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Journal of Psychiatry & Neuroscience : JPN logoLink to Journal of Psychiatry & Neuroscience : JPN
. 2000 May;25(3):255–261.

Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria.

K Black 1, C Shea 1, S Dursun 1, S Kutcher 1
PMCID: PMC1407715  PMID: 10863885

Abstract

OBJECTIVE: To establish specific criteria by which selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome may be identified. DATA SOURCES: MEDLINE and PSYCHLIT databases were searched for case reports published from 1986 to 1997 inclusive, and references of relevant articles were also searched. STUDY SELECTION: Forty-six case reports of symptoms following the discontinuation of fluoxetine, fluvoxamine, paroxetine or sertraline were selected. Three studies of SSRI discontinuation were also reviewed. DATA EXTRACTION: Demographic and treatment information, as well as the timing, duration, number, nature and frequency of dicontinuation symptoms. DATA SYNTHESIS: Paroxetine was most frequently implicated. The drug had been tapered in half of the cases. In some cases, symptom onset began during taper, whereas, in most cases, symptoms began within 1 to 3 days of drug discontinuation. Fifty-three different symptoms were reported, with dizziness being the most common. Other common symptoms were nausea or emesis, fatigue, headache, gait instability and insomnia. Shock-like sensations, paresthesia and visual disturbances were the most rare. Without intervention, symptoms persisted for more than a week in half of the cases. In cases in which the SSRI was restarted, symptoms resolved within 72 hours. In some cases, withdrawal symptoms recurred when the same SSRI was again discontinued. CONCLUSIONS: Findings were used to construct diagnostic criteria for the SSRI discontinuation syndrome. These criteria are 2 or more of the following symptoms developing within 1 to 7 days of discontinuation or reduction in dosage of an SSRI after at least 1 month's use, when these symptoms cause clinically significant distress or impairment and are not due to a general medical condition or recurrence of a mental disorder: dizziness, light-headedness, vertigo or feeling faint; shock-like sensations or paresthesia; anxiety; diarrhea; fatigue; gait instability; headache; insomnia; irritability; nausea or emesis; tremor; and visual disturbances.

