Evidence-Based Reviews

Using atypicals for patients without psychosis: The strength of evidence varies with the diagnosis

Current Psychiatry. 2002 October;1(10):54-64

References

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3. Hanson L. Olanzapine in the treatment of anorexia nervosa. Br J Psychiatry 1999;175:592.-

4. Lavid N, Franklin DL, Maguire GA. Management of child and adolescent stuttering with olanzapine: three case reports. Ann Clin Psychiatry 1999;11(4):233-6.

5. American Academy of Child and Adolescent Psychiatry. AACAP official action: practice parameters for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry 1997;36:69-84.

6. Anderson LT, Campbell M, Grega DM, et al. Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms. Am J Psychiatry 1984;141(10):1195-1202.

7. Masi G, Cosenza A, Mucci M, Brovedani P. Open trial of risperidone in 24 young children with pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry 2001;40(10):1206-14.

8. Zuddis A, Di Martino A, Muglia P, et al. Long-term risperidone for pervasive developmental disorder: efficacy, tolerability, and discontinuation. J Child Adolesc Psychopharmacol 2000;10(2):79-90.

9. Posey DJ, Walsh KH, Wilson GA, McDougle CJ. Risperidone in the treatment of two very young children with autism. J Child Adolesc Psychopharmacol 1999;9(4):273-6.

10. McDougle CJ, Homes JP, Bronson MR, et al. Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open-label study. J Am Acad Child Adolesc Psychiatry 1997;36:685-93.

11. McCracken JT, McGough J, et al. Risperidone in children with autism and serious behavioral problems. Research Units on Pediatric Psychopharmacology Autism Network. N Eng J Med. 2002;347(5):314-21.

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13. Malone RP, Cater J, Sheikh RM, et al. Olanzapine versus haloperidol in children with autistic disorder: an open pilot study. J Am Acad Child Adolesc Psychiatry 2001;40:887-94.

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19. Campbell M, Small AM, Green WH, et al. Behavioral efficacy of haloperidol and lithium carbonate: a comparison of hospitalized aggressive children with conduct disorder. Arch Gen Psychiatry 1984;41:650-6.

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the Children’s Psychiatric Rating Scale (CPRS)
hyperactivity, fidgetiness, rhythmic motions, mood lability, and angry affect, as measured by the Childhood Autism Rating Scale (CARS)
functional impairment, as determined by the Children’s Global Assessment Scale (C-GAS).

Overall, risperidone was well-tolerated at this low dosage, although two children did not complete the study because of side effects. Three children gained more than 10% of their body weight.⁷

In a 12-month semi-naturalistic prospective study, 11 children and adolescents ages 7 to 17 (mean age 12.3) with autism (n=9) or PDD (n=2) were treated with risperidone. Starting dosage was 0.5 mg/d, mean dosage was 2.7 mg/d, and maximum dosage was 6 mg/d (0.1/mg/kg/d). Behavioral symptoms improved significantly with risperidone in 10 of the 11 subjects during the first 6 months of treatment. Autism’s core symptoms were also mildly improved, although more slowly and later in treatment. Risperidone continued to work in patients treated for 12 months, whereas behavioral symptoms reemerged in those who discontinued drug therapy after 6 months. Weight gain was the most common side effect.

After 6 months of therapy two patients developed facial dystonia, which resolved after the risperidone dosage was reduced or discontinued. Amenorrhea was observed in one patient, but no changes were reported in liver function, blood tests, or electrocardiogram (ECG) readings.⁸

Box 2

STUTTERING: 3 CASE REPORTS SHOW IMPROVEMENT

Haloperidol and risperidone have shown efficacy in managing stuttering in double-blind studies. Olanzapine has improved stuttering symptoms in three case reports: a 10-year-old boy, a 16-year-old youth with developmental stuttering, and a 9-year-old boy with medication-induced stuttering.⁴ These studies, albeit very limited, suggest that antipsychotics may be an appropriate option for managing this impairing disorder.

Others have contributed greatly to our understanding of using atypicals in treating autism and PDD.^9,10 Posey et al reported using risperidone to treat two boys, ages 23 months and 29 months. In both cases, aggression was reduced and social relatedness improved significantly. One patient’s treatment was complicated by dose-related presistent tachycardia and QTc prolongation.⁹

McDougle conducted an initial prospective, 12-week, open-label study examining risperidone treatment in 18 children and adolescents (15 boys and 3 girls, mean age 10) with PDD,¹⁰ followed by an 8-week, double-blind, placebo-controlled study of risperidone in 100 children with autistic disorders (excluding Asperger’s disorder).¹¹ Mean dosage was 2.1 mg/d (0.75 mg to 3.5 mg/d) divided into two doses. The study examined the benefit in a relatively young cohort (Tanner stages I and II—children who have yet to complete sexual development).

After 2 to 4 weeks of treatment, irritability improved most significantly (>25% improvement on the Aberrant Behavior Checklist), and stereotypic behavior also improved. Inappropriate speech patterns did not change. Anecdotal reports suggested that social relatedness improved, although quantitative evaluation was inconclusive. EPS, as measured by the Simpson Angus EPS score, were mild and generally seen in early treatment. Side effects included increased appetite, weight gain, decreased energy, and sedation.¹¹

Olanzapine. Most studies of olanzapine in children and adolescents with autistic disorders have been open-label:

Eight patients (four adults, ages 18 to 42, and four children, ages 5 to 17) were treated with olanzapine, mean dosage 7.8 mg/d for 12 weeks. Seven completed the study, and six were rated “much improved” or “very much improved” on the global improvement item of the Clinical Global Impression (CGI) scale. Hyperactivity, aggression, anger, and self-injurious behavior improved significantly, as did social relatedness, affectual reactions, sensory responses, and language use. The drug was well tolerated, with the most significant side effect being increased appetite and weight gain (mean increase 8.3 kg).¹²

In an open-label pilot study, 12 children with autism (mean age 8) were randomly assigned to 6 weeks of treatment with olanzapine (mean final dosage 7.9 mg/d) or haloperidol (mean final dosage 1.4 mg/d). Symptoms were reduced in both groups. Five of six children in the olanzapine group and three of six children in the haloperidol group were noted as responders, according to the CGI improvement item and the Children’s Psychiatric Rating Scale (CPRS) Autism Factor. Drowsiness and weight gain were seen with olanzapine.¹³

Similar results were obtained in another study, with significant improvements in irritability, hyperactivity, and excessive speech, as evaluated by the Aberrant Behavior Checklist.^14,15

Summary. Atypical antipsychotics appear to be effective and well tolerated in children and adolescents with autistic and developmental disorders. Double-blind, placebo-controlled studies confirm the benefit of risperidone; open-label trials likewise suggest the benefit of olanzapine. Research is limited on quetiapine and ziprasidone in this population.

Weight gain appears to be the most problematic side effect and should be monitored. Early dietary education and discussion with the patient, parents, and family can help keep weight gain to a minimum.