Skip to main content
SpringerLink
Log in

Pharmacotherapy of Mood Disorders and Treatment Discontinuation

  • Leading Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Depression is the most frequent and costly problem in primary care, where most of these patients are seen and treated. In many countries, the public regard antidepressant drugs as ‘addictive’, partly because of the withdrawal symptoms that can occur when they are discontinued. Indeed, discontinuation (withdrawal) symptoms can follow the stoppage of almost all classes of antidepressants, including selective serotonin receptor inhibitors (SSRIs). This is important because they are widely regarded as drugs of choice for both depression and the anxiety disorders. But is this true withdrawal or merely rebound? The antidepressant discontinuation syndrome is characterised by the time-locked emergence of new, clearly defined and quantifiable signs and symptoms that ensue on stopping or reducing the dose of an antidepressant. Thereby, it meets the criteria for a withdrawal syndrome. The symptoms are not usually severe or protracted. SSRIs vary in their propensity to be associated with a discontinuation syndrome: paroxetine appears to be the most likely. Patients should be warned of the possibility of developing such a reaction, but reassured that it is usually mild and self limiting. Tapering the dose, if practicable, is worthwhile. In severe cases, temporary reinstatement of the SSRI and slower tapering may be necessary. Escalation of antidepressant dosage, or ‘street abuse’, is rare with antidepressants. The use of antidepressants is generally beneficial, and efforts should be made to optimise our current use of these drugs as well as encouraging the development of newer, better and innovative compounds. To this end, physicians should educate themselves and the public about discontinuation and withdrawal, so that these clinical features can be put in a realistic context.

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

Table I
Table II

Similar content being viewed by others

References

  1. Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry 1992; 14: 237–47

    Article  PubMed  CAS  Google Scholar 

  2. Paykel ES, Hart D, Priest RG. Changes in public attitudes to depression during the Defeat Depression Campaign. Br J Psychiatry 1998; 173: 519–22

    Article  PubMed  CAS  Google Scholar 

  3. Kessing LV, Hansen HV, Demyttenaere K, et al. Depressive and bipolar disorders: patients’ attitudes and beliefs towards depression and antidepressants. Psychol Med 2005; 35: 1205–13

    Article  PubMed  Google Scholar 

  4. Sirey JA, Bruce ML, Alexopoulos GS, et al. Stigma as a barrier to recovery: perceived stigma and patient-rated severity of illness as predictors of antidepressant drug adherence. Psychiat Serv 2001;52: 1615–20

    Article  CAS  Google Scholar 

  5. Van Voorhees BW, Fogel J, Houston TK, et al. Beliefs and attitudes associated with the intention to not accept the diagnosis of depression among young adults. Ann Fam Med 2005; 3: 38–46

    Article  PubMed  Google Scholar 

  6. Melfi CA, Chawla AJ, Croghan TW, et al. The effects of adherence to antidepressant treatment: guidelines on relapse and recurrence of depression. Arch Gen Psychiatry 1998; 55: 1128–32

    Article  PubMed  CAS  Google Scholar 

  7. Demyttenaere K. Compliance during treatment with antidepressants. J Affect Disord 1997; 43: 27–39

    Article  PubMed  CAS  Google Scholar 

  8. Demyttenaere K, Enzlin P, Dewe W, et al. Compliance with antidepressants in a primary care setting, 1: beyond lack of efficacy and adverse events. J Clin Psychiatry 2001; 62 Suppl. 22: 30–3

    PubMed  CAS  Google Scholar 

  9. Demyttenaere K, Mesters P, Boulanger B, et al. Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine. J Affect Disord 2001; 65: 43–252

    Article  Google Scholar 

  10. Demyttenaere K, Haddad P. Compliance with antidepressant therapy and antidepressant discontinuation symptoms. Acta Psychiatr Scand 2000; 101 Suppl. 403: 50–9

    Article  Google Scholar 

  11. Medawar C. The antidepressant web: marketing depression and making medicines work. Int J Risk Saf Med 1997; 10: 75–126

