Treatment of Mania Symptoms With Drug Therapy

Mania is a serious condition characterized by extreme excitement, mental and physical
hyperactivity, insomnia, and disconnected thoughts. Symptoms of mania are common in patients
with schizophrenia or bipolar disorder. When associated with these conditions, mania reaches
psychotic proportions and often includes hallucinations, paranoia, and feelings of
omnipotence. Such symptoms may put individuals with mania and those around them at risk for
physical harm. Drug therapies that can safely and effectively treat symptoms of mania are
needed. This study will compare three drug combinations in their ability to treat symptoms of
mania in people with schizophrenia or bipolar I disorder.

This study will comprise a 12-week acute phase and a 14-week continuation phase. While the
acute phase is the primary component of this study, the continuation phase will provide
extended data on the characteristics and course of responders to the initial treatment
combinations. Results from the continuation phase will be reported elsewhere. In the acute
phase, participants will be randomly assigned to receive one of three treatments:
divalproex-extended release (DV-ER) and lithium, DV-ER and quetiapine, or DV-ER and placebo.
Participants will receive their intervention for 12 weeks. Participants will have weekly
study visits for the first 4 weeks of the acute phase; biweekly study visits will occur for
the following 8 weeks. After the acute phase, participants who have not responded to their
drug regimen will complete their participation in the study.

Participants whose symptoms of mania have decreased will be offered enrollment in the 14-week
continuation phase, during which time participants will continue the drug regimen they began
in the acute phase. Participants will have biweekly study visits in the continuation phase.
During each study visit in both phases, participants will be interviewed about their mania
symptoms. Mania, depression, quality of life, and overall functioning scales will assess
participants at study entry, at the end of the acute phase, and at the end of the
continuation phase. Participants over 50 years of age will have an electrocardiogram (EKG) at
study entry to determine cardiac function.

Inclusion Criteria:

- Diagnosis of bipolar I disorder or schizophrenia

- Experiencing symptoms of mania at study entry

- Able to speak and understand English

- Willing and able to comply with all study requirements

Exclusion Criteria:

- History of partial response or nonresponse to any of the drugs or drug combinations
given in this study

- History of intolerance to DVP, DVP-ER, lithium, or quetiapine

- Disorders that would contraindicate the use of DV, DV-ER, lithium, or quetiapine

- Use of antidepressants within 1 month prior to study entry

- Use of fluoxetine within 3 months prior to study entry

- Impaired cardiac function, as evidenced by abnormal EKG in participants 50 or over

- Unstable medical illness within 2 months prior to study entry

- At risk for suicide

- Substance abuse or dependence within 1 month prior to study entry

- Pregnancy, breastfeeding, or plans to become pregnant during the study