Mixed depression

by | Jun 16, 2023 | Education

Depression with psychomotor excitation is not just a “major depressive episode”


Clinicians use the word “depression” loosely. The DSM concept of a “major depressive episode” combines very different kinds of depressive states:  Take melancholic: there is no reactivity of mood, which means that the patient is just plain sad all the time –  not angry or anxious or anything else.  There is marked anhedonia, meaning the patient has basically no interests at all, and is often unable to get out of bed or function at all. Now take its opposite: “mixed depression”, where the patient his highly reactive in mood, ranging from very sad to very angry to very anxious to very agitated; there is decreased interest but such patients can still function somewhat.  

“Major” depression isn’t really one thing:  it includes many things, including types of depression that can be completely opposite in their symptoms. 

Does this matter, practically?  It may.  If  agitated, labile, angry “mixed depression” is different than the slowed down, solely sad, anhedonic “melancholia”, they may have different treatments.

European researchers, often less influenced by DSM, have been studying the concept of mixed depression a great deal in recent decades. They’ve shown that it occurs more commonly in bipolar than unipolar depression, that it seems to respond especially well to dopamine blockers (neuroleptics), and that it worsens with antidepressants. 

In one study of over 5000 depressed patients, Angst and colleagues reported that 47% of DSM-defined “major depressive” episodes included 3 or more DSM manic symptoms. This was the case even with DSM-defined “major depressive disorder”, not just bipolar disorder.  In other words, about half of depressive episodes in major depressive disorder involve multiple manic symptoms, i.e., are mixed depressive states. 

This may seem odd: how can you have “major depression” with three manic symptoms?  It happens because DSM doesn’t allow you to diagnose mania or hypomania unless those manic symptoms occur for 4 or more days.  But these “mixed depressed” states often involve consistent depression, with bursts of manic symptoms for a few hours or a day or two.  DSM says: Ignore those manic symptoms; they don’t matter. Just diagnose a major depressive episode. Yet those are exactly the kind of agitated, labile depressive states that seem to respond to dopamine blockers.  

As importantly, if we give antidepressants to those agitated, labile, angry depressed patients, they seem to get more agitated, labile, and angry.  This sometimes ends in suicide, which may explain why some depressed patients get more suicidal on antidepressants (see the PL website on this controversial topic). 

In short, there is a kind of depression where, despite being sad and low in interest and energy and sometimes suicidal, patients also have psychomotor excitation: they are angry, revved up at times, sometimes high in libido, and very agitated. In other words, some manic-like  symptoms are mixed into the depressive state.

This is the concept of mixed depression, organized into diagnostic criteria by Athanasios Koukopoulos, who was the leading thinker on this topic.

Koukopoulos’ mixed depression criteria:

  •  A DSM-defined major depressive episode 
  • At least 3 of 8 items:

                   1. Psychic agitation or inner tension

                  2. Racing or crowded thoughts

                  3. Irritability or unprovoked rage

                  4. Absence of retardation

                 5. Talkativeness

                6. Dramatic description of suffering or frequent spells                                     of weeping

               7. Mood lability or marked reactivity

               8. Early insomnia

The PL Bottom Line

  • About one-half of all depressive episodes, irrespective of whether the overall mood diagnosis is bipolar or unipolar, involve “mixed depression”.
  • Psychomotor excited mixed depressive states worsen with antidepressants and improve with dopamine blockers.