Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)

All subjects meeting study inclusion criteria will be started on lithium. Those that fail
lithium will be crossed over to valproate (VPA). Those that also fail VPA will be again
crossed-over to a standardized treatment as usual (TAU) arm. Subjects who are eligible for
the study must be at least 18 years of age and have been diagnosed or are thought to have
bipolar I disorder with at least one episode of mood instability in the last 12 months. They
must also be eligible to take lithium and, if female and of child bearing age, agree to use
adequate birth control methods and to inform their doctor of their plans to become pregnant.

Inclusion Criteria:

- Any phase of bipolar I disorder including, depressive, manic, hypomanic, mixed, or
baseline/euthymic/not symptomatic;

- Lithium naïve patients and inadequately past lithium treated patients will be
required to have had at least one affective episode in the last 12 months meeting
DSM-IV criteria. Current lithium treated patients (CLTPs) will be stable on lithium
monotherapy and will be exempted from this criterion if they have had no mood
episodes meeting DSM-IV criteria in the last 6 months;

- Both outpatients and inpatients will be permitted to enroll into this study;

- Able to give informed consent, in the judgment of the investigator;

- Age greater than or equal to 18 years;

- Women of child bearing potential agree to inform their doctor at the earliest
possible time of their plans to conceive, and to use adequate contraception (e.g.
oral contraceptives, intrauterine device, barrier methods, or total abstinence from
intercourse), and to understand the risks of lithium to the fetus and infant. Depo
Provera is acceptable if it is started 3 months prior to enrollment.

Exclusion Criteria:

- Unwilling or unable to comply with study requirements;

- Renal impairment (serum creatinine >1.5 mg/dL);

- Thyroid stimulating hormone (TSH) over >20% above the upper normal limit
(participants maintained on thyroid medication must be euthyroid for at least 3
months before Visit 1;

- Other contraindication to lithium;

- Currently in crisis such that inpatient hospitalization or other crisis management
should take priority;

- Subjects with alcohol/drug dependence who meet criteria for physical dependence
requiring acute detoxification;

- Pregnant or breastfeeding;

- Women of child-bearing potential who aren't able to agree to the requirements
specified above;

- Those who have participated in a clinical trial of an investigational drug within the
past 1 month;

- Inability to agree to comply with the visit schedule or study procedures;

- History of lithium toxicity, not due to mismanagement or overdose that required
treatment;

- Current unstable medical condition.