Exploring treatment strategies for mood stabilization in patients with major depressive disorder and mixed features

We discuss strategies for mood stabilization in patients with major depressive disorder (MDD) and mixed features, challenging traditional paradigms and calling for a reevaluation of current diagnostic classifications. The DSM-5 "mixed features specifier" applies to several mood disorders, including MDD. In patients with MDD, this specifier blurs the traditional distinctions between depression and mania by introducing criteria that include symptoms such as elevated, expansive mood, inflated self-esteem, increased talkativeness, flight of ideas, increased energy, involvement in activities with potentially painful consequences, and decreased need for sleep. According to the DSM, when 3 of the above 7 symptoms are present during a major depressive episode, the episode may be characterized by the specifier "with mixed features". Despite the relatively high prevalence of mixed features in patients with MDD, no specific pharmacological treatments have been approved for these cases. We propose a treatment approach that includes: 1) initiating treatment with an antimanic agent (e.g., a mood stabilizer or a new-generation antipsychotic); 2) considering adjunctive low-dose serotonergic antidepressants; and then 3) considering discontinuation of the antimanic agent once the acute episode has resolved. We emphasize the lack of adequate studies of maintenance treatment with mood stabilizers and antipsychotics in patients with MDD and mixed features and the need for further research to improve our mood stabilization strategies for these patients.