Effectiveness of Lithium Plus Optimized Medication in Treating People With Bipolar Disorder - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00667745

Purpose

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.

Condition	Intervention	Phase
Bipolar Disorder	Drug: Lithium Carbonate Drug: Optimized Treatment (OPT)	Phase IV

MedlinePlus related topics: Bipolar Disorder

Drug Information available for: Risperidone Quetiapine Quetiapine fumarate Olanzapine Ziprasidone Ziprasidone hydrochloride Ziprasidone mesylate Aripiprazole Carbamazepine Lithium carbonate Lithium citrate Benzocaine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Outcomes Assessor), Parallel Assignment
Official Title:	Lithium Use for Bipolar Disorder (LiTMUS): A Randomized Controlled Effectiveness Trial

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Overall improvement in bipolar illness severity as measured by the CGI-BP-S [ Time Frame: Measured over 6 months ] [ Designated as safety issue: No ]
Number of necessary medication adjustments [ Time Frame: Measured over 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Symptoms as measured by QIDS-SR and YMRS [ Time Frame: Measured over 6 months ] [ Designated as safety issue: No ]
Quality of life as measured by Q-LES-Q [ Time Frame: Measured over 6 months ] [ Designated as safety issue: No ]
Suicidality [ Time Frame: Measured over 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	264
Study Start Date:	April 2008
Estimated Study Completion Date:	September 2010
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

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

Assigned Interventions

1: Experimental

Participants will receive lithium plus optimized medication treatment, as needed.

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.

2: Active Comparator

Participants will only receive optimized medication treatment, as needed; lithium will not be used.

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.

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 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, 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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667745

Contacts

Contact: Louisa G. Sylvia, PhD

617-643-4804

lsylvia2@partners.org

Locations

United States, California
Stanford University	Recruiting
Stanford, California, United States, 94035-5723
Contact: Shelley Hill 650-498-4801 shill@stanford.edu
Principal Investigator: Terence Ketter, MD
United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Christine Kansky, BA 617-726-7591 ckansky@partners.org
Principal Investigator: Dan Iosifescu, MD
United States, Ohio
Case Western Reserve University	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Carla Conroy 216-844-2871 carla.conroy@Uhhospitals.org
Principal Investigator: Joseph Calabrese, MD
United States, Pennsylvania
University of Pennsylvania	Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Marna Barnett, PhD 215-898-4301 msb@mail.med.upenn.edu
Principal Investigator: Michael Thase, MD
University of Pittsburgh Medical Center	Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Luann Shutt 412-246-5762 shuttls@upmc.edu
Principal Investigator: Edward Friedman, MD
United States, Texas
University of Texas Health Science Center	Recruiting
San Antonio, Texas, United States, 78229
Contact: Melissa Hernandez 210-567-0780 Hernandezma0@uthscsa.edu
Principal Investigator: Charles Bowden, MD

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

More Information

Responsible Party:	Massachusetts General Hospital ( Andrew A. Nierenberg, MD )
Study ID Numbers:	N01 MH80001-01, DSIR AT
Study First Received:	April 24, 2008
Last Updated:	September 25, 2008
ClinicalTrials.gov Identifier:	NCT00667745
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

Lithium
Symptoms
Medication Changes

Study placed in the following topic categories:

Bipolar Disorder
Benzocaine
Olanzapine
Risperidone
Lithium Carbonate
Affective Disorders, Psychotic
Quetiapine

Carbamazepine
Mental Disorders
Mood Disorders
Psychotic Disorders
Aripiprazole
Ziprasidone
Lithium

Additional relevant MeSH terms:

Disease
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Enzyme Inhibitors

Antipsychotic Agents
Antimanic Agents
Pharmacologic Actions
Pathologic Processes
Therapeutic Uses
Central Nervous System Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on January 30, 2009