Journal of Child and Adolescent Psychopharmacology

To describe the methodological challenges and decisions made in developing a multisite, controlled study of risperidone in children and adolescents with autism.

Review the design considerations for clinical trials in children with autistic disorder accompanied by severe tantrums, aggressive and/or self-injurious behaviors. These design considerations include the definition of inclusion criteria that are relevant to clinical practice and matching study design to the goal of evaluating short- and long-term effects. Additional ethical and scientific issues concern the length of trial and sample size.

We undertook a short-term, placebo-controlled study to evaluate the efficacy and safety of risperidone in children and adolescents with autistic disorder.This trial design was followed by an extended open-label maintenance on risperidone to confirm durability of treatment effects and to monitor safety. Finally, a placebo-controlled discontinuation study tested the need for continuous treatment.

In the absence of standard pharmacological treatment for children with autistic disorder, a placebo-controlled study remains the most appropriate method of testing efficacy and safety. The clinical relevance of this study is enhanced by the addition of an extended maintenance phase followed by a placebo discontinuation.

Considering the well-documented low level of agreement between youth and parent reports on the diagnosis of major depressive disorder (MDD), uncertainties remain as to the informativeness of discrepant youth and parent reports in clinical studies. To this end we evaluated whether morbidity and functional correlates on the diagnosis of MDD in youth vary by informant source.

The sample consisted of 186 pairs of independently assessed mother and youth self-reports on the diagnosis of MDD using structured diagnostic interviews ascertained in a large study of youth with and without attention deficit hyperactivity disorder of both genders. Subjects were also assessed on measures of interpersonal, school, and family functioning as well as prior treatment history.

The diagnosis of MDD endorsed by youth self-report only when compared with that reported by the mother was characterized by significantly: shorter duration episode, later age at onset, milder depression-associated impairment, less impairment in interpersonal functioning, lower rates of comorbid disorders, and decreased likelihood to receive any course of treatment for depression. The morbidity and dysfunction associated with MDD varied significantly by informant source, and followed a dose-response association with the highest morbidity associated with the concurrent reports of the youth and the mothers, followed by mother report alone, with the least morbidity and dysfunction when endorsed by youth alone.

These findings suggest that exclusive reliance on youth self-reports may identify a mild form of depression associated with limited morbidity and disability compared with that identified by parental reports.

To study the effectiveness, safety, and tolerability of quetiapine in adolescents with psychotic disorders.

This study was an 8-week, open trial using quetiapine with 15 adolescents, ages 13-17 years, mean age 15.1 years, with a diagnosis of a psychotic disorder. Our primary instruments focused on psychotic symptomatology as measured by the Brief Psychiatric Rating Scale(BPRS), Clinical Global Impression (CGI), Positive and Negative Syndrome Scale (PANSS), and the Young Mania Rating Scale (YMRS). Other measures included adverse events, clinical laboratory tests, vital signs, electrocardiogram (ECG), extrapyramidal (EPS) measures, and ophthalmologic examination.

Quetiapine significantly reduced psychotic symptoms as measured by the BPRS, PANSS, YMRS, CGI, and CGI Severity of Illness scale. The average weight gain was 4.1 kg. After correction for expected weight gain, the mean weight gain over the 8-week period was 3.4 kg. Prolactin and cholesterol remained unchanged. Trends were found for a decrease in T₄ and an increase in thyroid-stimulating hormone. Common adverse effects were somnolence, agitation, drowsiness, and headache. No significant findings were noted on repeat ECGs, EPS measures, or ophthalmic examination. The final average treatment dose was 467 mg/day (range 300-800 mg/day).

Quetiapine is suggested to be effective treatment of youths with psychotic disorders and to have a favorable side-effect profile.

Risperidone, a potent antagonist of both serotonergic (5HT_2A) and dopaminergic D₂ receptors is associated with hyperprolactinemia in adults and children. Chronically elevated prolactin levels in children with prolactinomas may be associated with arrested growth and development resulting in either delayed puberty or short stature. These possibilities stress the importance of developing a safe and effective approach to drug-induced hyperprolactinemia in youth. We report the successful treatment of risperidone-induced hyperprolactinemia with cabergoline in youth.

We undertook a retrospective case review of four children with risperidone-induced hyperprolactinemia treated with cabergoline.

Four males (age 6-11 years) with Diagnostic and Statistical Manual of Mental Disorders (fourth edition) bipolar disorder or psychoses, with risperidone-induced elevations in serum prolactin levels (57.5-129 ng/mL, normal 5-15 ng/mL), were treated with cabergoline(mean dose 2.13 ± 0.09 mg/week). When serum prolactin levels normalized in all four subjects (mean 11.2 ± 10.9 ng/mL), the cabergoline dose was reduced to 1 mg/week in three of four subjects. The mean duration of therapy with cabergoline was 523.5 ± 129.7 days, and the mean duration of therapy with risperidone was 788.5 ± 162.5 days. Cabergoline was well tolerated without adverse effects.

Cabergoline may be useful for the treatment of risperidone-induced hyperprolactinemia in youth; however, further research is needed.