Evidence-Based Reviews

New uses for atypicals in pediatric patients: How to offer the benefits while minimizing side effects

Current Psychiatry. 2002 October;1(10):44-52

References

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10. Meaney AM. Elevated prolactin levels and the effect with atypical antipsychotics. Presentation at the Winter Workshop on Schizophrenia Research. Davos, Switzerland: February 2002.

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Sedation was reported in 90% of patients.
2 of 10 patients had a seizure during clozapine therapy.
A 2% rate of agranulocytosis was disconcerting, given the lower adult rate (0.38%) and the brevity of the trial. As older age is a known risk factor for clozapine-induced agranulocytosis, it may be that children and the elderly are more susceptible to this side effect.

Risperidone. Most of the information on risperidone therapy in childhood/adolescent-onset schizophrenia is derived from small case series,⁷ which confirm its efficacy for both positive and negative symptoms. Recently, low-dose risperidone (less than 1.5 mg/d) was shown to be effective in young patients with schizophrenia’s prodrome.²⁰ In general, risperidone dosages of 1 to 2 mg/d are appropriate for patients with childhood/adolescent-onset schizophrenia. Children have been observed to be particularly sensitive to the drug’s EPS and prolactin-elevating effects.

Olanzapine has been effective in this patient population at dosages up to 10 mg/d.^7,16,21 In a pilot study, Kumra et al administered olanzapine to 23 children with schizophrenia who had not previously responded to neuroleptic treatment. After 8 weeks, the children improved on the Brief Psychiatric Rating Scale, the Scale for the Assessment for Negative Symptoms, and the Scale for the Assessment of Positive Symptoms.²¹

Similarities and differences in olanzapine’s side effects in adults and children/adolescents with schizophrenia were seen in a recent study. Children had more weight gain, sedation, and dystonia, whereas adults had significantly more cardiac arrhythmias.²²

Quetiapine. McConville and colleagues examined the efficacy and tolerability of quetiapine in 10 adolescents with chronic psychosis (7 with schizoaffective disorder and 3 with bipolar disorder). In this 3-week study, quetiapine was well-tolerated; in several patients, dosages exceeded 750 mg/d. Psychotic symptoms were reduced, and there was global improvement in functioning.²³

Other antipsychotics. There are no published data on the use of ziprasidone or aripiprazole in childhood/adolescent-onset schizophrenia.

Comparative data are very limited. One retrospective analysis compared the tolerability of risperidone, olanzapine, and quetiapine in 116 adolescent patients.²⁴ Over 3 months, 75 patients received risperidone (mean 2.6 mg/d), 16 received olanzapine (mean 13.3 mg/d), and 25 were treated with quetiapine (mean 210.3 mg/d). Weight gain was the most common side effect; patients gained an average 8.6 lb with risperidone, 7.2 lb with quetiapine, and 14.1 lb with olanzapine. EPS were treated in seven (10%) patients taking risperidone, four (25%) taking olanzapine, and no patients taking quetiapine.

Bipolar disorder

As in the adult population, there has been substantial use of antipsychotics in children and adolescents with bipolar illness. Bipolar I disorder affects an estimated 0.6% of adolescents and is even being diagnosed in prepubertal patients.

Lithium, valproate, carbamazapine, and adjunctive treatment with benzodiazapines traditionally have been used to treat bipolar I disorders. Although practice guidelines recommend lithium and divalproex sodium as first-line treatments for bipolar illness, these recommendations are generally based on a preference for first-line agents that have potential use in maintenance treatment. The benefit of medications in bipolar disorder, however, is two-fold:

Initial pharmacotherapy is usually instituted to target manic or mixed symptoms, and continued treatment is necessary to avoid relapse. The new antipsychotics—particularly risperidone, olanzapine, and quetiapine—are beneficial to treat agitated mania and disrupted sleep that may impair function and/or mandate inpatient stabilization. The highly sedative properties offer an acute benefit in restoring disrupted sleep.
Psychotic symptoms seen in mania may need to be targeted independent of the mood symptoms and would thus suggest the use of an antipsychotic. In early-onset bipolar disorder, antipsychotics are used primarily as adjuncts to mood stabilizers.

Evidence. The 1997 AACAP practice parameters on treating bipolar disorders included limited information on the use of antipsychotics. No studies had examined the efficacy of neuroleptics (i.e., haloperidol) in children and adolescents, and only one case study had been published on the benefit on a newer antipsychotic agent.²⁵ Since then, case reports and open studies have contributed to our understanding of the role the newer antipsychotics may play in treating this disorder:

In the 1994 case report, an adolescent with bipolar disorder showed benefit when treated with clozapine.²⁶
In a retrospective chart review, 28 children ages 4 to 17 with bipolar disorder (25 mixed and 3 hypomanic) were treated with adjunctive risperidone for 6 months. Most (82%) showed significant improvement in mania and aggression on a mean dosage of 1.7 +/- 1.3 mg/d. Attention-deficit/hyperactivity disorder symptoms improved in 8% of the patients.²⁷
Affective symptoms (predominantly suggestive of bipolar disorder), aggression, and violent behavior in 11 children and adolescents ages 5 to 16 showed therapeutic response to an open trial of adjunctive low-dose (0.75 to 2.5 mg/d) risperidone.²⁸