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Trial record 59 of 69 for:    "Bipolar Disorder" | "Olanzapine"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00667745
Recruitment Status : Completed
First Posted : April 28, 2008
Results First Posted : June 28, 2013
Last Update Posted : February 13, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Mental Health (NIMH)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Bipolar Disorder
Interventions Drug: Lithium Carbonate
Drug: Optimized Treatment (OPT)
Enrollment 283
Recruitment Details  
Pre-assignment Details  
Arm/Group Title OPT With Lithium OPT Without Lithium
Hide Arm/Group Description

Participants received lithium plus optimized medication treatment, as needed.

Lithium Carbonate : Lithium was started at 300 mg and then increased to 600 mg after 3 days. Lithium doses were maintained at 600 mg per day for 8 weeks, but may have been adjusted after that time as needed up to a serum level of 1.2 mEq/L.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Participants only received optimized medication treatment, as needed; lithium was not be used.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Period Title: Overall Study
Started 141 142
Completed 116 121
Not Completed 25 21
Arm/Group Title OPT With Lithium OPT Without Lithium Total
Hide Arm/Group Description

Participants received lithium plus optimized medication treatment, as needed.

Lithium Carbonate : Lithium was started at 300 mg and then increased to 600 mg after 3 days. Lithium doses were maintained at 600 mg per day for 8 weeks, but may have been adjusted after that time as needed up to a serum level of 1.2 mEq/L.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Participants only received optimized medication treatment, as needed; lithium was not be used.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Total of all reporting groups
Overall Number of Baseline Participants 141 142 283
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
141
 100.0%
142
 100.0%
283
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 141 participants 142 participants 283 participants
38.7  (11.7) 39.4  (13.0) 39.1  (12.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
Female
77
  54.6%
83
  58.5%
160
  56.5%
Male
64
  45.4%
59
  41.5%
123
  43.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 141 participants 142 participants 283 participants
141 142 283
1.Primary Outcome
Title Overall Change in Bipolar Illness Severity as Measured by Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Score
Hide Description

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.

Time Frame Relevant time points: baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title OPT With Lithium OPT Without Lithium
Hide Arm/Group Description:

Participants received lithium plus optimized medication treatment, as needed.

Lithium Carbonate : Lithium was started at 300 mg and then increased to 600 mg after 3 days. Lithium doses were maintained at 600 mg per day for 8 weeks, but may have been adjusted after that time as needed up to a serum level of 1.2 mEq/L.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Participants only received optimized medication treatment, as needed; lithium was not be used.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Overall Number of Participants Analyzed 141 142
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.22  (1.50) -1.48  (1.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPT With Lithium, OPT Without Lithium
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter F value, main effect
Estimated Value 0.94
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Necessary Medication Adjustments
Hide Description

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.

Time Frame Measured over 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title OPT With Lithium OPT Without Lithium
Hide Arm/Group Description:

Participants received lithium plus optimized medication treatment, as needed.

Lithium Carbonate : Lithium was started at 300 mg and then increased to 600 mg after 3 days. Lithium doses were maintained at 600 mg per day for 8 weeks, but may have been adjusted after that time as needed up to a serum level of 1.2 mEq/L.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Participants only received optimized medication treatment, as needed; lithium was not be used.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Overall Number of Participants Analyzed 141 142
Mean (Standard Deviation)
Unit of Measure: Adjustments
1.17  (0.96) 1.26  (1.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPT With Lithium, OPT Without Lithium
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.967
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Chi-squared
Estimated Value 0.00
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Depression Symptoms as Measured Self Report Montgomery Asberg Depression Rating Scale (MADRS)
Hide Description

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

Time Frame Measured over 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title OPT With Lithium OPT Without Lithium
Hide Arm/Group Description:

Participants received lithium plus optimized medication treatment, as needed.

Lithium Carbonate : Lithium was started at 300 mg and then increased to 600 mg after 3 days. Lithium doses were maintained at 600 mg per day for 8 weeks, but may have been adjusted after that time as needed up to a serum level of 1.2 mEq/L.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Participants only received optimized medication treatment, as needed; lithium was not be used.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Overall Number of Participants Analyzed 141 142
Mean (Standard Deviation)
Unit of Measure: units on a scale
8.20  (12.29) 8.84  (13.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPT With Lithium, OPT Without Lithium
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.45
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mania Symptoms as Measured by the Young Mania Rating Scale (YMRS)
Hide Description 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.
Time Frame Measured over 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title OPT With Lithium OPT Without Lithium
Hide Arm/Group Description:

Participants received lithium plus optimized medication treatment, as needed. Lithium Carbonate : Lithium was started at 300 mg and then increased to 600 mg after 3 days. Lithium doses were maintained at 600 mg per day for 8 weeks, but may have been adjusted after that time as needed up to a serum level of 1.2 mEq/L.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Participants only received optimized medication treatment, as needed; lithium was not be used.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Overall Number of Participants Analyzed 141 142
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.35  (10.09) 5.79  (8.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPT With Lithium, OPT Without Lithium
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.02
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Suicidality as Measured by the Modified Scale for Suicidal Ideation (MSSI)
Hide Description 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.
Time Frame Measured over 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title OPT With Lithium OPT Without Lithium
Hide Arm/Group Description:

