Skip to main content
SpringerLink
Log in

Antidepressant Withdrawal Syndrome

Recognition, Prevention and Management

  • Drug Therapy
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Summary

Withdrawal from tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs) and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) can produce somatic and psychological distress. Influenza-like syndromes, gastrointestinal adverse effects, arrhythmias, anxiety, sleep disturbances, movement disorders, mania or hypomania, panic attacks and delirium may follow antidepressant withdrawal. At present, the aetiology of withdrawal symptoms is not fully known.

Withdrawal phenomena are usually prevented by gradually reducing the total daily dosage of the drug in question rather than abruptly discontinuing it. Antimuscarinic agents can be prescribed in order to alleviate the symptoms produced by the withdrawal of TCAs and MAOIs. To date, no drugs have been shown to be useful in the treatment of SSRI-associated withdrawal symptoms. The withdrawal syndrome associated with MAOIs may constitute a medical emergency.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mann AM, MacPherson A. Clinical experience with imipramine (G22355) in the treatment of depression. Can Psychiatr Assoc J 1959; 4: 38–47

    PubMed  CAS  Google Scholar 

  2. Andersen H, Kristiansen ES. Tofranil treatment of endogenous depressions. Acta Psychiatr Scand 1959; 34: 387–97

    Article  PubMed  CAS  Google Scholar 

  3. Kramer JC, Klein DF, Fink M. Withdrawal symptoms following discontinuation of imipramine therapy. Am J Psychiatry 1961; 118: 549–50

    PubMed  CAS  Google Scholar 

  4. Law W, Petti TA, Kazdin A. Withdrawal symptoms after graduated cessation of imipramine in children. Am J Psychiatry 1981; 118: 647–50

    Google Scholar 

  5. Bialos D, Giller E, Jatlow P, et al. Recurrence of depression after discontinuation of amitriptyline. Am J Psychiatry 1982; 139: 325–9

    PubMed  CAS  Google Scholar 

  6. Tyrer P. Clinical effects of abrupt withdrawal from tricyclic antidepressants and monoamine oxidase inhibitors after longterm treatment. J Affect Disord 1984; 6: 1–7

    Article  PubMed  CAS  Google Scholar 

  7. Geller B, Cooper TB, Carr LG. Prospective study of scheduled withdrawal from nortriptyline in children and adolescents. J Clin Psychopharmacol 1987; 7: 252–4

    PubMed  CAS  Google Scholar 

  8. Diamond BI, Borison RL, Katz R, et al. Rebound reactions due to clomipramine. Psychopharmacol Bull 1989; 25 (2): 209–12

    PubMed  CAS  Google Scholar 

  9. Otani K, Sasa H, Kaneko S, et al. Lack of withdrawal symptoms after discontinuation of mianserin. Lancet 1991; 337: 673–4

    Article  PubMed  CAS  Google Scholar 

  10. Ceccherini-Nelli A, Bardellini L, Guazzalli M, et al. Antidepressant withdrawal phenomena: prospective findings [letter). Am J Psychiatry 1993; 150 (1): 165

    PubMed  CAS  Google Scholar 

  11. Mallya G, White K, Gunderson C. Is there a serotoninergic withdrawal syndrome? Biol Psychiatry 1993; 33: 851–2

    Article  PubMed  CAS  Google Scholar 

  12. Barr Le, Goodman WK, Price LH. Physical symptoms associated with paroxetine discontinuation [letter]. Am J Psychiatry 1994; 151 (21): 289

    PubMed  CAS  Google Scholar 

  13. Keuthen NJ, Cyr P, Ricciardi JA, et al. Medication withdrawal symptoms in obsessivecompulsive disorder patients treated with paroxetine. J Clin Psychopharmacol 1994; 14 (31): 206–7

    Article  PubMed  CAS  Google Scholar 

  14. Einbinder E. Fluoxetine withdrawailleneri? Am J Psychiatry 1995; 152 (81): 1235

    PubMed  CAS  Google Scholar 

  15. Baer L, Ricciardi J, Keuthen N, et al. Discontinuing obsessivecompulsive disorder medication with behavior therapy Ilet terl. Am J Psychiatry 1995; 151 (121: 1842

    Google Scholar 

  16. Lejoyeux M, Rouillon F, Ades J, et al. A retrospective study of the effects of withdrawing antidepressants [abstract]. Neuropsychopharmacology 1994 May; 10 (35Pt2): 47S

