Pharmacotherapy of Irritability in Pervasive Developmental Disorders

https://doi.org/10.1016/j.chc.2008.06.002Get rights and content

Children and adolescents diagnosed with autism and related pervasive developmental disorders (PDDs) often sustain irritability, including aggression, self-injurious behavior, and tantrums. Research to date supports the use of the atypical antipsychotics as a first-line pharmacologic treatment for this target symptom domain in PDDs. Currently, the atypical antipsychotic risperidone is the only medication approved by the US Food and Drug Administration for irritability in youth with autism. Additional large-scale, placebo-controlled studies of other medications are needed to determine their efficacy for the treatment of irritability in this diagnostic group.

Section snippets

Typical antipsychotics

Research into the pharmacotherapy of autism and related disorders began in the 1960s. The development of the typical antipsychotic chlorpromazine for schizophrenia led to the dawn of a new era in psychiatry based on the pharmacologic treatment of psychiatric disorders. Over time as more compounds were developed investigators actively sought to determine their potential use in targeting the severe and often debilitating symptoms of aggression and SIB in autism; however, these studies were

Clonidine

A 6-week double-blind, placebo-controlled crossover study of clonidine was conducted in eight children and adolescents aged 5 to 13 years (mean, 8.1 years) with autism [41]. Treatment at doses ranging from 4 to 10 μg/kg/d led to significant improvement of irritability, hyperactivity, stereotypies, inappropriate speech, and oppositional behavior according to parent and teacher ratings on the ABC and Connors scales; however, the investigators did not record any significant changes. Adverse

Summary

Research to date supports use of the atypical antipsychotics as a first-line pharmacologic treatment for children and adolescents with PDDs and associated irritability (aggression, SIB, tantrums). Indeed, the only medication treatment currently approved for irritability in youth with autism is risperidone. Other atypical antipsychotics, including olanzapine and aripiprazole, are currently being investigated via double-blind, placebo-controlled trials. In addition to ongoing research on the

References (51)

  • American Psychiatric Association

    Diagnostic and statistical manual of mental disorders. 4th edition, text revision (DSM-IV-TR)

    (2000)
  • C.J. McDougle et al.

    Pharmacological treatments

  • M. Campbell et al.

    Current status of drug research and treatment with autistic children

    J Pediatr Psychol

    (1977)
  • B. Fish

    Children's Psychiatric Rating Scale (scoring)

    Psychopharmacol Bull

    (1985)
  • L.T. Anderson et al.

    Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms

    Am J Psychiatry

    (1984)
  • L.T. Anderson et al.

    The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children

    J Autism Dev Disord

    (1989)
  • J.M. Pierre

    Extrapyramidal symptoms with atypical antipsychotics: incidence, prevention and management

    Drug Saf

    (2005)
  • A. Zuddas et al.

    Clinical effects of clozapine on autistic disorder

    Am J Psychiatry

    (1996)
  • N.C. Chen et al.

    Clozapine in the treatment of aggression in an adolescent with autistic disorder

    J Clin Psychiatry

    (2001)
  • G. Gobbi et al.

    Long-term treatment with clozapine in an adult with autistic disorder accompanied by aggressive behavior

    J Psychiatry Neurosci

    (2001)
  • Research Units on Pediatric Psychopharmacology Autism Network

    Risperidone in children with autism and serious behavioral problems

    N Engl J Med

    (2002)
  • M.G. Aman et al.

    The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects

    Am J Ment Defic

    (1985)
  • C.J. McDougle et al.

    Risperidone for the core symptom domains of autism: results from the study by the autism network of the Research Units on Pediatric Psychopharmacology

    Am J Psychiatry

    (2005)
  • Research Units on Pediatric Psychopharmacology Autism Network

    Risperidone treatment of autistic disorder: longer-term benefits and blinded discontinuation after 6 months

    Am J Psychiatry

    (2005)
  • S. Shea et al.

    Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders

    Pediatrics

    (2004)
  • Cited by (48)

    • Autism Spectrum Disorders: Clinical Considerations

      2014, Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease: Fifth Edition
    • Concurrent reductions in psychotropic medication, assault, and physical restraint in two residential treatment programs for youth

      2013, Children and Youth Services Review
      Citation Excerpt :

      Several studies have indicated that psychotropic medications have effectively reduced mental health and behavioral symptoms. For example, research on the use of psychostimulants for youth with ADHD has demonstrated their effectiveness in reducing symptoms with moderate to large effects (Schachter, Pham, King, Langford, & Moher, 2001); positive effects also have been found when medications and psychosocial treatments were combined for youth with depression (March, Silva, Vitiello, & The TADS Team, 2006; Vitiello et al., 2006); and second generation antipsychotics have been effective for youth with behavioral disturbances and cognitive delay or autism spectrum disorders (Stigler & McDougle, 2008; Van Bellinghen & De Troch, 2001). These research gains showing positive effects of some psychotropic medications for specific target populations or clinical symptoms have been associated with the exponential growth in the popularity of these medications for aggressive behaviors in youth (Najjar et al., 2004; Naylor et al., 2007).

    • Youth at entry to residential treatment: Understanding psychotropic medication use

      2012, Children and Youth Services Review
      Citation Excerpt :

      For youth with depression, selective serotonin reuptake inhibitors have been shown to be more effective than usual care when used either alone or in combination with psychosocial treatments (March, Silva, Vitiello, & The TADS Team, 2006). In addition, second generation antipsychotics have been shown to reduce levels of aggression for youth with both developmental delays and autism spectrum disorders (Stigler & McDougle, 2008; Van Bellinghen & De Troch, 2001). However, despite emerging evidence for the effectiveness of some psychotropic medications, widespread and frequent use of psychotropic medications for pediatric populations remains a controversial issue (Correll et al., 2006; Vitiello, 2007).

    View all citing articles on Scopus

    This work was supported in part by a Research Unit on Pediatric Psychopharmacology-Psychosocial Intervention grant (U10 MH066766) from the National Institute of Mental Health (NIMH) to Indiana University (Drs. McDougle and Stigler), research grant (R01 MH072964) from the NIMH (Drs. McDougle and Stigler), a General Clinical Research Center grant (M01 RR00750) from the National Institutes of Health to Indiana University (Drs. McDougle and Stigler), and a Daniel X. and Mary Freedman Psychiatric Research Fellowship Award (Dr. Stigler).

    View full text