How to Diagnose Mixed Features Without Overdiagnosing Bipolar

RESEARCH UPDATE

Mixed features are common in practice but poorly described in DSM. They are caused by the overlap of depressive and manic symptoms, but it’s hard to understand them by reading separate descriptions of these two states. It would be like trying to imagine green by studying yellow and blue.

Classic hypomania is difficult enough to detect. These euphoric states are brief, rare, and easily forgotten. Mixed cases bring a different set of challenges. Mixed features cause intense desperation. Rather than missing their appointments in a carefree, hypomanic bliss, these patients often call for urgent appointments. The issue is not that these states will be forgotten, but that they’ll present with symptoms that resemble those of many other psychiatric disorders.

A diagnostic chameleon

Mixed features can look like anxiety, ADHD, borderline personality disorder, or depression with an agitated edge. The Table contrasts the features of hypomania as they appear in mixed and pure forms. Unlike euphoric hypomania, mixed symptoms are not pleasurable, and the interview needs to be adjusted to capture that.

Ask a patient with mixed features, “Do you have times when you don’t need much sleep” and he or she will answer “No.” In truth, these patients do keep going with little rest, but they usually have a strong desire to sleep. Often the desire is not to sleep but to “turn my mind off,” a dangerous wish that can lead to sedative overdose when sleep does not come.

Ask a patient with mixed features, “Do you feel unusually confident, happy, or euphoric” and you’ll get a big “No.” How does confidence look when mixed with depression? Self-esteem is low, but patients are also demanding and aggressive, asserting themselves in a way that’s not consistent with the usual passivity of depression. Euphoria is replaced by lability, and most of these patients recall only the aversive turns of that emotional carousel. Relatives, on the other hand, may notice rare bursts of giddy excitation.¹

DSM-5 made an important advance in understanding mixed states: it removed the word “pleasurable” from the impulsivity criteria. Sometimes these patients do pursue hedonic pleasures, but they are quick to point out that they only shop, binge on carbs, or masturbate excessively to “relieve the depression” and “not because I’m manic.” More often, the impulsivity is destructive. They will quit jobs, end relationships, break television sets, fire their psychiatrist, and tragically turn to self-harm and suicide, the rates of which are higher in mixed states than they are in depression.²

Substance abuse is also elevated. The association between depression and addiction may be entirely explained by mixed features, according to three studies involving more than 12,000 patients followed for at least 10 years. However, most of the mixed features in those studies would not be classified as bipolar, as we’ll see next.^3-5

Clinical implications

Mixed hypomania is more common than the purer form, and it’s more likely to bring patients into treatment. It also counts toward a bipolar diagnosis. As long as the hypomanic symptoms are long enough in duration (4 or more days) and sufficient in number, the diagnosis is bipolar, even if the patient never has an episode of pure hypomania. Often, these symptoms don’t cross the bipolar threshold and are due to a form of unipolar depression newly recognized in DSM-5 as Major Depressive Episode with Mixed Features. This diagnosis is surprisingly common, occurring in up to 25% of patients with unipolar depression.⁶

Mixed unipolar disorder

Is mixed unipolar a form of bipolar disorder? Yes, and no. It falls somewhere between bipolar and unipolar in terms of family history, course of illness, associated features, and treatment response.⁷ Those four areas are the non-manic markers of bipolar disorder, and they are useful legs to stand on when faced with the non-specific symptoms of a mixed state.⁸The Bipolarity Index is a quick tool that gathers and ranks these markers. It is available free online (www.moodtreatmentcenter.com/measurement) and has proven useful in distinguishing bipolar disorder from unipolar depression as well as from conditions that resemble mixed states such as borderline personality disorder.^8,9

The bottom line

In the end, this is a diagnosis that matters. Antidepressants are a two-edged sword that can make these states better in some and worse in others. The latest treatment guidelines recommend minimizing antidepressants, even in the unipolar form of mixed features and argue instead for mood stabilizers and atypical antipsychotics.²

This article was originally published on 7/6/18 and has since been updated.

Disclosures:

Dr. Aiken is the Director of the Mood Treatment Center, Editor in Chief of The Carlat Psychiatry Report, and Instructor in Clinical Psychiatry at the Wake Forest University School of Medicine. He does not accept honoraria from pharmaceutical companies but he receives honoraria from W.W. Norton & Co. for Bipolar, Not So Much, a book he coauthored with Jim Phelps, MD.

References:

1. Koukopoulos A, Faedda G, Proietti R. et al. [Mixed depressive syndrome].Encephale, 1992;Spec No 1:19-21.

2. Stahl SM, Morrissette DA, Faedda G, et al. Guidelines for the recognition and management of mixed depression.CNS Spect, 2017;22:203-219.

3. Zimmermann P, Brückl T, Nocon A, et al. Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity.Arch Gen Psychiatry, 2009;66:1341-1352. 

4. Angst J, Gamma A, Endrass J, et al. Is the association of alcohol use disorders with major depressive disorder a consequence of undiagnosed bipolar-II disorder?Eur Arch Psychiatry Clin Neurosci, 2006;256:452-457.

5. Angst J, Azorin JM, Bowden CL, et al. Prevalence and characteristics of undiagnosed bipolar disorders in patients with a major depressive episode: the BRIDGE study.Arch Gen Psychiatry, 2011;68:791-798.

6. 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.

7. Aiken C. “The Bipolar Spectrum,” in Bipolar II Disorder: Modelling, Measuring and Managing, 3nd Edition, Parker G editor. Cambridge University, in press.

8. Aiken CB, Weisler RH, Sachs GS. The Bipolarity Index: a clinician-rated measure of diagnostic confidence.J Affect Disord. 2015;177:59-64.

9. Apfelbaum S, Regalado P, Herman L, et al. Comorbidity between bipolar disorder and cluster B personality disorders as indicator of affective dysregulation and clinical severity.Actas Esp Psiquiatr. 2013;41:269-278.