Chonnam Med J.  2018 May;54(2):101-112. 10.4068/cmj.2018.54.2.101.

Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review

  • 1Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Korea.
  • 2International Health Care Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 3Department of Psychiatry, Korea University, College of Medicine, Seoul, Korea.
  • 4Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
  • 5Global Medical Education, New York, NY, USA.
  • 6Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.


Randomized trials have shown that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have better safety profiles than classical tricyclic antidepressants (TCAs). However, an increasing number of studies, including meta-analyses, naturalistic studies, and longer-term studies suggested that SSRIs and SNRIs are no less safe than TCAs. We focused on comparing the common side effects of TCAs with those of newer generation antidepressants including SSRIs, SNRIs, mirtazapine, and bupropion. The main purpose was to investigate safety profile differences among drug classes rather than the individual antidepressants, so studies containing comparison data on drug groups were prioritized. In terms of safety after overdose, the common belief on newer generation antidepressants having fewer side effects than TCAs appears to be true. TCAs were also associated with higher drop-out rates, lower tolerability, and higher cardiac side-effects. However, evidence regarding side effects including dry mouth, gastrointestinal side effects, hepatotoxicity, seizure, and weight has been inconsistent, some studies demonstrated the superiority of SSRIs and SNRIs over TCAs, while others found the opposite. Some other side effects such as sexual dysfunction, bleeding, and hyponatremia were more prominent with either SSRIs or SNRIs.


Antidepressive Agents; Depressive Disorder; Drug-related Side Effects and Adverse Reactions

MeSH Terms

Antidepressive Agents*
Antidepressive Agents, Tricyclic
Depressive Disorder
Drug-Related Side Effects and Adverse Reactions
Serotonin and Noradrenaline Reuptake Inhibitors
Serotonin Uptake Inhibitors
Antidepressive Agents
Antidepressive Agents, Tricyclic
Serotonin Uptake Inhibitors
Serotonin and Noradrenaline Reuptake Inhibitors
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