The adult SSRI/SNRI withdrawal syndrome: A clinically heterogeneous entity

Giorgio D. Kotzalidis, Barbara Patrizi, Saverio Simone Caltagirone, Alexia Koukopoulos, Valeria Savoja, Gaia Ruberto, Caterina Tatarelli, Isabella Pacchiarotti, Simone Lazanio, Gabriele Sani, Giovanni Manfredi, Eleonora de Pisa, Roberto Tatarelli, Paolo Girardi

Research output: Contribution to journalArticlepeer-review


Various reports and controlled studies show that, in some patients interrupting treatment with selective serotonin re-uptake inhibitors or serotonin and noradrenaline re-uptake inhibitors, symptoms develop which cannot be attributed to rebound of their underlying condition. These symptoms are variable and patient-specific, rather than drug specific, but occur more with some drugs than others. It has been claimed that the shorter the half-live, the more a drug is likely to induce a withdrawal syndrome; however, this is not supported by data. The drugs most often involved with withdrawal are paroxetine and venlafaxine, while it appears that withdrawal syndrome associated with discontinuation (or steep dose reduction) of fluoxetine is milder and occurs later. Acute lack of serotonin or its drug substitute on receptors or transporters is thought to be at the basis of the development of the syndrome. However, the fact that the symptoms described for withdrawal overlap to a great extent with those of the serotonin syndrome makes it possible that both serotonergic hypo- and hyperactivity, alternating and fluctuating, may be responsible for the syndrome and for the multitude of its expressions. There is no specific treatment other than reintroduction of the drug or substitution with a similar drug. The syndrome usually resolves in days or weeks, even if untreated. Current practice is to gradually withdraw drugs like paroxetine and venlafaxine, but even with extremely slow tapering, some patients will develop some symptoms or will be unable to completely discontinue the drug.

Original languageEnglish
Pages (from-to)61-75
Number of pages15
JournalClinical Neuropsychiatry
Issue number2
Publication statusPublished - Apr 2007


  • Discontinuation syndrome
  • Drug dependence
  • Paroxetine
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin syndrome
  • Serotonin-noradrenaline reuptake inhibitors (SNRIs)
  • Venlafaxine
  • Withdrawal syndrome

ASJC Scopus subject areas

  • Psychiatry and Mental health


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