Effectiveness of Lithium Plus Optimized Medication in Treating People With Bipolar Disorder

Bipolar illness, a brain disorder that causes dramatic changes in a person's mood and energy,
affects about 2.6% of adults in the United States. Bipolar disorder is characterized by
cyclical periods of extreme highs and lows, known as episodes of mania and depression. A
person undergoing an episode of mania often experiences euphoric moods, increased energy, and
aggressive behaviors, while a person in a depressed state often experiences low moods, lack
of energy, and feelings of sadness. Lithium is a widely used mood stabilizing medication that
has been shown to reduce the occurrence and intensity of manic episodes and may lessen
depressive episodes as well. Including lithium as a part of a personalized medication
treatment approach may be the most effective means of improving symptoms of bipolar disorder.
This study will evaluate whether lithium included as part of optimized medication treatment
improves overall level of illness, symptoms of mania and depression, and quality of life in
people with bipolar disorder.

Participation in this study lasted for 6 months. All participants had an initial assessment
that included an interview and questionnaires to confirm a diagnosis of bipolar disorder,
vital sign measurements, a blood draw, and if female, pregnancy. Eligible participants were
then assigned randomly to receive either optimized medication plus lithium or optimized
medication without lithium. Participants in both groups received 6 months of monitored
treatment with their medication regimens, as prescribed by their study doctor. Participants
attended study visits every 2 weeks for the first 8 weeks and then once a month for 4 more
months. These visits lasted between 45 and 60 minutes and included medication adjustments and
questions about symptoms, side effects, and quality of life.

We would like to acknowledge that medication was kindly donated by Ortho-McNeil Janssen
Scientific Affairs, LLC.

Inclusion Criteria:

- Meets DSM-IV Criteria for bipolar disorder (type I or II)

- Currently symptomatic, as defined as a Clinical Global Impressions Scale-Bipolar
Version, Overall Severity Index (CGI-BP-S) of greater than or equal to 3

- If taking or has taken lithium, must be off lithium for at least 30 days before study
entry

- If a woman of child bearing potential, agrees to inform their doctor at the earliest
possible time of their plans to conceive, to use adequate contraception (e.g. oral
contraceptives, intrauterine device, barrier methods, total abstinence from
intercourse), and to acknowledge the risks of lithium to the fetus and infant (Depo
Provera is acceptable if it is started 3 months before study entry)

Exclusion Criteria:

- Renal impairment (serum creatinine greater than 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)

- History of lithium toxicity that was not caused by mismanagement or overdose

- Other contraindication to lithium (e.g., hypersensitivity to lithium or any component
of the formulation, severe cardiovascular or renal disease, severe debilitation,
dehydration, sodium depletion, pregnancy)

- Currently in crisis such that inpatient hospitalization or other crisis - Participated
in a clinical trial of an investigational drug within the 1 months before study entry

- Pregnant or breastfeeding