Depressive mixed state: A feature of the natural course of bipolar II (and major depressive) disorder?

Background: Depressive mixed state (DMX), i.e., a combination of hypomanic and depressive symptoms during the same episode, has recently seen a rebirth of studies after Kraepelin's description. Kraepelin observed, in an inpatient sample, that DMX was related to the number of episodes and to duration of manic-depressive insanity ( illness). Study Aim: The aim was to test Kraepelin's observations in a very different sample. Methods: 563 consecutive outpatients with major depressive episode (MDE)-320 with bipolar II disorder and 243 with major depressive disorder-were interviewed, in a private practice, by the Structured Clinical Interview for DSM-IV as modified by Benazzi and Akiskal ( 2003). Hypomanic symptoms during MDE were systematically assessed in patients while off psychoactive drugs. DMX was dimensionally defined, following Akiskal and Benazzi ( 2003), as an MDE plus 3 or more combined hypomanic symptoms. Kraepelin's examples of DMX, i.e., agitated depression ( MDE plus psychomotor agitation) and depression with flight of ideas ( MDE plus racing thoughts) were also tested. Univariate and multivariate logistic regression was used to study associations. Results: DMX was present in 49.5% of the patients. Multiple logistic regression of DMX versus MDE recurrences and duration of illness, controlled for age, found a strong and significant association only between DMX and duration of illness. The same association was found between agitated depression and duration of illness ( but not in depression with racing thoughts). Limitation: There was only a single interviewer. Discussion: The findings support Kraepelin's observation of a link between DMX and durations of illness, but not that between DMX and recurrences. Onset of DMX could be more related to the natural course of manic-depressive illness than to a kindling process. Copyright (C) 2004 S. Karger AG, Basel.