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Clozapine vs. Placebo in Treatment-Refractory Bipolar Disorder in Children and Adolescents

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00036582
Recruitment Status : Completed
First Posted : May 13, 2002
Last Update Posted : March 4, 2008
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:
The purpose of this study is to determine the safety and effectiveness of clozapine in children and adolescents with treatment resistant bipolar disorder. This study will also explore how the brain functions in early-onset bipolar disorder.

Condition or disease Intervention/treatment Phase
Bipolar Disorder Drug: Clozapine Phase 3

Detailed Description:
Bipolar disorder (BPD) in children and adolescents is a serious illness that carries a high risk for chronicity, impairing comorbidities, and completed suicide. Treatment options are often limited by inefficacy or intolerable side effects. Open trials in adult bipolar subjects and several case series in children and adolescents provide preliminary evidence that clozapine, an atypical antipsychotic, may be effective in treatment-resistant bipolar disorder. The first specific aim of this study is to test the efficacy and safety of clozapine compared to placebo in a double-blind study of children and adolescents with treatment refractory BPD. Other specific aims involve exploring the pathophysiology of early-onset BPD by 1) testing the hypotheses that, compared to controls, children with BPD have increased psychophysiological reactivity to emotional stimuli and decreased prepulse inhibition; 2) obtaining samples of genetic material from affected probands and their parents for later analysis; and 3) identifying anatomic changes in the brains of children with BPD using structural MRI.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 116 participants
Primary Purpose: Treatment
Official Title: Clozapine vs Placebo In Treatment-Refractory Bipolar Disorder In Children And Adolescents
Study Start Date : May 2002
Study Completion Date : February 2004

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bipolar Disorder
Drug Information available for: Clozapine

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

INCLUSION CRITERIA (All 5 must be met): Children with BPD

Ages 8-17

Currently meets criteria for bipolar disorder, manic or mixed, as determined by the K-SADS diagnostic interview.

Treatment-resistant, defined as a history of unsuccessful trials of lithium (documented level of greater than 0.8 mEq/L), valproic acid (documented level of greater than 50 ug/ml), carbamazepine (documented level greater than or equal to 6 ug/ml), a neuroleptic as well as a combination of two of these agents. Each trial must have been at least 6 weeks long. A trial will be considered unsuccessful if the medication was discontinued because of intolerable side-effects.

The child should be in treatment with a community psychiatrist to whom they will return upon completion of the study.

Current CGAS score less than 50


Full scale IQ less than 80

Meets criteria for substance use disorder in the three months prior to randomization

Currently pregnant, lactating, or sexually active without using a barrier method of contraception

Previous treatment with clozapine

History of seizures

History of leukopenia or agranulocytosis

Presence of an unstable medical illness


Control subjects will be age- and sex- matched to the BPD subjects. They will have normal physical and neurological examinations, and an identified primary care physician. Both control subjects and their first-degree relatives must be free of current or past psychopathology.


I.Q less than 80; ongoing medical illness; neurologic disorder (including seizures); pregnancy; meeting past or present criteria for any diagnosis on the K-SADS-PL; meeting criterion A of post-traumatic stress disorder (exposure to a traumatic event).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00036582

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United States, Maryland
National Institute of Mental Health (NIMH)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Layout table for additonal information Identifier: NCT00036582    
Other Study ID Numbers: 020198
First Posted: May 13, 2002    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: February 2004
Keywords provided by National Institutes of Health Clinical Center (CC):
Structural MRI
Bipolar Disorder
Children and Adolescents
Healthy Volunteer
Normal Control
Additional relevant MeSH terms:
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Bipolar Disorder
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
GABA Antagonists
GABA Agents