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| ID | Type | Description | Link |
|---|---|---|---|
| DSIR AT | |||
| N01MH080001 | U.S. NIH Grant/Contract | View source |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Participants received lithium plus optimized medication treatment, as needed. |
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| 2 | Active Comparator | Participants only received optimized medication treatment, as needed; lithium was not be used. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lithium Carbonate | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Change in Bipolar Illness Severity as Measured by Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Score | 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. | Relevant time points: baseline and week 24 |
| Number of Necessary Medication Adjustments | 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. | Measured over 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Depression Symptoms as Measured Self Report Montgomery Asberg Depression Rating Scale (MADRS) | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Stanford | California | 94035-5723 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26476489 | Derived | 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. | |
| 23911057 |
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| ID | Title | Description |
|---|---|---|
| FG000 | OPT With Lithium | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Optimized Treatment (OPT) | Drug | 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. |
|
| Measured over 6 months |
| Mania Symptoms as Measured by the Young Mania Rating Scale (YMRS) | 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. | Measured over 6 months |
| Suicidality as Measured by the Modified Scale for Suicidal Ideation (MSSI) | 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. | Measured over 6 months |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Case Western Reserve University | Cleveland | Ohio | 44106 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
| University of Texas Health Science Center | San Antonio | Texas | 78229 | United States |
| 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. |
| 23670706 | Derived | 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. |
| 23288387 | Derived | 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. |
| 22076437 | Derived | 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. |
| FG001 | OPT Without Lithium | 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. |
| COMPLETED |
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| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | OPT With Lithium | 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. |
| BG001 | OPT Without Lithium | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Change in Bipolar Illness Severity as Measured by Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Score | 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. | Posted | Mean | Standard Deviation | units on a scale | Relevant time points: baseline and week 24 |
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| Primary | Number of Necessary Medication Adjustments | 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. | Posted | Mean | Standard Deviation | Adjustments | Measured over 6 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Depression Symptoms as Measured Self Report Montgomery Asberg Depression Rating Scale (MADRS) | 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 | Posted | Mean | Standard Deviation | units on a scale | Measured over 6 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mania Symptoms as Measured by the Young Mania Rating Scale (YMRS) | 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. | Posted | Mean | Standard Deviation | units on a scale | Measured over 6 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Suicidality as Measured by the Modified Scale for Suicidal Ideation (MSSI) | 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. | Posted | Mean | Standard Deviation | units of scale | Measured over 6 months |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | OPT With Lithium | 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. | 14 | 141 | 69 | 141 | ||
| EG001 | OPT Without Lithium | 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. | 12 | 142 | 61 | 142 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alcohol Detoxification | Psychiatric disorders |
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| Cholecystitis | Gastrointestinal disorders |
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| Chron's Disease | Gastrointestinal disorders |
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| Dehydration | General disorders |
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| Mania | Psychiatric disorders |
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| Myocardial Infarction | Cardiac disorders |
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| Pancreatitis | Gastrointestinal disorders |
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| Pneumonia | Nervous system disorders |
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| Pregnancy | Reproductive system and breast disorders |
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| Acute Renal Failure | Renal and urinary disorders |
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| Suicidal ideation | Psychiatric disorders |
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| Breast Cancer | Reproductive system and breast disorders |
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| Confusion | Psychiatric disorders |
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| Fluid Retention | Renal and urinary disorders |
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| Upper limb fracture | Musculoskeletal and connective tissue disorders |
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| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aches/pains | Musculoskeletal and connective tissue disorders |
| |||
| Diarrhea/gastrointestinal distress | Gastrointestinal disorders |
| |||
| Fatigue/sedation/drowsiness | General disorders |
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| Dizziness/Headaches | General disorders |
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| Memory/Concentration/Cognitive Impairment | Psychiatric disorders |
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| Tremors | Musculoskeletal and connective tissue disorders |
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| Increased appetite/weight gain | Metabolism and nutrition disorders |
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| Dry mouth/thirst | General disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Andrew Nierenberg, Director of the Bipolar Trials Network | Bipolar Clinic and Research Program at | 617-724-0837 | ANIERENBERG@PARTNERS.ORG |
| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D016651 | Lithium Carbonate |
| D008094 | Lithium |
| ID | Term |
|---|---|
| D002254 | Carbonates |
| D000468 | Alkalies |
| D007287 | Inorganic Chemicals |
| D002255 | Carbonic Acid |
| D017554 | Carbon Compounds, Inorganic |
| D018020 | Lithium Compounds |
| D008672 | Metals, Alkali |
| D004602 | Elements |
| D019565 | Metals, Light |
| D008670 | Metals |
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| >=65 years |
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| Male |
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| OG001 |
| OPT Without Lithium |
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. |
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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. |
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