Phase 4 N=25 Randomized Triple-blind Treatment

Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders

Childhood Schizophrenia · Psychotic Disorder · Schizophrenia

Bottom Line

View on ClinicalTrials.gov: NCT00001656 ↗

Enrolled (actual)

Serious AEs

12.0%

Results posted

Apr 2011

Primary outcome: Primary: Change in the Scale for the Assessment of Negative Symptoms — -14; -25 Scores on a scale — p=.04

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Olanzapine (Drug); Clozapine (Drug)
Age: Pediatric, Adult · 7+ yrs
Sex: All
Sponsor: National Institute of Mental Health (NIMH)
Primary completion: Jun 2008

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in the Scale for the Assessment of Negative Symptoms	-14; -25	.04 sig
PRIMARY Change in the Clinical Global Impression Severity of Symptoms Scale	-0.6; -1.6	0.21
PRIMARY Change in the Brief Psychiatric Rating Scale-24	-13; -19	0.35
PRIMARY Change in the Scale for the Assessment of Positive Symptoms	-7; -21	0.19
PRIMARY Change in the Bunney-Hamburg Rating Scale for Psychosis	-3.1; -4	0.59
PRIMARY Change in Bunney-Hamburg Rating Scale for Depression	0.4; 0.2	0.72
PRIMARY Change in Bunney-Hamburg Rating Scale for Mania	-0.4; -0.8	0.27
PRIMARY Change in the Bunney-Hamburg Rating Scale for Anxiety	-0.5; 0.6	0.11

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.

Eligibility Criteria

INCLUSION CRITERIA:

Males and females, age 7 to 18 years

Onset of psychotic symptoms before 13th birthday and a DSM-IV diagnosis of either schizophrenia, schizoaffective disorder, MDI syndrome, or psychosis NOS (not otherwise specified).

Current significant impairment due to the illness (current psychotic symptoms, decline of functioning academically and socially, significant discomfort due to psychotic symptoms).

Failure of two prior trials with antipsychotic medications (either typical or atypical) used at adequate doses (greater than or equal to 100 mg/day in chlorpromazine equivalents) and for adequate duration (at least 4 weeks, unless terminated due to intolerable side effects). Failure is defined as either insufficient response with persistence of symptoms significantly impairing child's functioning, according to child's and parental reports and medical and school records, or intolerable side effects to drugs other than clozapine and olanzapine.

Subjects may be included if their previous trial(s) of olanzapine failed to reach the dose of 20. mg/day or a duration of fewer than four weeks.

Subjects may be included if their previous trial(s) of clozapine failed to reach the dose of 200. mg/day or a duration of fewer than six weeks.

Comorbid psychiatric disorders in the past 12 months are permitted as long as not clinically significant.

EXCLUSION CRITERIA

Prepsychotic full-scale IQ less than 70.

Unstable major neurological or medical conditions.

Current pregnancy or plan to become pregnant during the first three months (the duration of the study) in woman of childbearing age; breast-feeding in woman with infants.

DSM-IV substance abuse or dependence in the past 6 months.

True non-responders to either olanzapine or clozapine. True non-response is defined as: a) intolerance to either of the medications preventing an adequate trial, or b) only minimal (less than 20%) benefit with the adequate trial of either of the medications. Adequate trial constitutes at least 8 weeks of the medication with the dose of 20 mg on olanzapine or 200 mg of clozapine.

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Data sourced from ClinicalTrials.gov (NCT00001656). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.