The purpose of this study is to evaluate the safety and effectiveness of clozapine as a
treatment for the manic phase of bipolar disorder.
A significant proportion of manic patients either do not respond adequately to conventional
treatment or cannot tolerate the adverse effects associated with therapeutic doses of these
agents. Clozapine may be a safe and effective treatment for mania. However, the efficacy of
clozapine as an alternative therapy in treatment-resistant bipolar disorder mania has not
been extensively researched.
The study will be conducted in three phases. Phase 1 is a screening phase that will take
place for 2 to 7 days. Participants will undergo a baseline positron emission tomography
(PET) scan of the brain at the end of this period. In Phase 2, participants will be randomly
assigned to receive either clozapine or placebo (an inactive pill) for 3 weeks. They may also
receive lorazepam for the first 10 days of Phase 2. After 3 weeks, patients treated with
clozapine will undergo a second PET scan. During Phase 3, participants who received placebo
and did not improve will be offered clozapine for 3 weeks. Those who received clozapine and
did not improve will receive other treatment for 3 weeks. At the end of Phase 3, participants
who were treated with clozapine will have another PET scan.