clozapine and Child-Development-Disorders--Pervasive

Atypical antipsychotics are emerging as the first-line pharmacologic treatment for irritability (i.e., aggression, self-injurious behavior, and severe tantrums) in children and adolescents with autistic and other pervasive developmental disorders. Results from placebo-controlled and open-label studies of clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole in this subject population are reviewed. Additional placebo-controlled trials and studies of longer-term safety and tolerability are needed.

Topics: Adolescent; Aggression; Antipsychotic Agents; Aripiprazole; Autistic Disorder; Benzodiazepines; Child; Child Development Disorders, Pervasive; Child, Preschool; Clozapine; Dibenzothiazepines; Disorders of Excessive Somnolence; Humans; Obesity; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

Atypical antipsychotics offer superior safety and similar efficacy compared with conventional agents in adults with psychotic disorders. Consequently, atypical antipsychotics have been increasingly used in children and adolescents. Because most information now available on pediatric use comes from case reports and small open-label studies rather than large controlled trials, treatment in pediatric patients is often guided by experience with adults or based on limited evidence in youths. Although the literature contains reports on the use of each agent in this class in children, risperidone has been the focus of the greatest number of reports. However, the atypical antipsychotics are not interchangeable; each has a unique pharmacologic profile and may differ considerably in terms of adverse effects. Evidence on the use of atypical antipsychotics in children and adolescents is summarized in this review.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Tic Disorders

The atypical antipsychotics have a low incidence of extrapyramidal side effects (EPS), have improved tardive dyskinesia profiles, and have a broad range of therapeutic efficacy. These agents offer important therapeutic advantages that extend beyond their initial regulatory approval in several conditions and patient groups. The use of atypical antipsychotics is most relevant in the treatment of mood disorders, where these medications are being used increasingly for acute mood stabilization and in patients who are resistant to other treatments. Similar circumstances and clinical advantages pertain to the use of atypical antipsychotics in the treatment of behavioral disturbances in patients with dementia and in the management of personality disorders-both circumstances where conventional antipsychotics were initially poorly tolerated because of EPS. The low incidence of EPS associated with atypical antipsychotics is highly beneficial in several neuropsychiatric conditions. The extent to which endocrine and metabolic dysregulations associated with atypical antipsychotics will influence antipsychotics' role remains to be determined. As therapeutic opportunities evolve and diversify, atypical antipsychotics, because of favorable adverse-effect profiles, will have enhanced patient tolerability and use in nonpsychiatric conditions.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Child Development Disorders, Pervasive; Clozapine; Dementia; Dibenzothiazepines; Humans; Mood Disorders; Olanzapine; Personality Disorders; Pirenzepine; Quetiapine Fumarate; Risperidone

This article reviews the published clinical experience with atypical neuroleptics in children and adolescents.. A computerized literature search was conducted (MEDLINE, 1974-1998) to retrieve all reports on the use of atypical neuroleptics in children and adolescents. A hand search was performed as well. All relevant clinical data were collated by type of drug.. We found 5 blind placebo-controlled clinical trials (105 patients), 24 open-label clinical trials (387 patients), and 33 case series (115 patients) describing the use of the atypical neuroleptics clozapine, risperidone, olanzapine, sulpiride, tiapride, amisulpride, remoxipride, and clothiapine in children and adolescents. Some of these agents, especially clozapine, risperidone, and olanzapine, were found to be efficacious in the treatment of schizophrenia, bipolar disorders, and pervasive developmental disorders. The role of atypical neuroleptics as augmenters of serotonin reuptake inhibitors in obsessive-compulsive disorder is unclear. Risperidone appears to possess anti-tic properties in patients with Tourette's disorder.. The most convincing evidence of the efficacy of atypical neuroleptics in children and adolescents concerns clozapine in the treatment of schizophrenia. Data on other atypical neuroleptics in other disorders are still sparse, and further research is needed. Some of the atypical neuroleptics may become the first-line treatment for childhood schizophrenia and pervasive developmental disorders.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Child; Child Development Disorders, Pervasive; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Remoxipride; Risperidone; Schizophrenia; Treatment Outcome

Autism spectrum disorder (ASD) is a serious childhood-onset disorder in which social and language development are primarily affected, with associated repetitive behavior and, in some patients, behavioral symptoms including aggression and self-injury. In ASD, risperidone and aripiprazole are the only second-generation antipsychotic drugs that have shown to decrease disruptive behaviors in large-scale, controlled, double-blind studies. However, in some patients, these medications are not effective. Clozapine, a second-generation antipsychotic drug known to be effective in the treatment of aggression associated with schizophrenia, has received little attention in ASD.We conducted a retrospective analysis of the changes in disruptive behaviors for all patients with ASD treated with clozapine from 2002 to 2010. Disruptive behaviors were monitored during the 4 to 6 months before and after the initiation of clozapine. Long-term tolerance (10 months to 7 years) was also assessed. The relationship between disruptive behaviors and period of treatment (before and after clozapine) was studied with a generalized linear marginal model. Clozapine resulted in a significant 2-fold decrease in the number of the days with aggression, a decrease in the number of psychotropic drugs, and a decrease in the dose of the antipsychotic drugs. The long-term tolerance of clozapine (white blood cell count and extrapyramidal effects) was good, with the exception of significant weight gain (14.3 ± 10.9 kg), the occurrence of metabolic syndrome in 1 patient, and tachycardia in another patient.These results suggest that clozapine should be considered for the management of disruptive behaviors in patients with ASD not improved by first-line antipsychotic drugs.

Topics: Adult; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Child Development Disorders, Pervasive; Child, Preschool; Clozapine; Female; Humans; Male; Psychiatric Status Rating Scales; Retrospective Studies

Topics: Administration, Oral; Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Child Development Disorders, Pervasive; Clozapine; Creatine Kinase; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Humans; Injections, Intramuscular; Male; Neuroleptic Malignant Syndrome; Olanzapine; Schizophrenia

There are not many studies on the use of clozapine in patients with intellectual disability (ID). The authors describe a case series of patients treated with clozapine, drawn from a medium secure unit, a low secure assessment and treatment service and a community team in the London region.. A retrospective file-review of patients treated in these three settings during the time period March-June 2002 was performed (n = 24). Information was collected using a semistructured proforma.. Of the 24 patients, 67% had schizophrenia, 17% had schizoaffective disorder and 8% had bipolar disorder. Patients had been unwell for a mean of 6 years and had been tried on a mean of four antipsychotics. The mean maximum dose of clozapine was 488 mg. The outcomes on the clinical global impression (CGI) scale showed 29% very much improved, 42% much improved, 21% minimally improved and 8% no change. 54% of the whole sample and 53% of those from the medium secure unit were discharged to homes in the community. The drug had to be stopped in four patients, of which three were because of neutropaenia.. Clozapine appears to be safe and efficacious in many people with ID. Careful monitoring of side-effects is needed during therapy.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Clozapine; Cognition Disorders; Drug Resistance; Drug Utilization; Epilepsy; Female; Humans; Male; Middle Aged; Personality Disorders; Psychotic Disorders; Retrospective Studies; Schizophrenia; Substance-Related Disorders