Clinical guidance for the use of trazodone in major depressive disorder and concomitant conditions: pharmacology and clinical practice

Riv Psichiatr. 2019 Jul-Aug;54(4):137-149. doi: 10.1708/3202.31796.


Aim: To provide a review of the clinically relevant evidence pertaining to the use of trazodone in major depressive disorder.

Methods: Medline and Cochrane Library searches were searched using the keywords 'trazodone' AND 'depression', to identify the most relevant literature pertinent to the pharmacological properties of trazodone and its use in clinical practice. Articles that were selected included basic pharmacology papers, clinical trials, clinical practice guidelines, and reviews. Related references were cross checked. European and United States prescribing information was reviewed as well. An effort was made to give weight to the information that was most relevant for daily clinical practice.

Results: Trazodone is an antidepressant with a mechanism of action that remains innovative and with a favorable profile for the treatment of depression. The appropriate antidepressant doses are usually 150-300 mg/day and are often higher than the doses that are used when trazodone is prescribed to augment the antidepressant effect of another medication, for instance when trazodone is prescribed to address insomnia in a patient treated with an SSRI. Trazodone is usually well tolerated and has a low risk of anticholinergic side effects, weight gain and sexual side effects.

Discussion: Trazodone is an established medication that is efficacious for the treatment of a broad array of depressive symptoms, including symptoms that are less likely to respond to other antidepressants (e.g. SSRI), such as insomnia. As an antidepressant, trazodone has proven as efficacious as the tricyclic and second-generation antidepressants and is tolerated relatively well. Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety or psychomotor agitation.

Conclusions: Trazodone is efficacious antidepressants with a relatively low risks of side effects such as weight gain, sexual or anticholinergic effects (such as constipation, urinary retention, dry mouth). In addition to being able to control a wide range of depressive symptoms, trazodone may improve sleep and be particularly helpful for patients whose symptoms of depression include insomnia.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents, Second-Generation* / adverse effects
  • Antidepressive Agents, Second-Generation* / metabolism
  • Antidepressive Agents, Second-Generation* / pharmacology
  • Antidepressive Agents, Second-Generation* / therapeutic use
  • Anxiety / drug therapy
  • Bulimia / drug therapy
  • Delayed-Action Preparations
  • Depressive Disorder, Major / drug therapy*
  • Drug Interactions
  • Fibromyalgia / drug therapy
  • Humans
  • Neurocognitive Disorders / drug therapy
  • Randomized Controlled Trials as Topic
  • Sexual Dysfunction, Physiological / drug therapy
  • Sleep Initiation and Maintenance Disorders / drug therapy
  • Stress Disorders, Post-Traumatic / drug therapy
  • Substance-Related Disorders / drug therapy
  • Trazodone* / adverse effects
  • Trazodone* / metabolism
  • Trazodone* / pharmacology
  • Trazodone* / therapeutic use


  • Antidepressive Agents, Second-Generation
  • Delayed-Action Preparations
  • Trazodone