Eli Lilly and Company: Once-Daily Administration of Atomoxetine Reduced ADHD Symptoms Into The Evening.Business Editors INDIANAPOLIS--(BUSINESS WIRE)--Nov. 1, 2002 A once-daily dose of atomoxetine, an investigational compound, significantly reduced core symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD Attention-Deficit/Hyperactivity Disorder (ADHD) Definition Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterized by distractibility, hyperactivity, impulsive behaviors, and the inability to remain focused on tasks or ) in children and adolescents, according to a paper published in the November issue of the American Journal of Psychiatry The American Journal of Psychiatry (AJP) is the most widely read psychiatric journal in the world. It covers topics on biological psychiatry, treatment innovations, forensic, ethical, economic, and social issues. (Volume 159, Number 11). Symptom reduction lasted into the evening without causing insomnia. Other studies have shown no significant differences in insomnia between atomoxetine and placebo. Atomoxetine is a selective norepinephrine reuptake inhibitor Norepinephrine reuptake inhibitors (NRIs), also known as noradrenaline reuptake inhibitors (NARIs), are compounds that elevate the extracellular level of the neurotransmitter norepinephrine in the central nervous system by inhibiting its reuptake from the . The 6-week, randomized ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. , placebo-controlled study of 171 patients found atomoxetine significantly reduced overall ADHD symptoms as well as inattentive in·at·ten·tive adj. Exhibiting a lack of attention; not attentive. in  at·ten and hyperactive/impulsive symptoms, as assessed by parents, teachers and clinical investigators. This was the first atomoxetine study to provide evidence of effect based on teacher ratings. In addition, parent ratings, using a diary scale developed by Lilly, suggested atomoxetine continued to work late in the day, significantly reducing inattention in·at·ten·tion n. Lack of attention, notice, or regard. Noun 1. inattention - lack of attention basic cognitive process - cognitive processes involved in obtaining and storing knowledge during late afternoon/early evening, and reducing difficulties settling at bedtime. "Effective treatment of ADHD involves not only a reduction of ADHD symptoms, but also an improvement in social and family function," said study co-author Jeffrey Newcorn, M.D., Associate Professor of Psychiatry and Pediatrics, Mount Sinai School of Medicine
Mount Sinai School of Medicine is a medical school found in the borough of Manhattan in New York City. , and Director, Division of Child and Adolescent Psychiatry A branch of psychiatry that specialises in work with children, teenagers, and their families. History An important antecedent to the specialty of child psychiatry was the social recognition of childhood as a special phase of life with its own developmental stages, starting with , Mount Sinai Medical Center. "A treatment that provides symptom control into the evening has the potential to significantly improve family interactions." Study Design The study included 171 children and adolescents, ages 6-16, who met criteria for ADHD as spelled out in the Diagnostic and Statistical Manual for Mental Disorders, 4th edition (DSM-IV DSM-IV Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). This reference book, published by the American Psychiatric Association, is the diagnostic standard for most mental health professionals in the United States. ). The DSM-IV includes 18 core symptoms of ADHD - nine related to inattention and nine related to hyperactivity and impulsivity. All diagnoses were confirmed through clinical interviews. Exclusion criteria exclusion criteria AIDS Donor exclusion criteria, see there included serious medical illness, a history of psychosis or bipolar disorder, alcohol or drug abuse within the past 3 months, and ongoing use of psychoactive psychoactive /psy·cho·ac·tive/ (-ak´tiv) psychotropic. psy·cho·ac·tive adj. Affecting the mind or mental processes. Used of a drug. medications other than the study drug. After an evaluation and drug washout washout to disperse or empty by flooding with water or other solvent. medullary solute washout a syndrome in which the relative hyperosmolarity of the renal medulla is reduced due to an excessive loss of sodium and chloride from period, patients were randomized to either atomoxetine or placebo under double-blind conditions for 6 weeks, with weekly visits. Atomoxetine dosages were based on weight, with an average final dose of 1.3 milligrams per kilogram per day. The primary measure of symptom response was assessed using the ADHD Rating Scale-IV-Parent Version: Investigator Administered (ADHD RS), an 18-item scale based on an interview with the patient's primary caretaker. Each item on the ADHD RS corresponds to one of the 18 DSM-IV criteria. In addition, a 13-item parent-rated diary was developed by Lilly to assess efficacy during evening and early morning periods. Symptoms assessed included evening and early morning inattentiveness/distractibility, ability to concentrate on structured tasks, hyperactivity/impulsivity and oppositionality. The study also used the Conners' Parent and Conners' Teacher Rating Scales. Results ADHD-RS total score fell by an average of 12.8 points for patients randomized to atomoxetine, compared with 5.0 points for patients on placebo. Improvements were measurable for patients randomized to atomoxetine beginning at 1 week and at all subsequent visits. Superiority to placebo was also demonstrated on the ADHD Index scores of the Conners' Parent Rating Scale (7.6, atomoxetine; 2.4, placebo) and the Conners' Teacher Rating Scale (5.1, atomoxetine; 1.6, placebo). "The most striking finding of this study is the suggestion that one dose of atomoxetine in the morning produced symptom improvements that persisted into the evening, despite the short plasma half-life of the medication, and without causing insomnia," said lead author David Michelson, M.D., medical director, Eli Lilly and Company Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the world's largest corporations. