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

53 Longitudinal perspective of mixed statesdistractibility were significantly more common in bipolar II than in unipolarpatients; racing thoughts were highly prevalent in both unipolar and bipolar II.Among the (hypo)manic symptoms reported in depressive MS, flight of ideas,racing thoughts, and distractibility belong to the same dimension of psychicexcitement. Increased mental activity (daydreaming, mental ruminations) hasbeen reported as one of the fundamental features of bipolar II ‘‘depression’’(Akiskal et al., 1995; Perugi et al., 1998). Other hypomanic symptoms such aseuphoria and grandiosity, by definition, are too rare in depression to be utilized forthe selection of patients with depressive MSs, whereas irritability and restlessnessmight be somewhat non-specific.According to Akiskal and Benazzi (2003), unipolar depressives with depressiveMS might be classified into the bipolar spectrum, and must be considered‘‘pseudo-unipolar.’’ The bipolar nature of these clinical pictures should, however,be further confirmed. No prospective longitudinal studies explored whetherintraepisodic hypomanic symptoms during a depressive episode predict a diagnosticswitch from unipolar depression to bipolar disorder. Clinical observationssuggest that unipolar depressive MS may not adequately respond to antidepressants,and that the use of antidepressants for unipolar depressives with intraepisodicmanic symptoms may be causative in treatment resistance or lead to cycling(Akiskal and Mallya, 1987; Koukopoulos et al., 1992). Well-designed controlledtrials with antidepressants versus mood stabilizers and/or other antimanic agentsshould be conducted comparing unipolar depressives with and without intraepisodeexcitatory symptoms.Long-term aspects of mixed statesThe literature on clinical and course characteristics of MS from Kraepelinthrough the last decade of the past century has been masterfully reviewed byMcElroy et al. (1992). Alcohol abuse and neuropsychiatric conditions are commoninMSs(Himmelhochetal., 1976). MS has been best characterized in femaleinpatients (Dell’Osso et al., 1991; Perugiet al., 1997; Akiskalet al., 1998), oftenarising from a course of illness with more depressive than manic episodes andwith a tendency to repeat over time (Perugi et al., 2000). The available datafurther suggest that MS patients, in comparison with mania and bipolar depressives,more frequently begin their illness with a mixed episode and have fewerepisodes of longer duration (Perugi et al., 1997).ThefactthatMSisoftenthefirst episode in the course of the illness seems to indicate that it cannot beconsidered an end-stage or ‘‘malignant’’ dénouement of the illness. Moreover,MS and rapid cycling seem to be two independent manifestations of manicdepressiveillness (Perugi et al., 2000).