Is she in a Manic or Depressed State or is it mixed?
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Understanding mixed features of bipolar I disorder
woman sitting with arms crossed

The challenge of recognizing mixed states1

Bipolar I disorder is characterized by recurring episodes of2: 

mania/hypomania

and

depression

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR), about one-third of patients with bipolar I experience mixed states.2 

Despite the prevalence of mixed states, they are not easily or consistently identified by clinicians.1

pie graph shaded approx. 1/3
ABOUT ONE-THIRD OF
PATIENTS WITH
BIPOLAR I 

experience mixed states2

What are mixed states in bipolar I disorder?

Bipolar I mixed states are an often debilitating combination of manic and
depressive states occurring at the same time.2,3
icon representing mania or hypomania

Full manic/hypomanic episode

AND

icon representing depression

At least 3 depressive symptoms2

icon representing depression

Full depressive episode

AND

icon representing mania or hypomania

At least 3 manic/hypomanic symptoms2

What factors may account for the difficulty of diagnosing mixed states?

Reliability of patient self-reporting

Patients typically seek help for one symptom (eg, depression):

  •  Depressive symptoms are more frequent than manic symptoms and patients are more likely to present during depressed episodes2,4
    •  May report depressive symptoms but may not report manic/hypomanic symptoms they are also experiencing2,5
The elusive clinical picture of bipolar I

Mixed states can be difficult to diagnose due to different aspects of how bipolar I presents: 

  •  Heterogeneous presentations between and within individual patients3
  • Changing course of illness over time2
  • Similarities between mixed states and “pure” mood states of bipolar I5
You will not know if a depressed patient has (hypo)manic symptoms or a positive family history of bipolar disorder unless you ask!”6

—Stahl SM, Morrissette DA, Faedda G, et al.

CNS Spectrums. 2017;22:203-219

Evolving definition of mixed states in patients with bipolar I disorder

In order to reflect the evolving understanding that most patients with bipolar I experience subsyndromal symptoms, criteria for mixed states shifted significantly from the DSM-IV-TR to DSM-5.3,5,7

DSM-IV-TR5,8,9
2000
Manic
Mixed
Depressive
DSM-52,8,9
2013
Manic
Manic with mixed features
Depressive with mixed features
Depressive

Hu J, Mansur R, McIntyre RS. The Primary Care Companion for CNS Disorders. Volume 16, PCC.13r01599. Copyright 2014. Physicians Postgraduate Press. Adapted with permission.

DSM-5 shifted from the DSM-IV concept of a “mixed episode” with full criteria for both depressive and manic episodes to that of an episode of mania or depression with a “mixed features specifier.”7 See full criteria below.

What is the impact & severity of mixed states?

Mixed states are associated with:

  •  Severe depression6
  •  Long duration of illness6
  •  Poor prognosis2,5,6
  •  Suicidal behavior2,3
  •  Frequent hospitalizations10

The severity of mixed states highlights the importance of assessing patients for the full spectrum of bipolar symptoms.5

How can you identify mixed states in patients with bipolar I?

Accurate clinical assessment and characterization is imperative to assist in diagnosis of mixed states of bipolar I.6

The current definition from DSM-5-TR allows clinicians to consider symptoms from the opposite pole. If at least 3 symptoms are present, a patient’s diagnosis may be specified as having mixed features. This definition is less restrictive than DSM-IV-TR. As a result, it expands the pool of patients recognized as experiencing mixed states and may lead to a more appropriate diagnosis.2,8

DSM-5-TR provides the following definition for mixed features specifiers occurring with a full manic or full depressive episode2:

icon representing mania or hypomania

Full criteria for a manic/hypomanic episode are met

AND

Icon representing depression

At least 3 depressive symptoms

At least 3 of the following symptoms present during majority of days of the current or most recent episode of mania or hypomania:

  •  Prominent dysphoria or depressed mood as indicated by either subjective report (eg, feel sad or empty) or observation made by others (eg, appears tearful)
  • Diminished interest or pleasure in all, or almost all, activities (as indicated by either subjective account or observation made by others)
  • Psychomotor retardation nearly every day (observable by others; not merely subjective feeling of being slowed down)
  • Fatigue or loss of energy
  • Feelings of worthlessness or excessive inappropriate guilt (not merely self-reproach or guilt about being sick)
  • Recurring thoughts of death (not just fear of dying), recurring suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
Icon representing depression

Full criteria for a depressive episode are met

AND

icon representing mania or hypomania

At least 3 manic/hypomanic symptoms

At least 3 of the following manic/hypomanic symptoms present during majority of days of the current or most recent episode of depression:

  • Elevated, expansive mood
  • Inflated self-esteem or grandiosity
  • More talkative than usual or pressure to keep talking
  • Flight of ideas or subjective experience that thoughts are racing
  • Increase in energy or goal-directed activity (either socially, at work or school, or sexually)
  • Increased or excessive involvement in activities that have a high potential for painful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
  • Decreased need for sleep (feeling rested despite sleeping less than usual; to be contrasted with insomnia)
DSM-5-TR criteria stipulate that mixed states must have symptoms that are2:

Observable by others and represent a change from a person’s usual behavior

Not attributable to physiological effects of a substance

When full episode criteria for both mania and depression occur simultaneously, DSM-5-TR states that the diagnosis should be manic episode with mixed features.

