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      Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan

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          Abstract

          This review outlines pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders (ASDs) in children, adolescents, and adults. Symptom domains include repetitive and stereotyped behaviors, irritability and aggression, hyperactivity and inattention, and social impairment. Medications covered include serotonin reuptake inhibitors (SRIs), mirtazapine, antipsychotics, psychostimulants, atomoxetine, α-2 agonists, D-cycloserine, and memantine. Overall, SRIs are less efficacious and more poorly tolerated in children with ASDs than in adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in ASDs, and may be useful in the treatment of other symptoms. Psychostimulants demonstrate some benefit for the treatment of hyperactivity and inattention in individuals with ASDs, but are less efficacious and associated with more adverse effects compared with individuals with ADHD. D-cycloserine and memantine appear helpful in the treatment of social impairment, although further research is needed.

          Translated abstract

          Esta revisión describe los tratamientos farmacológicos para los síntomas conductuales asociados con los trastornos del espectro autista (TEA) en niños, adolescentes y adultos. Los síntomas incluyen conductas estereotipadas repetitivas, irritabilidad y agresividad, hiperactividad e inatención, y deterioro social. Los fármacos incluyen inhibidores de la recaptura de serotonina (IRSs), mírtazapina, anti-psicótícos, psicoestimulantes, atomoxetina, agonistas α-2, D-cicloserina y memantína. Los IRSs como grupo son menos eficaces y peor tolerados en niños que en adultos con TEA. Los antipsicóticos son los fármacos más eficaces para el tratamiento de la irritabilidad en los TEA y pueden ser útiles para el tratamiento de otros síntomas. Los psicoestimulantes muestran algún beneficio para el tratamiento de la hiperactividad y la inatención en sujetos con TEA, pero son menos efectivos y se asocian con más efectos adversos en comparación con sujetos con ADHD. La D-cicloserina y la memantina parecen útiles para el tratamiento del aislamiento social, pero se requiere de más investigación.

          Translated abstract

          Cet article présente les traitements pharmacologiques des symptômes comportementaux associés aux troubles autistiques (TA) chez les enfants, les adolescents et les adultes. Ces symptômes incluent des comportements répétitifs et stéréotypés, une irritabilité et une agressivité, une hyperactivité et un manque d'attention ainsi qu'un handicap social. Les traitements utilisés incluent les inhibiteurs de la recapture de la sérotonine (IRS), la mirtazapine, les antipsychotiques, les psychostimulants, l'atomoxétine, les α-2 agonistes, la D-cyclosérine et la mémantine. Globalement les IRS sont moins efficaces et moins bien tolérés chez les enfants que chez les adultes. Les antipsychotiques sont les produits les plus efficaces pour le traitement de l'irritabilité dans les TA et peuvent être utiles dans le traitement d'autres symptômes. Les psychostimulants font preuve de quelques avantages dans le traitement de l'hyperactivité et de l'inattention chez ceux ayant un TA, mais ils sont moins efficaces et associés à plus d'effets indésirables comparés à ceux ayant un TDAH (trouble déficitaire de l'attention avec hyperactivité). Si la D-cyclosérine et la mémantine sont utiles dans le traitement du dysfonctionnement social, de plus amples recherches sont nécessaires.

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          Most cited references145

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          Behavioral and emotional problems in young people with pervasive developmental disorders: relative prevalence, effects of subject characteristics, and empirical classification.

          Parents or teachers rated 487 non-clinically referred young people with Pervasive Developmental Disorders on the Nisonger Child Behavior Rating Form. The objectives of the study were to examine the relative prevalence of specific behavior problems, assess the impact of subject characteristics, and derive an empirical classification of behavioral and emotional problems for this population. Results indicated that the youngsters experienced high rates of behavior and emotional problems. Cluster analysis suggested that six- and eight-cluster solutions best fit the ratings provided by parents and teachers, respectively. Both parent and teacher cluster solutions contained groups of children characterized as problem free, well adapted, hyperactive, anxious, and with undifferentiated behavior disturbances. The empirically derived clusters were supported by data external to the analyses.
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            Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children.

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              Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism.

              Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders. To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders. National Institutes of Health-sponsored randomized controlled trial. Six academic centers, including Mount Sinai School of Medicine, North Shore-Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School. One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d). Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form. There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P > .99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], -2.0 [3.4] points for the citalopram-treated group and -1.9 [2.5] points for the placebo group; P = .81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus. Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645.
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                Author and article information

                Contributors
                Department of Psychiatry, Harvard Medical School; Lurie Center for Autism, Massachusetts General Hospital, Boston, Massachusetts, USA
                Department of Psychiatry, Harvard Medical School; Lurie Center for Autism, Massachusetts General Hospital, Boston, Massachusetts, USA
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                September 2012
                September 2012
                : 14
                : 3
                : 263-279
                Affiliations
                Department of Psychiatry, Harvard Medical School; Lurie Center for Autism, Massachusetts General Hospital, Boston, Massachusetts, USA
                Department of Psychiatry, Harvard Medical School; Lurie Center for Autism, Massachusetts General Hospital, Boston, Massachusetts, USA
                Author notes
                Article
                10.31887/DCNS.2012.14.3/cdoyle
                3513681
                23226952
                3174e080-c607-48a4-9fdf-96770b269644
                Copyright: © 2012 LLS

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Pharmacological Aspects

                Neurosciences
                autistic disorder,treatment,autism,pervasive developmental disorder,autism spectrum disorder

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