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J Affect Disord. 2005 Feb;84(2-3):267-72.

Antidepressant-associated chronic irritable dysphoria (acid) in bipolar disorder: a case series.

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  • 1Mood Disorders Research Program, Department of Psychiatry and behavioral Science, University of Louisville School of Medicine, Louisville, KY, USA.



Antidepressants administered to bipolar subjects may induce manias, mixed states, or rapid cycling. More recently, we have noted that long-term use of antidepressants may induce a chronic dysphoric, irritable state.


A case series is presented in which six type I bipolar subjects receiving antidepressants continuously for several years developed chronic irritable dysphoria.


A triad of dysphoric mood, irritability, and middle insomnia that is frequently associated with occupational and social dysfunction can occur in some bipolar patients receiving antidepressants for at least 3 years. Typically, initial treatments with antidepressants for the index episode were effective. Over time, depressive symptoms returned and would transiently improve with dose increase or change of agents. Ultimately, the dysphoria and associated symptoms became chronic and resulted in dysfunction. Concomitant mood stabilizer did not appear to alter this pattern. Discontinuation of antidepressants was associated with a slow and gradual improvement in these symptoms over the ensuing year.


Additional studies are required to investigate safety of long-term use of antidepressants in bipolar illness.

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