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
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Olanzapine; Clozapine
Intervention type(s): Drug; Drug
Intervention description(s): tablet; 5-20mg/day; 8 weeks; tablet; 12.5-900mg/day; 8 weeks
Other intervention name(s): "Zyprexa"; "Clozaril"
Intervention MeSH terms: Olanzapine; Clozapine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Clozapine; Olanzapine; Drug Response; Safety; Childhood Onset Schizophrenia; Schizoaffective Disorder; Multidimensionally Impaired Syndrome; Phenomenology; Biochemical Correlates; Brain Imaging; Schizophrenia; Childhood Schizophrenia; Psychosis