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

70 O. Elhaj and J. R. Calabreserecommended that the initial treatment for patients who experience rapid cyclingshould include lithium or valproate, lamotrigine has also been considered a firstchoiceoption. It was also advised that for many patients, combinations of medicationsare required (American Psychiatric Association, 2002).Most researchers and clinicians have come to realize that the depressive phase ofbipolar disorder is probably more difficult to treat, especially in the rapid-cyclingsubtype (Ghaemi et al., 2000; Möller and Grunze, 2000; Perugi et al., 2000; Sachset al., 2000a; Calabrese et al., 2001, 2002). Nevertheless, the use of antidepressantsin treating the depressive phase of rapid-cycling bipolar disorder continues todraw significant controversy. While most have warned about the likelihood ofantidepressants worsening the course of rapid-cycling bipolar disorder, and havestrongly cautioned against using them alone (Ghaemi et al., 2000, Perugi et al.,2000; Sachs et al., 2000a, 2000b; Calabrese et al., 2001, American PsychiatricAssociation, 2002), others have warned that the decreased use of antidepressantsmight increase the risk of suicide (Möller and Grunze, 2000), and that antidepressantuse along with a mood stabilizer constitutes a low risk for worsening rapidcyclingcourse (Amsterdam and Garcia-España, 2000; Sachs et al., 2000a).Amsterdam and Garcia-España (2000) reported results indicating that no episodesof drug-induced hypomania or rapid cycling were observed during 6 weeks ofvenlafaxine monotherapy for depression in women with BP-II and unipolar majordepression. This study’s limitations included that it was retrospective in nature andlimited in patient number, that only BP-II women were included in this study, and itis possible that efficacy and the manic switch rate might have differed if BP-I womenwere included. However, it is noteworthy that the limitations of this study make itvery difficult to formulate any generalizable conclusions about the use of antidepressantsin treating rapid-cycling bipolar disorder.A respective chart review of outpatients with affective disorders (n ¼ 85, withboth bipolar and unipolar disorders) was conducted over a 1-year period (Ghaemiet al., 2000). The results indicated that bipolar disorder was found to be misdiagnosedas unipolar depression in 37% of patients who first saw a mental healthprofessional after their first manic/hypomanic episode. Antidepressants were usedearlier and more frequently than mood stabilizers, and 23% of this unselectedsample experienced a new or worsening rapid-cycling course attributable toantidepressant use. These results suggest that bipolar disorder tends be misdiagnosedas unipolar major depressive disorder and that antidepressants seem to beassociated with a worsened course of bipolar illness. While the results of this studyare informative regarding the misdiagnosis of bipolar disorder and the eventualnegative consequences on its course, longer, more controlled studies with largersample size are still needed to clarify this long-lived controversy in the managementof bipolar disorder, and especially the rapid-cycling course.