Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Discontinuing antidepressant medications in adults

Michael Hirsch, MD
Robert J Birnbaum, MD, PhD
Section Editor
Peter P Roy-Byrne, MD
Deputy Editor
David Solomon, MD


Patients who discontinue their antidepressants after a therapeutic course are at risk for discontinuation symptoms, especially if they are not starting a new antidepressant with a similar pharmacodynamic profile.

Discontinuing antidepressants without switching to another drug is discussed in this topic. Switching antidepressants is discussed separately. (See "Switching antidepressant medications in adults".)


Abruptly stopping or rapidly tapering antidepressants often causes adverse effects, especially if a new drug with overlapping pharmacodynamic activity is not started. The constellation of discontinuation effects, sometimes referred to as a "discontinuation syndrome," has been best characterized in patients who abruptly stop selective serotonin reuptake inhibitors (SSRIs). The most common discontinuation symptoms include [1-4]:




Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Aug 2, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Warner CH, Bobo W, Warner C, et al. Antidepressant discontinuation syndrome. Am Fam Physician 2006; 74:449.
  2. Tint A, Haddad PM, Anderson IM. The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study. J Psychopharmacol 2008; 22:330.
  3. Fava M. Prospective studies of adverse events related to antidepressant discontinuation. J Clin Psychiatry 2006; 67 Suppl 4:14.
  4. Fava GA, Gatti A, Belaise C, et al. Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review. Psychother Psychosom 2015; 84:72.
  5. Price JS, Waller PC, Wood SM, MacKay AV. 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; 42:757.
  6. Yasui-Furukori N, Kaneko S. Hallucination induced by paroxetine discontinuation in patients with major depressive disorders. Psychiatry Clin Neurosci 2011; 65:384.
  7. Astorne Figari WJ, Herrmann S, Akogyeram C, Qian Q. New onset hypertension following abrupt discontinuation of citalopram. Clin Nephrol 2014; 82:202.
  8. 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.
  9. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition. October, 2010. http://psychiatryonline.org/guidelines (Accessed on November 06, 2015).
  10. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition. Am J Psychiatry 2010; 167 (supplement):1.
  11. National Institute for Health and Care Excellence (NICE). Depression: The Treatment and Management of Depression in Adults (Updated Edition). Clinical Guideline 90. October, 2009. http://www.nice.org.uk/guidance/cg90 (Accessed on November 06, 2015).
  12. Lejoyeux M, Adès J. Antidepressant discontinuation: a review of the literature. J Clin Psychiatry 1997; 58 Suppl 7:11.
  13. Rosenbaum JF, Zajecka J. Clinical management of antidepressant discontinuation. J Clin Psychiatry 1997; 58 Suppl 7:37.
  14. Ogle NR, Akkerman SR. Guidance for the discontinuation or switching of antidepressant therapies in adults. J Pharm Pract 2013; 26:389.
  15. Baldessarini RJ, Tondo L, Ghiani C, Lepri B. Illness risk following rapid versus gradual discontinuation of antidepressants. Am J Psychiatry 2010; 167:934.
  16. Judge R, Parry MG, Quail D, Jacobson JG. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. Int Clin Psychopharmacol 2002; 17:217.
  17. Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry 1998; 44:77.
  18. Michelson D, Fava M, Amsterdam J, et al. Interruption of selective serotonin reuptake inhibitor treatment. Double-blind, placebo-controlled trial. Br J Psychiatry 2000; 176:363.
  19. 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.
  20. Markowitz JS, DeVane CL, Liston HL, Montgomery SA. An assessment of selective serotonin reuptake inhibitor discontinuation symptoms with citalopram. Int Clin Psychopharmacol 2000; 15:329.
  21. Montgomery SA, Huusom AK, Bothmer J. A randomised study comparing escitalopram with venlafaxine XR in primary care patients with major depressive disorder. Neuropsychobiology 2004; 50:57.
  22. Baldwin DS, Cooper JA, Huusom AK, Hindmarch I. A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder. Int Clin Psychopharmacol 2006; 21:159.
  23. Black DW, Wesner R, Gabel J. The abrupt discontinuation of fluvoxamine in patients with panic disorder. J Clin Psychiatry 1993; 54:146.