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Selected References

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  1. Amsden G. W., Georgian F. Orthostatic hypotension induced by sertraline withdrawal. Pharmacotherapy. 1996 Jul-Aug;16(4):684–686. [PubMed] [Google Scholar]
  2. Arya D. K. Withdrawal after discontinuation of paroxetine. Aust N Z J Psychiatry. 1996 Oct;30(5):702–702. [PubMed] [Google Scholar]
  3. Barr L. C., Goodman W. K., Price L. H. Physical symptoms associated with paroxetine discontinuation. Am J Psychiatry. 1994 Feb;151(2):289–289. doi: 10.1176/ajp.151.2.289. [DOI] [PubMed] [Google Scholar]
  4. Berlin C. S. Fluoxetine withdrawal symptoms. J Clin Psychiatry. 1996 Feb;57(2):93–94. [PubMed] [Google Scholar]
  5. Black D. W., Wesner R., Gabel J. The abrupt discontinuation of fluvoxamine in patients with panic disorder. J Clin Psychiatry. 1993 Apr;54(4):146–149. [PubMed] [Google Scholar]
  6. Bloch M., Stager S. V., Braun A. R., Rubinow D. R. Severe psychiatric symptoms associated with paroxetine withdrawal. Lancet. 1995 Jul 1;346(8966):57–57. doi: 10.1016/s0140-6736(95)92691-7. [DOI] [PubMed] [Google Scholar]
  7. Cooper G. L. The safety of fluoxetine--an update. Br J Psychiatry Suppl. 1988 Sep;(3):77–86. [PubMed] [Google Scholar]
  8. Coupland N. J., Bell C. J., Potokar J. P. Serotonin reuptake inhibitor withdrawal. J Clin Psychopharmacol. 1996 Oct;16(5):356–362. doi: 10.1097/00004714-199610000-00003. [DOI] [PubMed] [Google Scholar]
  9. Debattista C., Schatzberg A. F. Physical symptoms associated with paroxetine withdrawal. Am J Psychiatry. 1995 Aug;152(8):1235–1234. doi: 10.1176/ajp.152.8.1235b. [DOI] [PubMed] [Google Scholar]
  10. Dilsaver S. C. Antidepressant withdrawal syndromes: phenomenology and pathophysiology. Acta Psychiatr Scand. 1989 Feb;79(2):113–117. doi: 10.1111/j.1600-0447.1989.tb08578.x. [DOI] [PubMed] [Google Scholar]
  11. Dilsaver S. C., Greden J. F. Antidepressant withdrawal phenomena. Biol Psychiatry. 1984 Feb;19(2):237–256. [PubMed] [Google Scholar]
  12. Dilsaver S. C. Heterocyclic antidepressant, monoamine oxidase inhibitor and neuroleptic withdrawal phenomena. Prog Neuropsychopharmacol Biol Psychiatry. 1990;14(2):137–161. doi: 10.1016/0278-5846(90)90097-z. [DOI] [PubMed] [Google Scholar]
  13. Dominguez R. A., Goodnick P. J. Adverse events after the abrupt discontinuation of paroxetine. Pharmacotherapy. 1995 Nov-Dec;15(6):778–780. [PubMed] [Google Scholar]
  14. Einbinder E. Fluoxetine withdrawal? Am J Psychiatry. 1995 Aug;152(8):1235–1235. doi: 10.1176/ajp.152.8.1235a. [DOI] [PubMed] [Google Scholar]
  15. Fava G. A., Grandi S. Withdrawal syndromes after paroxetine and sertraline discontinuation. J Clin Psychopharmacol. 1995 Oct;15(5):374–375. doi: 10.1097/00004714-199510000-00012. [DOI] [PubMed] [Google Scholar]
  16. Frost L., Lal S. Shock-like sensations after discontinuation of selective serotonin reuptake inhibitors. Am J Psychiatry. 1995 May;152(5):810–810. doi: 10.1176/ajp.152.5.810a. [DOI] [PubMed] [Google Scholar]
  17. Gilbert P. L., Harris M. J., McAdams L. A., Jeste D. V. Neuroleptic withdrawal in schizophrenic patients. A review of the literature. Arch Gen Psychiatry. 1995 Mar;52(3):173–188. doi: 10.1001/archpsyc.1995.03950150005001. [DOI] [PubMed] [Google Scholar]
  18. Haddad P. Newer antidepressants and the discontinuation syndrome. J Clin Psychiatry. 1997;58 (Suppl 7):17–22. [PubMed] [Google Scholar]
  19. Keuthen N. J., Cyr P., Ricciardi J. A., Minichiello W. E., Buttolph M. L., Jenike M. A. Medication withdrawal symptoms in obsessive-compulsive disorder patients treated with paroxetine. J Clin Psychopharmacol. 1994 Jun;14(3):206–207. doi: 10.1097/00004714-199406000-00010. [DOI] [PubMed] [Google Scholar]
