Bipolar disorder mixed state

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

In the context of mental illness, a mixed state (also known as dysphoric mania, agitated depression, or a mixed episode) is a condition during which symptoms of mania and depression occur simultaneously (e.g., agitation, anxiety, fatigue, guilt, impulsiveness, irritability, morbid or suicidal ideation, panic, paranoia, pressured speech and rage). Typical examples include tearfulness during a manic episode or racing thoughts during a depressive episode. One may also feel incredibly frustrated in this state, since one may feel like a failure and at the same time have a flight of ideas. Mixed states can be the most dangerous period of mood disorders, during which substance abuse, panic disorder, suicide attempts, and other complications increase greatly.

Diagnostic criteria

As affirmed by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), a mixed state must meet the criteria for a major depressive episode and a manic episode nearly every day for at least one week. However, mixed episodes rarely conform to these qualifications; they may be described more practically as any combination of depressive and manic symptoms (Akiskal & Pinto, 1999; Goldman, 1999; Perugi et al., 1999). The Merck Manual of Diagnosis and Therapy (MMDT) splits the DSM-IV diagnosis into dysphoric mania and an agitated depression state.

A dysphoric mania consists of a manic episode with depressive symptoms. Increased energy and some form of anger, from irritability to full blown rage, are the most common symptoms (MMDT). Symptoms may also include auditory hallucinations, confusion, insomnia, persecutory delusions, racing thoughts, restlessness, and suicidal ideation. Alcohol, drug abuse, and some antidepressant drugs may trigger dysphoric mania in susceptible individuals.

An agitated depression is a "major depressive [episode] with superimposed hypomanic symptoms" (Benazzi, 2000). Mixed episodes in which major depression is the primary state, concurrent with atypical manic features were described in two studies (Benazzi & Akiskal, 2001; Perugi et al., 2001). A study by Goodwin and Ghaemi (2003) reported manic symptoms in two-thirds of patients with agitated depression, which they suggest calling "mixed-state agitated depression".

Treatment

Mood stabilizers (lithium and some anticonvulsants) and antidepressants are the traditional medications used in the treatment of bipolar disorder and major depression, respectively. Antidepressants, however, may induce mixed states and rapid cycling; hence, coadministration with an anticonvulsant and/or lithium reduces (but does not eliminate) this risk. Among the anticonvulsants, only lamotrigine (Lamictal) has strong antidepressant effects. Lamotrigine and lithium (not an anticonvulsant) are the only drugs FDA-approved for the maintenance treatment of bipolar disorder. These are the only "true" mood stabilizers in that they possess antidepressant as well as antimanic properties. Of the two, lamotrigine is the more effective treatment for bipolar depression and lithium is more effective for mania (Calabrese, Vieta & Shelton, 2003).

Mixed states require medication (psychotherapy is best reserved for a more stable period). There are doubts as to lithium's efficacy in mixed states. The anticonvulsant divalproex (Depakote) is used frequently, particularly when psychotic features are present (MMDT). The atypical antipsychotics (such as clozapine (Clozaril), quetiapine (Seroquel) and olanzapine (Zyprexa)) are also effective, but clozapine, quetiapine and lithium are not US FDA-approved for bipolar mixed states. Electroconvulsive therapy may benefit the most severe cases.

References

• Akiskal, H.S. Pinto, O. (1999). The evolving bipolar spectrum. Prototypes I, II, III, and IV. Psychiatr Clin North Am. 22(3):517–34.
• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Press, Inc., 1994.
• Benazzi, F. (2000). Depressive mixed states: unipolar and bipolar II [Abstract]. Eur Arch Psychiatry Clin Neurosci. 250(5):249–53.
• Benazzi, F. (2003). Bipolar II depressive mixed state: Finding a useful definition Compr Psychiatry. 44(1):21–7.
• Bipolar Disorders. (2005). The Merck Manual of Diagnosis and Therapy [Electronic version]. Accessed on April 1, 2005.
• Calabrese, J.R. Vieta, E. Shelton, M.D. (2003). Latest maintenance data on lamotrigine in bipolar disorder. Eur Neuropsychopharmacol. Suppl 2:S57–66.
• Goldman, E. (1999). Severe Anxiety, Agitation are Warning Signals of Suicide in Bipolar Patients. Clin Psychiatr News. pg 25.
• mixed states/atypical depression. neurotransmitter.net. Accessed on April 1, 2005.
• Perugi, G. Toni, C. Akiskal, H.S. (1999). Anxious-bipolar comorbidity. Diagnostic and treatment challenges. Psychiatr Clin North Am. 22(3):565–83.