Mixed Episode

In psychiatry, a mixed episode is a clinical condition in which symptoms characteristic of both a manic episode and a depressive episode coexist within the same period. Due to its symptomatic complexity, this form of presentation tends to severely impair the patient’s overall functioning, making both diagnosis and therapeutic management more challenging than in pure mood episodes.

The current diagnostic criteria are based on the DSM-IV TR, which defines a mixed episode as follows:

• The diagnostic criteria for both a manic episode and a major depressive episode are simultaneously met and persist for at least one week.
• The mood disturbance is severe enough to cause marked impairment in social, occupational, or relational functioning, or to require hospitalization to prevent harm to self or others.
• The symptoms are not attributable to the direct physiological effects of substances (medications, drugs) or general medical conditions (e.g., hyperthyroidism).

Unlike pure manic or depressive episodes, the mixed episode is marked by emotional instability, with rapid shifts from euphoria to despair, and the simultaneous presence of conflicting symptoms. For instance, a patient may display psychomotor agitation accompanied by suicidal ideation, or pressured speech alongside feelings of guilt and worthlessness.

Epidemiologically, this condition is more frequent in young individuals and in adults over 60, and its onset may occur de novo or as a progression from a previously diagnosed manic or depressive episode.

Clinical Presentation

The coexistence of manic and depressive symptoms makes the mixed episode particularly difficult to identify. Patients may present with:

• Psychomotor hyperactivity and agitation
• Dysphoric mood with marked irritability
• Severe insomnia, with early awakenings and difficulty falling asleep
• Suicidal ideation despite apparent increased energy
• Pressured speech and flight of ideas associated with feelings of guilt or worthlessness

This simultaneous presence of manic and depressive features often results in high behavioral reactivity and an increased risk of self-harm or suicide attempts, making the mixed episode a psychiatric emergency requiring prompt and specialized intervention.

Classification and Specifiers

When the mixed episode is the most recent manifestation of a mood disorder, it may be further qualified according to the severity of symptoms and degree of functional impairment:

1. Mild: meets the minimal diagnostic criteria with mild functional impairment.
2. Moderate: intermediate severity with clinically significant symptoms and dysfunction.
3. Severe without psychotic features: symptoms may require supervision or hospitalization, but no delusions or hallucinations are present.
4. Severe with psychotic features: presence of delusions (guilt, ruin, grandeur, persecution) or hallucinations, which may be mood-congruent or mood-incongruent.

Based on temporal evolution, the episode can be described as:

• In partial remission: some symptoms persist but do not meet full diagnostic criteria, or the symptom-free interval is less than two months.
• In full remission: the individual has been completely asymptomatic for at least two months.

Like other mood episodes, mixed episodes may also occur:

• With catatonic features, such as mutism, echolalia, negativism, or stereotyped postures.
• With postpartum onset, involving mood disturbances, emotional lability, and dysfunctional behavior toward the newborn within the first four weeks postpartum.

Diagnostic and therapeutic evaluation should be entrusted to a specialist, as the instability of the mixed state requires dynamic assessment, close monitoring of suicidal behavior, and a complex treatment strategy, often involving the combined use of mood stabilizers, atypical antipsychotics, and—in selected cases—short-term benzodiazepines.

References
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition – Text Revision (DSM-IV-TR). Masson, 2001.
2. Angst J et al. Prevalence, course and outcome of hypomania and depression in a prospective study of young adults. Eur Arch Psychiatry Clin Neurosci. 2010;260(6):427-436.
3. Akiskal HS et al. Recurrent brief depressive episodes with hypomanic features: the bipolar spectrum disorder. J Affect Disord. 2000;59(1):89-98.
4. Perugi G et al. Mixed states: diagnostic issues and operational definitions. CNS Spectr. 2001;6(5):389-397.
5. Swann AC et al. Mixed features and suicide risk in bipolar disorder. J Clin Psychiatry. 2013;74(4):362-369.
6. Benazzi F. Symptoms of depression as possible predictors of bipolar II disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(7):1029-1035.
7. Koukopoulos A, Sani G. Mixed states: a nosological entity. Curr Psychiatry Rep. 2014;16(11):514.
8. Zimmerman M et al. Diagnosing bipolar disorder: a review of the performance of diagnostic instruments. J Clin Psychiatry. 2009;70(5):715-725.
9. Post RM, Leverich GS. Use of valproate in mixed affective states. J Clin Psychopharmacol. 2003;23(1):45-52.
10. Goodwin FK, Jamison KR. Manic-depressive illness: Bipolar disorders and recurrent depression. Oxford University Press, 2007.