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Ann Clin Psychiatry. 2011 Aug;23(3):186-92.

Long-term worsening of bipolar disorder related with frequency of antidepressant exposure.

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  • 1Bipolar Disorders Program, Department of Psychiatry, Institute of Cognitive Neurology, Favaloro Foundation Neuroscience Institute, Buenos Aires, Argentina.



The aim of this study of 53 persons with bipolar disorder (BD) was to evaluate the relationship between history of exposure to antidepressants (AD) and mood stabilizers (MS) and the percentage of time spent ill.


BD outpatients with more than 12 months of prospective follow-up were included. Outcome was documented using a life charting technique. Current and previous exposure to AD and MS were assessed using a scale that provides a quantitative measure of exposure to psychotropic medications. Regression models were used to correct for possible confounders.


Previous treatment with AD was an independent predictor of polarity changes (P < .001) and mixed symptoms (P = .01). In contrast, "years of exposure to MS" was an independent predictor of time spent asymptomatic (P = .019). The ratio between exposure to AD vs MS was associated with less weeks asymptomatic (P = .03), more mixed symptomatology (P = .019), and more polarity changes (P = .001).


Antidepressant exposure was a major predictor of mood instability in the long-term outcome of BD. The ratio used of previous exposure to AD vs MS was associated with poor outcomes, suggesting that the harmful effect of AD may be additive and related to how much they are used.

[PubMed - indexed for MEDLINE]
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