BACKGROUND: Depressive mixed states (DMX), described systematically by Kraepelin, have recently been found common among depressed outpatients, with possible important impact on treatment. Study aim was to find if DMX in bipolar II disorder was often a transition period between depression and hypomania, as suggested by Kraepelin. METHODS: 194 consecutive bipolar II major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV. Hypomanic symptoms during the index MDE were systematically assessed. DMX was defined as a MDE plus > 2 hypomanic symptoms appearing during the MDE (not before it), following Akiskal and Benazzi (2003). History of depression-hypomania cycles and vice versa (without symptom-free intervals) was assessed. If DMX were a transition period, cycles should have been more common in bipolar II with DMX than in bipolar II without DMX. To test if there were differences between DMX with history of cycles and DMX without history of cycles, the twosubgroups were compared on many clinical, family history, and temperamental variables. To test if there were differences between bipolar II with DMX and bipolar II without DMX, comparisons between the two subgroups were done on variables often reported to be typically found in bipolar disorders and to be diagnostic validators (young onset, many recurrences, atypical features of depression, bipolar family history, temperamental mood lability, gender). RESULTS: DMX was present in 70.1, and history of cycles in 79.8. In bipolar II without index DMX (n = 58) history of cycles was present in 86.2; in bipolar with index DMX (n = 136) history of cycles was present in 77.2 (p = 0.175). DMX with cycles was not significantly different from DMX without cycles on all study variables (apart from agitation). Bipolar II with index DMX, versus bipolar II MDE without index DMX, had significantly more depressions with atypical features, temperamental mood lability, and more females, while age of onset, recurrences, and bipolar family history were not significantly different. LIMITATIONS: Single interviewer, cross-sectional assessment. CONCLUSIONS: Findings do not support Kraepelin's view of DMX as a transition period between depression and hypomania, and a distinction between DMX with and without cycles. Findings only partly support DMX as a distinct subtype of bipolar II, which seems to require temperamental mood lability for its onset during a bipolar II MDE.
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