Treatment of Bipolar Mania in Older Adults (GERI-BD)

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

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.

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).

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).

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).

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.

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

Al Jurdi RK, Schulberg HC, Greenberg RL, Kunik ME, Gildengers A, Sajatovic M, Mulsant BH, Young RC; GERI-BD Study Group. Characteristics associated with inpatient versus outpatient status in older adults with bipolar disorder. J Geriatr Psychiatry Neurol. 2012 Mar;25(1):62-8. doi: 10.1177/0891988712436684.

Beyer JL, Greenberg RL, Marino P, Bruce ML, Al Jurdi RK, Sajatovic M, Gyulai L, Mulsant BH, Gildengers A, Young RC. Social support in late life mania: GERI-BD. Int J Geriatr Psychiatry. 2014 Oct;29(10):1028-32. doi: 10.1002/gps.4093. Epub 2014 Mar 24.

Sajatovic M, Al Jurdi R, Gildengers A, Greenberg RL, Tenhave T, Bruce ML, Mulsant B, Young RC. Depression symptom ratings in geriatric patients with bipolar mania. Int J Geriatr Psychiatry. 2011 Nov;26(11):1201-8. doi: 10.1002/gps.2664. Epub 2011 Mar 1.

Gildengers AG, Mulsant BH, Al Jurdi RK, Beyer JL, Greenberg RL, Gyulai L, Moberg PJ, Sajatovic M, ten Have T, Young RC; GERI-BD Study Group. The relationship of bipolar disorder lifetime duration and vascular burden to cognition in older adults. Bipolar Disord. 2010 Dec;12(8):851-8. doi: 10.1111/j.1399-5618.2010.00877.x.

Young RC, Schulberg HC, Gildengers AG, Sajatovic M, Mulsant BH, Gyulai L, Beyer J, Marangell L, Kunik M, Ten Have T, Bruce ML, Gur R, Marino P, Evans JD, Reynolds CF 3rd, Alexopoulos GS. Conceptual and methodological issues in designing a randomized, controlled treatment trial for geriatric bipolar disorder: GERI-BD. Bipolar Disord. 2010 Feb;12(1):56-67. doi: 10.1111/j.1399-5618.2009.00779.x.

Young RC, Mulsant BH, Sajatovic M, Gildengers AG, Gyulai L, Al Jurdi RK, Beyer J, Evans J, Banerjee S, Greenberg R, Marino P, Kunik ME, Chen P, Barrett M, Schulberg HC, Bruce ML, Reynolds CF 3rd, Alexopoulos GS; GERI-BD Study Group. GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder. Am J Psychiatry. 2017 Nov 1;174(11):1086-1093. doi: 10.1176/appi.ajp.2017.15050657. Epub 2017 Aug 4.