Second-generation antidepressant discontinuation and depressive relapse in adult patients with bipolar depression: Results of a retrospective database analysis

Background: To date, few postmarketing studies have addressed whether long-term prophylactic treatment with second-generation antidepressants (ADs) delays depressive episodes in patients with bipolar disorder. Objective: The aim of this study was to compare the risk of depressive relapse between patients with bipolar disorder who took second-generation ADs >= 6 months after depressive remission with those who discontinued AD use early. Methods: Using a large US managed-care claims database, continuously enrolled bipolar subjects who took second-generation ADs after a depressive remission were identified between January 1, 1998, and December 31, 2002. Duration of AD and concurrent mood stabilizer use were based on coded diagnoses and pharmacy records. A Cox proportional hazards model was developed to predict time from depressive remission to next depressive relapse with continuous AD use, categorized as either >= 6 months or < 6 months. Propensity scoring with greedy matching was used to help balance the observed background covariates and baseline disease severity between groups. Results: Five hundred eighty-nine subjects met the inclusion criteria. A Kaplan-Meier estimate found that the median depressive relapse times for the continuous (ie, >= 6 months) and early discontinuation (ie, <6 months) AD treatment groups were 16.5 and 6.8 months, respectively (P < 0.05). The Cox proportional hazards model with propensity score matching identified a significantly lower risk of depressive relapse over a 2-year period among those who continued AD treatment >= 6 months after remission, compared with those who discontinued treatment within 6 months (hazard ratio, 0.61 [95% CI, 0.42-0.88]; continuous vs early discontinuation, P < 0.01). Conclusions: Continuous second-generation AD therapy for >= 6 months after depressive remission was associated with a lower risk of depressive relapse over a 2-year period in patients with bipolar depression. Given concerns regarding the risk of AD users with bipolar disorder switching to mania, an optimal prophylactic treatment after depressive remission should balance the risks between manic switching and depressive relapse.