Psychopharmacology of Aggression in Children and Adolescents with Autism: A Critical Review of Efficacy and Tolerability

Mount Sinai School of Medicine, New York, New York 10029, USA.
Journal of Child and Adolescent Psychopharmacology (Impact Factor: 2.93). 05/2008; 18(2):157-78. DOI: 10.1089/cap.2007.0041
Source: PubMed


Autism is characterized by a clinical triad of symptoms that affect social, language, and behavioral domains. Aggression and self-injury may be associated symptoms of autism and can result in significant harm to those affected as well as marked distress for their families. The precise nature of the relationship between aggressive or self-injurious behavior (SIB) and autism remains unclear and as a result, these symptoms are treated with a broad range of pharmacological approaches. This review seeks to systematically and critically examine the evidence for the pharmacological management of aggression and SIB in children with autism spectrum disorders.
The entire PubMed database was searched for English language biomedical articles on clinical trials with medication in autism spectrum disorders. Studies were selected based on the following inclusion criteria: (1) randomized placebo-controlled trials; (2) a sample population that included children and adolescents; (3) at least one standardized assessment of aggression as a primary outcome measure of the study.
Twenty one trials with 12 medications were identified. Five medications produced significant improvement as compared to placebo, including tianeptine, methylphenidate, risperidone, clonidine, and naltrexone. Only risperidone and methylphenidate demonstrate results that have been replicated across at least two studies.
Although many medications have been studied under placebo-controlled conditions, few produce significant improvement. Additional placebo-controlled trials are needed to increase the number of therapeutic options available in the treatment of aggression in autism.

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Available from: Eric Hollander, Aug 10, 2014
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    • "However, the prevalence of these behaviors, specifically in autism, has not been as systematically evaluated.9,10 Irritability, aggression, and SIB can result in significant harm to those affected, and it can also lead to marked distress for the children’s families.11 In addition to its inherent potential dangerousness, irritability is frequently of sufficient severity to negatively impact the efficacy of educational and therapeutic interventions.12,13 "
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    ABSTRACT: Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed.
    Full-text · Article · May 2014
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    • "Autism spectrum disorders (ASDs) are a group of developmental conditions defined by the convergence of core symptoms consisting of repetitive behaviour and limited range of interests, impaired communication and decreased social interaction (DSM-IV). ASD is often accompanied by hyperexcitable states, including aggression (Parikh et al. 2008), anxiety (Spiker et al. 2012), hyperactivity (Antshel et al. 2011), epilepsy (Tuchman et al. 2010 ; Tuchman and Cuccaro, 2011), as well as a plethora of sleep disorders (Goldman et al. 2009 ; Souders et al. 2009 ; Thatcher et al. 2009 ; Glickman, 2010). The reliable presence of cell–cell communication abnormalities in such heterogeneous group of conditions, as in fragile X (Selby et al. 2007 ; Bassell and Warren, 2008), Rett (Calfa et al. 2011) and Angelman syndromes (Roden et al. 2010) and the tuberous sclerosis complex (Curatolo et al. 2008) suggests that impaired synaptic function is an important factor in the aetiology and general mechanisms of ASDs. "
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    • "Small open-trials were promising, with optimal prosocial effects at quite low doses (e.g., ∼0.25 mg/kg p.o. given every other day, with higher doses needed for regulating self-injurious behaviors ), suggesting some type of beneficial rebound effects following short periods of endogenous opioid blockade (Panksepp et al., 1991). High doses of naltrexone have been especially effective in controlling self-injurious behavior in autism (Elchaar et al., 2006; Parikh et al., 2008; Symons et al., 2004). Indeed, the benefits of naltrexone in the self-injurious behaviors in autistic individuals have been linked to abnormal release patterns of POMC (proopiomelanocortin ) of the precursor beta-endorphin (Sandman et al., 2000). "
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    ABSTRACT: Early childhood autism is characterized by deficits in social approach and play behaviors, socio-emotional relatedness, and communication/speech abnormalities, as well as repetitive behaviors. These core neuropsychological features of autism can be modeled in laboratory rats, and the results may be useful for drug discovery and therapeutic development. We review data that show that rats selectively bred for low rates of play-related pro-social ultrasonic vocalizations (USVs) can be used to model social deficit symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non-frequency modulated (i.e. monotonous) ultrasonic vocalizations compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes, and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR functional glycine site partial agonist, GLYX-13, rescued the deficits in play-induced pro-social 50-kHz USVs and reduced monotonous USVs. Since the NMDA receptor has been implicated in the genesis of autistic symptoms, it is possible that GLYX-13 may be of therapeutic value in the treatment of autism.
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