Prescribing of atypical antipsychotics for children and adolescents is increasing, despite a lack of randomized controlled clinical trials. Like many psychiatrists, you may be treating pediatric patients with these medications for a variety of indications beyond psychosis.
Three factors are driving the use of atypical antipsychotics for broader indications:
- substantial evidence that these newer agents are safer and more effective than typical antipsychotics1
- inadequate response of childhood and adolescent psychiatric disorders to their primary treatments
- evidence that atypical antipsychotics have potential thymoleptic, antiaggressive, and anxiolytic properties.
These attributes already have expanded atypical antipsychotic use in adult patients. In fact, atypicals are being used more extensively in adults for affective and nonpsychotic conditions than for schizophrenia.2
In preparing the following two-part article for Current Psychiatry, we scoured the available literature—Medline, abstracts from scientific meetings, and American Academy of Child and Adolescent Psychiatry (AACAP) practice parameters—to examine the evolving role of atypical antipsychotics in children and adolescents. In part 1 of this article, we discuss using atypicals in childhood/adolescent-onset schizophrenia, bipolar disorder, and psychotic depression. In part 2, we look at evidence for using atypicals in children with autism and developmental disorders, Tourette’s and other tic disorders, disruptive behavior disorders, anorexia nervosa, anxiety disorders, and stuttering.
RECOMMENDED WORK-UP BEFORE PRESCRIBING ANTIPSYCHOTICS
Before prescribing antipsychotic medications for children and adolescents, always conduct a comprehensive history and complete physical examination.
History. Include information about:
- seizures, head trauma, and cardiac or endocrine problems (often elicited with questions about fatigue, temperature intolerance, or weight concerns)
- perinatal history (apnea, Apgar scores, days in hospital)
- family history (e.g., significant medical problems).
Physical exam. Obtain baseline blood pressure, pulse, body weight and habitus, and laboratory tests—complete blood count, comprehensive metabolic profile with liver function tests, and cholesterol/triglyceride levels.
Educate the parent and child about possible side effects, whether they are likely to be transient or persistent, and ways to minimize them (e.g., bedtime dosing to prevent daytime sedation, dietary recommendations to lessen potential weight gain).
Monitor lab values and weight throughout treatment (compared with normal growth curves). Use words the child understands when asking about side effects (e.g., “Have you had leakage from your breasts?”). Continually weigh the benefits versus the risks of antipsychotics, and discuss this balance with the parent and child.
Shift in pharmacotherapy of schizophrenia.
One-quarter of patients with schizophrenia develop the disorder before age 15, and subtle psychotic manifestations are often observed in early childhood.3 In general, schizophrenia’s presenting symptoms are comparable in adults and children, but the childhood/adolescent-onset form is more severe.4,5
During the past 5 years, pharmacotherapy of adult schizophrenia has shifted dramatically away from typical antipsychotics. Atypical agents have shown greater efficacy and tolerability, especially with respect to extrapyramidal symptoms (EPS) and tardive dyskinesia (TD).1
In a recent survey, most general and specialist psychiatrists (86%) said they prefer using atypical antipsychotics as first-line treatment for new-onset schizophrenia and as maintenance therapy. They also reported using atypicals to treat patients with dementia (80%), personality disorders (69%), developmental delay/mental retardation (65%), and autism (40%).6
Translating adult findings to children. Most evidence of atypical antipsychotics’ efficacy and tolerability is derived from adult studies, which likely will continue to influence clinical practice more than the limited number of child and adolescent studies. In 1998, a thorough review of atypical antipsychotic use in child and adolescent psychiatry found only five blinded placebo-controlled clinical trials, 24 open-label trials, and 33 case series.7 A follow-up review in 1999 again found mainly case reports and case series, with a handful of controlled studies.8
Available atypical antipsychotics include clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. An investigational agent—aripiprazole—is likely to be available soon for clinical use.
Issues in pediatric use of atypicals
When prescribing atypical antipsychotics, it is important to balance the benefit of treatment with the risk of exposing children to possible adverse effects. Side effects associated with atypicals include weight gain, secondary metabolic disturbances such as hyperglycemia, hyperprolactinemia, and cardiac conduction abnormalities. These side effects are health concerns for all patients but particularly for children and adolescents, who may require years of exposure to antipsychotics.
Weight gain. Younger patients may be particularly susceptible to weight gain with the use of the atypicals. In a state hospital adult population, Buckley et al found a strong inverse relationship between patient age and weight gain associated with atypical antipsychotic use.9 Key issues for pediatric populations are:
- Will children have difficulties losing weight over time?
- Will they stop their medications over time?
- Will they stop their medications because of this effect?
- Will they be further stigmatized at school because of obesity?
- Are they at increased risk to develop diabetes mellitus?
- What are the long-term consequences of antipsychotic-induced obesity and metabolic disturbances for this patient population?