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
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
Full manic/hypomanic
episode
episode
AND
At least 3depressive symptoms2
Full depressive
episode
episode
AND
At least 3manic/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
- May report depressive symptoms but may not report manic/
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
CNS Spectrums. 2017;22:203-219
Actor portrayal.
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
2000Manic
Mixed
Depressive
DSM-52,8,9
2013Manic
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
Actor portrayal.
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:
Manic/hypomanic episode with mixed features
Full criteria for a
manic/hypomanic
episode are met
manic/hypomanic
episode are met
AND
At least 3depressive 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
Depressive episode with mixed features
Full criteria for a
depressive
episode are met
depressive
episode are met
AND
At least 3manic/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:
| F31.60 | Bipolar disorder, current episode mixed, unspecified |
|---|---|
| F31.61 | Bipolar disorder, current episode mixed, mild |
| F31.62 | Bipolar disorder, current episode mixed, moderate |
| F31.63 | Bipolar disorder, current episode mixed, severe, without psychotic features |
| F31.64 | Bipolar disorder, current episode mixed, severe, with psychotic features |
| F31.77 | Bipolar disorder, in partial remission, most recent episode mixed |
| F31.78 | Bipolar 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
Thorough and accurate assessment of mixed states in bipolar I is essential.6
Actor portrayal.
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 July 17, 2023. 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.