The place for the tricyclic antidepressants in the treatment of depression

Aust N Z J Psychiatry. 1999 Jun;33(3):323-7. doi: 10.1046/j.1440-1614.1999.00580.x.


Objective: The new generation antidepressants have been an important advance in the treatment of depression. Since their introduction, their use has become widespread and the role of the older tricyclic antidepressants (TCAs) has been suggested only as a second-line choice. This assumption is questioned and the role of the TCAs as a first-line treatment for severe depression is discussed.

Method: The relevant literature concerning the efficacy, tolerability and safety of the antidepressant drugs is reviewed, particularly those studies which compare the newer antidepressant agents with the TCAs.

Results: The newer agents are equally as efficient as the tricyclics in the treatment of mild to moderate depression. There are indications that the TCAs are more efficacious for severe depression. The tolerability of the drugs appear about equivalent in terms of discontinuation rates; however, the side effects are different and clinicians need to be mindful of drug interactions and the potential of the serotonin syndrome with the selective serotonin re-uptake inhibitors (SSRIs), problems not found with the TCAs. The TCAs are potentially lethal in overdose; however, appropriate clinical management appears to be a more important issue than the toxicity of the medication.

Conclusions: The newer antidepressant agents are important advances in the treatment of depression. However, the TCAs still have an important place as the first-line treatment for patients with severe (melancholic/endogenous) depression.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents, Second-Generation / therapeutic use
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Depression / classification
  • Depression / drug therapy*
  • Humans
  • Psychiatry / trends
  • Serotonin Uptake Inhibitors / therapeutic use
  • Suicide / prevention & control
  • Treatment Outcome


  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors