Depressive illness is now widely recognized as a major cause of morbidity and mortality in old age. Although it represents a significant public health concern by virtue of its high cost in human suffering, disability, and potential for suicide, it has not been studied extensively, and specific criteria for optimal treatment are lacking. Depression in the elderly is also associated with poor prognosis and the potential role of maintenance antidepressant therapy in the elderly has not been investigated. Towards this end, our initial investigations have indicated that both major antidepressants, Nortriptyline (NT) and Phenelzine (PE) are significantly superior to placebo for successful treatment of geriatric depressions. In terms of safety, it has been shown that if judiciously used, both drugs are well tolerated in treating the acute phase of the depressive episode. Furthermore, preliminary results of our pilot longitudinal study provided evidence for the efficacy of antidepressant prophylaxis in geriatric depression. The objective of the present project is to validate and extend our preliminary findings. Specifically we will: 1) Further assess the validity of the preliminary findings on the comparative efficacy and safety of phenelzine (PE) and nortriptyline (NT), by extending our sample size (N=50) to another 80 (40 per group) carefully screened depressed elderly who will be randomly assigned to either NT or PE under double-blind conditions. We eliminate the placebo of the current study. 2) Investigate the comparative efficacy and safety of NT vs. PE vs. placebo for successful maintenance in acute phase responders to NT or PE. 3) Determine prognostic factors associated with optimal antidepressant efficacy and safety or preferential response to either drug during the acute phase, or optimal maintenance during the follow-up phase. To accomplish these aims, we intend to do the following: 1) Extend our original sample size (N=50) to another 80 (40 per group) carefully screened depressed elderly randomly assigned to NT or PE following a two week single blind placebo washout period. 2) Responders, following a period of stabilization (4 months), will be randomly assigned to NT or PE or to placebo for a period of two years. These further investigations will enable us to validate and extend our preliminary findings and provide important information regarding optimal pharmacological treatment and prophylaxis for this illness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH035196-08
Application #
3375621
Study Section
(TDAB)
Project Start
1982-04-01
Project End
1991-03-31
Budget Start
1989-05-01
Budget End
1991-03-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
McCue, R E; Georgotas, A; Suckow, R F et al. (1989) 10-Hydroxynortriptyline and treatment effects in elderly depressed patients. J Neuropsychiatry Clin Neurosci 1:176-80
Georgotas, A; McCue, R E; Reisberg, B et al. (1989) The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients. Int Psychogeriatr 1:135-43
Georgotas, A; McCue, R E; Cooper, T B et al. (1989) Factors affecting the delay of antidepressant effect in responders to nortriptyline and phenelzine. Psychiatry Res 28:1-9
Georgotas, A; McCue, R E (1989) Relapse of depressed patients after effective continuation therapy. J Affect Disord 17:159-64
Georgotas, A; McCue, R E; Cooper, T B (1989) A placebo-controlled comparison of nortriptyline and phenelzine in maintenance therapy of elderly depressed patients. Arch Gen Psychiatry 46:783-6
McCue, R E; Georgotas, A; Nagachandran, N et al. (1989) Plasma levels of nortriptyline and 10-hydroxynortriptyline and treatment-related electrocardiographic changes in the elderly depressed. J Psychiatr Res 23:73-9
Georgotas, A; McCue, R E; Cooper, T B et al. (1988) How effective and safe is continuation therapy in elderly depressed patients? Factors affecting relapse rate. Arch Gen Psychiatry 45:929-32
Georgotas, A; Schweitzer, J; McCue, R E et al. (1987) Clinical and treatment effects on 3H-clonidine and 3H-imipramine binding in elderly depressed patients. Life Sci 40:2137-43
Georgotas, A; McCue, R E; Friedman, E et al. (1987) Response of depressive symptoms to nortriptyline, phenelzine and placebo. Br J Psychiatry 151:102-6
Georgotas, A; McCue, R E; Friedman, E et al. (1987) A placebo-controlled comparison of the effect of nortriptyline and phenelzine on orthostatic hypotension in elderly depressed patients. J Clin Psychopharmacol 7:413-6

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