title: Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.
abstract: OBJECTIVE
  Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials.
  
  
  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 attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics.
  
  
  RESULTS
  We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials.
  
  
  CONCLUSIONS
  Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.
authors: Yale School of Medicine.
authors: Stephanie C
authors: SC
authors: Cohen
authors: Yale Child Study Center, New Haven, CT.
authors: Jilian M
authors: JM
authors: Mulqueen
authors: University of São Paulo, Brazil.
authors: Eduardo
authors: E
authors: Ferracioli-Oda
authors: Yale Child Study Center, New Haven, CT.
authors: Zachary D
authors: ZD
authors: Stuckelman
authors: Yale Child Study Center, New Haven, CT.
authors: Catherine G
authors: CG
authors: Coughlin
authors: Yale Child Study Center and Yale University.
authors: James F
authors: JF
authors: Leckman
authors: Yale Child Study Center and Yale University. Electronic address: Michael.Bloch@yale.edu.
authors: Michael H
authors: MH
authors: Bloch
mesh_terms: D000293:Adolescent; D000661:Amphetamine / Q000009:adverse effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D002648:Child; D006801:Humans; D008774:Methylphenidate / Q000009:adverse effects*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D020323:Tics / Q000453:epidemiology*
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D000661:Amphetamine
keywords: amphetamine; meta-analysis; methylphenidate; psychostimulants; tics