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. OBJECTIVES:To systematically review and quantitatively analyze the efficacy and safety of pharmacologic treatments for IA in youth with ASD.DATA SOURCES: 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.

Irritability and Problem Behavior in Autism Spectrum Disorder: A Practice Pathway for Pediatric Primary Care

“…6 Importantly, I/PB can jeopardize educational and recreational placements and even lead to inpatient psychiatric hospitalization 7 or residential placement. 8 As presented by Fung and colleagues 9 in this issue, meta-analysis of controlled trials confirms the efficacy of 2 atypical neuroleptics, risperidone and aripiprazole, approved by the US Food and Drug Administration for the management of "severe irritability" based on clinical trials in children with ASD who have frequent I/PB that is interfering with development, functioning, or relationships. Atypical neuroleptics have become widely used in patients with ASD 10 but carry a significant risk of metabolic 11 and neurologic adverse events.…”

“…Atypical neuroleptics have become widely used in patients with ASD 10 but carry a significant risk of metabolic 11 and neurologic adverse events. 9,12 These concerns mandate consideration of lower-risk interventions, even for severe I/PB, targeting other factors, such as medical problems or communication challenges that have been identified as potentially contributory to I/PB in the individual patient.…”

Psychopharmacotherapy in children and adolescents

“…Pharmacologic treatment of severe irritability and problem behaviours in autism: A systematic review and metaanalysis (5) Autism spectrum disorder (ASD) is increasingly recognised as a public health issue. Irritability and aggression (IA) often negatively affect the lives of people with ASD and their families.…”

Antioxidant sulfur compounds: potential therapies for autism?

“…For many such trials the compounds tested showed little or no measureable efficacy relative to controls [1,21]. Some compounds where double-blind trials did show statistically significant efficacy relative to control are: n-acetylcysteine where Hardan et al, found irritability decreased based on the Aberrant Behavioral Checklist (ABC) irritability subscale [22]; sulforaphane where Singh et al, found behavior improved based on an ABC and Social Responsiveness Scale measures [23]; l-carnitine where Fahmy et al, found behavior improved based on a Childhood Autism Rating Scale [24]; and a multivitamin that contained substantial amounts of methyl-sufonyl-methane and n-acetyl cysteine where Adams et al, found behavior improved based on a Parental Global Impressions measure [25].…”

“…With the exception of some antipsychotics which have significant side effects, there are few pharmaceuticals which have shown efficacy as treatments for the debilitating symptoms commonly associated with autism [1]. While autism is traditionally defined behaviorally, the literature suggests that many with autism have some similarities of biochemistry [2,3].…”