Three controlled studies (112 patients with schizophrenia) were used to evaluate the efficacy of typical antipsychotics.
One randomised controlled (RCT) double-blind trial (21 patients), 3 open uncontrolled trials (68 patients), and 4 case reports/series were used to evaluate the efficacy of clozapine.
Two open uncontrolled trials (14 patients), 2 retrospective chart reviews (29 patients) and 5 case reports/series were used to evaluate the efficacy of risperidone.
There was one open trial (8 patients) of olanzapine.
The following types of studies in children and adolescents were not identified: controlled or systematic long-term follow-up studies of antipsychotics; well-controlled studies of risperidone; and reports on the use of quetiapine or any of the newer atypical antipsychotics. Results were reported without levels of statistical significance making interpretation difficult.
Typical antipsychotics: the three studies ranged from 4 to 10 weeks in duration and compared different drugs. One 4 week double-blind trial (75 patients) studied loxapine vs haloperidol vs placebo and found that both active drugs were superior to placebo in terms of reduced schizophrenic symptoms but there were few significant differences between the active agents. Somnolence and sedation affecting 21/26 loxapine subjects compared to 13/25 haloperidol subjects.
One single blind 4 to 6 week study (21 adolescents) compared thioridazine and thiothixene and found no significant difference in efficacy or overall occurrence of side-effects between the two drugs. Sedation occurred in 75% of the thioridazine group compared with 54% in the thiothixene group. Extrapyramidal symptoms (EPS) occurred in 54% of the thiothixene group compared to 0% of the thioridazine group. Dose changes to reduce side-effects were reported to be ineffective. One double-blind placebo controlled cross-over trial studied haloperidol in 16 children aged 5 to 12 years and found that 16/16 on haloperidol showed mild/marked improvement compared to 12/16 on placebo. Side-effects were only reported for the first 12 subjects, of whom 8 experienced drowsiness, 1 experienced parkinsonian symptoms and 2 suffered acute dystonic reactions.
Atypical antipsychotics.
Clozapine: 1 RCT of 6 weeks duration compared haloperidol and clozapine and found that clozapine was statistically significantly better than haloperidol on all measure of psychosis. Adverse reactions on clozapine included neutropenia (4/10), seizures (2/10), drowsiness, salivation and weight gain. One of eleven patients on haloperidol developed the neuroleptic malignant syndrome. Other studies were either uncontrolled (3 open trials, including one retrospective study) or case reports (9 patients). Rates of improvement ranged from 11/21 showing 'marked improvement' to 75% showing 'notable symptom improvement'. Side effects included: drowsiness, dizziness, orthostatic hypotension, and hypersalivation, leukopenia (3/36 patients), neutropenia (4/21 on clozapine), EEG changes (44% of 36 patients), seizures (2/21 on clozapine), EPS, and weight gain.
Risperidone: Adverse reaction reported in the case series, chart reviews, and observational studies included extrapyramidal symptoms, dysphoric mood, weight gain, galactorrhea, asymptomatic leukocytopenia, amenorrhoea, and hepatotoxicity. Studies suggested improvement in symptoms.