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Background: We examined the influence of prior antidepressant treatment trials on the likelihood of depressive relapse, and time to depressive relapse, during maintenance therapy of bipolar II disorder in treatment-responsive subjects who had recovered from a major depressive episode.

Methods: Data were derived from a prospective, randomized, double-blind trial of 148 adult subjects with bipolar II major depressive episode who were initially administered open-label fluoxetine monotherapy for 12 weeks. Remitters with a final Hamilton Rating Scale for Depression score of 8 or lower were then randomized to continuation therapy with either fluoxetine (n = 28), lithium (n = 26), or placebo (n = 27) for 50 additional weeks.

Results: An increase in the number of prior antidepressant treatment trials was significantly associated with a greater likelihood of depressive relapse for all treatment conditions taken together [odds ratio (OR) = 1.42, z = 2.49, P = 0.01] and for the 2 active treatment conditions together (OR = 1.51, z = 2.28, P = 0.02). An increase in the number of prior antidepressant trials was also associated with a trend-level shortening in the time to relapse for all treatment conditions taken together (hazard ratio = 1.15; confidence interval, 0.99-1.35; P = 0.07) and a significantly shorter time to relapse for subjects in the 2 active treatment conditions (hazard ratio = 1.30; confidence interval, 1.05-1.62; P = 0.02).

Conclusions: These findings support prior evidence of a negative influence of the number of prior antidepressant treatment trials on the likelihood of response and suggest that the number of prior antidepressant trials may also be associated with a greater odds of depressive relapse, and a shorter time to relapse, during antidepressant maintenance therapy in recovered depressed subjects with bipolar II disorder.

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