Using atypicals for patients without psychosis: The strength of evidence varies with the diagnosis
Antipsychotics are being investigated for pediatric conditions including anxiety disorder, autism, and Tourette’s syndrome. Studies show benefit in some—but not all—of these uses.
Tourette’s disorder: Modest benefit
Tourette’s disorder and simple motor or vocal tics have traditionally been treated with the older neuroleptics, particularly haloperidol and pimozide. These agents have fallen out of favor in younger patients, however, because of the risk of short- and long-term side effects, including EPS, tardive dyskinesia, cognitive blunting, and school phobia.
Clinicians have turned to alternate agents, such as clonidine and guanfacine (alpha-2 agonists) to treat tic disorders, and now are trying atypical antipsychotics. In open and controlled studies, the atypicals have demonstrated moderate improvement in Tourette’s disorder. Even so, none of the newer agents has shown benefits comparable to haloperidol, which recently demonstrated 66% improvement in tic symptoms when compared with a placebo.16 For example:
- ziprasidone—35% improvement in tic symptoms when compared with a placebo17
- risperidone—44% improvement when compared with a placebo in 17 pediatric patients18
- clozapine—no effect on tic symptoms16 (clozapine causes little or no dopamine [D2] blockade, which most likely explains this result)
- olanzapine—modest to moderate benefit, but somewhat less effective than risperidone or ziprasidone (small sample size and inclusion of adult patients have confounded interpretation in the studies examining response to risperidone and olanzapine).16,17
Sedation was the most common side effect seen with use of risperidone, ziprasidone, or olanzapine, and weight gain was particularly problematic with olanzapine.16 No ECG abnormalities were noted in the 28 children treated with ziprasidone.17
Disruptive behavior: Improved conduct
The disruptive behavior disorders of childhood and adolescence include conduct disorder and oppositional defiant disorder. The only two antipsychotic medications approved to treat behavioral symptoms are chlorpromazine and thioridazine. These indications were approved in the 1980s, based on limited trials with poor statistical comparison and controlled study groups. Moreover, thioridazine has since been issued a black-box warning because of concerns about cardiac complications from QTc prolongation.
Among the typical antipsychotics, haloperidol has been studied the most extensively in disruptive behavior disorders, although it is not FDA-approved for this indication. Haloperidol has decreased destructive and aggressive behavior, oppositionality, and hostility, and has improved scores on children’s psychiatric and CGI scales.19
More recent studies have examined the role of atypical antipsychotics in disruptive behavior disorders, primarily risperidone.
Risperidone. In a double-blind, placebo-controlled study, use of risperidone (average dosage 0.75 to 1.50 mg/d) improved aggression and delinquent behavior in 20 children, ages 5 to 15, diagnosed with conduct disorder.20 In a larger 6-week, multisite, double-blind, placebo-controlled study, researchers examined the use of risperidone (mean dosage 1.11 mg/kg/d) in 118 children with conduct problems and borderline intellectual functioning (60% had oppositional defiant disorder, 40% had conduct disorder, and 60% had ADHD). Behaviors—anxious, hyperactive, self-injurious, isolative, and stereotypic—improved, as did adaptive skills. The most common side effects were sedation, GI distress, weight gain, hyperprolactinemia, rhinitis, and headaches.21 Replication of this study produced similar findings.22
In an extension study of conduct disorder, 34 children ages 5 to 14 with comorbid borderline intellectual functioning were treated for approximately 1 year with risperidone (mean dosage 1.48 mg/d). Clinical benefit, defined by statistically significant improvement in the conduct problem subscale of the Nisonger Child Behavior Rating Form, was noted throughout the study. Prolactin levels were elevated after 3 months of treatment but declined thereafter.23
No controlled studies have been published using olanzapine in children and adolescents with disruptive behavior disorders. As other medications—lithium, anticonvulsants, and psychostimulants—are available for symptomatic treatment of this population, questions remain. Are antipsychotics the best class of medication for this purpose, and should they be tried as first-line therapy? Few studies have compared the efficacy of antipsychotics and other pharmacologic options.
Summary
Pharmacotherapy of childhood psychiatric conditions is complex and an extremely underdeveloped area of research. Even so, clinicians are experimenting with the use of atypical antipsychotics on a trial-and-error basis or as adjuncts to other medications for childhood conditions beyond schizophrenia.24
Even more than in adult populations, judicious use of atypical antipsychotics is warranted in children and adolescents because of potential long-term consequences. The risk of interfering with normal development and the unique pharmacokinetics of childhood are important considerations. At the same time, atypical antipsychotics may offer the potential to improve behavior and function in children with intractable psychiatric conditions.
Related resources
- Pappadopulas E, Jensen PS, Schur SB, et al. Real world atypical antipsychotic prescribing practices in public child and adolescent inpatient settings. Schizophr Bull 2002;28(1):111-121.
- Malone RP, Sheikh R, Zito JM. Novel antipsychotic medications is the treatment of children and adolescents. Psychiatr Serv 1999; 50(2):171-174.
Drug brand names
- Chlorpromazine • Thorazine
- Clonidine • Catapres
- Clozapine • Clozaril
- Guanfacine • Tenex
- Haloperidol • Haldol
- Olanzapine • Zyprexa
- Pimozide • Orap
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Thioridazine • Mellaril
- Ziprasidone • Geodon
