Long-term harms from previous use of selective serotonin reuptake inhibitors: A systematic review

Int J Risk Saf Med. 2019;30(2):59-71. doi: 10.3233/JRS-180046.


Background: Millions of people are treated with antidepressants like selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). This clinical practice is based on short-term trials that have exaggerated the benefits and underestimated the harms. We also know too little about long-term harms.

Aim: To assess harms of SSRIs and SNRIs that persist after end of drug intake.

Methods: Systematic review of placebo-controlled randomised trials of any length in patients with a psychiatric diagnosis and a follow-up of at least six months. Our primary outcomes were mortality, functional outcomes, quality of life and core psychiatric events. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and checked the references for eligible articles. One researcher extracted data and another checked the data extraction.

Results: Our searches returned 9,153 unique records. We included 22 papers for 12 trials on SSRIs. Median intervention and follow-up periods were 15 and 52 weeks, respectively. Median number of randomised participants was 51; only two trials had a drop-out rate below 20%.Outcome reporting was less thorough during follow-up than for the intervention period and only two trials maintained the blind during follow-up. All authors concluded that the drugs were not beneficial in the long term.All trials reported harms outcomes selectively or did not report any. Only two trials reported on any of our primary outcomes (school attendance and number of heavy drinking days).

Conclusion: The randomised trials currently available cannot be used to investigate persistent harms of antidepressants.

Keywords: SNRI; SSRI; antidepressants; harms; long-term.

Publication types

  • Systematic Review

MeSH terms

  • Depression / drug therapy*
  • Humans
  • Long Term Adverse Effects / chemically induced*
  • Risk Assessment
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin and Noradrenaline Reuptake Inhibitors / pharmacology*


  • Serotonin Uptake Inhibitors
  • Serotonin and Noradrenaline Reuptake Inhibitors