The argument of antidepressant drugs in the treatment of bipolar depression: Mixed evidence or mixed states?

Introduction: The role of antidepressant drugs in acute and maintenance treatment of bipolar depression is a matter of debate that cannot be decided from the evidence available in the current literature. Areas covered: This review includes two sections: in the first, important contributions from the current literature, emphasizing randomized controlled trials (RCTs) and meta-analysis, highlight current controversies and methodological issues; in the second, the impact of mixed depressive features in bipolar depression is evaluated from a psychopathological perspective. Expert opinion: Methodological issues may complicate evaluation of the evidence from RCTs regarding antidepressants and mixed states. Moreover, nosological constructs may also contribute to the inconclusive findings, by introducing heterogeneity in patient selection and diagnosis. Acknowledging the impact of mixed features in the course of bipolar depression, essentially by the careful reading of classical Kraepelinian contributions, could enhance clinical management. This would in turn allow a more judicious use of antidepressants, ideally helping to shed some light on the much controversial 'antidepressant-related suicidality', and help to further clarify the reasons for the current literature discordance on this topic.