title: Changes in symptoms and adverse events after discontinuation of atomoxetine in children and adults with attention deficit/hyperactivity disorder: a prospective, placebo-controlled assessment.
abstract: Drugs that affect neurotransmitter release can induce changes in neuroregulation during chronic administration. Thus, in addition to recurrence of symptoms of the illness, discontinuation of treatment can be associated with clinical signs and symptoms related to these changes. Atomoxetine, a new drug approved in the United States for treatment of attention deficit/hyperactivity disorder (ADHD), is associated with blockade of the presynaptic norepinephrine transporter. Because treatment of ADHD typically involves chronic treatment, the potential for production of a discontinuation syndrome as well as recurrence of symptoms upon drug discontinuation were assessed as part of the clinical development process. The effects of discontinuation of atomoxetine were assessed in children and adults with ADHD following 9 to 10 weeks of continuous therapy in 4 large studies. Symptoms of ADHD worsened following drug discontinuation but did not return to pretreatment levels. The incidence of discontinuation-emergent adverse events was low and there were no statistically significant differences between the patients abruptly discontinuing from atomoxetine and those continuing on placebo. Discontinuation of atomoxetine did not result in the development of an acute discontinuation syndrome and was well tolerated. It appears that atomoxetine may be discontinued without risk for symptom rebound or discontinuation-emergent adverse effects. Tapering of doses is not necessary when atomoxetine is discontinued.
authors.affiliation: Lilly Research Laboratories, Indianapolis IN 46285, USA. jfwernicke@lilly.com
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Wernicke
authors.forename: Lenard
authors.initials: L
authors.lastname: Adler
authors.forename: Thomas
authors.initials: T
authors.lastname: Spencer
authors.forename: Scott A
authors.initials: SA
authors.lastname: West
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Allen
authors.forename: John
authors.initials: J
authors.lastname: Heiligenstein
authors.forename: Denái
authors.initials: D
authors.lastname: Milton
authors.forename: Dustin
authors.initials: D
authors.lastname: Ruff
authors.forename: W Jeffrey
authors.initials: WJ
authors.lastname: Brown
authors.forename: Douglas
authors.initials: D
authors.lastname: Kelsey
authors.forename: David
authors.initials: D
authors.lastname: Michelson
mesh_terms: D000328:Adult; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004334:Drug Administration Schedule; D006801:Humans; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D012008:Recurrence; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D011437:Propylamines; D000069445:Atomoxetine Hydrochloride