    Google Scholar 

  17. MacMahon TC. A clinical overview of syndromes following withdrawal of antidepressants. Hosp Community Psychiatry 1986 Sept; 37 (9): 883–4

    Google Scholar 

  18. Dilsaver Se, Greden JE, Snider RM. Antidepressant withdrawal syndromes: phenomenology and physiopathology. Int Clin Psychopharmacol 1987; 2: 1–19

    Article  PubMed  CAS  Google Scholar 

  19. Dilsaver Se. Withdrawal phenomena associated with antidepressant and antipsychotic agents. Drug Saf 1994; 10 (21: 103–14

    Article  PubMed  CAS  Google Scholar 

  20. Boisvert D, Chouinard G. Rebound cardiac arrhythmia after withdrawal from imipramine: a case repon. Am J Psychiatry 1981; 138: 985–6

    PubMed  CAS  Google Scholar 

  21. Dilsaver Se, Feinberg M, Greden JE. Antidepressant withdrawal symptoms treated with anticholinergic agents. Am J Psychiatry 1983; 140 (2): 249–51

    PubMed  CAS  Google Scholar 

  22. Gualtieri CT, Staye J. Withdrawal symptoms after abrupt cessation of amitriptyline in an eight-year-old boy. Am J Psychiatry 1979; 136: 457–8

    PubMed  CAS  Google Scholar 

  23. Shatan C. Withdrawal after abrupt termination of imipramine. Can Psychiatr Assoc J 1966 Suppl.: 150–8

    Google Scholar 

  24. Webster PAC. Withdrawal symptoms in neonates associated with maternal antidepressant therapy. Lancet 1973; 2: 318–9

    Article  PubMed  CAS  Google Scholar 

  25. Gawin FH, Markoff RA. Panic anxiety after abrupt discontinuation of amitriptyline. Am J Psychiatry 1981; 138: 117–8

    PubMed  CAS  Google Scholar 

  26. Davison P, Wardrope J. Acute amitriptyline withdrawal and hyponatraemia. Drug Saf 1993; 8 (1): 78–80

    Article  PubMed  CAS  Google Scholar 

  27. Brown GM, Stancer He, Moldofsky H, et al. Withdrawal from long-term high-dose desipramine therapy; clinical and biological changes. Arch Gen Psychiatry 1978; 35: 1261–4

    Article  PubMed  CAS  Google Scholar 

  28. Dilsaver Se, Kronfol Z, Greden JF, et al. Antidepressant withdrawal syndromes: evidences supponing the cholinergic overdrive hypothesis. J Clin Psychopharmacol 1983; 3: 157–64

    PubMed  CAS  Google Scholar 

  29. Sathananthan GL, Gershon S. Imipramine withdrawal: an akathisia-Iike syndrome. Am J Psychiatry 1973; 130: 1286–7

    PubMed  CAS  Google Scholar 

  30. Weller RA, McKnelly Jr wv. Case repon of withdrawal dyskinesia associated with amoxapine. Am J Psychiatry 1983; 140 (111: 1515–6

    PubMed  CAS  Google Scholar 

  31. Lejoyeux M, Rodiere-Rein C, Ades J. Syndrome de seHage des antiJepreeurs, Desiptiun de cin4 cas. Encephalc 1992; 18: 251–5

    CAS  Google Scholar 

  32. Dilsaver Sc, Greden JF. Antidepressant withdrawal-induced activation I hypomania and mania): mechanism and theoretical significance. Brain Res Rev 1984; 7: 29–48

    Article  CAS  Google Scholar 

  33. Ghadirian AM. Paradoxical mood response following antidepressant withdrawal. Bioi Psychiatry 1986; 21: 1298–300

    Article  CAS  Google Scholar 

  34. Hanman PM. Mania or hypomania after withdrawal from antidepressants. J Fam Pract 1990; 30: 4712

    Google Scholar 

  35. Mirin SM, Schatzberg AF, Creasey DE. Hypomania and mania after withdrawal of tricyclic antidepressants. Am J Psychiatr 1981; 138: 87–9

    PubMed  CAS  Google Scholar 

  36. Nelson Je, Schonenfield RS, Condrad ED. Hypomania after desipramine withdrawal. Am J Psychiatry 1983; 140: 624–5

    PubMed  CAS  Google Scholar 

  37. Van Scheyen JD, van Kammen DP. Clomipramine-induced mania in unipolar depression. Arch Gen Psychiatry 1979; 560-5

  38. Halle MH, Del Medico VJ, Dilsaver Sc. Symptoms of major depression: acute effect of withdrawing antidepressants. Acta Psychiatr Scand 1991; 83: 238–9

