What Is Depression With Mixed Features?

woman looking out window

 martin-dm / Getty Images

What Is Depression With Mixed Features? (MDD-MX)

Depressive disorder with mixed features (also referred to as "mixed episode," "mixed state," or "agitated depression" ) is a mood disorder in which a person has symptoms of both depression and mania or hypomania at the same time. 

When it was first introduced, the diagnosis of major depressive disorder with mixed features (MDD-MX) was met with skepticism and remains controversial among some researchers and clinicians. However, in 2013, MDD-MX was included in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and has begun to gain acceptance.

Symptoms of MDD-MX

Researchers have come to believe that mood disorders exist on a continuum from depression to mania; pure depression is thought to be much less common and some researchers consider it rare. In general, a person who has one of these conditions experiences symptoms across the spectrum but tends to lean more toward one end than the other.

As they are trying to make a diagnosis, your doctor will ask you about where your symptoms typically fall on the spectrum. This will help them distinguish between depression and bipolar disorder.

People who have depression with mixed features usually experience mostly depressive symptoms, but may have certain manic symptoms (such as racing thoughts) as well.

To be diagnosed with major depressive disorder, you must have experienced certain symptoms every day for at least the past two weeks or longer. 

Classic features of depression include low mood and decreased interest or pleasure in activities you typically enjoy. However, to be diagnosed with depression, you must also have at least four of the following symptoms:

  • Fatigue, loss of energy and motivation
  • Feeling worthless, ashamed, or guilty
  • Inability to fall asleep or sleeping too much
  • Losing or gaining weight, eating more or less than usual
  • Psychomotor agitation (pacing, restlessness) or retardation (sluggish thought or movement)
  • Recurrent thoughts of death/dying, suicidal ideation or attempts
  • Troubling thinking, focusing, and concentrating

If you are having suicidal thoughts, contact the National Suicide Prevention Lifeline at 988 for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see our National Helpline Database.

If your doctor feels you meet the criteria for a diagnosis of depression, the next step will be to determine whether you are also experiencing symptoms of hypomania or mania, such as:

If you have experienced at least three symptoms of hypomania or mania almost every day for the past two weeks of your current depressive episode, your doctor will add the specifier "with mixed features" to your depression diagnosis. 

Causes of MDD-MX

The specific causes of depression with mixed features are unclear and not well understood. As with other types of depression, researchers suspect there are a number of different factors that contribute to the development of the MDD-MX, including an individual’s family history, genetics, environment, and other health conditions. 

While MDD-MX can be difficult to diagnose, research has suggested it’s fairly common: As many as 25% of people with unipolar depression may have mixed episodes.

Since the condition can easily be misdiagnosed as bipolar disorder, the number of people who have depression with mixed features may, in fact, be much higher. In the past, differentiating between depression with mixed episodes and bipolar disorder was much more challenging for clinicians. Recent updates to diagnostic guidelines that consider the subtleties of each condition have been helpful.

Continued research into the factors that contribute to depression, such as environmental exposure and genetics, are also giving researchers a better understanding.

Diagnosis of MDD-MX

It can be very challenging to diagnose depression with mixed features. For a long time, mental health professionals were taught that the presence of manic symptoms meant a person had bipolar, rather than unipolar, depression. 

While mania or hypomania is still part of the fundamental diagnostic criteria for bipolar disorder, it is now also understood that people with depression may also experience these symptoms—albeit to a lesser degree. 

The classic signs and symptoms of major depression may be relatively easy to spot, but subtle episodes of mania or hypomania may go undetected—both by the person with the condition and the doctors treating them.

A person with symptoms of hypomania or mania and depression may initially be misdiagnosed with bipolar disorder. While the conditions may look (and at times feel) the same, there are some important distinctions—especially when it comes to treatment. A correct diagnosis is necessary to ensure someone with either condition is able to access the most effective type of treatment. 

Obvious similarities between mixed episodes of depression and bipolar disorder, such as shared symptoms, might be clear to doctors and researchers but these conditions may also share risk factors (like a family history of mental illness). 

Doctors must carefully consider all the information as they are formulating a diagnosis, as only looking at symptoms can be misleading. The consequences of being diagnosed with the wrong mood disorder can have a major impact on someone’s life. 

