A mixed state (aka dysphoric mania, agitated depression) is a condition during which symptoms of mania and depression occur simultaneously (e.g., agitation, anxiety, fatigue, guilt, impulsiveness, insomnia, irritability, morbid and/or suicidal ideation, panic, paranoia, pressured speech and rage). Typical examples include tearfulness during a manic episode or racing thoughts during a depressive episode. Mixed states can be the most dangerous period of mood disorders, during which substance abuse, panic disorder, suicide attempts, and other complications increase greatly.
As categorized 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 a depressive mixed 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.
A depressive mixed state is a "major depressive episodes 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".
Anticonvulsants (aka mood stabilizers) and antidepressants are the traditional medications used in the treatment of bipolar disorder and major depression, respectively. Antidepressants may induce mixed states and rapid cycling; 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 posses 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). The anticonvulsant divalproex (Depakote) is used frequently, particularly when psychotic features are present (MMDT). The atypical antipsychotics (such as clozapine, Clozaril and olanzapine, Zyprexa) are also effective. Electroconvulsive therapy may benefit the most severe cases.
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