Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder

Psychopharmacol Bull. 1990;26(2):191-6.


Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amitriptyline / therapeutic use*
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Mianserin / analogs & derivatives*
  • Mianserin / therapeutic use
  • Mirtazapine
  • Psychiatric Status Rating Scales


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Amitriptyline
  • Mianserin
  • Mirtazapine