Clozapine for Treatment-Resistant Mania

Summary

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.

Timeline

Start

2002-01

Primary completion

—

Completion

2005-10

Publications

• Background Ahlfors UG, Baastrup PC, Dencker SJ, Elgen K, Lingjaerde O, Pedersen V, Schou M, Aaskoven O. Flupenthixol decanoate in recurrent manic-depressive illness. A comparison with lithium. Acta Psychiatr Scand. 1981 Sep;64(3):226-37. doi: 10.1111/j.1600-0447.1981.tb00778.x.
• Background Altshuler LL, Bartzokis G, Grieder T, Curran J, Mintz J. Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch Gen Psychiatry. 1998 Jul;55(7):663-4. doi: 10.1001/archpsyc.55.7.663. No abstract available.
• Background American Psychiatric Association Practice Guidelines. Practice guideline for the treatment of patients with borderline personality disorder. American Psychiatric Association. Am J Psychiatry. 2001 Oct;158(10 Suppl):1-52. No abstract available.

Drugs

Indications