A Focus on Abuse/Misuse and Withdrawal Issues with Selective Serotonin Reuptake Inhibitors (SSRIs): Analysis of Both the European EMA and the US FAERS Pharmacovigilance Databases

Stefania Chiappini, Rachel Vickers-Smith, Amira Guirguis, John Martin Corkery, Giovanni Martinotti, Fabrizio Schifano

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7 Citations (SciVal)


Despite increasing reports, antidepressant (AD) misuse and dependence remain underes-timated issues, possibly due to limited epidemiological and pharmacovigilance evidence. Thus, here we aimed to determine available pharmacovigilance misuse/abuse/dependence/withdrawal signals relating to the Selective Serotonin Reuptake Inhibitors (SSRI) citalopram, escitalopram, paroxetine, fluoxetine, and sertraline. Both EudraVigilance (EV) and Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) datasets were analysed to identify AD misuse/abuse/dependence/withdrawal issues. A descriptive analysis was performed; moreover, pharmacovigilance measures, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayesian geometric mean (EBGM) were calculated. Both datasets showed increasing trends of yearly reporting and similar signals regarding abuse and dependence. From the EV, a total of 5335 individual ADR reports were analysed, of which 30% corresponded to paroxetine (n = 1,592), 27% cital-opram (n = 1,419), 22% sertraline (n = 1,149), 14% fluoxetine (n = 771), and 8% escitalopram (n = 404). From FAERS, a total of 144,395 individual ADR reports were analysed, of which 27% were related to paroxe-tine, 27% sertraline, 18% citalopram, 16% fluoxetine, and 13% escitalopram. Comparing SSRIs, the EV misuse/abuse-related ADRs were mostly recorded for citalopram, fluoxetine, and sertraline; conversely, dependence was mostly associated with paroxetine, and withdrawal to escitalopram. Similarly, in the FAERS dataset, dependence/withdrawal-related signals were more frequently reported for paroxetine. Although SSRIs are considered non-addictive pharmacological agents, a range of proper withdrawal symptoms can occur well after discontinuation, especially with paroxetine. Prescribers should be aware of the potential for dependence and withdrawal associated with SSRIs.

Original languageEnglish
Article number565
Issue number5
StatePublished - May 2022

Bibliographical note

Funding Information:
Conflicts of Interest: F.S. was a member of the UK Advisory Council on the Misuse of Drugs (ACMD; 2011–2019) and is currently a member of the EMA Advisory Board (Psychiatry). J.M.C. is a member of the ACMD’s Novel Psychoactive Substances and Technical Committees. G.M. has been a consultant and/or a speaker and/or has received research grants from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier, and Recordati. A.G., S.C., and R.V.-S. declare no conflict of interest.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • antidepressants
  • drug misuse
  • pharmacovigilance
  • prescription drug abuse
  • selective serotonin reuptake inhibitor (SSRI)
  • withdrawal

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery


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