Delineating depressive mixed states: Their therapeutic significance

Depressive mixed state (DMX) is a major depressive episode (MDE) with a few intra-episode hypomanic signs or symptoms. DMX is well described in the classic European literature, but has been largely ignored until recently.Current data indicate that DMX is common in ∼60% of bipolar II MDE out-patients, and up to one third of 'unipolar' major depressive patients. Common hypomanic features intruding into depression are irritability, mood lability, racing (crowded) thoughts, sexual arousal, and psychomotor acceleration. The temperamental background of these patients is often cyclothymic or hyperthymic, supporting the hypothesis that DMX occurs when such 'opposite' temperaments intrude into depressive episodes. The bipolar nature of DMX is validated by a strong association with bipolar family history. DMX could have an important impact on treatment of depression, as angry-disinhibited hypomanic symptoms can arise, or worsen, during antidepressant therapy without concurrent mood stabilizers. The increasing clinical use of anticonvulsant mood stabilizers and 'sedating' atypical antipsychotics in such patients would require further systematic investigation. The clinical problems posed by DMX are at least 10 times more prevalent in practice than dysphoric mixed mania which has attracted much of the recent research investment.