Looking for bipolarity in antidepressant discontinuation manic states: Update and diagnostic considerations of the phenomenon

J Affect Disord. 2018 Aug 1:235:551-556. doi: 10.1016/j.jad.2018.04.080. Epub 2018 Apr 16.


Background: Antidepressant withdrawal manic states are intriguing and under-recognized phenomena. The associated patho-physiological pathways are ill defined and the inclusion of the phenomena in the bipolar spectrum disorders is questionable. This study aims to update a review on antidepressant discontinuation manic states published in 2008 and to look for hints alluding to bipolar disorder in the affected published cases and in the literature. It also reviews the different hypotheses proposed to explain discontinuation mania.

Methods: We searched Pubmed using the key words: 'antidepressant withdrawal' or 'antidepressant discontinuation' plus 'mania' or 'hypomania' from January 2008 until January 2018.

Results: Five new eligible reports were identified since the last review in 2008, involving the antidepressants Amitriptyline, Fluoxetine, Escitalopram and Mirtazapine. Hypotheses involve the implication of Catecholamines, Acetylcholine and Serotonin in the pathophysiology of this paradoxical phenomenon. Careful analysis of the total 29 cases revealed psychiatric histories in favor of a bipolar spectrum disorder in 12 individuals while five were already known to have bipolar disorder.

Limitations: This review is based on case reports with associated recall bias, and lack of in-depth description at times.

Conclusions: Antidepressant discontinuation manic or hypomanic states do not occur randomly. An individual susceptibility to bipolar disorder must be considered.

Keywords: Antidepressant; Bipolar III 1/4; Discontinuation; Mania.

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents, Second-Generation / adverse effects*
  • Bipolar Disorder / drug therapy*
  • Child
  • Citalopram / adverse effects
  • Cyclothymic Disorder / complications
  • Female
  • Fluoxetine / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Substance Withdrawal Syndrome / diagnosis
  • Substance Withdrawal Syndrome / etiology*
  • Surveys and Questionnaires
  • Young Adult


  • Antidepressive Agents, Second-Generation
  • Fluoxetine
  • Citalopram