/hyperactivity disorder. Med Clin of North Am. 2001; 85(3): 757-777

3. Murphy K, Barkley, RA. J Atten disord. 1996; 1:147-161.

4. United States Census Summary File; 2000.

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