  20. Leiter F. L., Nierenberg A. A., Sanders K. M., Stern T. A. Discontinuation reactions following sertraline. Biol Psychiatry. 1995 Nov 15;38(10):694–695. doi: 10.1016/0006-3223(95)00311-8. [DOI] [PubMed] [Google Scholar]
  21. Louie A. K., Lannon R. A., Ajari L. J. Withdrawal reaction after sertraline discontinuation. Am J Psychiatry. 1994 Mar;151(3):450–451. doi: 10.1176/ajp.151.3.450b. [DOI] [PubMed] [Google Scholar]
  22. Luchins D. J., Freed W. J., Wyatt R. J. The role of cholinergic supersensitivity in the medical symptoms associated with withdrawal of antipsychotic drugs. Am J Psychiatry. 1980 Nov;137(11):1395–1398. doi: 10.1176/ajp.137.11.1395. [DOI] [PubMed] [Google Scholar]
  23. Mallya G., White K., Gunderson C. Is there a serotonergic withdrawal syndrome? Biol Psychiatry. 1993 Jun 1;33(11-12):851–852. doi: 10.1016/0006-3223(93)90032-9. [DOI] [PubMed] [Google Scholar]
  24. Montgomery S. A. Efficacy in long-term treatment of depression. J Clin Psychiatry. 1996;57 (Suppl 2):24–30. [PubMed] [Google Scholar]
  25. Oehrberg S., Christiansen P. E., Behnke K., Borup A. L., Severin B., Soegaard J., Calberg H., Judge R., Ohrstrom J. K., Manniche P. M. Paroxetine in the treatment of panic disorder. A randomised, double-blind, placebo-controlled study. Br J Psychiatry. 1995 Sep;167(3):374–379. doi: 10.1192/bjp.167.3.374. [DOI] [PubMed] [Google Scholar]
  26. Pacheco L., Malo P., Aragues E., Etxebeste M. More cases of paroxetine withdrawal syndrome. Br J Psychiatry. 1996 Sep;169(3):384–384. doi: 10.1192/bjp.169.3.384a. [DOI] [PubMed] [Google Scholar]
  27. Phillips S. D. A possible paroxetine withdrawal syndrome. Am J Psychiatry. 1995 Apr;152(4):645–646. doi: 10.1176/ajp.152.4.645b. [DOI] [PubMed] [Google Scholar]
  28. Price J. S., Waller P. C., Wood S. M., MacKay A. V. A comparison of the post-marketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal. Br J Clin Pharmacol. 1996 Dec;42(6):757–763. doi: 10.1046/j.1365-2125.1996.00498.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pyke R. E. Paroxetine withdrawal syndrome. Am J Psychiatry. 1995 Jan;152(1):149–150. doi: 10.1176/ajp.152.1.149b. [DOI] [PubMed] [Google Scholar]
  30. Reeves R. R., Pinkofsky H. B. Lhermitte's sign in paroxetine withdrawal. J Clin Psychopharmacol. 1996 Oct;16(5):411–412. doi: 10.1097/00004714-199610000-00013. [DOI] [PubMed] [Google Scholar]
  31. Rosenstock H. A. Sertraline withdrawal in two brothers: a case report. Int Clin Psychopharmacol. 1996 Mar;11(1):58–59. doi: 10.1097/00004850-199603000-00009. [DOI] [PubMed] [Google Scholar]
  32. Schatzberg A. F., Haddad P., Kaplan E. M., Lejoyeux M., Rosenbaum J. F., Young A. H., Zajecka J. Possible biological mechanisms of the serotonin reuptake inhibitor discontinuation syndrome. Discontinuation Consensus Panel. J Clin Psychiatry. 1997;58 (Suppl 7):23–27. [PubMed] [Google Scholar]
  33. Schatzberg A. F., Haddad P., Kaplan E. M., Lejoyeux M., Rosenbaum J. F., Young A. H., Zajecka J. Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. Discontinuation Consensus panel. J Clin Psychiatry. 1997;58 (Suppl 7):5–10. [PubMed] [Google Scholar]
  34. Stoukides J. A., Stoukides C. A. Extrapyramidal symptoms upon discontinuation of fluoxetine. Am J Psychiatry. 1991 Sep;148(9):1263–1263. doi: 10.1176/ajp.148.9.1263a. [DOI] [PubMed] [Google Scholar]
  35. Szabadi E. Fluvoxamine withdrawal syndrome. Br J Psychiatry. 1992 Feb;160:283–284. doi: 10.1192/bjp.160.2.283b. [DOI] [PubMed] [Google Scholar]
  36. Weiden P. J., Aquila R., Dalheim L., Standard J. M. Switching antipsychotic medications. J Clin Psychiatry. 1997;58 (Suppl 10):63–72. [PubMed] [Google Scholar]
  37. Zajecka J., Tracy K. A., Mitchell S. Discontinuation symptoms after treatment with serotonin reuptake inhibitors: a literature review. J Clin Psychiatry. 1997 Jul;58(7):291–297. doi: 10.4088/jcp.v58n0702. [DOI] [PubMed] [Google Scholar]

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