Treatment of major depression with nortriptyline and paroxetine in patients with ischemic heart disease

Am J Psychiatry. 1999 Jul;156(7):1024-8. doi: 10.1176/ajp.156.7.1024.


Objective: This study compared the efficacy, tolerability, and safety of paroxetine and nortriptyline in depressed patients with ischemic heart disease.

Method: After a 2-week, single-blind placebo lead-in phase, 81 outpatients with DSM-III-R-defined nonpsychotic unipolar major depression and ischemic heart disease were randomly assigned to double-blind treatment with paroxetine or nortriptyline for 6 weeks. Paroxetine was administered at a fixed-flexible dose of 20-30 mg/day. Nortriptyline dose was adjusted with the use of blood-level monitoring to reach a plasma concentration of 50-150 ng/ml.

Results: Twenty-seven of the 41 patients who started treatment with paroxetine and 29 of the 40 patients who started treatment with nortriptyline had an improvement of at least 50% in their Hamilton Depression Rating Scale scores. Significantly more patients taking nortriptyline discontinued treatment prematurely (35% versus 10%), and more patients taking nortriptyline had adverse events resulting in termination (25% versus 5%).

Conclusions: Both treatments were efficacious. Sixty-three percent of all patients improved at least 50%, and of these, 90% met the criteria for remission. Paroxetine was better tolerated than nortriptyline and less likely to produce cardiovascular side effects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Comorbidity
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / epidemiology
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Ischemia / epidemiology*
  • Nortriptyline / therapeutic use*
  • Paroxetine / therapeutic use*
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors
  • Paroxetine
  • Nortriptyline