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Bipolar disorder
Seeing the Full Picture: Making Sense of Mixed Features and Anxious Distress in Bipolar Disorder

Released: August 13, 2025

Kristin Raj
Kristin Raj, MD
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Key Takeaways
  • Always assess for mixed features in depressive episodes. Subthreshold manic symptoms such as racing thoughts, increased activity, or pressured speech may suggest bipolar depression with mixed features, especially if symptoms worsen with antidepressants.
  • Do not overlook anxious distress. When patients experiencing mood episodes report excessive worry, restlessness, or fear of failure, consider the “anxious distress” specifier, even in the absence of a formal anxiety disorder, as it signals a more severe course and poorer treatment response.
  • Tailor treatment based on specifiers. Recognizing mixed features and anxious distress can help avoid misdiagnosis and guide appropriate therapy, often favoring mood stabilizers or atypical antipsychotics over antidepressant monotherapy.

Maria, a 34-year-old IT analyst, walked into my clinic for a second opinion about her depression. She had been receiving a selective serotonin reuptake inhibitor (SSRI) for years but recently reported low mood and being more agitated and snappier. “I’m so depressed and irritable,” she said, “and I can’t stop moving. I feel compelled to do so much at work, and even when I come back home. I’m so tense and worried that I’m failing at everything, which just makes it worse because I can’t concentrate. My mind won’t stop racing, day and night. My coworkers and my husband are all telling me I just can’t stop going on about it.” Her provider had increased the SSRI 2 weeks earlier. Things had only gotten worse.

Maria is the kind of patient who reminds us that the DSM specifiers are not just academic definitions. They are also critical tools that can refine diagnosis, guide treatment, and help us avoid harm. In her case, the specifiers for “mixed features” and “anxious distress” offer a crucial lens.

The Value of DSM-5-TR Specifiers
When the DSM-5 introduced the “with mixed features” specifier in 2013, it marked a turning point. Rather than requiring patients to meet full syndromic criteria for both mania and depression to qualify for a “mixed episode,” the specifier allowed us to recognize subthreshold symptoms of the opposite pole occurring simultaneously. The anxious distress specifier was created to describe anxiety that co-occurs within the context of a mood episode.

As healthcare professionals (HCPs), it can be tempting to overlook specifiers or treat them as secondary. But I would argue the opposite: These descriptors often hold the key to nuanced treatment decisions and can prevent clinical missteps, especially in complex or ambiguous cases.

Let us return to Maria. Although she presented with what seemed like a straightforward depressive episode, her increased activity level, racing thoughts, and talkativeness painted a different picture, one consistent with a “major depressive episode with mixed features.”

Per DSM-5-TR, the “mixed features” specifier can be applied to a depressive episode if at least 3 manic/hypomanic symptoms are present during most days of the depressive episode. Of importance, symptoms must be observable by others or cause significant distress, and they must not overlap with the depressive symptoms themselves (eg, distractibility cannot count toward the mixed symptoms).

In Maria’s case, increased talkativeness, flight of ideas, and increased activity were clear indicators. Identifying this pattern had major implications. Increasing her SSRI, a common practice in unipolar depression, had likely worsened her agitation. Recognizing mixed features steered us toward mood stabilizers and away from antidepressant monotherapy.

Why Mixed Features Matter
Patients with mixed features are at higher risk of treatment-emergent mania, rapid cycling, and suicidality. They often have a more refractory course and poorer functional outcomes. Of importance, they are more likely to be misdiagnosed, especially if HCPs rely solely on classic manic symptoms like euphoria or grandiosity, which may be absent.

Asking about energy, racing thoughts, and goal-directed activity in depressive episodes is key. Patients do not always volunteer to discuss these symptoms unless we specifically ask.

The Overlooked Anxious Distress Specifier
In Maria’s case, her tenseness and persistent worry that she was “failing” at everything and trouble concentrating because of worry added another layer of anxious distress. Applied during a mood episode when patients also experience 2 or more symptoms of anxiety—such as feeling keyed up, unusually restless, having difficulty concentrating because of worry, or fearing that something awful may happen—those are highly prevalent in both unipolar and bipolar depression.

Why does it matter? Anxious distress predicts worse outcomes across the board: higher suicidality, more functional impairment, longer time to remission, and poorer response to standard antidepressant treatments.

Practical Pearls for Everyday Practice

  1. Ask the right questions. When seeing a patient with depression, always assess for increased energy/activity level, pressured speech, and racing thoughts. These may signal mixed features.
  2. Think beyond anxiety disorders. If patients with depression report worries or restlessness, consider the anxious distress specifier, even if they do not meet criteria for generalized anxiety disorder.
  3. Rethink antidepressants. Antidepressant monotherapy in patients with mixed features can worsen outcomes. Consider mood stabilizers or atypical antipsychotics instead.
  4. Validate complexity. These specifiers remind us that mood disorders are rarely textbook. Embracing their nuances helps us avoid oversimplified treatment.

Closing the Loop
For Maria, adding a mood stabilizer and slowly tapering her SSRI brought significant relief. Her agitation subsided, her sleep improved, and over time, her depressive symptoms lifted. By learning to recognize mixed features and anxious distress, HCPs can radically improve the lives of patients.

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How often do you assess whether patients experiencing mood episodes also have co-occurring restlessness, excessive worry, or tense feelings?

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