Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison

Int Clin Psychopharmacol. 1999 Nov;14(6):321-7. doi: 10.1097/00004850-199911000-00001.


Although common in clinical settings, major depressive disorder with associated anxious symptoms ('anxious depression') has not been well studied in antidepressant clinical trials. The aim of this study was to compare the effects of fluoxetine versus amitriptyline in this group of patients. After a single-blind placebo run-in period of 2 weeks, patients were treated on a double-blind basis with fluoxetine or amitriptyline for 8 weeks. Assessment instruments included: 21-item Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions, Raskin Depression Scale and Covi Anxiety Scale. A total of 157 patients were randomized to either fluoxetine or amitriptyline. Fluoxetine was given at a fixed dose of 20 mg/day and amitriptyline was given in a range of 50-250 mg/day (mean of 138.1 mg/day). Fluoxetine was comparable to amitriptyline in all efficacy measures except the HAMD sleep factor. Unwanted effects were more frequent and more severe in the amitriptyline-treated patients. Fluoxetine was comparably efficacious to amitriptyline in the treatment of major depression with associated anxiety. Since fluoxetine was far better tolerated, it is a promising alternative for this frequent and disabling condition.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amitriptyline / adverse effects
  • Amitriptyline / therapeutic use*
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Anxiety Disorders / complications
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / psychology
  • Depressive Disorder / complications
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Double-Blind Method
  • Female
  • Fluoxetine / adverse effects
  • Fluoxetine / therapeutic use*
  • Humans
  • Male
  • Psychiatric Status Rating Scales


  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Fluoxetine
  • Amitriptyline