    Google Scholar 

  12. Medawar C, Herxheimer A, Bell A, et al. Paroxetine: panorama and user reporting of ADRs. Int J Risk Saf Med 2002; 15: 161–9

    Google Scholar 

  13. Taylor D, Stewart S, Connolly A. Antidepressant withdrawal symptoms: telephone calls to a national medication helpline. J Affect Disord 2006; 95: 129–33

    Article  PubMed  CAS  Google Scholar 

  14. Moncrieff J. The antidepressant debate. Br J Psychiatry 2002; 180: 193–4

    Article  PubMed  Google Scholar 

  15. Mitchell AJ. High medication discontinuation rates in psychiatry: how often is it understandable? J Clin Psychopharmacol 2006; 26: 109–12

    Article  PubMed  Google Scholar 

  16. Blier P, Tremblay P. Physiologic mechanisms underlying the antidepressant discontinuation syndrome. J Clin Psychiatry 2006; 67 Suppl. 4: 8–13

    PubMed  CAS  Google Scholar 

  17. Weiler I. Report of the Committee on Safety of Medicines Expert Working Group on the safety of selective serotonin reuptake inhibitor antidepressants. London: London Stationery Office, 2005

    Google Scholar 

  18. Schatzberg A, Haddad P, Kaplan E, et al. Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. J Clin Psychiatry 1997; 58 Suppl. 7: 5–10

    PubMed  CAS  Google Scholar 

  19. Shelton RC. The nature of the discontinuation syndrome associated with antidepressant drugs. J Clin Psychiatry 2006; 67 Suppl. 4: 3–7

    PubMed  CAS  Google Scholar 

  20. Tyrer P. Invited comment. Acta Psychiatr Scand 2000; 102: 467–8

    Google Scholar 

  21. Lader M. Discontinuing SSRI antidepressants: prediction, assessment and management of symptoms. Neuropsychiatr Dis Treat 2006; 2 Suppl. 1: 13–20

    Google Scholar 

  22. Black K, Shea C, Dursun S, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci 2000; 25: 255–61

    PubMed  CAS  Google Scholar 

  23. Haddad P. The SSRI discontinuation syndrome. J Psychopharmacol 1998; 2: 305–13

    Article  Google Scholar 

  24. Warner CH, Bobo W, Warner C, et al. Antidepressant discontinuation syndrome. Am Family Physician 2006; 74: 449–56

    Google Scholar 

  25. Tamam L, Ozpoyraz N. Selective serotonin reuptake inhibitor discontinuation syndrome: a review. Adv Ther 2002; 19: 17–26

    Article  PubMed  CAS  Google Scholar 

  26. van Geffen ECG, Hugtenburg JG, Heerdink ER, et al. Discontinuation symptoms in users of selective serotonin reuptake inhibitors in clinical practice: tapering versus abrupt discontinuation. Eur J Clin Pharmacol 2005; 61: 303–7

    Article  PubMed  Google Scholar 

  27. Haddad P, Lejoyeux M, Young A. Antidepressant discontinuation reactions are preventable and simple to treat. Br Med J 1998; 316: 1105–6

    Article  CAS  Google Scholar 

  28. Schatzberg A, Blier P, Delgado PL, et al. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry 2006; 67 Suppl. 4: 27–30

    PubMed  CAS  Google Scholar 

  29. Price J, Waller P, Wood S, et al. A comparison of the postmarketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal. Br J Clin Pharmacol 1996; 42: 757–63

    Article  PubMed  CAS  Google Scholar 

  30. Haddad P, Anderson I, Rosenbaum J. Antidepressant discontinuation syndromes. In: Haddad P, Dursun S, Deakin B, editors. Adverse syndromes and psychiatric drugs. Oxford: Oxford University Press, 2004: 184–205

    Google Scholar 

  31. Rosenbaum J, Fava M, Hood S, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomised clinical trial. Biol Psychiatry 1998; 44: 75–6

