In 1987, Akiskal and Mallya introduced the notion of antidepressant-induced, chronic symptoms that include irritability and sleep disturbance in relatives of bipolar patients who have only manifested unipolar depressions. These patients developed a syndrome that consists of 1) unrelenting dysphoria, 2) severe agitation, 3) refractory anxiety, 4) unendurable sexual excitement, 5) intractable insomnia, 6) suicidal obsessions and impulses, and 7) "histrionic demeanor" (Akiskal and Mallya 1987). More recently, El-Mallakh and Karippot (2005) have described a chronic irritable depressive state that develops after long-term (several years) treatment with antidepressants in both type I and type II patients. This syndrome is specifically manifested by a triad of dyspho-ria, middle insomnia, and irritability, and thus has been labeled antide-pressant-associated chronic irritable dysphoria (ACID). Patients with ACID invariably experience significant social and occupational dysfunction such as divorce, separation, and disability. Discontinuation of the antidepressants usually results in improvement of all ACID symptoms and a return of both social and occupational function within about 6-8 months of not taking antidepressants. In 83 subjects studied in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study who developed a depression after entering the study, those receiving antidepressants were more likely to develop ACID than those not receiving an antidepressant (R.S. El-Mallakh, S.N. Ghaemi, K. Sagduyu, et al., "Antidepressant-associated chronic irritable dysphoria [ACID] in STEP-BD patients," University of Louisville, 2005). Additional work is required to investigate this syndrome.
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