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States. . Atomoxetine showed greater improvement than placebo on two items tracked in the parent diaries: inattention during late afternoon and early evening, and difficulty settling at bedtime. The average scores for "inattentive and distractable during the evening" fell 36.8 percent for patients on atomoxetine, from 1.9 to 1.2. That compares with a reduction from 1.8 to 1.5, or 16.7 percent, for patients on placebo. The average scores for difficulty settling at bedtime fell from 1.8 to 1.1, or 38.9 percent, for patients on atomoxetine, compared with a reduction from 1.7 to 1.4, or 17.6 percent, for those on placebo. Other aspects of behavior were tracked in the parental diaries, but changes observed were not statistically significant. Limitations Interpretation of the results is limited by several factors. This study did not include a twice-daily dosing arm, therefore no direct comparison of the relative efficacy of once- versus twice-daily atomoxetine administration can be definitively determined. Also, the dose range used in this study was based on the results of a dose-response study that employed twice-daily dosing, and it is possible that a different range would be optimal for once-daily dosing. Safety Information In the study,the overall safety and tolerability of atomoxetine was good. There were no statistically significant differences in the number of discontinuations between atomoxetine and placebo. Only two patients receiving atomoxetine discontinued because of adverse events (2 percent) compared to one patient in the placebo group (1 percent). The most common side effects for atomoxetine (greater than 16 percent) were headache, rhinitis Rhinitis Definition Rhinitis is inflammation of the mucous lining of the nose. Description Rhinitis is a nonspecific term that covers infections, allergies, and other disorders whose common feature is the location of their symptoms. , abdominal pain and decreased appetite. Atomoxetine Atomoxetine is a selective norepinephrine reuptake inhibitor being developed by Eli Lilly and Company (NYSE NYSE See: New York Stock Exchange :LLY) as a treatment for ADHD in children, adolescents and adults. Scientists believe it works by selectively blocking the reabsorption reabsorption /re·ab·sorp·tion/ (re?ab-sorp´shun) 1. the act or process of absorbing again, as the absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules. 2. of norepinephrine norepinephrine (nôr'ĕpīnĕf`rən), a neurotransmitter in the catecholamine family that mediates chemical communication in the sympathetic nervous system, a branch of the autonomic nervous system. into certain nerve cells in the brain. Norepinephrine is a neurotransmitter, a chemical that moves messages from brain cell to brain cell, and is thought to be important in regulating attention and controlling impulses. While significant symptom reduction was observed at one week in this study, data presented at a recent scientific meeting may suggest symptom improvement as early as one day.(1) Lilly received an approvable letter from the U.S. Food and Drug Administration (FDA FDA abbr. Food and Drug Administration FDA, n.pr See Food and Drug Administration. FDA, n.pr the abbreviation for the Food and Drug Administration. ) for Strattera(TM) (atomoxetine hydrochloride) in August 2002. If approved by regulators, atomoxetine will be the first new class of medication for ADHD in decades. It also will be the only medication indicated for the treatment of ADHD that is not a stimulant. ADHD affects 3-7 percent of school age children(2) and manifests itself in levels of attention, concentration, activity, distractibility, and impulsivity that are inappropriate to the child's age.(3) Experts estimate 60 percent of children with the disorder carry their symptoms into adulthood.(4) 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. This news release contains forward-looking statements that reflect management's current beliefs about the potential for atomoxetine in the treatment of attention deficit hyperactivity disorder attention deficit hyperactivity disorder (ADHD), formerly called hyperkinesis or minimal brain dysfunction, a chronic, neurologically based syndrome characterized by any or all of three types of behavior: hyperactivity, distractibility, and impulsivity. (ADHD) in children. However, as with any pharmaceutical under development, there are significant risks and uncertainties in the process of development and regulatory review. There are no guarantees that the product will receive regulatory approvals or prove to be commercially successful. There is also no assurance of the timing of final FDA action on the compound. For additional information about the factors that affect the company's business, please see Exhibit 99 to the company's latest Form 10-Q. The company undertakes no duty to update forward-looking statements. (1) Data on file. Eli Lilly and Company. (2) American Psychiatric Association The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential world-wide. Its some 148,000 members are mainly American but some are international. : Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision. Washington, DC, American Psychiatric Association, 2000. (3) American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Washington, DC, American Psychiatric Association, 1994. (4) American Psychiatric Association: DSM-IV-TR DSM-IV-TR Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (Text Revision) (American Psychiatric Association) .2000.85-93 Schweitzer JB, et al. Attention-deficit/hyperactivity disorder. Med Clin of North Am. 2001; 85(3):757-777 |
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