Nortriptyline for treatment-resistant depression

Andrew A. Nierenberg, George I. Papakostas, Timothy Petersen, Karen E. Kelly, Brian M. Iacoviello, John J. Worthington, Joyce Tedlow, Jonathan E. Alpert, Maurizio Fava

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Background: Up to 30% of patients with major depression fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as initial treatment. While the tricyclic antidepressants might be effective for SSRI nonresponders, they have been relegated to third- and fourth-line treatment. This study assesses the efficacy of nortriptyline for patients with treatment-resistant major depression. Method: 92 patients with treatment-resistant DSM-III-R major depression, with resistance defined by at least 1, but no more than 5, well- documented adequate trials of antidepressants during the current episode, were treated openly with nortriptyline for 6 weeks. Patients were titrated up to full target doses of nortriptyline within 1 week, with target blood levels of 100 ng/mL. Response was defined as a 50% or greater decrease of baseline 17-item Hamilton Rating Scale for Depression score. We performed an intent-to-treat analysis with the last observation carried forward. Results: Approximately 40% of patients were responders (N = 39) and 12% were remitters (N = 11) after 6 weeks of nortriptyline. Over a third of patients were unable to complete the trial. Conclusion: Nortriptyline was effective for over a third of patients with treatment-resistant depression, and nortriptyline should be considered as potential treatment if patients fail to respond to other antidepressants.

Original languageEnglish (US)
Pages (from-to)35-39
Number of pages5
JournalJournal of Clinical Psychiatry
Issue number1
StatePublished - Jan 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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