title: Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  Autism spectrum disorder (ASD) is increasingly recognized as a public health issue. Irritability and aggression (IA) often negatively affect the lives of people with ASD and their families. Although many medications have been tested for IA in ASDs in randomized controlled trials (RCTs), critical quantitative analyses of these trials are lacking in the literature.
  
  
  OBJECTIVE
  To systematically review and quantitatively analyze the efficacy and safety of pharmacologic treatments for IA in youth with ASD.
  
  
  METHODS
  Studies were identified from Medline, PsycINFO, Embase, and review articles.
  
  
  METHODS
  Original articles on placebo-controlled RCTs of pharmacologic treatments of IA in youth age 2 to 17 years with ASD were included. Data items included study design, study goals, details of study participants, details of intervention, study results, statistical methods, side effects, and risks of bias. The primary study outcome measure was the effect size of reduction in the Aberrant Behavioral Checklist-Irritability (ABC-I) scores in the medication group, as compared with placebo, in RCTs using parallel groups design.
  
  
  RESULTS
  Forty-six RCTs were identified. Compared with placebo, 3 compounds resulted in significant improvement in ABC-I at the end of treatment. Risperidone and aripiprazole were found to be the most effective, with the largest effect sizes. Sedation, extrapyramidal sides effects, and weight gain were assessed quantitatively.
  
  
  CONCLUSIONS
  Although risperidone and aripiprazole have the strongest evidence in reducing ABC-I in youth with ASD, a few other compounds also showed significant efficacy with fewer potential side effects and adverse reactions in single studies.
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, California;
authors.forename: Lawrence K
authors.initials: LK
authors.lastname: Fung
authors.affiliation: Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Mahajan
authors.affiliation: Center for Child & Adolescent Health Research and Policy, MassGeneral Hospital for Children, Boston, Massachusetts;
authors.forename: Alixandra
authors.initials: A
authors.lastname: Nozzolillo
authors.affiliation: Kaiser Permanente Northern California, San Jose, California;
authors.forename: Pilar
authors.initials: P
authors.lastname: Bernal
authors.affiliation: New York-Presbyterian Hospital/Columbia University Medical Center, New York, New York; and.
authors.forename: Aaron
authors.initials: A
authors.lastname: Krasner
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, California;
authors.forename: Booil
authors.initials: B
authors.lastname: Jo
authors.affiliation: Department of Developmental & Behavioral Pediatrics, The Ohio State University, Columbus, Ohio.
authors.forename: Daniel
authors.initials: D
authors.lastname: Coury
authors.affiliation: New York-Presbyterian Hospital/Columbia University Medical Center, New York, New York; and.
authors.forename: Agnes
authors.initials: A
authors.lastname: Whitaker
authors.affiliation: New York-Presbyterian Hospital/Columbia University Medical Center, New York, New York; and.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Veenstra-Vanderweele
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, California; hardanay@stanford.edu.
authors.forename: Antonio Y
authors.initials: AY
authors.lastname: Hardan
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole / Q000627:therapeutic use; D000067877:Autism Spectrum Disorder / Q000188:drug therapy* / Q000523:psychology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy; D002675:Child, Preschool; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D000066553:Problem Behavior; D018967:Risperidone / Q000627:therapeutic use; D016728:Self-Injurious Behavior / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D000068180:Aripiprazole; D018967:Risperidone