Official Title: “Lithium Use for Bipolar Disorder (LiTMUS): A Randomized Controlled Effectiveness Trial”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind (Outcomes Assessor), Parallel Assignment

Study Primary Completion Date: September 2010

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 will last 6 months. All participants will first undergo initial assessments that will include an interview and questionnaires to confirm a diagnosis of bipolar disorder, vital sign measurements, an electrocardiogram (ECG), a blood draw, and if female, a pregnancy test. Eligible participants will then be assigned randomly to receive either optimized medication plus lithium or optimized medication without lithium.

Participants in both groups will undergo 6 months of monitored treatment with their medication regimens, as prescribed by their study doctor. Participants will attend study visits every 2 weeks for the first 8 weeks and then once a month for 4 more months. These visits will last between 45 and 60 minutes and will include medication adjustments and questions about symptoms, side effects, and quality of life.

Intervention(s) in this Clinical Trial

• Drug: Lithium Carbonate
  • Lithium will be started at 300 mg and then increased to 600 mg after 3 days. Lithium doses will be maintained at 600 mg per day for 8 weeks, but may be adjusted after that time as needed up to a serum level of 1.2 mEq/L.
• Drug: Optimized Treatment (OPT)
  • The foundation of OPT is to maintain treatment that will typically include at least one FDA-approved mood stabilizer other than lithium (e.g., divalproex, carbamazepine, risperidone, quetiapine, olanzapine, aripiprazole, ziprasidone) and to follow the recommendations summarized in the evidence-based stages of the Texas Implementation of Medication Algorithm (TIMA) revised guidelines.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Participants will receive lithium plus optimized medication treatment, as needed.
• Active Comparator: 2
  • Participants will only receive optimized medication treatment, as needed; lithium will not be used.

Primary Measures

• Overall improvement in bipolar illness severity as measured by the CGI-BP-S
  • Time Frame: Measured over 6 months
    Safety Issue?: No
• Number of necessary medication adjustments
  • Time Frame: Measured over 6 months
    Safety Issue?: No

Secondary Measures

• Symptoms as measured by QIDS-SR and YMRS
  • Time Frame: Measured over 6 months
    Safety Issue?: No
• Quality of life as measured by Q-LES-Q
  • Time Frame: Measured over 6 months
    Safety Issue?: No
• Suicidality
  • Time Frame: Measured over 6 months
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00667745

Study ID Number: N01 MH80001-01

ClinicalTrials.gov Identifier: NCT00667745

Health Authority: United States: Federal Government