Mania and Depression Sequence

Peter ForsterBest Practices, Bipolar Treatment

One of the key features of bipolar disorder that, in our experience, is most useful in predicting treatment response is the usual sequence of manic (or hypomanic) and depressive episodes. For years we have used the mnemonics MDI and DMI as ways of categorizing patients’ course. But we could not find the reference to that idea. We are indebted to Leonardo Tondo from the Department of Psychiatry at Harvard University for finding that reference.

Dr. Athanasios Koukopoulos first wrote about this distinction in 1975. DMI referred to a pattern of depressive episodes followed by manic or hypomanic episodes and then an interval of relatively normal mood. MDI referred to the pattern of a crash from mania or hypomania into depression which then was followed by a period of relative normality. The key distinction, then, has to do with the direction of the “switch” or more rapid change in mood.

We have written a bit more about this process on the MoodSurfing website (Watch the Mood Waves) where we described the MDI process of switching from energized to depressed states as something akin to Icarus’ fall when he flew too close to the sun and the wax holding his wings together melted.

All literary comparisons aside, the distinction has been very useful in predicting treatment response. Those with the MDI pattern (which is more common in bipolar 1 patients) tend to be good responders to lithium. And those with the DMI pattern tend to be good responders to lamotrigine. This can be understood by considering that the thing that drives the mood switch is the severity of the preceding episode. So that what drives mood cycling in MDI pattern patients is how energized they get which then causes the switch into depression (and lithium is better at preventing energized episodes). And vice versa, what drives mood instability in those with the DMI pattern is the severity of the depressive episode (and lamotrigine is most useful as an agent that prevents depressions).

Not every patient falls into one of these patterns. Some have unstable mood switches, and others have rapid mood cycles which switch in both directions rapidly. But when there is a dominant pattern it is a very useful way of guiding treatment.


A. Koukopoulos, et al. Journal of Affective Disorders 151 (2013) 105–110.