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, -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.
Keywords: autism, autism spectrum disorder, autistic disorder, pervasive developmental disorder, treatment
Esta revisin describe los tratamientos farmacolgicos para los sntomas conductuales asociados con los trastornos del espectro autista (TEA) en nios, adolescentes y adultos. Los sntomas incluyen conductas estereotipadas repetitivas, irritabilidad y agresividad, hiperactividad e inatencin, y deterioro social. Los frmacos incluyen inhibidores de la recaptura de serotonina (IRSs), mrtazapina, anti-psictcos, psicoestimulantes, atomoxetina, agonistas -2, D-cicloserina y memantna. Los IRSs como grupo son menos eficaces y peor tolerados en nios que en adultos con TEA. Los antipsicticos son los frmacos ms eficaces para el tratamiento de la irritabilidad en los TEA y pueden ser tiles para el tratamiento de otros sntomas. Los psicoestimulantes muestran algn beneficio para el tratamiento de la hiperactividad y la inatencin en sujetos con TEA, pero son menos efectivos y se asocian con ms efectos adversos en comparacin con sujetos con ADHD. La D-cicloserina y la memantina parecen tiles para el tratamiento del aislamiento social, pero se requiere de ms investigacin.
Cet article prsente les traitements pharmacologiques des symptmes comportementaux associs aux troubles autistiques (TA) chez les enfants, les adolescents et les adultes. Ces symptmes incluent des comportements rptitifs et strotyps, une irritabilit et une agressivit, une hyperactivit et un manque d'attention ainsi qu'un handicap social. Les traitements utiliss incluent les inhibiteurs de la recapture de la srotonine (IRS), la mirtazapine, les antipsychotiques, les psychostimulants, l'atomoxtine, les -2 agonistes, la D-cyclosrine et la mmantine. Globalement les IRS sont moins efficaces et moins bien tolrs chez les enfants que chez les adultes. Les antipsychotiques sont les produits les plus efficaces pour le traitement de l'irritabilit dans les TA et peuvent tre utiles dans le traitement d'autres symptmes. Les psychostimulants font preuve de quelques avantages dans le traitement de l'hyperactivit et de l'inattention chez ceux ayant un TA, mais ils sont moins efficaces et associs plus d'effets indsirables compars ceux ayant un TDAH (trouble dficitaire de l'attention avec hyperactivit). Si la D-cyclosrine et la mmantine sont utiles dans le traitement du dysfonctionnement social, de plus amples recherches sont ncessaires.
Autistic disorder (autism), Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS) are diagnostic subtypes of Pervasive Developmental Disorders (PDDs) in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). In this review, these three diagnostic subtypes will collectively be referred to as autism spectrum disorders (ASDs), given the widespread use of this terminology in the recent literature. The following is a comprehensive review of available pharmacotherapies for the behavioral symptoms associated with ASDs in children, adolescents, and adults.
Autism, as defined in DSM-IV-TR, is characterized by impaired reciprocal social interaction, aberrant language development or communication skills, and the presence of repetitive, stereotyped behavior, interests, or activities.1 Delay in or dysfunction of social interaction, language, or symbolic or imaginative play must be present before age 3 years. Asperger's disorder also requires impairment in social interaction and a pattern of restricted or stereotyped behavior, but differs in that language and cognitive development are preserved. The prevalence of Asperger's disorder is not known, but it is diagnosed five times more frequently in males than females. PDD-NOS is diagnosed when there is a severe and pervasive social impairment associated with abnormal communication, or with the presence of stereotyped behaviors, but the criteria for autistic disorder or Asperger's disorder are not met. Other pervasive developmental disorders include Rett's disorder and childhood disintegrative disorder; subjects with these disorders are rarely included in pharmacotherapy studies of ASDs. These disorders are believed to be quite rare. Unless otherwise noted, they are not included in the present review.
Behavioral symptoms associated with ASDs that will be reviewed here include repetitive and stereotyped behaviors, irritability and aggression, hyperactivity and inattention, and social impairment. Repetitive behaviors may entail stereotyped motor mannerisms, such as hand-flapping, clapping, rocking, or spinning, or may include inflexible adherence to nonfunctional routines or rituals. These symptoms are often difficult to distinguish from those of obsessive-compulsive disorder (OCD), so treatment for both will be included in this review. Irritability in ASDs may include severe temper outbursts and/or impulsive aggression towards self or others. Moderate-to-severe irritability is known to occur in up to 30% of children and adolescents with ASDs.2 Hyperactivity and inattention are common in individuals with ASDs, although a diagnosis of an ASD excludes a concurrent diagnosis of attention-deficit/hyperactivity disorder (ADHD) based on DSM-W-TR criteria. An estimated 40% to 59% of children diagnosed with ASDs also meet criteria for ADHD.3,4 Qualitative impairments in social interaction, such as lack of social or emotional reciprocity and impaired gestures used to regulate social interaction, are key diagnostic features of ASDs, although few medications are known to improve this domain.
The most common psychotropic medications used to treat the behavioral symptoms associated with ASDs include serotonin reuptake inhibitors (SRIs), antipsychotics, and medications used to treat ADHD. Overall, SRIs are less efficacious and more poorly tolerated in children with ASDs compared with adults. The 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. Other medications that may be useful in individuals with ASDs for various symptoms include mirtazapine, atomoxetine, -2 agonists, Dcycloserine, and memantine, although further research is needed.
Articles for this review were located using Medline, under the keywords autism, pervasive developmental disorders, treatment, and using the names of specific medications. Articles were limited to the English language and those published in 1982 or later.
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