Mixed States

Last updated 11/11/2024

Depression combined with over-energized symptoms like anxiety, anger, agitation and attention problems is called a Mixed State. Treatment focuses on lowering the energy level while also easing the depression, using “mood stabilizers with antidepressant effects” (one of which is a simple therapy, not a pill).

Treatment of mixed states

Of course the first step, before treatment, is to make sure you’re really in a mixed state. You might have to read this whole page for that. It’s complicated. Or you can pause and discuss your diagnosis with your providers (in the meantime, you can still work on self-change and look at psychotherapy options).

When you’re ready to look at treatments for mixed states, there’s a whole page on that. Summarizing: if you’re taking an antidepressant now, an important part of treatment is carefully tapering it off. If you’re not taking an antidepressant, treatment of a mixed depression focuses on “mood stabilizers with antidepressant effects” (one of which is not a pill).

Definitions

Making a long story short: mixed states combine depression with over-energized symptoms. Among the most frequent high-energy symptoms are the 4 A’s: anxiety, anger, agitation and attention problems. Extreme insomnia is also common. (Here’s a longer version of this story).

When symptoms like the 4 A’s are included as markers of a Mixed State, this version of depression is common. It’s not “bipolar disorder”, but it’s related. A mixed state means that people with depression are also having some “manic” symptoms.

Agitation and irritability and insomnia are common in depression. But this creates a problem. In the view of many mood experts, there is no cut-off, no clear separation, between a plain depression and a mixed depression (depression plus anxiety, anger, anxiety, attention problems and more). But the most common treatment for depression, antidepressants, can make mixed states worse.

Antidepressants can make mixed states worse

Antidepressants can actually cause mixed states in some people. They raise energy levels and make unstable moods more unstable. Indeed, antidepressants can cause a full manic episode, but that’s not common. What’s common in response to an antidepressant is the start of some high-energy symptoms, like the 4 A’s: anxiety, anger, agitation, and attention problems.  If depression improves but only a little bit, or remains unchanged, and these overenergized symptoms are added — now that depression is “mixed”.

Antidepressants can also make an existing mixed state worse, by bringing on more manic-side symptoms. More agitation. More anxiety. Or new symptoms, like impulsive risky decision-making (e.g. “ah, I’ll just skip work today”).

When to skip antidepressants: how mixed?

Well then: if antidepressants can cause or make a mixed state worse … when is a depression mixed enough to make antidepressants a bad idea? One “manic” symptom, like irritability? Two, like irritability and agitation? Three? Simple answer: the more such symptoms, the riskier the antidepressant becomes (risk of making things worse, or causing new manic symptoms).

Conflicting diagnoses

Confusion about mixed depression is common. The following table compares the symptoms one might expect to see in several psychiatric diagnoses (GAD stands for Generalized Anxiety Disorder, a diagnosis for plain anxiety; and blue checks are symptoms of depression):

As you can see, when these conditions are combined with depression, their symptoms almost completely overlap with symptoms of mixed states. To help solve this problem, the MoodCheck questionnaire asks about 4 other features of bipolarity, not just symptoms . These are:

1. family history of bipolar disorder
2. early onset of depression (before 25)
3. repeated episodes of depression
4. weird reactions to antidepressants.

None of those features is routinely found in these other diagnoses whose symptoms look so much like Mixed States.

Guiding your decision

MoodCheck doesn’t give you definite yes/no answers. Maybe you have just one bipolar marker; does that mean you shouldn’t take an antidepressant? No. It just means you have more risk for an antidepressant making things worse than a person with no bipolar markers.

Put another way, say someone thinks you have depression with PTSD, or GAD, or ADHD. The more bipolar markers you have, the more you should wonder about those diagnoses.

If your diagnosis is not obvious (and often it’s not), then your decision will be based on comparing the side effects and risks of antidepressants versus mood stabilizers with antidepressant effects. (Here’s a specific page about that challenging decision-making: antidepressants versus lamotrigine).

Links from here:

• Mixed states: treatment options
• DSM definition of mixed states: the controversies
• What causes mixed states? The “waves” model

References

Suppes T, Eberhard J, Lemming O, Young AH, McIntyre RS. Anxiety, irritability, and agitation as indicators of bipolar mania with depressive symptoms: a post hoc analysis of two clinical trials. International journal of bipolar disorders. 2017 Dec;5(1):1-1.

Sani G, Vöhringer PA, Napoletano F, Holtzman NS, Dalley S, Girardi P, Ghaemi SN, Koukopoulos A. Koukopoulos׳ diagnostic criteria for mixed depression: a validation study. Journal of affective disorders. 2014 Aug 1;164:14-8.

Yatham, L.N., Chakrabarty, T., Bond, D.J., Schaffer, A., Beaulieu, S., Parikh, S.V., McIntyre, R.S., Milev, R.V., Alda, M., Vazquez, G. and Ravindran, A.V., 2021. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations. Bipolar disorders, 23(8), pp.767-788.