    Article  PubMed  CAS  Google Scholar 

  39. Van Sweden B. Rebound antidepressant cardiac arrhythmia. Bioi Psychiatry 1988; 24: 363–4

    Article  Google Scholar 

  40. Liskin B, Roose S, Walsh T. Acute psychosis following phenelzine discontinuation. J Clin Psychopharmacol 1984; 5: 46–7

    Google Scholar 

  41. Roth SD. More on psychosis following phenelzine discontinuation. J Clin Psychopharmacology 1985; 5: 360–1

    Article  Google Scholar 

  42. Halle MT, Dilsaver Sc. Tranylcypromine withdrawal phenomena. J Psychiatry Neurosci 1993; 18 (11: 49–50

    PubMed  CAS  Google Scholar 

  43. Frankel DA, Raskin DE. Psychosis following phenelzine discontinuation [letter]. J Clin Psychopharmacol 1985; 5: 360

    Google Scholar 

  44. Le Gassicke J, Ashcroft GW, Eccleston D, et al. The clinical state, sleep and amine metabolism uf a tranylcypromine spamatel addict. Br J Psychiatry 1965; 3: 357–64

    Article  Google Scholar 

  45. Dilsaver Sc, Greden JF. Antidepressant withdrawal phenomena. Bioi Psychiatry 1984; 19: 237–56

    CAS  Google Scholar 

  46. Pagliaro LA, Pagliaro AM. Abuse potential of antidepressants: does it exist? CNS Drugs 1995; 4: 247–52

    Article  Google Scholar 

  47. Lejoyeux M. Dependance aux antidepresseurs: authentique addiction? L’Encephale 1995; 21 (No Special 1: 63–5

    PubMed  Google Scholar 

  48. Vartzopulos D, Krull E. Dependence on monoamine oxidase inhibitors in high dose. Br J Psychiatry 1991; 158: 856–7

    Article  Google Scholar 

  49. Debanista C, Schatzberg AE. Physical symptoms associated with paroxetine withdrawal. Am J Psychiatry 1995; 152 (8): 12356

    Google Scholar 

  50. Fava GA, Grandi S. Withdrawal syndromes after paroxetine and sertraline discontinuation. J Clin Psychopharmacol 1995; 15: 374–5

    Article  PubMed  CAS  Google Scholar 

  51. Pyke RE. Paroxetine withdrawal syndrome. Am J Psychiatry 1995; 152 (1): 149–50

    PubMed  CAS  Google Scholar 

  52. D’Arcy PE. Dystonia and withdrawal symptoms with paroxetine [letter]. Int Pharm J 1993; 7: 140

    Google Scholar 

  53. Bioch M, Stager SV, Braun AR, et al. Severe psychiatric symptoms associated with paroxetine withdrawal [letter]. Lancet 1995 Jul; 346: 57

    Google Scholar 

  54. Frost L, Lal S. Shock-like sensations after discontinuation of selective reuptake inhibitors IIenerl. Am J Psychiatry 1995; 152 (5): 810

    PubMed  CAS  Google Scholar 

  55. Stoukides JA, Stoukides CA. Extrapyramidal symptoms upon discontinuation of fluoxetine Ileneri. Am J Psychiatry 1991; 148 (9): 1263

    PubMed  CAS  Google Scholar 

  56. Lipinski Jr JE, Mallya G, Zimmerman P, et al. Fluoxetineinduced akathisia: clinical and theoretical implications. J Clin Psychiatry 1989; 50: 339–42

    PubMed  Google Scholar 

  57. Lejoyeux M, Ades J, Rouillon F. Serutonin syndrome: incidence, symptoms and outcome. CNS Drugs 1994; 2 (2): 132–43

    Article  Google Scholar 

  58. Kasantikul D. Reversible delirium after discontinuation of fluoxetine. J Med Assoc Thailand 1995; 78: 53–4

    CAS  Google Scholar 

  59. Otani K, Tanaka O, Kaneko S, et al. Mechanisms of the development of trazodone withdrawal symptoms. Int Clin Psychopharmacol 1994; 9: 131–3

    Article  PubMed  CAS  Google Scholar 

  60. Petersen RC, Richelson E. Anticholinergic activity of imipramine and some analogues at muscarinic receptors of culture mouse neuroblastoma cells. Psychopharmacology 1982; 76: 26–8

