Evidence-Based Reviews

4 drugs can improve autism’s repetitive behaviors

Current Psychiatry. 2006 April;5(4):55-64

References

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16. McDougle CJ, Scahill L, Aman MG, 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;162:1142-8.

17. Potenza MN, Holmes JP, Kanes SJ, McDougle CJ. Olanzapine treatment of children, adolescents and adults with pervasive developmental disorders: an open-label pilot study. J Clin Psychopharmacol 1999;19:37-44.

18. Martin A, Koenig K, Scahill L, Bregman J. Open-label quetiapine in the treatment of children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol 1999;9:99-107.

19. Hollander E, Dolgoff-Kaspar R, Cartwright C, et al. An open trial of divalproex sodium in autism spectrum disorders. J Clin Psychiatry 2001;62:530-4.

20. Hollander E, Soorya LV, Wasserman S, et al. Divalproex sodium vs. placebo in the treatment of repetitive behaviours in autism spectrum disorder. Int J Neuropsychopharmacol 2006;9:209-13.

Risperidone. The double-blind, placebo-controlled RUPP trial examined risperidone’s efficacy in treating autism’s core symptoms (primarily irritability) in 101 children.¹³ Mean dosages after 8 weeks and during a 16-week open-label extension for 63 children were 2 and 2.1 mg/d, respectively.

Repetitive behavior—as measured with the CY-BOCS, using RUPP trial data¹⁶—improved significantly with risperidone compared with placebo. During the 8-week controlled trial, CY-BOCS scores improved from 15.51 (SD±2.73) to 11.65 (SD±4.02) in the risperidone group, compared with 15.18 (SD±3.88) to 14.21 (SD±4.81) in the placebo group. This response was maintained through the open-label trial.

Side effects included weight gain, fatigue, drowsiness, and drooling. No children receiving risperidone dropped out because of side effects. No EPS were reported, based on weekly Abnormal Involuntary Movement scale and Simpson-Angus scale scores.

Olanzapine. Only open-label studies have examined olanzapine in autism, and one systematically measured repetitive behaviors.¹⁷ Eight children with autism or other pervasive developmental disorders were given olanzapine, mean dosage 7.8 (±4.7) mg/d at the end of the 12-week trial.

Repetitive behaviors did not change significantly, as measured with YBOCS. Seven of eight patients completed the trial. Mean weight for the group after 12 weeks was 156±55 lbs, compared with 137±56 lbs at baseline.

Quetiapine. No data support using quetiapine for autism’s repetitive behaviors. Quetiapine, 100 to 350 mg/d (1.6 to 5.2 mg/kg/day) was poorly tolerated in a 16-week open-label safety and efficacy trial among 6 mentally retarded boys with autistic disorder. Side effects included a possible seizure, behavioral activation, increased appetite, and weight gain (0.9 to 8.2 kg). Two patients completed the trial.¹⁸

Ziprasidone. Small open-label studies and anecdotal reports of ziprasidone in autism have not examined this drug’s effect on repetitive behaviors.

Aripiprazole. Anecdotal information suggests that clinicians are using this medication to treat patients with autism, but no supporting data exist.

Evidence for valproate

Preliminary trials by our group suggest that valproate may reduce repetitive behaviors in autism. In a retrospective, open-label study, 14 patients (mean age 17) with autism spectrum disorder received divalproex sodium (mean 768±582 mg/d) for a mean 11 months. Ten patients (71%) showed sustained improvement in function, as measured by the CGI-improvement scale, and valproate was generally well-tolerated.¹⁹

We then measured valproate’s effect on repetitive behaviors in an 8-week, double-blind, placebo-controlled study of 13 patients (mean age 9) with autism spectrum disorder. Repetitive behaviors improved significantly compared with placebo, as measured by the CY-BOCS, in those who received divalproex (mean 833.93±326.21 mg/d).²⁰

Further studies are needed to replicate this finding. Although it is too early to make general recommendations, valproate may be a reasonable choice for children with autism and epilepsy or affective instability.

Related resources

Hollander E, Phillips AT, Yeh CC. Targeted treatments for symptom domains in child and adolescent autism. Lancet 2003;362:732-4.
Hollander E (ed). Autism spectrum disorders. New York: Marcel Decker; 2003.
National Institute of Health multicenter study of citalopram for repetitive behaviors in autism. http://www.clinicaltrials.gov/ct/show/nct00086645?order=2

Drug brand names

Aripiprazole • Abilify
Citalopram • Celexa
Escitalopram • Lexapro
Fluoxetine • Prozac
Fluvoxamine • Luvox
Olanzapine • Zyprexa
Quetiapine • Seroquel
Risperidone • Risperdal
Sertraline • Zoloft
Valproic acid • Depakote, Depakene
Ziprasidone • Geodon

Disclosures

Dr. Anagnostou reports no financial interest with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Hollander receives research/grant support from and is a consultant to Abbott Laboratories. He also receives support from the National Institutes of Health (STAART Center) to investigate orphan drug status for fluoxetine in treating autism symptoms.