Risperidone augmentation for treatment-resistant aggression in attention-deficit/hyperactivity disorder: a placebo-controlled pilot study.

OBJECTIVE: To evaluate the effects of risperidone augmentation for treatment-resistant aggression in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Twenty-five children (ages 7-12 years) with attention-deficit/hyperactivity disorder (ADHD) and significant aggressive behaviors were randomized to risperidone or placebo for 4 weeks for this double-blind study. Subjects were already in treatment with a constant dose of psychostimulant medication. The primary efficacy measure was change from baseline in the Children's Aggression Scale-Parent (CAS-P) and -Teacher (CAS-T) total scores. RESULTS: The mean risperidone dose at endpoint was 1.08 mg/day. For the CAS-P total score, a significant difference was found (chi(1)(2) = 4.30, p < .05) with 100% of risperidone subjects improving by more than 30% from baseline to endpoint, whereas only 77% of the placebo group reported a similar response. No differences were found on the CAS-T total score. For the CAS-P and CAS-T, no significant interaction was found between treatment group and time. Rates of adverse events did not differ significantly between groups. CONCLUSIONS: Risperidone treatment appears to be well tolerated and modestly effective when used in combination with psychostimulants for treatment-resistant aggression in children with ADHD.

Antipsychotics in early onset Schizophrenia: Systematic review and meta-analysis.

BACKGROUND: To develop an evidence base for using antipsychotic medications for schizophrenia in children and adolescents. METHOD: Data sources were identified in PsychINFO (1872-2003), MEDLINE (1966-2003), and articles in reference lists. Study selection criteria: (1) treatment with antipsychotics; (2) ages were between 5 and 18 years; (3) sample diagnosed with schizophrenia; (4) prospective design; (5) rating instruments used. Fifteen studies met inclusion criteria and were rated. Study quality was independently rated. RESULTS: Average response rate among 8 studies employing atypicals was 55.7% compared to 72.3% among 13 studies employing typicals. The difference was statistically different at the trend level (z = 1.65, P < 0.10). The effect size on a continuous measure was 0.36 in favor of typicals. When study quality was included in the model, the effect of medication type remained unchanged. Average weight gain in patients treated with typicals was 1.4 Kg. compared to 4.5 Kg for those treated with atypicals. Sedation was more common among those on atypicals. The rate of extrapyramidal side effects was similar among the two groups CONCLUSIONS: Antipsychotic medications seem effective for schizophrenia treatment in children and adolescents. Typicals appear to be more effective and cause less weight gain than atypicals. However, more rigorous clinical trials are necessary.

Risperidone reduces aggression in boys with a disruptive behaviour disorder and below average intelligence quotient: analysis of two placebo-controlled randomized trials.

The present study aimed to analyse the effect of risperidone on a priori defined core aggression items. Data were pooled from 163 boys (aged 5-12 years, with or without comorbid attention-deficit/hyperactivity disorder) with a DSM-IV diagnosis of either conduct disorder or oppositional defiant disorder who had participated in either of two identical, 6-week, randomized, double-blind, placebo-controlled trials. All received treatment with either placebo or oral risperidone solution (0.01-0.06 mg/kg/day). Subjects had below average intelligence [intelligence quotient (IQ) 36-84] and a score of > or =24 on the Conduct Problem subscale of the Nisonger Child Behaviour Rating Form (N-CBRF). An expert advisory panel selected six core aggression items from the N-CBRF, from which a total Aggression Score (AS, range 0-18) was constructed. Compared to those treated with placebo, risperidone-treated subjects experienced significantly greater mean decreases from baseline in the AS at each of weeks 1-6 (P<0.001). By study endpoint, aggression among risperidone-treated subjects had declined by 56.4% (mean baseline AS 10.1; mean endpoint AS 4.4), which was more than twice that of placebo-treated subjects (mean baseline AS 10.6; mean endpoint AS 8.3; 21.7% reduction). Risperidone was efficacious in reducing symptoms of aggression in boys of below average IQ with disruptive behaviour disorders.

Citalopram treatment for impulsive aggression in children and adolescents: an open pilot study.

OBJECTIVE: To assess the short-term effect and safety of citalopram in the reduction of impulsive aggression in children and adolescents. METHOD: Twelve subjects, aged 7 to 15 years, were attending a psychiatric outpatient clinic and had a profile of impulsive aggression. Subjects were treated in an open trial with citalopram for 6 weeks after a 1-week washout period. Dosage was regulated individually over a period of 4 weeks. The starting dose was 10 mg/day followed by 10 mg increments on a weekly basis. The maximum dose was not to exceed 40 mg/day. Outcome measures included the Modified Overt Aggression Scale (MOAS), the Child Behavioral Checklist (CBCL), and the Clinical Global Impressions (CGI). RESULTS: Eleven subjects completed the study Citalopram produced clinically and statistically significant reductions on target symptoms of impulsive aggression, independent of other behavioral problems, as measured by the MOAS, the CBCL, and the CGI at doses ranging from 20 to 40 mg/day (mean = 27 mg). No major adverse reactions were associated with citalopram use. CONCLUSION: Citalopram appears to be effective and well tolerated in this sample of children and adolescents with impulsive aggression.

Do we need placebos to evaluate new drugs in children with schizophrenia?

RATIONALE: Ethical issues are raised when placebos are used in human experimentation. This ethical concern is accentuated when research is contemplated among special sub-groups such as children, especially if they suffer from schizophrenia. OBJECTIVES: To review critically current ethical and scientific issues regarding the use of placebos in children with schizophrenia. METHODS: Manual review of literature and agency policies on pertinent issues and presentation of thoughtful original ideas as to the ethical use of placebos in children. RESULTS: There is compelling scientific and ethical justification underscoring the need and appropriateness of placebo-controlled studies in the treatment of childhood schizophrenia. CONCLUSION: The authors believe that children will gain access to new medications and receive safe and optimal drug therapy through well-conducted research that employs placebo controls.