Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
Condition: Childhood Schizophrenia; Psychotic Disorder; Schizophrenia
MeSH terms: Schizophrenia; Mental Disorders; Psychotic Disorders; Schizophrenia, Childhood
Intervention: Olanzapine; Clozapine
Intervention description: tablet; 5-20mg/day; 8 weeks; tablet; 12.5-900mg/day; 8 weeks
Intervention MeSH terms: Olanzapine; Clozapine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 25.0
Sex: All
Minimum age: 7 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Clozapine; Olanzapine; Drug Response; Safety; Childhood Onset Schizophrenia; Schizoaffective Disorder; Multidimensionally Impaired Syndrome; Phenomenology; Biochemical Correlates; Brain Imaging; Schizophrenia; Childhood Schizophrenia; Psychosis

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.