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The simultaneous occurrence of manic and depressive features has been recognized since classical times, but the term ‘mixed state’ was first used by Kraepelin at the end of the 19th century. From the 1980s, until the advent of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), psychiatric disorders were classified using a categorical approach. However, it was recognized that such an approach was too rigid to encompass the range of symptomatology encountered in clinical practice. Therefore, a dimensional approach was adopted in DSM-5, in which affective states are considered to be distributed across a continuum ranging from pure mania to pure depression. In addition, the copresence of symptoms of the opposite pole are captured using a ‘with mixed features’ specifier, applied when three or more nonoverlapping subthreshold symptoms of the opposite pole are present. Mixed features are common in patients with mood episodes, complicating the course of illness, reducing treatment response and worsening outcomes. However, research in this area is scarce and treatment options are limited. Current evidence indicates that antidepressants should be avoided for the treatment of bipolar mixed states. Evidence for bipolar mixed states supports the use of several second-generation antipsychotics, valproate and electroconvulsive therapy. One randomized controlled trial has demonstrated the efficacy of lurasidone, compared with placebo, in patients with major depressive disorder with mixed features, and there is limited evidence supporting the use of ziprasidone in such patients. Further research is required to determine whether other antipsychotic agents, or additional therapeutic approaches, might also be effective in this setting.

therapeutic advances in psychopharmacology

Rethinking the spectrum of mood disorders: implications for diagnosis and management – Proceedings of a symposium presented at the 30th Annual European College of Neuropsychopharmacology Congress, 4 September 2017, Paris, France