 

It should be noted that certain symptoms including irritability, distractibility, and psychomotor agitation, are excluded from the DSM-5-TR criteria for mixed features. This was done to reduce the potential for overdiagnosis due to overlapping symptoms, since these symptoms are common to episodes of both depression and mania.6

How are mixed states coded?

The following ICD-10-CM codes are available for mixed states of bipolar disorder11:
F31.60Bipolar disorder, current episode mixed, unspecified
F31.61Bipolar disorder, current episode mixed, mild
F31.62Bipolar disorder, current episode mixed, moderate
F31.63Bipolar disorder, current episode mixed, severe, without psychotic features
F31.64Bipolar disorder, current episode mixed, severe, with psychotic features
F31.77Bipolar disorder, in partial remission, most recent episode mixed
F31.78Bipolar disorder, in full remission, most recent episode mixed

What specific tool can be used to help detect mixed states?

Clinically Useful Depression Outcome Scale - Mixed feature specifier (CUDOS-M):

A patient self-report measure of DSM-5 mixed features during depression. CUDOS-M has been validated and demonstrated high internal consistency and test-retest reliability, as well as high correlation with self-report measures of mania and depression.12

Downloads available for your practice

Is It Mixed? Brochure

A summary of the content on this website for you and your team

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Thumbnail of the 'Is It Mixed? Brochure'
Mixed States Tearpad

A checklist you can use with your patients to help identify symptoms of mixed states

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Thumbnail of the 'Mixed States Tearpad'

Thorough and accurate assessment of mixed states in bipolar I is essential.6

woman sitting with arms crossed

References: 1. Young AH, Eberhard J. Evaluating depressive symptoms in mania: a naturalistic study of patients with bipolar disorder. Neuropsychiatr Dis Treat. 2015;11:1137-1143. Published 2015 Apr 29. doi:10.2147/NDT.S82532 2. Diagnostic and Statistical Manual of Mental Disorders, DSM-5-TR. American Psychiatric Association; 2022. 3. Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97-170. doi:10.1111/bdi.12609 4. Calabrese JR, Hirschfeld RM, Frye MA, Reed ML. Impact of depressive symptoms compared with manic symptoms in bipolar disorder: results of a U.S. community-based sample. J Clin Psychiatry. 2004;65(11):1499-1504. doi:10.4088/jcp.v65n1109 5. Goldberg JF, Perlis RH, Bowden CL, et al. Manic symptoms during depressive episodes in 1,380 patients with bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2009;166(2):173-181. doi:10.1176/appi.ajp.2008.08050746 6. Stahl SM, Morrissette DA, Faedda G, et al. Guidelines for the recognition and management of mixed depression. CNS Spectr. 2017;22(2):203-219. doi:10.1017/S1092852917000165 7. American Psychiatric Association. Highlights of changes from DSM-IV-TR to DSM-5. 2013. https://www.psychiatry.org/File%20Library/Psychiatrists/Practice/DSM/APA_DSM_Changes_from_DSM-IV-TR_-to_DSM-5.pdf. Accessed January 9, 2025. 8. Hu J, Mansur R, McIntyre RS. Mixed specifier for bipolar mania and depression: highlights of DSM-5 changes and implications for diagnosis and treatment in primary care. Prim Care Companion CNS Disord. 2014;16(2):PCC.13r01599. doi:10.4088/PCC.13r01599 9. Diagnostic and Statistical Manual of Mental Disorders, DSM-5. American Psychiatric Association; 2013. 10. Shim IH, Woo YS, Bahk WM. Prevalence rates and clinical implications of bipolar disorder “with mixed features” as defined by DSM-5. J Affect Disord. 2015;173:120-125. doi:10.1016/j.jad.2014.10.061 11. American Academy of Professional Coders. ICD-10-CM Expert Diagnosis Codes for Providers & Facilities. AAPC; 2021. 12. Zimmerman M, Chelminski I, Young D, Dalrymple K, Martinez JH. A clinically useful self-report measure of the DSM-5 mixed features specifier of major depressive disorder. J Affect Disord. 2014;168:357-362.

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