Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders

Phase 4

Completed

Conditions: Childhood Schizophrenia
Schizophrenia
Psychotic Disorder

Interventions: Drug: Olanzapine
Drug: Clozapine

Registration Number: NCT00001656

Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary: The purpose of this study is to compare the effectiveness and side effects of the drugs clozapine and olanzapine in children and adolescents with schizophrenia and psychoses.

Childhood psychosis is a serious disorder that may have devastating consequences. Effective treatments for the condition are under continual investigation. This study will examine the causes of and offer treatment for childhood psychosis.

Participants in this study will undergo psychological tests, blood and urine tests, electroencephalogram (EEG), electrocardiogram (EKG), and magnetic resonance imaging (MRI) scans of the brain for the first 1 to 2 weeks of the study while taking their regular medications. Participants will then be tapered off their medications over 1 to 3 weeks and will continue to stay off medications for an additional 2 days to 3 weeks. During this time, participants will undergo psychiatric, neurological, and cardiac examinations as well as blood tests. After this period without medications, participants will be randomly assigned to receive either clozapine or olanzapine for 8 weeks. An EEG will be performed prior to treatment and after 6 weeks of study medication. Participants who respond well to the study drugs may continue to receive them through their own physician. Participants who do not respond to either clozapine or olanzapine or cannot tolerate their side effects will be treated individually with other drugs until optimum treatment is identified. Regular telephone updates and in person visits to NIH for repeat testing and MRIs will be conducted.

Detailed Description: The purpose of this protocol is to compare efficacy of clozapine and olanzapine in children and adolescents with schizophrenia and psychoses, as well as to learn about side effects of these medication in pediatric population. The underlying hypothesis is that clozapine has superior efficacy over olanzapine.

Children and adolescents, ages 7 to 18 years, meeting DSM-IV criteria for schizophrenia, schizoaffective disorder and psychotic disorder not otherwise specified, with onset of psychosis before their 13th birthday, who have not responded to at least two prior trials with typical or a typical neuroleptics, will be eligible to participate in a double-blind, parallel group, trial of olanzapine-clozapine.

This study will be done in conjunction with the Screening protocol, which will include characterization by clinical phenomenology, eye tracking, MRI brain imaging, plasma biochemistry, and chromosomal analysis.

This study will consist of the following phases 1) Tapering of psychotropic medications (1-4 weeks, depending upon type and dosage). 2) Observation for up to 2 weeks drug free, in order to establish a baseline prior to starting medication trial. 3) An 8 week double-blind trial of either clozapine or olanzapine. Efficacy and tolerability of clozapine and olanzapine will be compared using specified criteria. 4) If desired improvement not achieved or trial is interrupted, an 8 week open trial of the second medication and 5) Discharge following medication optimization for up to 4 weeks, or as clinically appropriate. This protocol also includes a follow-up every 2 to 3 years for a period of 10 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Olanzapine	Olanzapine	-
Clozapine	Clozapine	-

Primary Outcome Measures

Name	Time	Method
Change in the Scale for the Assessment of Negative Symptoms	8 week double-blind study period; baseline and 8 weeks	Measures change in affective flattening or blunting, alogia, avolition/apathy, anhedonia/asociality, attention; minimum score = 0; maximum score = 125; lower values are considered a better outcome
Change in the Bunney-Hamburg Rating Scale for Anxiety	8 week double-blind study period; baseline and 8 weeks	Measures change in the severity of anxiety; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.
Change in the Clinical Global Impression Severity of Symptoms Scale	8 week double-blind study period; baseline and 8 weeks	Measures change in the severity of symptoms; Minimum score = 1; maximum score = 7; lower score is considered a better outcome.
Change in Bunney-Hamburg Rating Scale for Depression	8 week double-blind study period; baseline and 8 weeks	Measures change in severity of depression; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.
Change in the Scale for the Assessment of Positive Symptoms	8 week double-blind study period; baseline and 8 weeks	Measures change in hallucinations, delusions, bizarre behavior, and thought organization. Minimum score = 0; maximum score = 170; lower score is considered a better outcome.
Change in the Bunney-Hamburg Rating Scale for Psychosis	8 week double-blind study period; baseline and 8 weeks	Measures change in psychosis severity; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.
Change in Bunney-Hamburg Rating Scale for Mania	8 week double-blind study period; baseline and 8 weeks	Measures change in the severity of mania; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.
Change in the Brief Psychiatric Rating Scale-24	8 week double-blind study period; baseline and 8 weeks	A 24-item scale measuring change in interpersonal behaviors, mood, psychosis, anxiety, speech, sleep, orientation and physical activity. Lowest score = 24; highest score = 168; lower score is considered a better outcome.