Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

52 G. Perugi and H. S. Akiskalwith the view that MS does not represent a mere superposition of affectivesymptoms of opposite polarity (Himmelhoch, 1979; Berner et al., 1983;Akiskal and Mallya, 1987; Koukopouloset al., 1992; Perugiet al., 1997; Akiskalet al., 1998). Long-lasting affective instability emerges as the core phenomenologicalfeatures; from this protracted instability seems to arise perplexity,psychotic experiences, and grossly disorganized behavior. This conclusion isfurther substantiated by the HAM-D symptomatological profile where MSpatients report more cognitive disorders,agitation,andparanoidsymptomswith less motor retardation, somatic symptoms, and sexual disturbances comparedwith bipolar pure depressives.In agreement with previous clinical observations (Akiskal and Mallya, 1987;Koukopoulos et al., 1992), the symptomatological profile of depressive MS is oneof agitated, mostly psychotic depression with irritable mood, pressured speech,and flight of ideas. Akiskal and Mallya (1987) had reported that 25 patientsreferred for treatment-resistant depression displayed subacute or chronic MSs,apparently induced by tricyclic antidepressants; these mixed depressive states werecharacterized by dysphoria, severe agitation, refractory anxiety, unendurablesexual excitement, intractable insomnia, suicidal obsessions and impulses, and‘‘histrionic’’ demeanor; they improved with antidepressant discontinuationand initiation of lithium or carbamazepine. Koukopoulos et al. (1992) foundthat45 patients with bipolar disorder suffering from a ‘‘mixed depressive syndrome’’ whomet DSM-IIIR criteria for major depression, but not for mania, deteriorated whentreated with antidepressants, experiencing increased agitation, insomnia and, insome cases, suicidal impulses; these same patients responded to low-dose neuroleptics,lithium, anticonvulsants, and electroconvulsive therapy. Koukopoulos andKoukopoulos (1999) have subsequently written a scholarly review on the clinicalrationale for the validity of the concept of agitated depression as an MS.Bipolar II and unipolar depressive mixed statesThe literature reviewed thus far pertains largely to mixed mania and agitateddepression observed among hospitalized and/or psychotic patients. We will nowconsider depressive MS among outpatients with bipolar II and unipolar depression,which is even less studied. The high prevalence of hypomanic features indepressed bipolar II and unipolar outpatients has recently been reported byBenazzi (2000) and Benazzi and Akiskal (2001). The prevalence of full syndromalhypomania among 70 outpatients with major depression was low (2.8%), butthree or more concurrent hypomanic symptoms were reported in 28.5% of thesample. About half (48.7%) of bipolar II patients had three or more concurrenthypomanic symptoms during major depression. Irritable mood, talkativeness, and