According to the DSM-5, the "with mixed features" specifier can be added to a diagnosis of major depressive disorder to indicate that a person has symptoms of both depression and mania but doesn’t quite meet the diagnostic criteria for a diagnosis of bipolar disorder.

Research has indicated that compared to those with depression, people who experience mixed episodes are more likely to misuse substances and are at an increased risk for suicide —yet another reason why getting a correct diagnosis is important. 

Treatment of MDD-MX

After being diagnosed with depressive disorder with mixed features, your doctor or psychiatrist will discuss treatment options with you. The first option may be therapy, medication, or both. Though there are similarities between depression with mixed features and bipolar disorder, the two conditions can differ quite a bit in how they respond to treatment—especially medications.

It’s important to know that this form of depression may not respond well—or at all—to treatment with antidepressant medications alone.

It’s also important to know that a diagnosis of depressive disorder with mixed features in and of itself is a significant risk factor for eventually developing bipolar disorder. When you and your doctor are creating a treatment plan, you will need to consider this risk. 

To help with manic symptoms, your doctor may also prescribe an atypical antipsychotic such as: 

  • Abilify (aripiprazole)
  • Geodon (ziprasidone)
  • Latuda (lurasidone)
  • Rexulti (brexipiprazole)
  • Saphris (asenapine)
  • Seroquel (quetiapine)
  • Zyprexa (olanzapine)

You may also be given a mood stabilizer like lithium or Depakote (divalproex) instead of, or in addition to, an antidepressant. Small studies in people with depression and mixed episodes have demonstrated that these medications may be helpful when given in doses lower than would be used for bipolar disorder. 

Some people who have depression with mixed features have trouble sleeping or feel especially agitated during periods of mania/hypomania. Your doctor may prescribe sedatives to help with these symptoms, such as:

Even if you are taking more than one medication, it may not be enough to effectively help manage symptoms of depression with mixed features. You may need to implement other types of treatment as well, such as psychotherapy or electroconvulsive therapy (ECT).

Coping With MDD-MX

For people who have MDD-MX, both the process of getting diagnosed and the demands of managing symptoms can become frustrating and overwhelming. If you have recently been diagnosed or are working with a doctor or mental health professional because you suspect you may have depressive disorder with mixed features, it’s important that you have the support you need. 

Begin to build your network of support with those around you at home, such as family members and friends, then reach out to your community (such as a church group or volunteer organization). You may want to find specific support groups (in-person, online, or both) for people with depression, bipolar disorder, and other mood disorders. 

If you’re not sure where to start, ask your doctor, psychiatrist, or therapist if they can point you toward local resources. You can also use the internet to search for social networks, forums, and patient advocacy networks.

A Word From Verywell

If you have depression with mixed features, you may share some experiences with someone who has been diagnosed with bipolar disorder. However, the conditions have some key differences that both you and your mental health care team need to be aware of—especially when deciding on treatment.

The process can be frustrating, particularly if you are initially misdiagnosed with another mood disorder and not given a treatment that works well for you. That’s why it’s important to do your best to create and maintain a network of support around you. 

24 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Akiskal HS, Benazzi F, Perugi G, Rihmer Z. Agitated "unipolar" depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy. J Affect Disord. 2005;85(3):245-58. doi:10.1016/j.jad.2004.12.004

  2. Stahl SM, Morrissette DA, Faedda G, et al. Guidelines for the recognition and management of mixed depression. CNS Spectr. 2017;22(2):203-219. doi:10.1017/S1092852917000165

  3. Liu X, Jiang K. Should major depressive disorder with mixed features be classified as a bipolar disorder?. Shanghai Arch Psychiatry. 2014;26(5):294-6. doi:10.11919/j.issn.1002-0829.214146

  4. Park YM. The mixed-features specifier of major depressive disorder in DSM-5: Is it practical?. Psychiatry Investig. 2018;15(11):1009-1010. doi:10.30773/pi.2018.11.10

  5. Progress in Mind. Diagnostic and therapeutic implications of the DSM-5 mixed features specifier. Psychiatry & Neurology Resource Center website.