  24. Coupland NJ, Bell CJ, Potokar JP. Serotonin reuptake inhibitor withdrawal. J Clin Psychopharmacol 1996; 16:356.
  25. Haddad PM, Devarajan S, Dursun SM. Antidepressant discontinuation (withdrawal) symptoms presenting as 'stroke'. J Psychopharmacol 2001; 15:139.
  26. Andrade C. Antidepressant-withdrawal mania:a critical review and synthesis of the literature. J Clin Psychiatry 2004; 65:987.
  27. Schatzberg AF, 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.
  28. Perahia DG, Kajdasz DK, Desaiah D, Haddad PM. Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect Disord 2005; 89:207.
  29. Labbate LA, Fava M, Rosenbaum JF, Arana GW. Drugs for the treatment of depression. In: Handbook of Psychiatric Drug Therapy, Sixth Edition, Lippincott Williams & Wilkins, Philadelphia 2010. p.54.
  30. Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord 2009; 117 Suppl 1:S26.
  31. Bauer M, Pfennig A, Severus E, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry 2013; 14:334.
  32. Benazzi F. SSRI discontinuation syndrome treated with fluoxetine. Int J Geriatr Psychiatry 1998; 13:421.
  33. Haddad PM. Antidepressant discontinuation syndromes. Drug Saf 2001; 24:183.
  34. van Geffen EC, 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.
  35. Yang LP, Plosker GL. Desvenlafaxine extended release. CNS Drugs 2008; 22:1061.
  36. Montgomery SA, Fava M, Padmanabhan SK, et al. Discontinuation symptoms and taper/poststudy-emergent adverse events with desvenlafaxine treatment for major depressive disorder. Int Clin Psychopharmacol 2009; 24:296.
  37. Palmer EC, Binns LN, Carey H. Levomilnacipran: A New Serotonin-Norepinephrine Reuptake Inhibitor for the Treatment of Major Depressive Disorder. Ann Pharmacother 2014; 48:1030.
  38. Vandel P, Sechter D, Weiller E, et al. Post-treatment emergent adverse events in depressed patients following treatment with milnacipran and paroxetine. Hum Psychopharmacol 2004; 19:585.
  39. Kyle JA, Dugan BD, Testerman KK. Milnacipran for treatment of fibromyalgia. Ann Pharmacother 2010; 44:1422.
  40. Fava M, Mulroy R, Alpert J, et al. Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine. Am J Psychiatry 1997; 154:1760.
  41. Parker G, Blennerhassett J. Withdrawal reactions associated with venlafaxine. Aust N Z J Psychiatry 1998; 32:291.
  42. Wellington K, Perry CM. Venlafaxine extended-release: a review of its use in the management of major depression. CNS Drugs 2001; 15:643.
  43. Montgomery SA, Kennedy SH, Burrows GD, et al. Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomized, double-blind, placebo-controlled discontinuation study. Int Clin Psychopharmacol 2004; 19:271.
  44. Berigan TR, Harazin JS. Bupropion-Associated Withdrawal Symptoms: A Case Report. Prim Care Companion J Clin Psychiatry 1999; 1:50.
  45. Benazzi F. Mirtazapine withdrawal symptoms. Can J Psychiatry 1998; 43:525.
  46. Klesmer J, Sarcevic A, Fomari V. Panic attacks during discontinuation of mirtazepine. Can J Psychiatry 2000; 45:570.
  47. Zhang J, Mathis MV, Sellers JW, et al. The US Food and Drug Administration's perspective on the new antidepressant vortioxetine. J Clin Psychiatry 2015; 76:8.
  48. Rajagopalan M, Little J. Discontinuation symptoms with nefazodone. Aust N Z J Psychiatry 1999; 33:594.
  49. Benazzi F. Nefazodone withdrawal symptoms. Can J Psychiatry 1998; 43:194.
  50. Haria M, Fitton A, McTavish D. Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. Drugs Aging 1994; 4:331.
  51. Otani K, Tanaka O, Kaneko S, et al. Mechanisms of the development of trazodone withdrawal symptoms. Int Clin Psychopharmacol 1994; 9:131.
  52. McCormack PL. Vilazodone: a review in major depressive disorder in adults. Drugs 2015; 75:1915.
  53. Garner EM, Kelly MW, Thompson DF. Tricyclic antidepressant withdrawal syndrome. Ann Pharmacother 1993; 27:1068.
  54. Dilsaver SC. Withdrawal phenomena associated with antidepressant and antipsychotic agents. Drug Saf 1994; 10:103.
  55. Ceccherini-Nelli A, Bardellini L, Cur A, et al. Antidepressant withdrawal: prospective findings. Am J Psychiatry 1993; 150:165.
  56. Gahr M, Schönfeldt-Lecuona C, Kölle MA, Freudenmann RW. Withdrawal and discontinuation phenomena associated with tranylcypromine: a systematic review. Pharmacopsychiatry 2013; 46:123.