Although the definition of depressive mixed state, more commonly known as mixed depression, is still controversial, about one-third of major depressive episodes are held to contain mixed components. The most frequent manifestations of mixed depression are irritability, distractibility and psychomotor agitation, although these symptoms are not included in the mixed features during a major depressive episode according to the DSM-5 criteria, which is therefore unlikely to cover the full scope of mixed depression in real-world settings. Mixed depression often accompanies risky behavior including impulsive suicide attempts. The early detection and treatment of these unstable conditions is therefore necessary. Also, sufficiently sensitive and specific screening methods for depressive mixed state are needed to avoid both under - and over-diagnosis. Antidepressants should be avoided since these drugs often worsen irritability, agitation and impulsivity, and increase risky behavior. Instead, combination therapy with mood stabilizer (s) to prevent the relapse of the depressive mixed state and atypical antipsychotics for rapid stabilization in the acute phase should be considered. Because there is very little evidence for effective pharmacotherapy in mixed depression, the efficacy of various mood-stabilizing agents, either as monotherapy or in combination therapies, should be extensively examined in the future using quantitative assessments of the psychopathology of mixed depression in patients with confirmed diagnoses of mixed depression.