CNS Drugs

, Volume 16, Issue 4, pp 273–283 | Cite as

Discontinuation Syndrome in Dysthymic Patients Treated with Selective Serotonin Reuptake Inhibitors

A Clinical Investigation
  • Filippo Bogetto
  • Silvio BellinoEmail author
  • Raffaele Bonatto Revello
  • Luca Patria
Original Research Article


Objective: Many authors have reported discontinuation symptoms associated with selective serotonin reuptake inhibitors (SSRIs). The aim of this study was to investigate the incidence and characteristics of the discontinuation syndrome in patients who stopped treatment with the SSRIs paroxetine and fluoxetine under the usual conditions of clinical practice, and to identify clinical predictors of the syndrome.

Methods: Ninety-seven outpatients who received an initial diagnosis of dysthymic disorder, who responded to ≥8 weeks treatment with paroxetine (n = 52) or fluoxetine (n = 45), and who discontinued the SSRI according to their psychiatrist’s instructions were included. They were assessed at the time of discontinuation using a semi-structured interview for clinical and treatment characteristics, the Hamilton Depression Rating Scale (HAM-D) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Patients were then assessed 4 weeks later using a checklist for discontinuation symptoms, a semi-structured interview for discontinuation symptom characteristics, and the HAM-D and the MADRS.

Results: A discontinuation syndrome was found in 26 patients (26.8% of our sample); of this group, 22 patients (84.6%) had received paroxetine, and 4 patients (15.4%) had received fluoxetine. The mean time at onset of symptoms was 2 days after drug discontinuation and the mean duration was 5 days. The statistical comparison between the groups with and without a discontinuation syndrome found two significant differences — a discontinuation syndrome was more common in patients treated with paroxetine and in patients with an earlier onset of dysthymic disorder. Multiple regression analysis confirmed that these two factors were related to the duration of discontinuation symptoms, while the number of symptoms was associated with three factors, including use of paroxetine, age at onset of dysthmia and female gender.

Conclusions: A discontinuation syndrome is common after treatment with SSRIs is stopped in patients with dysthymia, and it appears to be more common in patients receiving paroxetine than in those receiving fluoxetine. The syndrome is related both to drug and clinical characteristics. The features of the syndrome in patients with different Axis I diagnoses should be compared in further investigations.


Fluoxetine Paroxetine Somatic Symptom Hamilton Depression Rate Scale Stepwise Multiple Regression Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was not funded by any research grants, and no pharmaceutical companies were informed of or involved in the investigation. The authors have no potential conflicts of interest that are directly relevant to the contents of the manuscript.


