Mixed States: Definitions ; Antidepressant Implications

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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).

Definitions: Mixed states and “mixity”

To make a long story short, the official (DSM) rules for mixed states are disregarded by many mood experts. Instead, they suggest using the most common symptoms of mixed depression.

Roger McIntyre calls the 4 A’s: anxiety, anger, agitation, and attention problems.

From my experience, I’d add extreme insomnia. References below.

The DSM criteria are narrower: only some symptoms count, and 3 or more are needed.

When a broader range of symptoms like the 4 A’s is considered, many more people have “mixity”.

This is not “bipolar disorder”, but it’s close. It means that people with depression are also having some “manic” symptoms.

And that means that there is no cut-off between plain depression and bipolar disorder. Some people have just depression.

Some people have obvious manic phases as well as depressions.

In the middle people have, well, call it Depression Plus: depression plus some “bipolarity”. But not bipolar disorder, not by the official DSM rules. 

For more on this, see the mood spectrum page.

No minimum to “mixity”

Recent treatment guidelines also suggest there is no minimum number of manic symptoms that can be mixed with depression (or vice versa, depression symptoms that can be mixed with mania).

Any combination of manic and depression symptoms is possible, as shown in the graph below.

This means there is no cut-off for mixed states. Instead of asking, “Is this a Mixed State?” we should ask, “How mixed is this depression?” 

Why does it matter? Because the more “mixity”, the more risk that antidepressants will make things worse. They can cause or increase anxiety, anger, agitation, attention problems, and extreme insomnia. 

There is no cut-off here either, no “safe” level of mixity below which antidepressants have no risk, as “mixity” increases.

Conflicting diagnoses

You might have seen this graph before on this site (GAD stands for Generalized Anxiety Disorder, a diagnosis for plain anxiety):

When combined with depression (blue checks), symptoms for these conditions overlap almost completely. But because mixed states have bipolarity (not necessarily enough for a bipolar diagnosis; just one or more manic symptoms), the markers of bipolarity that aren’t symptoms can be used to help sort this out.

The MoodCheck questionnaire asks about 4 other features of bipolarity, not just symptoms. Remember? : family history, early onset, episodic course, and weird reactions to antidepressants. None of these is found in all the other diagnoses whose symptoms look so much like Mixed States.

The MoodCheck can help guide treatment decisions

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 of an antidepressant making things worse than a person with no bipolar markers.

Put another way, if someone thinks you have depression with PTSD, or GAD, or ADHD, they won’t be suggesting a mood stabilizer. The more bipolar markers you have (more bipolarity, so more reason to think your mixed-state symptoms are from a mixed state), the more you should wonder about those diagnoses.

If your diagnosis is not obvious (and it so often is not), then your decision will be based on comparing the side effects and risks of antidepressants versus mood stabilizers with antidepressant effects.

If you are already on an antidepressant

If you’re already on an antidepressant, and things are going great … then, great!

But if they’re not going great, and you’re thinking about a medication change, then try this logic: wouldn’t you rather make things better by removing a medication, rather than adding one?

Unfortunately not so simple. Stopping an antidepressant cause causes mixed-state symptoms. Huh? Yeah, that’s right: antidepressants can cause mixity when they’re added, and also when they are removed. To avoid that, you have to taper them, usually very slowly. That means you won’t get better right away by removing your antidepressant.

Worse, there’s a chance you might wait for a few months (sorry, yes, probably that long) and not be any better. But if you taper the antidepressant carefully, you should not be any worse than you now are. And, you’ll be on one less medication. And have one less question hanging.

Reminder: DO NOT do this on your own. Tell your prescriber if you’re thinking about tapering your antidepressant. They’ll be better able to help you if they know what’s going on.

One more thing to know first.

Depression during a taper

What if depression gets worse while you’re tapering? You could talk to your prescriber about going back up a step, or all the way to your previous dose. But then you’ll be back where you were. Here are some alternatives.

First, you can buy time. Just getting farther from your last antidepressant dose reduction might make it clear that you’re going in the right direction (but should probably slow down a bit). Buy time how?

You can add self-change or psychotherapy. These are great ideas for the long run anyway. Probably the best idea by far.

One simple behavioral therapy is particularly useful in mixed states: social rhythm therapy (link below).

If that’s not doable in full right now, then at least working on a regular sleep rhythm could make a noticeable difference, with basically no risk (video linked below).

And, if that’s not enough, not doable, or doesn’t help, you can add another mood stabilizer with antidepressant effects (or talk to your prescriber about maybe increasing the dose of one you’re on, but hopefully that’s already been optimized).

Here’s one with the least risk: omega-3 fatty acids from fish oil. More on that in the links below.

Lastly, you might wonder what causes mixed states. Long answer, separate page.


  • 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.
  • 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 presentationsBipolar disorders23(8), pp.767-788.

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