title: Risk of Suicidal Events With Atomoxetine Compared to Stimulant Treatment: A Cohort Study.
abstract: Antidepressant effects on increased suicidality in children have raised public concern in recent years. Approved in 2002 for attention-deficit/hyperactivity disorder treatment, the selective noradrenalin-reuptake-inhibitor atomoxetine was initially investigated for the treatment of depression. In post-hoc analyses of clinical trial data, atomoxetine has been associated with an increased risk of suicidal ideation in children and adolescents. We analyzed whether the observed increased risk of suicidal ideation in clinical trials translates into an increased risk of suicidal events in pediatric patients treated with atomoxetine compared with stimulants in 26 Medicaid programs.
  
  
  
  Employing a retrospective cohort design, we used propensity score-adjusted Cox proportional hazard models to evaluate the risk of suicide and suicide attempt in pediatric patients initiating treatment with atomoxetine compared with stimulants from 2002 to 2006.
  
  
  
  The first-line treatment cohort included 279 315 patients. During the first year of follow-up, the adjusted hazard ratio for current atomoxetine use compared with current stimulant use was 0.95 (95% CI 0.47-1.92, P = .88). The second-line treatment cohort included 220 215 patients. During the first year of follow-up, the adjusted hazard ratio for current atomoxetine use compared with current stimulant use was 0.71 (95% CI 0.30-1.67, P = .43).
  
  
  
  First- and second-line treatment of youths age 5 to 18 with atomoxetine compared with stimulants was not significantly associated with an increased risk of suicidal events. The low incidence of suicide and suicide attempt resulted in wide confidence intervals and did not allow stratified analysis of high-risk groups or assessment of suicidal risk associated with long-term use of atomoxetine.
authors.affiliation: Pharmaceutical Outcomes and Policy, College of Pharmacy, slinden@ufl.edu.
authors.forename: Stephan
authors.initials: S
authors.lastname: Linden
authors.affiliation: Departments of Psychiatry and Pediatrics, College of Medicine, Clinical and Health Psychology, College of Public Health and Health Professions.
authors.forename: Regina
authors.initials: R
authors.lastname: Bussing
authors.affiliation: Pharmaceutical Outcomes and Policy, College of Pharmacy.
authors.forename: Paul
authors.initials: P
authors.lastname: Kubilis
authors.affiliation: Ernest Mario School of Pharmacy and Institute for Health, Health Care Policy, and Aging Research, Rutgers University, New Brunswick, New Jersey.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gerhard
authors.affiliation: Pharmaceutical Outcomes and Policy, College of Pharmacy.
authors.forename: Richard
authors.initials: R
authors.lastname: Segal
authors.affiliation: Health Outcomes and Policy, UF Clinical Research Center, College of Medicine, and.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Shuster
authors.affiliation: Pharmaceutical Outcomes and Policy, College of Pharmacy, Epidemiology, College of Public Health and Health Professions and College of Medicine. University of Florida, Gainesville, Florida; and.
authors.forename: Almut G
authors.initials: AG
authors.lastname: Winterstein
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects*; D000928:Antidepressive Agents / Q000009:adverse effects*; D000069445:Atomoxetine Hydrochloride / Q000009:adverse effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D057216:Propensity Score; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D059020:Suicidal Ideation; D013405:Suicide; D013406:Suicide, Attempted
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D000697:Central Nervous System Stimulants; D000069445:Atomoxetine Hydrochloride