A Pilot Study of Risperidone, Olanzapine, and Haloperidol in Psychotic Youth: A Double-Blind, Randomized, 8-Week Trial

Abstract

This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population, in comparison to haloperidol, a conventional antipsychotic with established efficacy. Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth, but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied. Subjects, selected because of prominent positive psychotic symptoms, were randomly assigned to double-blind, parallel treatment with risperidone, olanzapine, or haloperidol for 8 weeks. The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination. An exploratory, descriptive analysis was done to compare the three treatments. A total of 50 patients, 8-19 years, participated. All treatments reduced symptoms significantly with p-values (corrected for multiple comparisons) of 0.0018 for each of the atypical agents and 0.012 for haloperidol. In all, 88% of subjects treated with olanzapine, 74% treated with risperidone, and 53% treated with haloperidol met response criteria. The primary side effects observed in all patients were mild to moderate sedation, extrapyramidal symptoms, and weight gain. Risperidone and olanzapine acutely reduced psychotic symptoms in this pediatric sample. Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol. However, youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults.

Olanzapine compared to quetiapine in adolescents with a first psychotic episode

“…In a previous 8-week doubleblind, randomized, controlled trial in 50 children and adolescents with psychotic symptoms, comparing risperidone, olanzapine, and haloperidol, there was no difference in efficacy among the drugs, with all three antipsychotics providing a significant reduction in psychotic symptoms [38]. More recently, a 12-week open-label, randomized study comparing risperidone and olanzapine efficacy in 25 child-onset schizophrenia patients reported that both drugs provided a similar significant reduction in psychotic symptoms [28].…”

“…In a more recent study, clozapine was significantly superior to olanzapine only for the treatment of negative symptoms [37]. In the only other double-blind randomized study, Sikich et al [38] studied 50 patients with psychotic symptoms, with a mean length of illness of 2.4 years. Haloperidol, olanzapine, and risperidone showed similar efficacy in symptom reduction.…”

“…In this study, weight gain and extrapyramidal effects appeared more prevalent and severe than reported in adults. Most studies are short term, usually lasting 6-8 weeks [37,38]. We are not aware of any previous randomized controlled trial with two SGAs in first episode psychosis in adolescence.…”

A comparison of depot and oral atypical antipsychotics in terms of metabolic syndrome markers

“…In another study, however, an insignificant decrease was reported in HDL levels after 8 weeks in patients treated with olanzapine, while a very small increase was determined in patients treated with risperidone. Low-density lipoprotein and triglyceride levels were reported to increase in both groups [35]. In contrast to these findings, another study involving a different patient group observed a small increase in HDL levels in patients receiving olanzapine after 8 weeks' treatment, while a decrease was observed in HDL levels in patients treated with risperidone [36].…”

Evaluating and treating the prodromal stage of schizophrenia

“…Unfortunately, adverse effects were not reported, making evaluation of the risk-benefit ratio difficult. However, clinical trials using risperidone in psychotic adolescents suggest that risperidone treatment is likely to be associated with weight gain, as well as neurologic and other side effects [43].…”