Clinical trial NCT00667745: Effectiveness of Lithium Plus Optimized Medication in Treating People With Bipolar Disorder
Official title: Lithium Use for Bipolar Disorder (LiTMUS): A Randomized Controlled Effectiveness Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Keywords: Lithium
Symptoms
Medication Changes
Lead sponsor: National Institute of Mental Health (NIMH)
Sponsor class: NIH
First posted: 2008-04-28
Enrollment: 283
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Change in Bipolar Illness Severity as Measured by Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Score
timeFrame: Relevant time points: baseline and week 24
measure: Number of Necessary Medication Adjustments
timeFrame: Measured over 6 months
Secondary outcomes:
measure: Depression Symptoms as Measured Self Report Montgomery Asberg Depression Rating Scale (MADRS)
timeFrame: Measured over 6 months
measure: Mania Symptoms as Measured by the Young Mania Rating Scale (YMRS)
timeFrame: Measured over 6 months
measure: Suicidality as Measured by the Modified Scale for Suicidal Ideation (MSSI)
timeFrame: Measured over 6 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
Study officials:
References:
citation: Ostacher MJ, Nierenberg AA, Rabideau D, Reilly-Harrington NA, Sylvia LG, Gold AK, Shesler LW, Ketter TA, Bowden CL, Calabrese JR, Friedman ES, Iosifescu DV, Thase ME, Leon AC, Trivedi MH. A clinical measure of suicidal ideation, suicidal behavior, and associated symptoms in bipolar disorder: Psychometric properties of the Concise Health Risk Tracking Self-Report (CHRT-SR). J Psychiatr Res. 2015 Dec;71:126-33. doi: 10.1016/j.jpsychires.2015.10.004. Epub 2015 Oct 9.
citation: Reilly-Harrington NA, Sylvia LG, Leon AC, Shesler LW, Ketter TA, Bowden CL, Calabrese JR, Friedman ES, Ostacher MJ, Iosifescu DV, Rabideau DJ, Thase ME, Nierenberg AA. The Medication Recommendation Tracking Form: a novel tool for tracking changes in prescribed medication, clinical decision making, and use in comparative effectiveness research. J Psychiatr Res. 2013 Nov;47(11):1686-93. doi: 10.1016/j.jpsychires.2013.07.009. Epub 2013 Jul 30.
citation: Beech RD, Leffert JJ, Lin A, Sylvia LG, Umlauf S, Mane S, Zhao H, Bowden C, Calabrese JR, Friedman ES, Ketter TA, Iosifescu DV, Reilly-Harrington NA, Ostacher M, Thase ME, Nierenberg A. Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (LiTMUS). Pharmacogenomics J. 2014 Apr;14(2):182-91. doi: 10.1038/tpj.2013.16. Epub 2013 May 14.
citation: Nierenberg AA, Friedman ES, Bowden CL, Sylvia LG, Thase ME, Ketter T, Ostacher MJ, Leon AC, Reilly-Harrington N, Iosifescu DV, Pencina M, Severe JB, Calabrese JR. Lithium treatment moderate-dose use study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium. Am J Psychiatry. 2013 Jan;170(1):102-10. doi: 10.1176/appi.ajp.2012.12060751.
citation: Sylvia LG, Reilly-Harrington NA, Leon AC, Kansky CI, Ketter TA, Calabrese JR, Thase ME, Bowden CL, Friedman ES, Ostacher MJ, Iosifescu DV, Severe J, Keyes M, Nierenberg AA. Methods to limit attrition in longitudinal comparative effectiveness trials: lessons from the Lithium Treatment - Moderate dose Use Study (LiTMUS) for bipolar disorder. Clin Trials. 2012 Feb;9(1):94-101. doi: 10.1177/1740774511427324. Epub 2011 Nov 10.