  1. 1.
    Zajecka J, Tracy KA, Mitchell S. Discontinuation symptoms after treatment with serotonin reuptake inhibitor: a literature review. J Clin Psychiatry 1997; 58: 291–7PubMedCrossRefGoogle Scholar
  2. 2.
    Andersen H, Kristiansen ES. Tofranil treatment of endogenous depressions. Acta Psychiatr Scand 1959; 34: 387–97PubMedCrossRefGoogle Scholar
  3. 3.
    Kramer JD, Klein DF, Fink M. Withdrawal symptoms following discontinuation of imipramine therapy. Am J Psychiatry 1961; 118: 549–50PubMedGoogle Scholar
  4. 4.
    Bialos D, Giller F, Jatlow P, et al. Recurrence of depression after discontinuation of amitryptiline. Am J Psychiatry 1982; 139: 325–9PubMedGoogle Scholar
  5. 5.
    Dilsaver SC, Greden JF. Antidepressant withdrawal phenomena. Biol Psychiatry 1984; 19: 237–56PubMedCrossRefGoogle Scholar
  6. 6.
    Diamond BI, Borison RL, Katz R, et al. Rebound reactions due to clomipramine. Psychopharmacol Bull 1989; 25: 209–12PubMedGoogle Scholar
  7. 7.
    Halle MT, Dilsaver SC. Tranylcypromine withdrawal phenomena. J Psychiatry Neurosci 1993; 18: 49–50PubMedGoogle Scholar
  8. 8.
    Stoukides JA, Stoukides CA. Extrapyramidal symptoms upon discontinuation of fluoxetine [letter]. Am J Psychiatry 1991; 148: 1263PubMedGoogle Scholar
  9. 9.
    Black DW, Wesner R, Gabel J. The abrupt discontinuation of fluvoxamine in patients with panic disorder. J Clin Psychiatry 1993; 54: 146–9PubMedGoogle Scholar
  10. 10.
    Mallya G, White K, Gunderson C. Is there a serotonergic withdrawal syndrome? Biol Psychiatry 1993; 33: 851–2PubMedCrossRefGoogle Scholar
  11. 11.
    Barr LC, Goodmann WK, Price LH. Physical symptoms associated with paroxetine discontinuation [letter]. Am J Psychiatry 1994; 151: 289PubMedGoogle Scholar
  12. 12.
    Keuthen NJ, Cyr P, Ricciardi JA, et al. Medication withdrawal symptoms in OCD patients treated with paroxetine. J Clin Psychopharmacol 1994; 14: 206–7PubMedCrossRefGoogle Scholar
  13. 13.
    Bloch M, Stager SV, Braun AR, et al. Severe psychiatric symptoms associated with paroxetine withdrawal [letter]. Lancet 1995; 346: 57PubMedCrossRefGoogle Scholar
  14. 14.
    Einbinder E. Fluoxetine withdrawal? [letter]. Am J Psychiatry 1995; 152: 1235PubMedGoogle Scholar
  15. 15.
    Fava GA, Grandi S. Withdrawal syndromes after paroxetine and sertraline discontinuation. J Clin Psychopharmacol 1995; 15: 374–5PubMedCrossRefGoogle Scholar
  16. 16.
    Frost L, Lal S. Shock-like sensations after discontinuation of selective serotonin reuptake inhibitors [letter]. Am J Psychiatry 1995; 152: 810PubMedGoogle Scholar
  17. 17.
    Kasantikul D. Reversible delirium after discontinuation of fluoxetine. J Med Assoc Thai 1995; 78: 53–4PubMedGoogle Scholar
  18. 18.
    Koopowitz LF, Berk M. Paroxetine induced withdrawal effects. Hum Psychopharmacol 1995; 10: 147–8CrossRefGoogle Scholar
  19. 19.
    Leiter FL, Nierenberg AA, Sanders KM, et al. Discontinuation reactions following sertraline. Biol Psychiatry 1995; 38: 694–5PubMedCrossRefGoogle Scholar
  20. 20.
    Pyke RE. Paroxetine withdrawal syndrome. Am J Psychiatry 1995; 152: 149–50PubMedGoogle Scholar
  21. 21.
    Berlin CS. Fluoxetine withdrawal symptoms. J Clin Psychiatry 1996; 57: 93–4PubMedGoogle Scholar
  22. 22.
    Coupland NJ, Bell CJ, Potokar JP. Serotonin reuptake inhibitor withdrawal. J Clin Psychopharmacol 1996; 16: 356–62PubMedCrossRefGoogle Scholar
  23. 23.
    Lejoyeux M, Adès J, Mourad I, et al. Antidepressant withdrawal syndrome: recognition, prevention and management. CNS Drugs 1996; 5(4): 278–92CrossRefGoogle Scholar
  24. 24.
    Pacheco L, Malo P, Aragues E, et al. More cases of paroxetine withdrawal syndrome [letter]. Br J Psychiatry 1996; 169: 384PubMedCrossRefGoogle Scholar
  25. 25.