Participants received lithium plus optimized medication treatment, as needed. Lithium Carbonate : Lithium was started at 300 mg and then increased to 600 mg after 3 days. Lithium doses were maintained at 600 mg per day for 8 weeks, but may have been adjusted after that time as needed up to a serum level of 1.2 mEq/L.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Participants only received optimized medication treatment, as needed; lithium was not be used.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Overall Number of Participants Analyzed 141 142
Mean (Standard Deviation)
Unit of Measure: units of scale
0.73  (4.12) 1.10  (3.77)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPT With Lithium, OPT Without Lithium
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .49
Comments Value shown above describes emergent suicidal ideation for participants with baseline MSSI = 0. P=.36 describes exacerbation of baseline suicidal ideation for those with baseline MSSI > 0.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value .92
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OPT With Lithium OPT Without Lithium
Hide Arm/Group Description

Participants received lithium plus optimized medication treatment, as needed.

Lithium Carbonate : Lithium was started at 300 mg and then increased to 600 mg after 3 days. Lithium doses were maintained at 600 mg per day for 8 weeks, but may have been adjusted after that time as needed up to a serum level of 1.2 mEq/L.

Optimized Treatment (OPT) : The foundation of OPT was 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.

Participants only received optimized medication treatment, as needed; lithium was not be used.

Optimized Treatment (OPT) : The foundation of OPT was 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.

All-Cause Mortality
OPT With Lithium OPT Without Lithium
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
OPT With Lithium OPT Without Lithium
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/141 (9.93%)      12/142 (8.45%)    
Cardiac disorders     
Myocardial Infarction  1/141 (0.71%)  1 1/142 (0.70%)  1
Gastrointestinal disorders     
Cholecystitis  2/141 (1.42%)  2 0/142 (0.00%)  0
Chron's Disease  1/141 (0.71%)  1 0/142 (0.00%)  0
Pancreatitis  1/141 (0.71%)  1 0/142 (0.00%)  0
General disorders     
Dehydration  1/141 (0.71%)  1 0/142 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Upper limb fracture  0/141 (0.00%)  0 1/142 (0.70%)  1
Nervous system disorders     
Pneumonia  1/141 (0.71%)  1 0/142 (0.00%)  0
Psychiatric disorders     
Alcohol Detoxification  1/141 (0.71%)  1 0/142 (0.00%)  0
Mania  2/141 (1.42%)  2 2/142 (1.41%)  2
Suicidal ideation  4/141 (2.84%)  4 6/142 (4.23%)  6
Confusion  0/141 (0.00%)  0 1/142 (0.70%)  1
Renal and urinary disorders     
Acute Renal Failure  1/141 (0.71%)  1 0/142 (0.00%)  0
Fluid Retention  0/141 (0.00%)  0 1/142 (0.70%)  1
Reproductive system and breast disorders     
Pregnancy  1/141 (0.71%)  1 0/142 (0.00%)  0
Breast Cancer  0/141 (0.00%)  0 1/142 (0.70%)  1
Respiratory, thoracic and mediastinal disorders     
Upper respiratory tract infection  0/141 (0.00%)  0 1/142 (0.70%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
OPT With Lithium OPT Without Lithium
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   69/141 (48.94%)      61/142 (42.96%)    
Gastrointestinal disorders     
Diarrhea/gastrointestinal distress  14/141 (9.93%)  21 5/142 (3.52%)  6
General disorders     
Fatigue/sedation/drowsiness  20/141 (14.18%)  20 19/142 (13.38%)  25
Dizziness/Headaches  8/141 (5.67%)  9 13/142 (9.15%)  19
Dry mouth/thirst  8/141 (5.67%)  8 5/142 (3.52%)  5
Metabolism and nutrition disorders     
Increased appetite/weight gain  15/141 (10.64%)  15 15/142 (10.56%)  16
Musculoskeletal and connective tissue disorders     
Aches/pains  13/141 (9.22%)  15 8/142 (5.63%)  9
Tremors  14/141 (9.93%)  14 7/142 (4.93%)  7
Psychiatric disorders     
Memory/Concentration/Cognitive Impairment  10/141 (7.09%)  11 1/142 (0.70%)  1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Andrew Nierenberg, Director of the Bipolar Trials Network
Organization: Bipolar Clinic and Research Program at
Phone: 617-724-0837
EMail: ANIERENBERG@PARTNERS.ORG
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00667745     History of Changes
Other Study ID Numbers: N01 MH080001-01
DSIR AT
First Submitted: April 24, 2008
First Posted: April 28, 2008
Results First Submitted: October 25, 2012
Results First Posted: June 28, 2013
Last Update Posted: February 13, 2018