Eli Lilly and Company: Nonstimulant Atomoxetine Provided Significant, Ongoing Improvement In Long-Term Study of Adults with ADHD

SAN FRANCISCO--(BUSINESS WIRE)--May 20, 2003-- Ongoing Trial Is Largest, Longest Ever of Adults with ADHD Atomoxetine, a nonstimulant, provided long-term improvement in adults' Attention-Deficit/Hyperactivity Disorder symptoms, with these gains increasing over time, according to data presented today at the 156th annual meeting of the American Psychiatric Association. Atomoxetine, the first and only ADHD medicine approved by the U.S. Food and Drug Administration that is clinically proven effective in adults - significantly improved all three measures of ADHD symptoms used throughout the 10-week acute and 34-week extension segments of the study, the data showed. The ongoing atomoxetine safety and efficacy study is believed to be the largest and longest ever conducted in adults with ADHD. Study Design The long-term study consisted of three phases: Two identical 10-week, double-blind, placebo-controlled segments (Study 1: n=280, atomoxetine=141, placebo=139; Study 2: n=256, atomoxetine=129, placebo=127), a 4-week discontinuation period and open-label treatment with atomoxetine for up to 34 weeks (n=384). The open-label segment remains ongoing. The trial, conducted at 31 sites in the United States and Canada, included adults who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for ADHD. Primary ADHD assessments were based upon the Conners' Adult ADHD Rating Scale (CAARS), Investigator and Self-rated versions, including hyperactive and inattentive subsets in both; the Clinician Global Impression of Severity (CGI-S); and the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). Atomoxetine was initiated at 60 mg/day for the acute studies and 50 mg/day for the extension studies. Atomoxetine was titrated to a maximum of 120 mg/day dosed either once or twice a day in these studies. Results Patients treated with atomoxetine showed statistically significant symptom improvement compared with placebo in all measures during the 10-week acute phase. More than 70 percent of patients randomized in the acute segments continued into the open-label extension. Specifically: -- CAARS: Inv Total ADHD Symptom scores for patients entering the extension phase decreased by 43.5 percent from 34.5 plus or minus 7.3 SD at baseline (acute phase) to 19.2 plus or minus 11.3 at the end of open-label treatment -- 67 percent of patients achieved at least a 30 percent decrease in CAARS: Inv Total ADHD Symptom scores -- CGI-S scores decreased almost 30 percent from 4.7 plus or minus 0.7 at baseline to 1.4 plus or minus 1.2 -- 80 percent of patients achieved at least one point decrease -- 47 percent achieved at least a two point decrease In this study, atomoxetine appeared to be generally well tolerated. The most common adverse events reported were dry mouth and headache. There were mild and clinically insignificant changes in heart rate and systolic and diastolic blood pressure. "Due to its proven efficacy in adults and lack of abuse potential, atomoxetine addresses a previously unmet need for adults with ADHD, who often remain untreated due to concerns about other treatment options, such as controlled substances," said David Michelson, M.D., senior medical director, Eli Lilly and Company. DSM-IV criteria for ADHD includes symptom onset before the age of 7. Recall bias of adult patients could affect the reliability of diagnosis and is a limitation of this study. Further, patients with common comorbid conditions, including depression and anxiety, were excluded. About Adult ADHD ADHD affects 3-7 percent of school-age children(1) and manifests itself in levels of attention, concentration, activity, distractibility and impulsivity that are inappropriate to the child's age.(2) Until the 1970s, it was believed that ADHD was strictly a childhood disorder, outgrown in adolescence. Gradually, however, scientists realized that while hyperactivity may diminish, clinically significant inattentiveness and impulsivity can persist into adulthood. Experts now estimate that 4 percent of adults, or more than 8 million people, have the disorder. There are 2 million adults in the United States seeking medical help for impairment associated with ADHD. However, the vast majority of adults who have ADHD are currently not being diagnosed or treated. In adults, ADHD manifests itself through symptoms including inability to focus, disorganization, restlessness and starting projects but not finishing them. Adults with ADHD have lower rates of employment, frequent job changes and lower self-esteem. About Atomoxetine The U.S. Food and Drug Administration approved atomoxetine on Nov. 26, 2002 for the treatment of ADHD in children, adolescents and adults. Atomoxetine, a selective norepinephrine reuptake inhibitor, works differently than other FDA-approved treatments for the disorder, all of which are stimulants. 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 tiny spaces between neurons in the brain. Atomoxetine should not be taken at the same time as, or within two weeks of taking, a monoamine oxidase inhibitor, 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. Some children may lose weight when starting treatment with atomoxetine. As with all ADHD medications, growth should be monitored during treatment. 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 in medical studies were problems sleeping, dry mouth, decreased appetite, upset stomach, nausea or vomiting, dizziness, problems urinating and sexual side effects. About Lilly Lilly, a leading innovation-driven corporation, is developing a growing portfolio of 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. For full prescribing information visit www.lilly.com.