title: Atomoxetine tolerability in pediatric and adult patients receiving different dosing strategies.
abstract: OBJECTIVE
  Examine how different dosing schedules and recent stimulant therapy effect incidence, time to onset, and duration of common treatment-emergent adverse events (TEAEs) during atomoxetine treatment.
  
  
  METHODS
  Post hoc analyses including safety data (open-ended questions) from 22 pediatric and 3 adult atomoxetine trials (1998-2009) in patients with attention-deficit/hyperactivity disorder. Most common TEAEs were determined by incidence rates and frequency of consumer and clinician inquiries. Onset and duration of TEAEs with slow versus fast titration, once-daily versus twice-daily dosing, and previous stimulant exposure were compared among treatment groups using Kaplan-Meier methods.
  
  
  RESULTS
  In pediatric patients, the most commonly reported TEAEs were abdominal pain, decreased appetite, fatigue, nausea, somnolence, and vomiting; time to onset of TEAEs was significantly shorter for once-daily versus twice-daily dosing for all TEAEs (P ≤ .007) and for fast versus slow titration for abdominal pain, decreased appetite, and somnolence (all P values ≤ .009); duration of TEAEs with once-daily dosing was significantly longer for decreased appetite (P = .001) and nausea (P = .041); and more common in stimulant-naive patients versus patients with prior stimulant use were abdominal pain, decreased appetite, and fatigue (P ≤ .047). In adult patients, the most commonly reported TEAEs (erectile dysfunction data were excluded) were nausea, insomnia, decreased appetite, urinary hesitation/urinary retention, and fatigue; insomnia had a significantly shorter time to onset and longer duration with twice-daily versus once-daily dosing (P ≤ .032) and fast versus slow titration (P ≤ .007).
  
  
  CONCLUSIONS
  Time to onset and resolution of TEAEs appear dependent on dosing schedule and titration speed. These findings can help to better manage tolerability issues and set appropriate expectations for clinicians and patients during atomoxetine titration, potentially improving treatment adherence and success.
authors.affiliation: Lilly USA, LLC, Lilly Corporate Center, DC 4135, Indianapolis, IN 46285 wietechala@lilly.com.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Wietecha
authors.forename: Dustin D
authors.initials: DD
authors.lastname: Ruff
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Allen
authors.forename: Laurence L
authors.initials: LL
authors.lastname: Greenhill
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Newcorn
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride