olanzapine 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

Atypical antipsychotics have been shown to improve disruptive and repetitive behaviors in pervasive developmental disorders (PDDs), but they require assessment of potential side effects. This is the first placebo-controlled trial of olanzapine in the treatment of children and adolescents with PDD. Eleven patients with a diagnosis of either autism, Asperger's syndrome, or PDD not otherwise specified (PDD-NOS) and aged 6-14 years were randomized into an 8-week double-blind, placebo-controlled, parallel treatment study with olanzapine. There was a significant linear trend x group interaction on the Clinical Global Impressions- Improvement (CGI-I) and 50% on olanzapine versus 20% on placebo were responders. Olanzapine was associated with significant weight gain (7.5 +/- 4.8 lbs vs. 1.5 +/- 1.5 lbs on placebo). Olanzapine may be a promising treatment for improving global functioning of PDDs, but the risk of significant weight gain remains a concern. Additional studies are needed to determine the efficacy and safety of olanzapine in the treatment of children with PDD.

Topics: Adolescent; Antipsychotic Agents; Asperger Syndrome; Autistic Disorder; Benzodiazepines; Child; Child Development Disorders, Pervasive; Double-Blind Method; Female; Humans; Male; Olanzapine; Pilot Projects; Treatment Outcome; Weight Gain

Conventional neuroleptics ameliorate symptoms in children with autistic disorder; however, they are known to cause dyskinesias. Atypical neuroleptics, including olanzapine, may have less risk for dyskinesia, but their efficacy in autistic disorder is not established. This study was designed to investigate the safety and effectiveness of open-label olanzapine as a treatment for children with autistic disorder by using haloperidol as a standard comparator treatment.. In a parallel groups design, 12 children with DSM-IV autistic disorder (mean age 7.8+/-2.1 years) were randomized to 6 weeks of open treatment with olanzapine or haloperidol. Mean final dosages were 7.9+/-2.5 mg/day for olanzapine and 1.4+/-0.7 mg/day for haloperidol. Outcome measures included the Clinical Global Impressions (CGI) and the Children's Psychiatric Rating Scale (CPRS).. Both groups had symptom reduction. Five of six in the olanzapine group and three of six in the haloperidol group were rated as responders according to the CGI Improvement item. Subjects showed improvement on the CPRS Autism Factor (F1,9 = 24.4, p = .0008). Side effects included drowsiness and weight gain.. The findings suggest that olanzapine is a promising treatment for children with autistic disorder. Further placebo-controlled and long-term studies of olanzapine in autistic disorder are required.

Topics: Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Child; Child Development Disorders, Pervasive; Child, Preschool; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; Male; Olanzapine; Pilot Projects; Pirenzepine; Treatment Outcome

This pilot study examined the efficacy and tolerability of olanzapine in the treatment of children, adolescents, and adults with pervasive developmental disorders (PDDs). Eight patients with principal diagnoses (DSM-IV) of autistic disorder (N = 5) or PDD not otherwise specified (N = 3) were given olanzapine in an open-label, prospective fashion for 12 weeks. Clinical ratings were obtained at baseline and at the end of weeks (EOWs) 4, 8, and 12. Seven of eight patients completed the 12-week trial, and six of the completers were deemed clinical responders as measured by ratings at the EOW 12 of "much improved" or "very much improved" on the global improvement item of the Clinical Global Impression Scale. Significant improvements in overall symptoms of autism, motor restlessness or hyperactivity, social relatedness, affectual reactions, sensory responses, language usage, self-injurious behavior, aggression, irritability or anger, anxiety, and depression were observed. Significant changes in repetitive behaviors were not observed for the group. The EOW 12 mean +/- SD daily dose of olanzapine was 7.8 +/- 4.7 mg/day. The drug was well tolerated with the most significant adverse effects noted to be increased appetite and weight gain in six patients and sedation in three. With respect to weight gain, the mean +/- SD weight for the group increased from 137.50 +/- 55.81 pounds (62.50 +/- 25.37 kilograms) at baseline to 155.94 +/- 55.13 pounds (70.88 +/- 25.06 kilograms) at EOW 12. No evidence of extrapyramidal side effects or liver function abnormalities was seen. These preliminary results suggest that olanzapine may be an effective and well tolerated drug in targeting core and related symptoms of PDDs in children, adolescents, and adults. Further studies, particularly those that are placebo-controlled and double-blinded, are indicated to better define the clinical use of olanzapine in these patient populations.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Child; Child Development Disorders, Pervasive; Child, Preschool; Female; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Pilot Projects; Pirenzepine; Psychomotor Performance; Treatment Outcome

The Academy of Medicine Singapore (AMS) and the Ministry of Health (MOH) publish clinical practice guidelines to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the AMS-MOH clinical practice guidelines on Autism Spectrum Disorders (ASD), for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh. gov.sg/mohcorp/publications.aspx?id=24048). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Topics: Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Benzodiazepines; Central Nervous System Stimulants; Child Development Disorders, Pervasive; Child, Preschool; Dopamine Antagonists; Humans; Mass Screening; Methylphenidate; Olanzapine; Prognosis; Propylamines; Risperidone; Selective Serotonin Reuptake Inhibitors; Singapore

Topics: Adolescent; Anorexia Nervosa; Antipsychotic Agents; Benzodiazepines; Child; Child Development Disorders, Pervasive; Feeding Behavior; Female; Humans; Olanzapine; Weight Gain

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

Controlling the symptoms that are characteristic of patients with pervasive developmental disorders is often challenging. We report on the safety and efficacy of olanzapine in the treatment of 7 patients with pervasive developmental disorders. The patients were all male and ranged in age from 8 to 52 years. They received olanzapine doses of 5-10 mg/d along with their various other drug regimens. Patients were monitored and evaluated for a mean duration of 17.7 (range 12-26) months while on olanzapine therapy. Very few side effects were observed during treatment. All patients showed clinically significant improvement on the Clinical Global Impressions scale, as well as an improved score as measured by the Global Assessment of Functioning scale. Our observations support the use of long-term olanzapine therapy for symptom control in patients with pervasive developmental disorders.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Child; Child Development Disorders, Pervasive; Humans; Male; Middle Aged; Olanzapine; Treatment Outcome

The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a diagnosis of either autistic disorder or pervasive developmental disorder not otherwise specified. Psychometric measures included the Clinical Global Impression of Severity/Improvement, the Aberrant Behavior Checklist, and the TARGET (a checklist of five target symptoms). Communication skills were assessed during behavioral analysis of a playroom session. Safety measures included clinical chemistry variables, electrocardiography, the SimpsonAngus Neurological Rating Scale, the Barnes Akathisia Scale, and vital signs. Twenty-three children completed the study and showed significant improvement on three subscales of the Aberrant Behavior Checklist (Irritability, Hyperactivity, and Excessive Speech) and the TARGET. The final mean dose was 10.7 mg/day. Several aspects of communication were also improved after olanzapine treatment. However, only three children were considered responders in terms of the Clinical Global Impression of Severity/Improvement scores. The most important adverse events were weight gain, increased appetite, and loss of strength. Three children showed extrapyramidal symptoms that disappeared after the dose was lowered. Thus, while olanzapine was a relatively safe medication in children, its clinical relevance in children with pervasive developmental disorder may be limited.

Topics: Adolescent; Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Child; Child Development Disorders, Pervasive; Communication Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychometrics; Severity of Illness Index

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Child; Child Development Disorders, Pervasive; Child, Preschool; Humans; Olanzapine; Pilot Projects; Pirenzepine; Weight Gain

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Child; Child Development Disorders, Pervasive; Humans; Olanzapine; Pilot Projects; Pirenzepine

Topics: Antipsychotic Agents; Benzodiazepines; Child; Child Development Disorders, Pervasive; Humans; Male; Olanzapine; Pirenzepine; Social Behavior Disorders; Treatment Outcome