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

Phase 4

Completed

Conditions: Bipolar Disorder

Interventions: Drug: Lithium Carbonate
Drug: Optimized Treatment (OPT)

Registration Number: NCT00667745

Lead Sponsor: National Institute of Mental Health (NIMH)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 283

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Optimized Treatment (OPT)	Participants received lithium plus optimized medication treatment, as needed.
2	Optimized Treatment (OPT)	Participants only received optimized medication treatment, as needed; lithium was not be used.
1	Lithium Carbonate	Participants received lithium plus optimized medication treatment, as needed.

Primary Outcome Measures

Name	Time	Method
Overall Change in Bipolar Illness Severity as Measured by Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Score	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	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 Outcome Measures

Name	Time	Method
Suicidality as Measured by the Modified Scale for Suicidal Ideation (MSSI)	Measured over 6 months	The Modified Scale for Suicide Ideation (MSSI) assesses the presence of absence of suicide ideation and the degree of severity of suicidal ideas. The time frame is from the point of interview and the previous 48 hours. It uses 13 items from the Scale for Suicidal Ideation (SSI) and 5 new items. The modifications increased both reliability and validity. The scale was also changed to range from 0 to 3, yielding a total score ranging from 0 to 54. A total score is attained by summing all of the items. A score between 0-8 indicates low suicidal ideation; 9-20 indiciates mild-moderate suicidal ideation; 21+ indicates severe suicidal ideation.
Depression Symptoms as Measured Self Report Montgomery Asberg Depression Rating Scale (MADRS)	Measured over 6 months	The MADRS is a 10-item measure and has a fixed scaling of seven points (from 0 through 6), with 0 representing sypmtoms that are not present and 6 being the most severe symptoms. When completed, the sum of each individual item is taken to create an overall score. Overall scores: 0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression
Mania Symptoms as Measured by the Young Mania Rating Scale (YMRS)	Measured over 6 months	The scale has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. There are four items that are graded on a 0 to 8 scale with 0 indicating that symptoms are absent and 8 indicating that symptoms are severe (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale, with 0 indicating that symptoms are absent and 4 indicating that symptoms are severe (Elevated mood, increased motor activity-energy, sexual interest, sleep, language-thought disorder, appearance, and insight). Total scores can vary from 0-60, with 0 indicating that symptoms are completely absent and 60 indicating that the patient is severely manic.

Trial Locations

Locations (6): Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Stanford University
🇺🇸
Stanford, California, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
University of Texas Health Science Center
🇺🇸
San Antonio, Texas, United States