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The Spinning World of Major Depression With Mixed Features

Part 7: Identifying and understanding major depression subtypes.

Key points

  • Major Depression with mixed features means manic/hypomanic symptoms are superimposed on the depressive episode.
  • Mixed features means manic/hypomanic symptoms are present, but it doesn't mean the person will develop a bipolar disorder.
  • Due to similarities to bipolar disorder, mixed features usually require psychiatry, along with psychotherapy, to stabilize.

Over the past three weeks, we've lifted the masks of many Major Depressive Disorder (MDD) presentation variations. Today, we'll investigate Mixed Features before moving onto specifiers of onset. Historically, a mixed presentation was only recognized as applied to Bipolar Disorder Type 1 when a patient simultaneously met criteria for Mania and Major Depression. This was called a Mixed Episode.

Sonu Agvan/Unsplash
Source: Sonu Agvan/Unsplash

This stringent criteria always puzzled me, as it didn't seem unusual to witness someone with just a few depressive symptoms superimposed on a full hypomanic/manic (hy/manic) episode, or, more relevant here, some hy/manic symptoms superimposed on a full MDD episode. It is now recognized in the DSM-5 that such presentations indeed occur, and we have the Mixed Features specifier.

As for how common it is, there again is minimal research. McIntyre et al. (2015) wrote that rates of MDD with Mixed Features ranged between 11 and 54%. This depended on the number of symptoms researchers believed were required to constitute Mixed Features. Currently, the sanctioned number (DSM-5) is at least three.

It is likely that the DSM threshold is three because a cluster of hy/manic symptoms makes an undeniable case it is indeed a mixed mood state. Otherwise, there could be confusion because other specifiers share some symptoms similar to hy/manic ones. For example, the restlessness of Anxious Distress; the inability to focus that many depressed patients experience in general; or the fact that it is not unusual for depressed people to simultaneously experience sadness and irritability, which could be mistaken for the "expansive" affective experience of hy/mania. Taken together, these three items are more likely a hy/manic experience; individually, they could simply represent a characteristic of another specifier.

Mixed Features is an interesting specifier because, not surprisingly, it can lead to full manic or hypomanic episodes, indicating a Bipolar Type 1 or 2 diagnosis. Despite the tendency for many with Mixed Features to develop Bipolar conditions, there are some MDD sufferers whose Mixed Features never seem to evolve that far (Suppes & Ostacher, 2017). This is not to say that these patients' lives are more easily endured than someone with distinct mood cycling. In fact, according to Wang et al. (2021):

...mixed features seriously affect the patient's quality of life and social functioning as well as lead to more frequent recurrence, more severe symptoms, greater risk of suicide, higher rates of comorbidities, lower efficacy of medication, and a poorer prognosis of the disease

The presentation

A good metaphor for mixed presentations could be "spinning in the darkness." Seeing a patient not only depressed but who is experiencing racing thoughts and impulsivity can be challenging for clinicians. Imagine what it is like for the patient! Kelly's case (name disguised) helps illustrate:

Kelly did really well in undergrad, and was slated to finish her master's degree ahead of schedule. After the first month of the semester, Kelly began losing her appetite and had insomnia. She figured that full time graduate school and working two jobs, coupled with trying to keep up a relationship, was wearing on her. As the semester advanced, her overall mood felt "gray" and often irritable. Friends noticed she lost her spunk and didn't hang out as much. She pushed through to finals, thankful to have made it. Kelly planned to slow her pace and only go part-time next semester if this was what stress would do to her.

During finals week, Kelly continued to feel gray and irritated, and didn't eat much, but seemed to be running on adrenaline. She felt the few hours of sleep she got was sufficient. However, her mind raced from subject to subject, and she couldn't focus to study well. Normally an A student and someone who handled stress well, she barely passed her exams, and was very concerned. Hoping the Holiday break would relax her mind, Kelly went home to rest. After a week at home, her symptoms stayed the same. Kelly's parents phoned Dr. H for an evaluation.

DSM-5 diagnostic criteria for MDD with Mixed Features is as follows:

The presence of an MDD episode during which there are at least three symptoms of hy/mania present for the majority of the episode. These are:

  • Elevated, irritable, or expansive mood coupled with increased energy
  • Significantly less sleep required to feel rested
  • Inflation of self-esteem
  • Pressure to keep talking/more talkative than normal
  • Flights of ideas/racing thoughts
  • Easily distracted
  • Increased goal-oriented activity or psychomotor agitation
  • Increased involvement in activities that can lead to troubling consequences (e.g., gambling, spending sprees, indiscriminate sex)

Returning to the three-symptom threshold, it's my experience that we should use clinical judgment. If only one or two symptoms are clearly present (i.e., the restlessness or affective alterations normally seen in some depression presentations become extreme, as if an energy is behind them, or the inability to focus often seen in depressed people seems driven by pressured thought or distractibility by irrelevant environmental stimuli) it's likely safe to be considering a Mixed Features specifier and to certainly be vigilant for additional evolving symptoms.

