Acute and long-term safety and tolerability of risperidone in children with autism

Michael G. Aman, L. Eugene Arnold, Christopher J. McDougle, Benedetto Vitiello, Lawrence Scahill, Mark Davies, James T. McCracken, Elaine Tierney, Patricia L. Nash, David J. Posey, Shirley Chuang, Andres Martin, Bhavik Shah, Nilda M. Gonzalez, Naomi Swiezy, Louise Ritz, Kathleen Koenig, James McGough, Jaswinder K. Ghuman, Ronald L. Lindsay

Research output: Contribution to journalArticle

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Abstract

Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n = 65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n = 16) or gradual replacement with placebo (n = 16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as assessed by the SARS, were no more common for drug than placebo, although drooling was reported more often in the risperidone group. There were no differences between groups on the AIMS. Two subjects had seizures (one taking placebo), but these were considered unrelated to active drug. Most AEs were mild to moderate and failed to interfere with therapeutic changes; there were no unanticipated AEs. The side effects of most concern were somnolence and weight gain.

Original languageEnglish
Pages (from-to)869-884
Number of pages16
JournalJournal of Child and Adolescent Psychopharmacology
Volume15
Issue number6
DOIs
StatePublished - Dec 2005

Fingerprint

Risperidone
Autistic Disorder
Safety
Placebos
Sialorrhea
Enuresis
Weights and Measures
Urinalysis
Vital Signs
Liver Function Tests
Appetite
Constipation
Therapeutics
Centers for Disease Control and Prevention (U.S.)
Rhinitis
Pharmaceutical Preparations
Electrolytes
Weight Gain
Sleep
Seizures

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Psychiatry and Mental health
  • Pediatrics, Perinatology, and Child Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Aman, M. G., Arnold, L. E., McDougle, C. J., Vitiello, B., Scahill, L., Davies, M., ... Lindsay, R. L. (2005). Acute and long-term safety and tolerability of risperidone in children with autism. Journal of Child and Adolescent Psychopharmacology, 15(6), 869-884. https://doi.org/10.1089/cap.2005.15.869

Acute and long-term safety and tolerability of risperidone in children with autism. / Aman, Michael G.; Arnold, L. Eugene; McDougle, Christopher J.; Vitiello, Benedetto; Scahill, Lawrence; Davies, Mark; McCracken, James T.; Tierney, Elaine; Nash, Patricia L.; Posey, David J.; Chuang, Shirley; Martin, Andres; Shah, Bhavik; Gonzalez, Nilda M.; Swiezy, Naomi; Ritz, Louise; Koenig, Kathleen; McGough, James; Ghuman, Jaswinder K.; Lindsay, Ronald L.

In: Journal of Child and Adolescent Psychopharmacology, Vol. 15, No. 6, 12.2005, p. 869-884.

Research output: Contribution to journalArticle

Aman, MG, Arnold, LE, McDougle, CJ, Vitiello, B, Scahill, L, Davies, M, McCracken, JT, Tierney, E, Nash, PL, Posey, DJ, Chuang, S, Martin, A, Shah, B, Gonzalez, NM, Swiezy, N, Ritz, L, Koenig, K, McGough, J, Ghuman, JK & Lindsay, RL 2005, 'Acute and long-term safety and tolerability of risperidone in children with autism', Journal of Child and Adolescent Psychopharmacology, vol. 15, no. 6, pp. 869-884. https://doi.org/10.1089/cap.2005.15.869
Aman, Michael G. ; Arnold, L. Eugene ; McDougle, Christopher J. ; Vitiello, Benedetto ; Scahill, Lawrence ; Davies, Mark ; McCracken, James T. ; Tierney, Elaine ; Nash, Patricia L. ; Posey, David J. ; Chuang, Shirley ; Martin, Andres ; Shah, Bhavik ; Gonzalez, Nilda M. ; Swiezy, Naomi ; Ritz, Louise ; Koenig, Kathleen ; McGough, James ; Ghuman, Jaswinder K. ; Lindsay, Ronald L. / Acute and long-term safety and tolerability of risperidone in children with autism. In: Journal of Child and Adolescent Psychopharmacology. 2005 ; Vol. 15, No. 6. pp. 869-884.
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AU - Aman, Michael G.

AU - Arnold, L. Eugene

AU - McDougle, Christopher J.

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AU - Scahill, Lawrence

AU - Davies, Mark

AU - McCracken, James T.

AU - Tierney, Elaine

AU - Nash, Patricia L.

AU - Posey, David J.

AU - Chuang, Shirley

AU - Martin, Andres

AU - Shah, Bhavik

AU - Gonzalez, Nilda M.

AU - Swiezy, Naomi

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