title: Meta-Analysis: Reduced Risk of Anxiety with Psychostimulant Treatment in Children with Attention-Deficit/Hyperactivity Disorder.
abstract: OBJECTIVE
  Anxiety is a commonly reported side-effect of psychostimulant treatment. Our goal was to quantify the risk of anxiety as a side effect of psychostimulant treatment for attention-deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with ADHD. We used a fixed-effects meta-analysis to examine the risk ratio of anxiety reported as a side effect in children treated with psychostimulants compared with those treated with placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of anxiety.
  
  
  RESULTS
  We identified 23 studies involving 2959 children with ADHD for inclusion in our meta-analysis. The risk of anxiety associated with psychostimulant treatment was significantly lower than that experienced with placebo (relative risk [RR] = 0.86 [95% CI: 0.77, 0.95], z = -2.90, p < 0.05). Higher doses of psychostimulants were associated with a reduced measured risk of anxiety of psychostimulants when compared with placebo (β = -0.0039 [95% CI: -0.00718, -0.00064], z = -2.34, p = 0.019).
  
  
  CONCLUSIONS
  Meta-analysis suggests that treatment with psychostimulants significantly reduced the risk of anxiety when compared with placebo. This finding does not rule out the possibility that some children experience increased anxiety when treated with psychostimulants, but suggests that those risks are outweighed by the number of children who experience improvement in anxiety symptoms (possibly as a secondary effect of improved control of ADHD symptoms). Clinicians should consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.
authors.affiliation: 1 Yale Child Study Center, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Catherine G
authors.initials: CG
authors.lastname: Coughlin
authors.affiliation: 1 Yale Child Study Center, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Cohen
authors.affiliation: 1 Yale Child Study Center, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Jilian M
authors.initials: JM
authors.lastname: Mulqueen
authors.affiliation: 2 University of São Paulo School of Medicine , São Paulo, Brazil .
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ferracioli-Oda
authors.affiliation: 1 Yale Child Study Center, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Stuckelman
authors.affiliation: 1 Yale Child Study Center, Yale University School of Medicine , New Haven, Connecticut.|3 Department of Psychiatry, Yale University , New Haven, Connecticut.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Bloch
mesh_terms: D000293:Adolescent; D001007:Anxiety / Q000150:complications* / Q000188:drug therapy*; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications* / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D000697:Central Nervous System Stimulants