Keys to identifying mixed features

Andrea Piacquaido/Pixabay
Source: Andrea Piacquaido/Pixabay

As noted above, the concern with mixed symptoms is the potential for patients to spin into full hy/manic episodes and enter full Bipolar territory. Thus, developing a skilled eye for emerging Mixed Features is key. At first, it may be difficult to differentiate Mixed Features from someone with the agitation and intense trouble focusing due to Anxious Distress or Melancholic Features. There are some key points to help differentiate these and to identify superimposed hy/manic symptoms in general:

  1. If the person's depressed mood is seasoned with elevated/euphoric periods or periods of expansive mood (i.e. marked alterations between brightness, irritation, and sadness), that is a clear indicator of Mixed Features, especially if an energized component is present.
  2. Most people with depression have slowed thinking and thus their trouble focusing. If the patient's thought process and speech are pressured/tangential (just can't stop talking) despite being depressed, that is a good indicator of a Mixed Feature.
  3. Another matter of thought process is flights of ideas where the person is jumping from topic to topic, as someone with ADHD might do.
  4. Depressed patients with agitation and anxiety often seem fatigued by their restlessness. Therefore, if it is noticed the patient has an energetic, or hyperactive, "flavor" about them, this is indicative of a Mixed Feature. Another tip-off is, despite not sleeping, they don't seem tired.
  5. Depressed people often experience inhibited impulsivity. If they begin exhibiting poor impulse control/behaviors that can lead to troubling consequences such as uninhibited purchasing, fighting, sexual activity, gambling, substance use, etc. is also quite different from the average depressed patient, and another sign of a Mixed Feature.
  6. If the person's demeanor shifts from poor self-esteem to thinking highly of themselves in some capacity, or develop grand ideas of things they plan to work on.

Treatment implications

Given patients with Mixed Features have one and a half feet in the realm of Bipolar spectrum conditions, it is no surprise that they need a referral for psychiatry. This is not depression that will likely resolve via talk therapy alone. Pharmacology can help them become less energetic and able to think more clearly, helping them focus on therapy.

Some MDD patients with Mixed Features seem prone to become fully hy/manic if treated with an anti-depressant alone (e.g., Faedda & Marangoni, 2017). Therefore, like Bipolar patients, they may be prescribed a mood stabilizer such as Lamictal, lithium, or an atypical antipsychotic medication, along with an antidepressant (e.g., Shim et al., 2018). Interestingly, researchers Sani & Fiorillo (2020) mentioned that lithium is not used as often as it perhaps should be in mixed states, and that, in their research, was the medication most correlated to preventing suicide in mixed state patients. Other researchers have also found ketamine to be an effective pharmacological intervention (McIntyre et al., 2020). Lastly, electroconvulsive therapy (ECT) may be required in hard-to-treat cases.

Talk therapy with someone prone to Mixed Features is similar to the work we do with Bipolar Disorders. Once again, for the therapist, it is not only important to get the patient stable in the current episode but to work towards episode relapse prevention. This, of course, begins with a plan if they stabilize and are discharged from therapy, to have them immediately reconnect if they or friends/loved ones notice any onset of mood symptoms.

Psychotherapy should also include stress management because for people prone to hy/mania, there is a correlation between hy/manic episode onset and environmental stressors. Since the person is indeed prone to some hy/manic features, and there is the possibility that could evolve into full hy/mania, keeping stress down is key. This often includes family therapy, since this is where a lot of the stress burden is rooted for many. Lastly, poor sleep is another significant correlate to unlocking hy/manic presentations in people prone, so sleep hygiene is also of utmost importance.

Mixed Features has been described as a "natural bridge" between MDD and Bipolar Disorders and, to some researchers, might constitute a distinct diagnostic category (Suppes & Ostacher, 2017). This remains to be seen, and if that would bring about new treatment approaches, which would likely be of a biological nature. For now, such patients may do well if therapists remain vigilant for such presentations and approach treatment similarly to Bipolar presentations.

As we round out this series on Major Depressive Disorder, the next two posts will be concerned with specifiers of onset, beginning with Peripartum MDD on 10/25/2021.


Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association, 2013.

Faedda, G., & Marangoni, C. (2017). What is the role of conventional antidepressants in the treatment of major depressive episodes with Mixed Features Specifier? CNS Spectrums, 22(2), 120-125. doi:10.1017/S1092852916000493

McIntyre, R. S., Cucchiaro, J., Pikalov, A., Kroger, H., & Loebel, A. (2015). Lurasidone in the treatment of bipolar depression with mixed features (subsyndromal hypomanic) features: post hoc analysis of a randomized placebo-controlled trial. Journal of Clinical Psychiatry, 76(4), 398-405

McIntyre, RS, Lipsitz, O, Rodrigues, NB, et al. The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. Bipolar Disorders, 22(8), 831– 840.

Shim, I. H., Bahk, W. M., Woo, Y. S., & Yoon, B. H. (2018). Pharmacological treatment of major depressive episodes with mixed features: A systematic review. Clinical Psychopharmacology and Neuroscience : The Official Scientific Journal of the Korean College of Neuropsychopharmacology, 16(4), 376–382.

Suppes, T., & Ostacher, M. (2017). Mixed features in major depressive disorder: diagnoses and treatments. CNS Spectrums, 22(2), 155–160

Wang, H., Xiao, Y., Du, J., Du, X., & Chen, L. (2021). Clinical features of patients with major depressive disorder and bipolar depressive disorder depressive episodes with mixed features. Research Square.