Advances in Therapy

, Volume 19, Issue 1, pp 17–26 | Cite as

Selective serotonin reuptake inhibitor discontinuation syndrome: A review

  • Lut Tamam
  • Nurgul Ozpoyraz


Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed in the treatment of depression and anxiety, as well as obsessive-compulsive, eating, and impulse-control disorders. Paralleling their widespread use has been an increase in adverse-effect reports not noted during short-term efficacy studies. Significant among these adverse effects is SSRI discontinuation syndrome, which follows the interruption of extended treatment or a reduction in drug dosage and entails somatic and psychological symptoms. These self-limiting symptoms resolve on reintroduction of the drug and cannot be explained as a remanifestation of the original disorder. To facilitate proper diagnosis and avoid unnecessary therapeutic or diagnostic interventions, all physicians who prescribe SSRIs should become familiar with these symptoms. The most appropriate approach to therapy for discontinuation syndrome involves educating patients and reassuring them that this is a reversible condition, reinstating the original SSRI, and further slowing the rate of tapering.


selective serotonin reuptake inhibitors antidepressants discontinuation syndrome adverse effects 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Haddad P. The SSRI discontinuation syndrome.J Psychopharmacol. 1998;2:305–313.CrossRefGoogle Scholar
  2. 2.
    Preskorn SH.Clinical Pharmacology of Selective Serotonin Reuptake Inhibitors. Professional Communications Inc; 1996.Google Scholar
  3. 3.
    Stahl MMS, Lindquist M, Peterson M, et al. Withdrawal reactions with selective serotonin reuptake inhibitors as reported to the WHO system.Eur J Clin Pharmacol. 1997;53:163–169.PubMedCrossRefGoogle Scholar
  4. 4.
    Price JS, Waller PC, Wood SM, Mackay AV. A comparison of post-marketing safety of four selective re-uptake inhibitors including the investigation of symptoms occurring on withdrawal.Br J Clin Pharmacol. 1996;42:757–763.PubMedCrossRefGoogle Scholar
  5. 5.
    Black DW, Wesner R, Gabel J. The abrupt discontinuation of fluvoxamine in patients with panic disorder.J Clin Psychiatry. 1993;54:146–149.PubMedGoogle Scholar
  6. 6.
    Black K, Shea C, Dursun S, Kutcher S. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria.J Psychiatry Neurosci. 2000;25:255–261.PubMedGoogle Scholar
  7. 7.
    Hindmarch I, Kimber S, Cockle SM. Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance.Int Clin Psychopharmacol. 2000;15:305–318.PubMedGoogle Scholar
  8. 8.
    Haddad P, Lejoyeux M, Young A. Antidepressant discontinuation reactions.BMJ. 1998;316: 1105–1106.PubMedGoogle Scholar
  9. 9.
    Lejoyeux M, Ades J. Antidepressant discontinuation: a review of the literature.J Clin Psychiatry. 1997;58(suppl 7):11–16.PubMedGoogle Scholar
  10. 10.
    Lane RM. Withdrawal symptoms after discontinuation of selective serotonin reuptake inhibitors.J Serotonin Res. 1996;3:75–83.Google Scholar
  11. 11.
    Rosenbaum JF, Fava M, Hoog SL, Ascroft RC, Krebs WB. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial.Biol Psychiatry. 1998;44:77–87.PubMedCrossRefGoogle Scholar
  12. 12.
    Zajecka J, Tracy KA, Mitchell S. Discontinuation symptoms after treatment with serotonin reuptake inhibitors: a literature review.J Clin Psychiatry. 1997;58:291–297.PubMedGoogle Scholar
  13. 13.
    Skaehill PA, Welch EB. SSRI withdrawal syndrome.Consult Pharm. 1997;12:1112–1118.Google Scholar
  14. 14.
    Benazzi F. Mirtazapine withdrawal symptoms.Can J Psychiatry. 1998;43:525.Google Scholar
  15. 15.
    Boyd IW. Venlafaxine withdrawal reactions.Med J Aust. 1998;169:91–92.PubMedGoogle Scholar
  16. 16.
    Diler RS, Tamam L, Avci A. Withdrawal symptoms associated with paroxetine discontinuation in a 9-year old boy.J Clin Psychopharmacol. 2000;20:586–587.PubMedCrossRefGoogle Scholar
  17. 17.
    Fava GA, Grandi S. Withdrawal syndromes after paroxetine and sertraline discontinuation.J Clin Psychopharmacol. 1995;15:374–375.PubMedCrossRefGoogle Scholar
  18. 18.
