Antipsychotics open-label studies

There have been numerous trials of use of the atypical antipsychotics in patients with developmental disabilities, but most of these trials were uncontrolled open-labeled studies or case reports (Aman and Madrid, 1999). Findings were reported for 86 adults and 1 child with prominent self-injury. The reports of adults assessed clozapine (1 report) and risperidone (4 reports). Improvement was observed for a majority of participants in all of these trials. The patients presented with a multitude of conditions, ranging from nonspecific MR and associated behavior problems, to pervasive developmental disorders (including autism), to various psychiatric disorders, including schizophrenia and manic disorder. Self-injury appeared to respond to treatment regardless of concomitant condition. In the only clozapine report with a child (who had autistic disorder), a mean dose of 283 mg/day caused a transient reduction in self-injury. 

Several small, open-label studies have supported TCA/antipsychotic combinations in the treatment of PMD. Minter and Mandel [1979) studied 54 inpatients with PMD who were treated openly with either TCAs alone, TCAs and antipsychotic combination, antipsychotics alone, or electroconvulsive therapy [ECT] in treatment failures. Although only 3 of 11 patients treated with TCAs alone responded, 16 of 16 patients treated with the combination of a TCA and an antipsychotic responded. Interestingly, 14 of 15 patients treated with antipsychotic drugs alone also responded, which is contrary to findings in other studies [Spiker et al. 1985). Several other open-label studies have confirmed the utility of the combination treatment for PMD [Charney and Nelson 1981 Frances et al. 1981), but few controlled studies have been completed. 

Among the atypical antipsychotics, clozapine has the most convincing evidence of efficacy in children and adolescents with schizophrenia ( 166,167, 170). Kumar and colleagues (171) conducted a double-blind, randomized trial of clozapine versus haloperidol in 21 children and adolescents (mean age = 14 years) whose psychosis had been previously unresponsive to typical antipsychotics. Clozapine at a mean dose of 176 mg per day was superior to haloperidol for both positive and negative symptoms. These results are consistent with an open-label study by Remschmidt and colleagues (172). This group found that clozapine at a mean dose of 154 mg per day produced notable improvement in 27 of 36 (75%) adolescents with schizophrenia previously unresponsive to at least two trials of typical antipsychotics. 

Stanilla et al. (1997) described three cases of delirium with psychotic symptoms due to clozapine withdrawal (see also Adams et al., 1991, for an early report of clozapine withdrawal psychosis). They believed that clozapine produces more severe withdrawal symptoms than typical antipsychotic agents. In a 3-year open label study of quetiapine, Margolese et al. (2004) switched 23 male patients from classical antipsychotics and risperidone to quetiapine Six of the seven patients who relapsed after being stabilized on quetiapine for at least three months met the criteria for supersensitivity psychosis. This is a very high rate, again raising questions about whether atypicals may be more prone to cause tardive psychosis. 

Other atypical antipsychotics commonly prescribed for treatment of autism include olanzapine, quetiapine, ziprasidone, and clozapine (Oswald and Sonenklar, 2007). Placebo-controlled trials of these agents in ASD populations have not been reported, with the exception of a small pilot study of olanzapine in which three of six children treated with olanzepine were rated as responders, compared to one of five in the placebo group (Hollander et al., 2006b). Open-label studies (reviewed by... 

All of the above trials were conducted in adults and, to the best of our knowledge, there are no trials of antipsychotic medication in children with psychoses and MR. To date there have been two double-blind trials of antipsychotic drugs in normal-IQ children and adolescents with schizophrenia, as well as several open-label trials (Ernst et al., 1999). The majority of these studies and case reports have demonstrated substantial reductions in schizophrenic symptoms. Given the lack of data on children and adolescents having both MR and schizophrenia, it seems that clinicians have little choice but to follow the standard of care applied with normal-IQ schizophrenic children, namely to use anti-... 

Risperidone Acute Clinical Trials. Hillert et al. (107) found risperidone to have both antipsychotic and antidepressive properties in 10 patients with schizoaffective disorder, depressed type. These investigators prescribed 2 to 10 mg/day for 6 weeks in an open-label pilot study, and found marked improvement in psychosis in all patients and clinically significant overall improvement in psychosis in 7 to 10 patients. Two patients required antiparkinsonian drugs otherwise risperidone was well tolerated by the group. 

Most studies in children and adolescents have been conducted with neuroleptics. A computerized literature search for the period 1974 to 1999 identified only five double-blind, placebo-controlled clinical trials that investigated the use of atypical antipsychotic medications in children and adolescents ( 166, 167). These studies involved a total of 105 patients. Numerous open-label and case series were also found. 

Observational studies An open-label, long-term study of patients switched to oral paliperidone from either risperidone or other antipsychotics found that extrapyramidal symptoms improved significantly for all patients [192 ]. Akathisia and weight gain were the main adverse events, and increased prolactin levels in female patients from the nonrisperidone group. 

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