Identifying and managing major depressive disorder with mixed features

One in five people with major depressive disorder (MDD) have at least three hypomanic symptoms, and present clinical challenges in terms of nonresponse to antidepressants, nonadherence, comorbid substance use disorder (SUD), and poor outcomes. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) therefore introduced a mixed specifier for MDD as a distinct entity. A clinical case role-play scenario highlighting the clinical presentation of MDD with mixed features and comorbid SUD, and how its management differs from that for patients with MDD without mixed features was presented at Psych Congress 2019 to a large audience of psychiatrists.

One in five people with major depressive disorder (MDD) have mixed features (i.e., hypomanic symptoms) but not enough hypomanic symptoms to diagnose bipolar disorder, although the manic symptoms may overwhelm the symptoms of MDD, said Rakesh Jain, Texas Tech Health Sciences Center, TX. This population of people with MDD:

  • present diagnostic and treatment challenges
  • have a worse outcome than people with MDD without hypomanic symptoms
  • commonly have a comorbid substance use disorder (SUD)

DSM-5 introduced the mixed specifier for MDD (to read more, please see to reflect the spectrum of mood disorders along a continuum from pure mania to pure depression, he added. Treatment can then be better tailored to manage the patient’s behaviors.

The criteria for diagnosing MDD with mixed features are full criteria for MDD and at least three specifying manic features during the majority of days of the current or recent depressive episode.1 These features are:

  • an excessively elevated mood (e.g., high or hyper)
  • inflated self-esteem or grandiosity
  • more talkative than usual or feeling pressured to keep talking
  • flight of ideas or racing thoughts
  • increase in energy or goal-directed activity
  • increased or excessive involvement in activities that have a high potential for painful consequences (e.g., unrestrained buying spree)
  • decreased need for sleep

It is important to note that Irritability, Distractibility, and Insomnia (IDI) are symptoms of both mania and depression


Challenges in making a diagnosis of MDD with mixed features — a clinical role play scenario

The challenges in identifying and managing MDD with mixed features were highlighted in a clinical-case role-play scenario in which Charles Raison, University of Wisconsin-Madison Madison, W Clay Jackson, University of TN College of Medicine Arlington, and Professor Jain, played the patient, primary care practitioner, and psychiatrist, respectively.

The patient is a middle-aged man who presents to a new primary care practitioner with a 2-month history of worsening depression triggered by a relationship breakdown resulting from his “moodiness.” He describes four episodes of significant depression over the previous 30 years and has been treated with a selective serotonin reuptake inhibitor (SSRI) once, but discontinued it after 2 weeks due to sexual dysfunction. All other episodes had resolved spontaneously.

The patient agrees to take a serotonin-norepinephrine reuptake inhibitor (SNRI), and after 8 weeks responds to treatment, but then deteriorates after a further 10 weeks.

At this point, the patient is experiencing worsening depressive symptoms, morning insomnia, and anxiety and agitation accompanied by tremor, which are attributed to his alcohol abuse disorder. Following a detoxification program, he discontinues his antidepressant and his depressive symptoms resolve.

15 months later, the patient re-presents with a rapid onset depressive episode associated with racing thoughts, not sleeping, impulsive excessive spending, and distractibility. His abstinence from alcohol is confirmed and he again agrees to take an SSRI; but stops it after a week, because he feels worse and is experiencing sexual dysfunction.

The psychiatrist now diagnoses MDD with the mixed features specifier.


Pharmacologic management of MDD with mixed features

According to the panel, successful treatment may require a combination of agents2,3 depending on the specific patient characteristics and recommended combinations include:

  • atypical antipsychotic and antidepressant4
  • mood stabilizer and antidepressant
  • atypical antipsychotic and mood stabilizer
This session was supported by an educational grant from Otsuka America Pharmaceutical, Inc. and Lundbeck
  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, Fifth edition. Arlington. VA: APA; 2013.
  2. Targum S, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2016;68:9–14.
  3. McIntyre R, et al. J Affect Disord. 2015;172:259–64.
  4. Papakostas G, et al. J Clin Psychiatry. 2007;68:826–31.
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