    Article  Google Scholar 

  32. Hindmarch I, Kimber S, Cockle S. Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance. Int Clin Psychopharmacol 2000; 15: 305–18

    Article  PubMed  CAS  Google Scholar 

  33. Judge R, Parry M, Quail D, et al. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. Int Clin Psychopharmacol 2004; 19: 217–25

    Google Scholar 

  34. Zajecka J, Fawcett J, Amsterdam J, et al. Safety of abrupt discontinuation of fluoxetine: a randomised, placebo-controlled study. J Clin Psychopharmacol 1998; 18: 193–7

    Article  PubMed  CAS  Google Scholar 

  35. Himei A, Okamura T. Discontinuation syndrome associated with paroxetine in depressed patients: a retrospective analysis of factors involved in the occurrence of the syndrome. CNS Drugs 2006; 20: 665–72

    Article  PubMed  CAS  Google Scholar 

  36. Montgomery S, Kennedy S, Burrows G, et al. Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomised double-blind placebo-controlled discontinuation study. Int Clin Psychopharmacol 2002; 17: 271–80

    Google Scholar 

  37. Baldwin D, Mongomery SA, Nil R, et al. Discontinuation symptoms in depression and anxiety disorders. Int J Neuropsy-chopharmacol 2005; 10: 73–84

    Article  Google Scholar 

  38. Sanz EJ, De-las-Cuevas C, Kiuru A, et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet 2005; 365: 482–7

    PubMed  CAS  Google Scholar 

  39. Moncrieff J, Wessely S, Hardy R. Meta-analysis of trials comparing antidepressants with active placebos. Br J Psychiat 1998; 172: 227–31

    Article  CAS  Google Scholar 

  40. Quitkin FM, Rabkin JG, Gerald J, et al. Validity of clinical trials of antidepressants. Am J Psychiat 2000; 157: 327–37

    Article  PubMed  CAS  Google Scholar 

  41. Cowen PJ. Panorama: the secrets of Seroxat. Br Med J 2002; 325: 910

    Article  Google Scholar 

  42. Whittal ML, Otto MW, Hong JJ. Cognitive-behavior therapy for discontinuation of SSRI treatment of panic disorder; a case series. Behav Res Ther 2001; 39: 939–45

    Article  PubMed  CAS  Google Scholar 

  43. Young AH, Currie A. Physicians’ knowledge of antidepressant withdrawal effects: a survey. J Clin Psychiat 1997; 58 Suppl. 7: 28–30

    Google Scholar 

  44. Khan A, Kelly R, Gill M. Survey of symptoms associated with antidepressant discontinuation. Irish J Psych Med 1999; 16: 84–9

    Google Scholar 

  45. Demyttenaere K. Quality of life in depression and anxiety: does it matter? Int J Psychiat Clin Practice 2006; 10 Suppl. 1: 27–30

    Article  Google Scholar 

  46. Bosker FJ, Westerink BHC, Cremers TIF, et al. Future antidepressants: what is in the pipeline and what is missing? CNS Drugs 2004; 18: 705–32

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The author has received honoraria for participation in advisory boards and/or lecturing for Lundbeck, Pfizer, Neurim, Procter and Gamble, Sepracor, Servier and Takeda. The author also declares that he is retained by a group of solicitors concerning some litigation issues. However, under English law, his duty is clearly to the Court and not to either of the parties. No sources of funding were used to assist in the preparation of this review.

Author information

Authors and Affiliations

  1. King’s College London, P 056, Institute of Psychiatry, Denmark Hill, London, SE5 8AF, UK

    Malcolm Lader

Authors
  1. Malcolm Lader
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Malcolm Lader.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lader, M. Pharmacotherapy of Mood Disorders and Treatment Discontinuation. Drugs 67, 1657–1663 (2007). https://doi.org/10.2165/00003495-200767120-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200767120-00001

Keywords

Search

Navigation