Mixed states are far more common than previously recognized, ranging from 20% to 70% of patients presenting with depression, depending on the definition and the setting.1 Really?
The majority of patients with depression might be mixed? That would be clinically very important, if true: mixed states are associated with increased risk of suicide.2
Antidepressants have been associated with the development of mixed states.3 Thus follows an ironic corollary: in theory, then, one way to address suicidal depression is to taper off the patient’s antidepressant. A 12-patient case series supports this idea.4
But this treatment plan is quite counterintuitive for patients: “Here I am severely depressed and your plan is to stop my antidepressant?” Such a plan will not make any sense unless they understand what mixed states are and that antidepressants can induce them.
So forgive my pedantry while I offer a quick explanation that has worked well for me, and I hope may help you. Remember, it’s critical that patients understand why they might do better with less medication than with more.
First, try to undo the understandable misconception the name “bipolar” implies. Using your right hand, extend your thumb vertically and your little finger in the opposite direction, toward the floor. “Bipolar disorder—like the North and South poles, right? Actually, no: it’s more like a graph.”
Now hold your right thumb horizontal and your index finger vertical, while you explain that “there’s a manic axis” (pointing with your left hand at your index finger) “and a depressive axis” (pointing at your thumb).
“In between, there can be many combinations of those symptoms: that’s what we call a mixed state.” (Notice that having done all this with your right hand, the graph you’ve displayed is oriented properly as you face your patient).
The Figure depicts several definitions of mixed states. The blue dot in the upper right corner is the DSM-IV definition: full manic and full depressive symptoms simultaneously. No other points on the graph were allowed. (If that seems limited, consider that there was no “Mixed State” at all in DSM-III.)
DSM-5 has expanded mixed states to include the red dots (with some restrictions). But back in 1995, just after DSM-IV came out, a group of mood specialists from the University of Cincinnati suggested any admixture of manic and depressive symptoms is possible, as shown by the black dots.5 In the Cincinnati view, the entire domain of the graph is mixed state territory (depicted by circling your left index finger in the space between your right thumb and index finger).
Dr Phelps is Director of the Mood Disorders Program at Samaritan Mental Health in Corvallis, Ore. He is the Bipolar Disorder Section Editor for Psychiatric Times. Dr Phelps stopped accepting honoraria from pharmaceutical companies in 2008.
1. Perugi G, Angst J, Azorin JM, et al. Mixed features in patients with a major depressive episode: the BRIDGE-II-MIX study. J Clin Psychiatry. 2015;76:e351-e358.
2. Rihmer A, Gonda X, Balazs J, Faludi G. The importance of depressive mixed states in suicidal behaviour. Neuropsychopharmacol Hung. 2008;10:45-49.
3. Swann AC, Lafer B, Perugi G, et al. Bipolar mixed states: an International Society for Bipolar Disorders task force report of symptom structure, course of illness, and diagnosis. Am J Psychiatry. 2013;170:31-42.
4. Phelps J, Manipod V. Treating anxiety by discontinuing antidepressants: a case series. Med Hypotheses. 2012;79:338-341.
5. McElroy SL, Strakowski SM, Keck PE Jr, et al. Differences and similarities in mixed and pure mania. Compr Psychiatry. 1995;36:187-194.
6. Frye MA, Helleman G, McElroy SL, et al. Correlates of treatment-emergent mania associated with antidepressant treatment in bipolar depression. Am J Psychiatry. 2009;166:164-172.
7. Goldberg JF. Mixed depression: a farewell to differential diagnosis? J Clin Psychiatry. 2015;76:e378-e380.
8. Maj M. “Mixed” depression: drawbacks of DSM-5 (and other) polythetic diagnostic criteria. J Clin Psychiatry. 2015;76:e381-e382.