Lithium Use for Bipolar Disorder (LiTMUS): A Randomized Controlled Effectiveness Trial
Overview
- Phase
- Phase 4
- Intervention
- Lithium Carbonate
- Conditions
- Bipolar Disorder
- Sponsor
- National Institute of Mental Health (NIMH)
- Enrollment
- 283
- Locations
- 6
- Primary Endpoint
- Overall Change in Bipolar Illness Severity as Measured by Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Score
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This study evaluated whether lithium included as part of optimized medication treatment improved overall level of illness, symptoms of mania and depression, and quality of life in people with bipolar disorder.
Detailed Description
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
1
Participants received lithium plus optimized medication treatment, as needed.
Intervention: Lithium Carbonate
1
Participants received lithium plus optimized medication treatment, as needed.
Intervention: Optimized Treatment (OPT)
2
Participants only received optimized medication treatment, as needed; lithium was not be used.
Intervention: Optimized Treatment (OPT)
Outcomes
Primary Outcomes
Overall Change in Bipolar Illness Severity as Measured by Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Score
Time Frame: Relevant time points: baseline and week 24
Scale: Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Construct: This scale holistically measures severity of a participant's depression, mania, and overall illness. Range: 0- not assessed, 1-normal (not at all ill), 2- borderline mentally ill, 3- mildly ill, 4- moderately ill, 5- markedly ill, 6- severely ill, 7- among the most extremely ill patients.
Number of Necessary Medication Adjustments
Time Frame: Measured over 6 months
Metric Definition (Necessary Clinical Adjustments (NCA)): Medication adjustments to reduce symptoms, optimize treatment response and functioning, or to address intolerable side effects. This was determined with the Medication Recommendation Tracking Form (MRTF), a novel method for capturing physician prescribing behavior and clinical decision making. Range: whole numbers Relevant time points: Weeks 2, 4, 6, 8, 12, 16, 20, and 24.
Secondary Outcomes
- Suicidality as Measured by the Modified Scale for Suicidal Ideation (MSSI)(Measured over 6 months)
- Depression Symptoms as Measured Self Report Montgomery Asberg Depression Rating Scale (MADRS)(Measured over 6 months)
- Mania Symptoms as Measured by the Young Mania Rating Scale (YMRS)(Measured over 6 months)