Notes The present study was performed at the University of lowa, lowa City, IA, USA, under the folowing grant support: NARSAD
Although mania, and hypomania are the essential and more florid features of bipolar disorder, debilitating depressive symptoms and episodes dominate the longitudinal course, and are less responsive to treatment. Moreover, the initial presentation of bipolar disorder is often depression, which delays the establishment of the correct, diagnosis and initiation Inhibitors,research,lifescience,medical of appropriate guideline concordant, care. During the past,

decade, there has been a growing appreciation of the harmful dysfunction associated with depression as part of bipolar disorder. For example, patients diagnosed with and/or screening positive for bipolar disorder evince greater deficits in work, social, and family functioning when experiencing depressive Stattic manufacturer versus manic symptoms.1 Similarly,

in a systematic 20-year prospective study Judd and colleagues2 identified minor depression or dysthymia to be more disabling than hypomania, Inhibitors,research,lifescience,medical as well as a trend for major depression to be more impairing than mania. Across the bipolar (BP) I and II subtypes, a parallel gradient between the level of psychosocial impairment, and severity of depressive symptoms Inhibitors,research,lifescience,medical has been documented. The risk of suicide, which averages 0.4% per year among patients with bipolar disorder, also appears greater during phases of depression and dysphoric-agitated mixed states than during mania.3 Severely disrupting the life course of afflicted Inhibitors,research,lifescience,medical individuals, bipolar disorder is associated with high rates of unemployment,4 medical comorbidity,5 decreased work productivity,6 and a reduced quality of life.7 Even when symptoms are subsyndromal in nature, impairments Inhibitors,research,lifescience,medical in role functioning arc frequently apparent.8 Collectively, the high

morbidity and mortality associated with bipolar depression warrants considerable attention. Despite intensified efforts to characterize the antimanic effects of atypical antipsychotics, relatively few studies had tested these agents in bipolar depression. For example, of the seven available atypical agents in the US, five have been studied in pivotal randomized, placebo-controlled acute mania registration to trals prior to the initiation of the first, placebo-controlled trial of an atypical antipsychotic (ie, quetiapine) in bipolar depression. Longitudinal observations which aim to characterize the symptomatic structure of bipolar disorder have highlighted its pleomorphic and changeable symptomatic expression. Bipolar disorder is more accurately categorized as a dimensional (versus modal) phenomenon, with substantial intraindividual shifts in polarity and symptom expression from threshold to subsyndromal severity. Patients with BP-T self-report, depressive symptoms three times more frequently than manic symptoms.