Antidepressant discontinuation syndrome

Not to be confused with Serotonin syndrome.

Antidepressant discontinuation syndrome
Other namesAntidepressant withdrawal syndrome[1]
SpecialtyPsychiatry
SymptomsFlu-like symptoms, trouble sleeping, anxiety, depression, dissociation, intrusive thoughts, nausea, poor balance, sensory changes[2]
Usual onsetWithin 3 days[2]
DurationFew weeks to months[3][4]
CausesStopping of an antidepressant medication[2][3]
Diagnostic methodBased on symptoms[2]
Differential diagnosisAnxiety, mania, stroke[2]
PreventionGradual dose reduction[2]
Frequency15–50% (with sudden stopping)[3][4]

Antidepressant discontinuation syndrome, also called antidepressant withdrawal syndrome, is a condition that can occur following the interruption, reduction, or discontinuation of antidepressant medication following its continuous use of at least a month.[5] The symptoms may include flu-like symptoms, trouble sleeping, nausea, poor balance, sensory changes, akathisia, intrusive thoughts, depersonalization and derealization, mania, anxiety, and depression.[2][3][4] The problem usually begins within three days[2] and may last for several weeks or months.[4] Psychosis may rarely occur.[2]

A discontinuation syndrome can occur after stopping any antidepressant including selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs).[2][3] The risk is greater among those who have taken the medication for longer and when the medication in question has a short half-life.[2] The underlying reason for its occurrence is unclear.[2] The diagnosis is based on the symptoms.[2]

Methods of prevention include gradually decreasing the dose among those who wish to stop, though it is possible for symptoms to occur with tapering.[2][6][4] Treatment may include restarting the medication and slowly decreasing the dose.[2] People may also be switched to the long-acting antidepressant fluoxetine which can then be gradually decreased.[6]

Approximately 15–50% of people who suddenly stop an antidepressant develop antidepressant discontinuation syndrome.[7][2][3][4] The condition is generally not serious,[2] though about half of people with symptoms describe them as severe.[4] Many restart antidepressants due to the severity of the symptoms.[4]

Antidepressant discontinuation syndrome is a relatively new phenomenon, being identified and described from 1950s onwards, in parallel with discovery and introduction of modern antidepressant medications, with the first MAOIs, and TCAs introduced from the 1950s onwards and the first SSRIs from the 1980s onwards.[8] There is still little research on this syndrome; most of the research is conflicting or consists only of clinical trials.[9]

  1. ^ Cite error: The named reference TI2018 was invoked but never defined (see the help page).
  2. ^ a b c d e f g h i j k l m n o p q Warner CH, Bobo W, Warner C, Reid S, Rachal J (1 August 2006). "Antidepressant discontinuation syndrome". American Family Physician. 74 (3): 449–56. PMID 16913164.
  3. ^ a b c d e f Gabriel M, Sharma V (29 May 2017). "Antidepressant discontinuation syndrome". Canadian Medical Association Journal. 189 (21): E747. doi:10.1503/cmaj.160991. PMC 5449237. PMID 28554948.
  4. ^ a b c d e f g h Davies J, Read J (4 September 2018). "A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based?". Addictive Behaviors. 97: 111–121. doi:10.1016/j.addbeh.2018.08.027. PMID 30292574.
  5. ^ Diagnostic and statistical manual of mental disorders : DSM-5 (5th ed.). American Psychiatric Association. 2013. pp. 712–714. ISBN 9780890425541.
  6. ^ a b Wilson E, Lader M (December 2015). "A review of the management of antidepressant discontinuation symptoms". Therapeutic Advances in Psychopharmacology. 5 (6): 357–68. doi:10.1177/2045125315612334. PMC 4722507. PMID 26834969.
  7. ^ Henssler, J.; Schmidt, Y.; Schmidt, U.; Schwarzer, G.; Bschor, T.; Baethge, C. (2024). "Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis". The Lancet Psychiatry. doi:10.1016/S2215-0366(24)00133-0.
  8. ^ Healy D (2001). "The Antidepressant Drama". In Weissman MM (ed.). The treatment of depression: bridging the 21st century. American Psychiatric Pub. ISBN 978-0-88048-397-1.
  9. ^ Johnston JA, Nelson DR, Bhatnagar P, Curtis SE, Chen Y, MacKrell JG (2021-02-23). "Prevalence and cardiometabolic correlates of ketohexokinase gene variants among UK Biobank participants". PLOS ONE. 16 (2): e0247683. Bibcode:2021PLoSO..1647683J. doi:10.1371/journal.pone.0247683. ISSN 1932-6203. PMC 7901775.