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Med Hypotheses. 2011 Jun;76(6):769-73. doi: 10.1016/j.mehy.2011.01.020. Epub 2011 Apr 2.

Tardive dysphoria: the role of long term antidepressant use in-inducing chronic depression.

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Mood Disorders Research Program, The University of Louisville Depression Center, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.



Treatment-resistant and chronic depression appear to be increasing. The recent identification of antidepressant tachyphylaxis, the loss of antidepressant efficacy over time, is only a partial explanation. This is an emerging evidence that, in some individuals, persistent use of antidepressants may be prodepressant.


A literature search of PubMed utilizing the terms: antidepressant tachyphylaxis, treatment-resistant depression, chronic depression, and antidepressant tolerance was performed, and relevant articles were used.


Depressed patients who ultimately become treatment resistant frequently have had a positive initial response to antidepressants and invariably have received these agents for prolonged time periods at high doses. Parallels between this course and tardive dyskinesia are noted. It is proposed that neuroplastic processes related to dendritic arborization may underlie the treatment resistant depression that occurs in the setting of chronic antidepressant use. Since the prodepressant effect is seen after prolonged antidepressant use, the term tardive dysphoria is proposed.


Tardive dysphoria, needs to be considered in studies of treatment resistant depression, and should be examined in blinded, randomized antidepressant discontinuation trials.

[Indexed for MEDLINE]

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