, Volume 235, Issue 9, pp 2779–2781 | Cite as

Subtherapeutic doses of SSRI antidepressants demonstrate considerable serotonin transporter occupancy: implications for tapering SSRIs

  • Bryan B. ShapiroEmail author

Antidepressants are usually tapered to mitigate the risk of antidepressant discontinuation syndrome, a new entity in DSM-5 characterized by nonspecific sensory, somatic and cognitive-emotional symptoms emerging within 2–4 days of the dose reduction or abrupt discontinuation of antidepressants taken continuously for at least 1 month (American Psychiatric Association 2013). Selective serotonin reuptake inhibitors (SSRIs) are commonly implicated, and among these, discontinuation symptom risk is highest with paroxetine and lowest with fluoxetine (Rosenbaum et al. 1998).

Three patterns of symptomatology have been observed in patients discontinuing SSRI antidepressants: (1) New symptoms, which consist of “classic” withdrawal symptoms that are not part of the patient’s original psychiatric illness, (2) rebound symptoms, consisting of the patient’s initial psychiatric symptoms necessitating SSRI treatment but of greater intensity; and (3) persistent postwithdrawal disorders, which resemble...


Compliance with ethical standards

Conflict of interest

The author declares that he has no conflict of interest.


  1. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association, Washington DCGoogle Scholar
  2. Arakawa R, Tateno A, Kim W, Sakayori T, Ogawa K, Okubo Y (2016) Time-course of serotonin transporter occupancy by single dose of three SSRIs in human brain: a positron emission tomography study with [11C] DASB. Psychiatry Res Neuroimaging 251:1–6CrossRefGoogle Scholar
  3. Baldessarini RJ, Tondo L, Ghiani C, Lepri B (2010) Illness risk following rapid versus gradual discontinuation of antidepressants. Am J Psychiatr 167(8):934–941CrossRefGoogle Scholar
  4. Chouinard G, Chouinard V-A (2015) New classification of selective serotonin reuptake inhibitor withdrawal. Psychother Psychosom 84(2):63–71CrossRefGoogle Scholar
  5. Fava GA, Offidani E (2011) The mechanisms of tolerance in antidepressant action. Prog Neuro-Psychopharmacol Biol Psychiatry 35(7):1593–1602CrossRefGoogle Scholar
  6. Fava GA, Bernardi M, Tomba E, Rafanelli C (2007) Effects of gradual discontinuation of selective serotonin reuptake inhibitors in panic disorder with agoraphobia. Int J Neuropsychopharmacol 10(6):835–838CrossRefGoogle Scholar
  7. Freeman MK, White W, Iranikhah M (2012) Tablet Splitting: A Review of Weight and Content Uniformity Part 1 of a 2-Part Series. Next month: Table Splitting—A Review of the Clinical and Economic Outcomes and Patient Acceptance. Consult Pharm 27(5):341–352CrossRefGoogle Scholar
  8. Keuthen NJ, Cyr P, Ricciardi JA, Minichiello WE, Buttolph ML, Jenike MA (1994) Medication withdrawal symptoms in obsessive-compulsive disorder patients treated with paroxetine. J Clin Psychopharmacol 14:206–207CrossRefGoogle Scholar
  9. Kotzalidis G, De Pisa E, Patrizi B et al (2008) Similar discontinuation symptoms for withdrawal from medium-dose paroxetine and venlafaxine after nine years in the same patient. J Psychopharmacol 22(5):581–584CrossRefGoogle Scholar
  10. Meyer JH, Wilson AA, Sagrati S, Hussey D, Carella A, Potter WZ, Ginovart N, Spencer EP, Cheok A, Houle S (2004) Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C] DASB positron emission tomography study. Am J Psychiatr 161(5):826–835CrossRefGoogle Scholar
  11. Murata Y, Kobayashi D, Imuta N, Haraguchi K, Ieiri I, Nishimura R, Koyama S, Mine K (2010) Effects of the serotonin 1A, 2A, 2C, 3A, and 3B and serotonin transporter gene polymorphisms on the occurrence of paroxetine discontinuation syndrome. J Clin Psychopharmacol 30(1):11–17CrossRefGoogle Scholar
  12. Rosenbaum JF, Fava M, Hoog SL, Ascroft RC, Krebs WB (1998) Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry 44(2):77–87CrossRefGoogle Scholar
  13. Sir A, D'Souza RF, Uguz S, George T, Vahip S, Hopwood M, Martin AJ, Lam W, Burt T (2005) Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. J Clin Psychiatry 66:1312–1320CrossRefGoogle Scholar
  14. Tint A, Haddad PM, Anderson IM (2008) The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study. J Psychopharmacol 22(3):330–332CrossRefGoogle Scholar
  15. Warner CH, Bobo W, Warner C, Reid S, Rachal J (2006) Antidepressant discontinuation syndrome. Am Fam Physician 74:449–456Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Psychiatry and Human BehaviorUC Irvine Medical CenterOrangeUSA

Personalised recommendations