Characteristics of Depressive and Bipolar Disorder Patients with Mixed Features

Tondo, et al examine differences in patients with mood disorders with or without mixed features.

Tina Matthews Hayes, DNP, FNP, PMHNP

What do the results of this study mean for a practicing NP?

“This is a helpful resource that reminds providers of the importance of screening and the identification of a mixed presentation in both depression and bipolar disorder. The figure here is especially powerful as it visually demonstrates the correlation of mixed presentation and worse outcomes, and reminds us of the insidious prevalence of suicidal ideation/acts in the mixed bipolar patients.”

NP Psych Navigator contributors are paid consultants of AbbVie Inc.

This study finds that demographic and clinical characteristics of patients with mood disorders (bipolar disorder and major depressive disorder [MDD]) and mixed features are distinct from mood disorders without mixed features. These differences suggest that the presence of mixed features constitute a clinical subtype of mood disorders, with implications for diagnostic and treatment approaches.

Why was the research needed?

Patients with bipolar disorder or MDD can have episodes with mixed features (an episode that is predominantly one polarity with some symptoms of the opposite polarity). With no professional agreement existing on which symptoms qualify as part of a mixed-features diagnosis, the data on prevalence are insufficient. An understanding of mixed features and their prevalence in mood disorders is important for appropriate diagnosis and treatment.

What did the researchers do?

The researchers hypothesized that demographic and clinical factors would vary between patients with bipolar disorder or MDD with mixed features and without mixed features. They defined mixed features as: “(i) presence of agitation, irritability, affective lability, crowded thoughts or pressured speech, with lack of psychomotor retardation in major depressive episodes; or (ii) dysphoria, irritability, anguish, or prominent mood-lability in [hypo]mania.” Through evaluation of a combination of clinical records, semi-structured interviews, and life-charts (compiled retrospective and prospective data on the course of illness and treatment2), the researchers followed patients with a diagnosis of bipolar disorder I (n=521), bipolar disorder II (n=657), or MDD (n=1921) with (n=679) and without (n=2420) mixed features over an average of 6 years. They then compared characteristics between the groups. 

What were the key results of the study?

Patients with bipolar disorder II had the highest prevalence of mixed features (36%), followed by patients with bipolar disorder I (23%) and patients with MDD (17%). Patients who had mixed features at intake (versus those who had no mixed features at intake) were 15.5 times more likely to have a history of mixed episodes and had an earlier age of onset for illness (29.5 vs 33.5 years). Additional differences between patients with mixed features and those without mixed features can be seen in the figure. 

A figure showing someof the differences between patients with and without mixed features that werefound in the study

The researchers followed patients with a diagnosis of bipolar disorder I, bipolar disorder II, or MDD with (n=679) and without (n=2420) mixed features over an average of 6 years. As compared with patients without mixed features, patients with mixed features had a greater incidence of switching from a diagnosis of depression to one for bipolar (18% vs 5%), more hospitalizations (31% vs 26%), more suicidal ideation (47% vs 19%), more suicidal acts (30% vs 9%), and a greater incidence of a substance abuse disorder (21% vs 6%). Patients with mixed features also had more frequent prescriptions of antipsychotic (42% vs 16%) and mood stabilizing (17% vs 5%) drugs.

Patients with bipolar disorder with or without mixed symptoms had no statistical difference in family history of bipolar disorder (35% vs 30%). However, patients who had MDD with mixed features were more likely to have a family history of bipolar disorder than patients who had MDD without mixed features (18% vs 11%).

Why are these results important?

Mixed features were associated with a more frequent and severe course of illness. The differences between patients with and without mixed features found in this study, including the frequency and pattern of mixed episodes, supports the view that mixed features may constitute a clinical subtype of mood disorders. This could have implications for the diagnostic approach and treatment plan for patients exhibiting mixed features.

Most comparisons were made between patients with and without mixed features and without distinguishing the primary diagnosis of bipolar disorder or MDD. Though there may be differences in demographics and presentation of mixed features in patients with bipolar disorder compared with MDD, the study design did not allow for a close examination of these differences. Another limitation of this study was the use of historical patient data for some measures. The study also used a definition of mixed features that included symptoms that can be present in both depressive and (hypo)manic episodes, which are excluded in some other diagnostic criteria.

What’s next?

Currently, there is no consensus as to which criteria a patient must meet to be given a diagnosis of mixed features. More research is needed to understand what constitutes mixed features and how mixed features may influence a patient’s response to different treatment plans. 

The author has declared no conflicts of interest.

This summary was prepared independently of the study’s authors.

The content presented here is provided for educational purposes only. It is not intended as, nor is it a substitute for medical care or advice. Healthcare professionals should use their clinical judgment when reviewing educational resources on NP Psych Navigator. 


  1. Tondo L, et al. Acta Psychiatr Scand. 2018;138(3):243‐252.
  2. Born C, et al. BMC Psychiatr. 2014;14:130.

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