Treatment of Bipolar Mania in Older Adults

Study Overview
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Brief Summary
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This study will compare the benefits and side effects of lithium and divalproex in the treatment of older adults with bipolar mania.

Detailed Description
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This is the first controlled acute treatment study of bipolar disorder in adults 60 years or older with current DSM-IV manic, mixed, or hypomanic episodes. The number of older adults with severe and disabling bipolar disorder is increasing, and information to guide the management of the treatment of the disease is lacking in this population. Guidelines for treatment of younger people with bipolar disorder cannot be used for older people, and there are no safety and efficacy data upon which to base initial treatment decisions for older patients with bipolar mania. Mood stabilizers (lithium and divalproex) are the first-line treatment for bipolar disorder. However, in aged patients physiological changes and comorbid diseases may increase vulnerability to side effects and limit the benefits of the medications. This double-blind study will compare the benefits and side-effects of 9 weeks of treatment with lithium and divalproex in people with bipolar mania. Participants, who may be treated during inpatient hospitalization or as outpatients, will be randomly assigned to receive either lithium or divalproex. During the first 3 weeks of treatment careful titration of lithium and divalproex will be done to reach dose ranges. All other psychotropic medications will be discontinued. Behavioral interventions and/or lorazepam may be added, if necessary. After the first 3 weeks, if symptoms do not improve, risperidone will be added to be taken everyday with the study medication.

Official Title
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Acute Pharmacotherapy of Late-Life Mania (GERI-BD)

Conditions
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Bipolar Disorder, Mania

Intervention / Treatment
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* Drug: Lithium (LI)
* Drug: Divalproex (DV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of DSM-IV Bipolar Disorder, Type I: current manic, mixed, or hypomanic episodes Exclusion Criteria: Rapid cycling bipolar disorder History of substance abuse or dependence within last 3 months Diagnosis of schizophrenia or other chronic psychotic conditions Acute or unstable medical illness Documented intolerance to Lithium, Depakote, Risperidone, or Lorazepam Dementia Inability to communicate in English

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lithium (LI)<br>Participants will receive 9 weeks of treatment with lithium | Drug: Lithium (LI)<br>* The starting LI dose will be 150 mg in the morning and evening. The dose of medication will be adjusted to achieve plasma LI level ranges between 0.40 and 0.99 mEq/L (target 0.80 to 0.99 mEq/L).<br>* Other names: Depakote;|
| Experimental: Divalproex (DV)<br>Participants will receive 9 weeks of treatment with divalproex | Drug: Divalproex (DV)<br>* Dosage of DV will be 250 mg in the morning and evening. The dose of medication will be adjusted to achieve plasma DV level ranges between 40 and 99 mcg/mL (target 80 to 99 mcg/ml).<br>* Other names: Valproate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sedation Score | The Sedation Item score of the UKU (Norwegian for Committee of Clinical Investigations) Side Effect Rating Scale. A higher value indicates greater severity. Range is 0-3 (not present, mild, moderate, or severe). | Day 4, Day 9, Day 15, and then Weekly from Week 3 to Week 9 | 
| Young Mania Rating Scale (YMRS) Scores | The Young Mania Rating Scale is an eleven item interviewer-rated instrument. Four items are scored 0-8, the others 0-4. The total score therefore ranges from 0-60, with higher values reflecting greater severity. | Day 4, Day 9, Day 15, and then Weekly from Week 3 to Week 9 |