    Price JS, Waller PC, Wood SM, et al. A comparison of the postmarketing safety of four selective serotonin reuptake inhibitors including reinvestigation of symptoms occurring on withdrawal. Br J Clin Pharmacol 1996; 42: 757–63PubMedCrossRefGoogle Scholar
  26. 26.
    Stahl MMS, Lindquist M, Petterson M, et al. Withdrawal reactions with selective serotonin reuptake inhibitors as reported to the WHO system. Eur J Clin Pharmacol 1997; 53: 163–9PubMedCrossRefGoogle Scholar
  27. 27.
    Haddad PM. Antidepressant discontinuation syndrome: clinical relevance, prevention and management. Drug Saf 2001; 24: 183–97PubMedCrossRefGoogle Scholar
  28. 28.
    Lejoyeux M, Adès J. Antidepressant discontinuation: a review of literature. J Clin Psychiatry 1997; 58Suppl. 7: 11–6PubMedGoogle Scholar
  29. 29.
    Young AH, Currie A. Physicians’ knowledge of antidepressant withdrawal effects: a survey. J Clin Psychiatry 1997; 58Suppl. 7: 28–30PubMedGoogle Scholar
  30. 30.
    Schatzberg AF, Haddad P, Kaplan EM, et al. Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. Discontinuation Consensus Panel. J Clin Psychiatry 1997; 58Suppl. 7: 5–10Google Scholar
  31. 31.
    Oehrberg S, Christiansen PE, Behnke K, et al. Paroxetine in the treatment of panic disorder: a randomised, double-blind, placebo-controlled study. Br J Psychiatry 1995; 167: 374–9PubMedCrossRefGoogle Scholar
  32. 32.
    Rosenbaum JF, Fava M, Hoog SL, et al. Serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry 1998; 44: 77–87PubMedCrossRefGoogle Scholar
  33. 33.
    Zajecka J, Fawcett J, Amsterdam J, et al. Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study. J Clin Psychopharmacol 1998; 18: 193–7PubMedCrossRefGoogle Scholar
  34. 34.
    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: 305–18PubMedCrossRefGoogle Scholar
  35. 35.
    Markowitz JS, DeVane CL, Liston HL, et al. An assessment of selective serotonin reuptake inhibitor discontinuation symptoms with citalopram. Int Clin Psychopharmacol 2000; 15: 329–33PubMedCrossRefGoogle Scholar
  36. 36.
    Michelson D, Fava M, Amsterdam J, et al. Interruption of selective serotonin reuptake inhibitor treatment. Br J Psychiatry 2000; 176: 363–8PubMedCrossRefGoogle Scholar
  37. 37.
    Olver JS, Burrows GD, Norman TR. Discontinuation syndromes with selective serotonin reuptake inhibitors: are there clinically relevant differences? CNS Drugs 1999; 12(3): 171–7CrossRefGoogle Scholar
  38. 38.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
  39. 39.
    Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56–62PubMedCrossRefGoogle Scholar
  40. 40.
    Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967; 6(4): 278–96PubMedCrossRefGoogle Scholar
  41. 41.
    Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382–9PubMedCrossRefGoogle Scholar
  42. 42.
    Haddad P. New antidepressants and the discontinuation syndrome. J Clin Psychiatry 1997; 58Suppl. 7: 17–22PubMedGoogle Scholar
  43. 43.
    Black K, Shea C, Dursun S, et al. Selective serotonin reuptake inhibitors discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci 2000; 25(3): 255–61PubMedGoogle Scholar
  44. 44.
    Lazowick A. Potential withdrawal syndrome associated with SSRI discontinuation. Ann Pharmacother 1995; 29: 1284–5PubMedGoogle Scholar
  45. 45.
    Rosenbaum JF, Zajecka J. Clinical management of antidepressant discontinuation. J Clin Psychiatry 1997; 58Suppl. 7: 37–40PubMedGoogle Scholar
  46. 46.
    Fava GA. Potential sensitising effects of antidepressant drugs on depression. CNS Drugs 1999; 12(4): 247–56CrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Filippo Bogetto
    • 1
  • Silvio Bellino
    • 1
    Email author
  • Raffaele Bonatto Revello
    • 1
  • Luca Patria
    • 1
  1. 1.Unit of Psychiatry, Department of NeuroscienceUniversity of TurinTurinItaly

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