As an increasing number of elderly are treated for depression, systematic data are crucially necessary to help guide continued clinical care. This study will: 1) determine clinical and neuroradiographic predictors of early relapse and recurrence; 2) test the efficacy and safety of maintenance nortriptyline (NT); and 3) identify those plasma levels of 10- OH-NT (an NT metabolite) associated with low protective power against relapse and recurrence and/or with cardiovascular and cognitive side effects. Thus, the study is expected to help clinicians identify patients in greatest need for long-term drug treatment, assess the risk-benefit ratio of preventive NT therapy, and refine guidelines for the NT prescription. Subjects will be 125 elderly patients who have recovered from an episode of non-delusional major depression after acute treatment with NT (50% of subjects will have mild to moderate dementia and the remainder will not have cognitive impairment). Upon completion of a continuation phase (4 months after recovery) with NT at plasma levels of 80-120 ng/ml, subjects will be randomly assigned to NT or placebo maintenance (after 4 months from recovery) gradually over 10 weeks. The principal methods of data analysis will be generalized regression models for repeated measures and survival analysis. We have previously characterized the heterogeneity of geriatric depression, tested its response to acute pharmacologic treatments, and described its course under naturalistic conditions. This pioneering controlled-treatment study therefore represents a logical next step. While well aware of the methodological problems and confounds posed by studying a """"""""sick and old"""""""" population, we bring to this project a committed and experienced research team, the support and structure of a Developing CRC specifically targeted to study the outcomes of geriatric affective disorders, and our established recruitment procedures in a remarkably large psychiatric inpatient/outpatient geriatric service. Accordingly, we are well positioned to meet the challenges inherent in this difficult but important area of research.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (SRCM (04))
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Weill Medical College of Cornell University
Schools of Medicine
New York
United States
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Alexopoulos, George S; Reynolds 3rd, Charles F; Bruce, Martha L et al. (2009) Reducing suicidal ideation and depression in older primary care patients: 24-month outcomes of the PROSPECT study. Am J Psychiatry 166:882-90
Alexopoulos, George S; Katz, Ira R; Bruce, Martha L et al. (2005) Remission in depressed geriatric primary care patients: a report from the PROSPECT study. Am J Psychiatry 162:718-24
Kiosses, Dimitris N; Alexopoulos, George S (2005) IADL functions, cognitive deficits, and severity of depression: a preliminary study. Am J Geriatr Psychiatry 13:244-9
Kalayam, Balu; Alexopoulos, George S (2003) A preliminary study of left frontal region error negativity and symptom improvement in geriatric depression. Am J Psychiatry 160:2054-6
Lockwood, Kathryn A; Alexopoulos, George S; van Gorp, Wilfred G (2002) Executive dysfunction in geriatric depression. Am J Psychiatry 159:1119-26
Abrams, Robert C; Lachs, Mark; McAvay, Gail et al. (2002) Predictors of self-neglect in community-dwelling elders. Am J Psychiatry 159:1724-30
Alexopoulos, G S (2001) ""The depression-executive dysfunction syndrome of late life"": a specific target for D3 agonists? Am J Geriatr Psychiatry 9:22-9
de Asis, J M; Stern, E; Alexopoulos, G S et al. (2001) Hippocampal and anterior cingulate activation deficits in patients with geriatric depression. Am J Psychiatry 158:1321-3
Kalayam, B; Alexopoulos, G S; Kindermann, S et al. (1998) P300 latency in geriatric depression. Am J Psychiatry 155:425-7
Kalayam, B; Alexopoulos, G S; Musiek, F E et al. (1997) Brainstem evoked response abnormalities in late-life depression with vascular disease. Am J Psychiatry 154:970-5

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