Safety and tolerability considerations: tricyclic antidepressants vs. selective serotonin reuptake inhibitors

Acta Psychiatr Scand Suppl. 2000;403:17-25. doi: 10.1111/j.1600-0447.2000.tb10944.x.


Objective: An important consideration in the choice of an antidepressant is its safety and tolerability.

Method: We present a review of literature, clinical trials and meta-analyses regarding the safety and tolerability of the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitors (SSRIs) in depressed patients.

Results: The SSRIs have a very favourable side-effect profile compared to the TCAs and are associated with fewer treatment discontinuations. Unlike the TCAs, they do not cause anticholinergic, hypotensive or sedating reactions, and are not associated with impaired cognitive function. Their most common side-effects (nausea, vomiting, nervousness, insomnia, headache and sexual dysfunction) are usually mild and typically disappear as treatment continues. The SSRIs also exhibit lower toxicity and lower lethality when taken in an overdose situation. Although the safety profiles of the principal SSRIs appear to be comparable, there is some data showing important differences in the severity and frequency of specific adverse events.

Conclusion: The SSRIs have a more favourable safety profile than the TCAs in both acute and long-term treatment of major depression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents, Tricyclic / adverse effects*
  • Clinical Trials as Topic
  • Cognition Disorders / chemically induced
  • Drug Tolerance
  • Humans
  • Meta-Analysis as Topic
  • Serotonin Uptake Inhibitors / adverse effects*


  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors