Off-label Uses of Selective Serotonin Reuptake Inhibitors (SSRIs)

Curr Neuropharmacol. 2022;20(4):693-712. doi: 10.2174/1570159X19666210517150418.


Psychiatric drugs have primacy for off-label prescribing. Among those, selective serotonin reuptake inhibitors (SSRIs) are highly versatile and, therefore, widely prescribed. Moreover, they are commonly considered as having a better safety profile compared to other antidepressants. Thus, when it comes to off-label prescribing, SSRIs rank among the top positions. In this review, we present the state of the art of off-label applications of selective serotonin reuptake inhibitors, ranging from migraine prophylaxis to SARS-CoV-2 antiviral properties. Research on SSRIs provided significant evidence in the treatment of premature ejaculation, both with the on-label dapoxetine 30 mg and the off-label paroxetine 20 mg. However, other than a serotoninergic syndrome, serious conditions like increased bleeding rates, hyponatremia, hepatoxicity, and post-SSRIs sexual dysfunctions, are consistently more prominent when using such compounds. These insidious side effects might be frequently underestimated during common clinical practice, especially by nonpsychiatrists. Thus, some points must be addressed when using SSRIs. Among these, a psychiatric evaluation before every administration that falls outside the regulatory agencies-approved guidelines has to be considered mandatory. For these reasons, we aim with the present article to identify the risks of inappropriate uses and to advocate the need to actively boost research encouraging future clinical trials on this topic.

Keywords: PSSD; SSRI; antidepressants; hypersexuality; off-label; paraphilic disorders; premature ejaculation.

Publication types

  • Review

MeSH terms

  • COVID-19 Drug Treatment*
  • Ejaculation
  • Humans
  • Male
  • Off-Label Use
  • SARS-CoV-2
  • Selective Serotonin Reuptake Inhibitors* / therapeutic use


  • Serotonin Uptake Inhibitors

Grants and funding