    Article  PubMed  CAS  Google Scholar 

  61. Snyder SH, Yarnamura HI. Antidepressants and muscarinic acetylcholine receptor. Arch Gen Psychiatry 1977; 34: 236–9

    Article  PubMed  CAS  Google Scholar 

  62. Tollefson GO, Senogles SE, Frey WH, et al. A comparison of peripheral and central human muscarinic cholinergic receptor affinities for psychotropic drugs. Biol Psychiatry 1982; 17: 555–67

    PubMed  CAS  Google Scholar 

  63. Rouillon F, Lejoyeux M, Filteau MJ. Unwanted effects of longtenn treatment. In: Montgomery S, Rouillon F, editors. Longtenn treatment of depression. Vol. 3. Chichester: John Wiley and Sons. 1992: 81–111

    Google Scholar 

  64. Dilsaver Sc. Antimuscarinic agents as substances of abuse: a review. J Clin Psychophannacol 1988; 8: 14–22

    CAS  Google Scholar 

  65. Dilsaver Sc. Cholinergic mechanisms in affective disorders. Further directions for investigation. Acta Psychiatr Scand 1986; 74: 312–34

    Article  PubMed  CAS  Google Scholar 

  66. Dilsaver Sc. Cholinergic mechanisms in depression. Brain Res Rev 1986; 11: 285–316

    Article  CAS  Google Scholar 

  67. Dilsaver SC. Phannacologic induction of cholinergic system up-regUlation and supersensitivity in affective disorders research. J Clin Psychophannacol 1986; 7: 56–72

    Google Scholar 

  68. Charney OS, Heninger GR, Sternberg DE, et al. Abrupt discontinuation of tricyclic antidepressant drugs: evidence for noradrenergic hyperactivity. Br J Psychiatry 1982; 141: 377–86

    Article  PubMed  CAS  Google Scholar 

  69. Charney OS, Menkes DB, Heninger GR. Receptor sensitivity and the mechanism of action of antidepressant treatment: implications for the etiology and theory of depression. Arch Gen Psychiatry 1981; 38: 1160–80

    Article  PubMed  CAS  Google Scholar 

  70. Walsh BT, Stewan JW, Wright L, et al. Treatment of bulimia with monoamine oxidase inhibitors. Am J Psychiatry 1982; 139: 1629–30

    PubMed  CAS  Google Scholar 

  71. Dilsaver SC. The pathophysiologies of substance abuse and affective disorders: an integrative model? J Clin Psychophannacol 1987; 7: 1–10

    Article  CAS  Google Scholar 

  72. Cohen RM, Campbell IC, Dauphin M, et al. Changes in alpha and beta receptor densities in rat brain as a result of treatment with monoamine oxidase inhibitor antidepressants. Neurophannacology 1982; 21: 293–8

    Article  CAS  Google Scholar 

  73. Chiodo LA, Antelman SM. Repeated tricyclics induce progressive dopamine autoreceptor subsensitivity independent of daily drug treatment. Nature 1980; 287: 451–4

    Article  PubMed  CAS  Google Scholar 

  74. Creese I, Sibley DR. Receptor adaptations to centrally acting drugs. Annu Rev Phannacol Toxicol 1981; 21: 317–91

    Google Scholar 

  75. Kupfer OJ, Frank E. The minimum length of treatment for recovery. In: Montgomery S, Rouillon F, editors. Long-term treatment of depression. New York: John Wiley. 1992: 33–52

    Google Scholar 

  76. Dilsaver SC. Antidepressant withdrawal syndromes: phenomenology and pathophysiology. Acta Psychiatr Scand 1989; 79: 113–7

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, Bichat-Claude Bernard Hospital, 46 rue Henri Huchard, 75877, Paris, France

    Michel Lejoyeux & Jacquelyn Solomon

  2. Department of Psychiatry, Louis Mourier Hospital, Colombes, France

    Jean Adès & Sabelle Mourad

  3. Department of Psychiatry and Behavioural Sciences, Harris County Psychiatric Center, The University of Texas, Health Science Center at Houston, Houston, Texas, USA

    Steven Dilsaver

Authors
  1. Michel Lejoyeux
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean Adès
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sabelle Mourad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacquelyn Solomon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Steven Dilsaver
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lejoyeux, M., Adès, J., Mourad, S. et al. Antidepressant Withdrawal Syndrome. CNS Drugs 5, 278–292 (1996). https://doi.org/10.2165/00023210-199605040-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-199605040-00006

Keywords

Search

Navigation