  6. Kim H, Kim W, Citrome L, et al. More inclusive bipolar mixed depression definition by permitting overlapping and non-overlapping mood elevation symptoms. Acta Psychiatr Scand. 2016;134(3):199-206. doi:10.1111/acps.12580

  7. Tondo L, Vázquez GH, Pinna M, Vaccotto PA, Baldessarini RJ. Characteristics of depressive and bipolar disorder patients with mixed features. Acta Psychiatr Scand. 2018;138(3):243-252. doi:10.1111/acps.12911

  8. Brancati GE, Vieta E, Azorin JM, et al. The role of overlapping excitatory symptoms in major depression: are they relevant for the diagnosis of mixed state?. J Psychiatr Res. 2019;115:151-157. doi:10.1016/j.jpsychires.2019.05.014

  9. Depression Basics. National Institute of Mental Health.

  10. Camacho M, Almeida S, Moura AR, et al. Hypomania Symptoms Across Psychiatric Disorders: Screening Use of the Hypomania Check-List 32 at Admission to an Outpatient Psychiatry Clinic. Front Psychiatry. 2018;9:527. doi:10.3389/fpsyt.2018.00527

  11. Malhi GS, Fritz K, Allwang C, et al. Are manic symptoms that 'dip' into depression the essence of mixed features?. J Affect Disord. 2016;192:104-8. doi:10.1016/j.jad.2015.12.009

  12. Park SC, Kim YK. Depression in DSM-5: Changes, Controversies, and Future Directions. In: Kim YK, ed. Understanding Depression. Singapore: Springer; 2017:3-14.

  13. Vázquez GH, Lolich M, Cabrera C, et al. Mixed symptoms in major depressive and bipolar disorders: A systematic review. J Affect Disord. 2018;225:756-760. doi:10.1016/j.jad.2017.09.006

  14. American Journal of Managed Care. The Effects of Misdiagnosing Depression With Mixed Features as Unipolar Depression. AJMC website.

  15. Swann AC. Mixed features: Evolution of the concept, past and current definitions, and future prospects. CNS Spectr. 2017;22(2):161-169. doi:10.1017/S1092852916000882

  16. Targum SD, Nierenberg A. The complexity of "mixed" depression: A common clinical presentation. Innov Clin Neurosci. 2011;8(6):38-42. PMID:21779541

  17. Aiken C. How to Diagnose Mixed Features Without Overdiagnosing Bipolar. Psychiatric Times. Vol. 35, Issue 9.

  18. Rosenberg J. The Effects of Misdiagnosing Depression With Mixed Features as Unipolar Depression. Neuroscience Education Institute (NEI) 2017 Congress. AJMC website.

  19. Koukopoulos A, Sani G. DSM-5 criteria for depression with mixed features: a farewell to mixed depression. Acta Psychiatr Scand. 2014;129(1):4-16. doi:10.1111/acps.12140

  20. Cooper DM, Riggs AR. Major Depressive Disorder With Mixed Features: Recognition and Management. U.S. Pharmacist.

  21. Mcintyre RS, Ng-Mak D, Chuang CC, et al. Major depressive disorder with subthreshold hypomanic (mixed) features: A real-world assessment of treatment patterns and economic burden. J Affect Disord. 2017;210:332-337. doi:10.1016/j.jad.2016.12.033

  22. Liu CC. Adjuvant valproate therapy for patients with suspected mixed-depressive features. Ther Adv Psychopharmacol. 2014;4(4):143-8. doi:10.1177/2045125314532868

  23. Verdolini N, Hidalgo-Mazzei D, Murru A, et al. Mixed states in bipolar and major depressive disorders: Systematic review and quality appraisal of guidelines. Acta Psychiatr Scand. 2018;138(3):196-222. doi:10.1111/acps.12896

  24. McKnight, W. New guidelines to focus on mixed features in depression, bipolar. Clinical Psychiatry News.

By Nancy Schimelpfening
Nancy Schimelpfening, MS is the administrator for the non-profit depression support group Depression Sanctuary. Nancy has a lifetime of experience with depression, experiencing firsthand how devastating this illness can be.