    Frost L, Lal S. Shock-like sensations after discontinuation of selective reuptake inhibitors.Am J Psychiatry. 1995;152:180.Google Scholar
  19. 19.
    Green B. Persistent adverse neurological effects (PANES) following SSRI discontinuation. Psychiatry On-line, 2000. Available at: Accessed November 2001.Google Scholar
  20. 20.
    Koopowitz LF, Berk M. Paroxetine induced withdrawal effects.Hum Psychopharmacol. 1995; 10:147–148.CrossRefGoogle Scholar
  21. 21.
    Lauber C. Nefazodone withdrawal symptoms.Can J Psychiatry. 1999;44:285–286.PubMedGoogle Scholar
  22. 22.
    Louie AK, Lannon RA, Ajari LJ. Withdrawal reactions after sertraline discontinuation.Am J Psychiatry. 1994;151:450–451.PubMedGoogle Scholar
  23. 23.
    Stoukides JA, Stoukides CA. Extrapyramidal symptoms upon discontinuation of fluoxetine.Am J Psychiatry. 1991;148:1263.PubMedGoogle Scholar
  24. 24.
    Szabadi E. Fluvoxamine withdrawal syndrome.Br J Psychiatry. 1992;160:283–284.PubMedGoogle Scholar
  25. 25.
    Rosenstock HA. Sertraline withdrawal in 2 brothers: a case report.Int Clin Psychopharmacol. 1996;11:58–59.PubMedCrossRefGoogle Scholar
  26. 26.
    Coupland N, Bell CJ, Potokar JP. Serotonin reuptake inhibitor withdrawal.J Clin Psychopharmacol. 1996;16:356–362.PubMedCrossRefGoogle Scholar
  27. 27.
    Michelson D, Fava M, Amsterdam J, et al. Interruption of selective serotonin reuptake inhibitor treatment.Br J Psychiatry. 2000;176:363–368.PubMedCrossRefGoogle Scholar
  28. 28.
    Olver JS, Burrows GD, Norman TR. Discontinuation syndromes with selective serotonin reuptake inhibitors. Are there clinically relevant differences?CNS Drugs. 1999;12:171–177.CrossRefGoogle Scholar
  29. 29.
    Mann AM, MacPherson AS. Clinical experience with imipramine in the treatment of depression.CMAJ. 1959;4:38–47.Google Scholar
  30. 30.
    Cooper GL. The safety of fluoxetine: an update.Br J Psychiatry. 1988;153(suppl 3):77–86.Google Scholar
  31. 31.
    Bryois C, Rubin C, Voirol P, Kosel M, Baumann P. Withdrawal symptoms after discontinuation of a citalopram treatment: a prospective study.Eur Neuropsychopharmacol. 1997;7(suppl 2):S142.CrossRefGoogle Scholar
  32. 32.
    Dilsaver SC, Greden JF, Snider RM. Antidepressant withdrawal syndromes: phenomenology and physiopathology.Int Clin Psychopharmacol. 1987;2:11–19.CrossRefGoogle Scholar
  33. 33.
    Schatzberg AF, Haddad P, Kaplan EM, et al. Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition.J Clin Psychiatry. 1997;58(suppl 7):5–10.PubMedGoogle Scholar
  34. 34.
    Goldstein DJ. Effects of third trimester fluoxetine exposure on the newborn.J Clin Psychopharmacol. 1995;15:417–420.PubMedCrossRefGoogle Scholar
  35. 35.
    Kent LSW, Laidlaw JDD. Suspected congenital sertraline dependence.Br J Psychiatry. 1995;167: 412–413.PubMedCrossRefGoogle Scholar
  36. 36.
    Spencer MJ. Fluoxetine hydrochloride toxicity in neonates.Pediatrics. 1993;92:721–722.PubMedGoogle Scholar
  37. 37.
    Schatzberg AF, Haddad P, Kaplan EM, et al. Possible biological mechanisms of serotonin reuptake inhibitor discontinuation syndrome.J Clin Psychiatry. 1997;58(suppl 7):23–27.PubMedGoogle Scholar
  38. 38.
    Rosenbaum JF, Zajecka J. Clinical management of antidepressant discontinuation.J Clin Psychiatry. 1997;58(suppl 7):37–40.PubMedGoogle Scholar
  39. 39.
    Kaplan EM. Antidepressant noncompliance as a factor in the discontinuation symptoms.J Clin Psychiatry. 1997;58(suppl 7):31–36.PubMedGoogle Scholar
  40. 40.
    Young AH, Currie A. Physician knowledge of antidepressant withdrawal effects: a survey.J Clin Psychiatry. 1997;58(suppl 7):28–30.PubMedGoogle Scholar
  41. 41.
    Debattista C, Schatzberg AF. Physical symptoms associated with paroxetine withdrawal.Am J Psychiatry. 1995;152:1234–1235.Google Scholar
  42. 42.
    Raby WN. Treatment of venlafaxine discontinuation symptoms with ondansetron.J Clin Psychiatry. 1998;59:621–622.PubMedGoogle Scholar

Copyright information

© Health Communications Inc 2002

Authors and Affiliations

  • Lut Tamam
    • 1
  • Nurgul Ozpoyraz
    • 1
  1. 1.Department of PsychiatryCukurova University Faculty of MedicineAdanaTurkey

Personalised recommendations