Predictors of Depressive Switch in Patients With Bipolar I Disorder Who Initiated or Changed Pharmacologic Treatment for Mania or Mixed-Mania: A Prospective Observational Study

Objective: To evaluate the prevalence and the predictors of depressive switch in patients with bipolar I disorder (BD-I) requiring the initiation or change (but not a dose change) of treatment with oral antipsychotics or mood stabilizers for mania or mixed-mania.

Methods: This was a 3-month, prospective, noninterventional study conducted in 34 Italian psychiatric centers from April 2012 to April 2013. The study sample comprised 234 patients aged 18 years or older presenting with a manic episode according to DSM-IV-TR criteria. Patients were assessed at baseline and at follow-up visits by a variety of measures, including the Clinical Global Impressions scale for use in bipolar illness (CGI-BP). The primary outcome measure was depressive switch, which was defined a posteriori on the basis of a Montgomery-Åsberg Depression Rating Scale total score ≥ 15 and a Young Mania Rating Scale total score < 10 at week 12. A stepwise backward logistic regression model was used to explore the effect of clinical variables on the occurrence of depressive switch.

Results: According to the definition used in this study, 26 (11.1%) of 234 patients switched to depression. The variables associated with a depressive switch were prescription of both first- and second-generation antipsychotics (P = .017), depressive-predominant polarity (P = .012), CGI-BP total score at baseline evaluation (P = .024), depressive temperament (P = .063), and age at evaluation (P = .020).

Conclusions: Depressive switch was observed in about 1 of 10 of the BD-I patients. Our results suggest an association between the depressive switch and treatment with both first- and second-generation antipsychotics, depressive-predominant polarity, greater severity of the symptomatology, and older age at evaluation. Further randomized controlled studies are needed to confirm possible predictors of a depressive switch during mania.