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Am J Geriatr Psychiatry. 2014 Jan;22(1):46-52. doi: 10.1016/j.jagp.2013.02.001. Epub 2013 Oct 8.

Antidepressant treatment of melancholia in older adults.

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Queens College and The Graduate Center, City University of New York, Queens, NY; Department of Psychiatry, the New York State Psychiatric Institute, New York, NY. Electronic address:



This is the first prospective trial in an outpatient sample comparing the effect of nortriptyline with sertraline in the treatment of depression with and without melancholia. We hypothesized that patients with melancholia would respond better to nortriptyline than sertraline, whereas among patients without melancholia, nortriptyline and sertraline would have equal efficacy.


We conducted a randomized 12-week trial comparing sertraline with nortriptyline in the treatment of patients with nonpsychotic, unipolar major depression stratified by the presence of melancholia. One hundred ten unipolar depressed patients with and without melancholia comprised our intent-to-treat sample. Seventy-two were nonmelancholic depressed and randomly assigned to treatment with sertraline (N = 40) or nortriptyline (N = 32). Thirty-eight were melancholic depressed and randomly assigned to treatment with sertraline (N = 18) or nortriptyline (N = 20).


The test of the interaction of medication group and melancholia status on response was not statistically significant. Among patients with melancholia, response rates were 47% to sertraline and 75% to nortriptyline, whereas among patients without melancholia, response rates were 51% to sertraline and 42% to nortriptyline. The odds of response for patients with melancholia treated with nortriptyline compared with sertraline was 3.46. The odds of response for patients without melancholia treated with sertraline compared with nortriptyline was 0.69. Similar findings were obtained in the remission and continuous outcome analyses.


This study did not find a significant difference between sertraline and nortriptyline in the treatment of depressed older adults with melancholia.


Randomized clinical trials; antidepressants; melancholia; nortriptyline; sertraline

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