Elders with bipolar disorders (BP) have severe and debilitating psychopathology, poor treatment outcomes, and high medical morbidity and mortality. Controlled treatment studies for late-life BP disorder are lacking, and findings in young patients may not be relevant because aging-related changes may reduce the tolerability and efficacy of treatments. Improving the treatment of late-life BP disorder was identified as a priority at the NIMH-DBPA Consensus Conference (2001). In response, we propose the first randomized, double-blind, controlled comparison of lithium (LI) and divalproex (DV) in elders with BP-I manic, mixed and hypomanic episodes, designed to test differences in side effects and benefits under dosing conditions relevant to geriatric practice. Hospitalized and ambulatory patients (n=306) aged 60 years and older will be studied for 9 weeks. Participants will be randomized to LI (0.4-0.99 mEq/L; target 0.80-0.99 mEq/L) or DV (valproate 40-99 meg/ml; target 80-99 meg/ml), and will be treated with monotherapy in the first three weeks at maximum tolerated concentrations. Patients with unsatisfactory response after three weeks will receive adjunctive olanzapine. The tolerability measures will be side effect ratings and the proportion treated at target concentrations. The efficacy measures will be improvement in mood symptoms and in function and quality of life. Data obtained for testing the primary hypotheses will allow secondary analyses of selected factors which may modify outcomes. Compatibility of selected measures with those of the STEP-BD study of younger patients will enhance the value of findings from this study. Recognizing the difficulties inherent in a randomized study of BP elders, we brought together six groups (Cornell, Baylor College of Medicine, Case Western Reserve, Duke, and Universities of Pennsylvania and Pittsburgh) with research expertise in late-life and young adult BP disorders, and with strong research infrastructure and clinical resources. The sites have a history of successful collaborative research, including demanding geriatric studies. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01MH068846-02
Application #
7101694
Study Section
Interventions Research Review Committee (ITV)
Program Officer
Niederehe, George T
Project Start
2005-08-01
Project End
2010-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$237,815
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Young, Robert C; Mulsant, Benoit H; Sajatovic, Martha et al. (2017) 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 174:1086-1093
Rej, Soham; Butters, Meryl A; Aizenstein, Howard J et al. (2014) Neuroimaging and neurocognitive abnormalities associated with bipolar disorder in old age. Int J Geriatr Psychiatry 29:421-7
Gildengers, A G; Chisholm, D; Butters, M A et al. (2013) Two-year course of cognitive function and instrumental activities of daily living in older adults with bipolar disorder: evidence for neuroprogression? Psychol Med 43:801-11
Gildengers, Ariel G; Butters, Meryl A; Chisholm, Denise et al. (2012) Cognition in older adults with bipolar disorder versus major depressive disorder. Bipolar Disord 14:198-205
Gildengers, Ariel G; Mulsant, Benoit H; Al Jurdi, Rayan K et al. (2010) The relationship of bipolar disorder lifetime duration and vascular burden to cognition in older adults. Bipolar Disord 12:851-8
Andreescu, Carmen; Mulsant, Benoit H; Emanuel, James E (2008) Complementary and alternative medicine in the treatment of bipolar disorder--a review of the evidence. J Affect Disord 110:16-26