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

328 J. Cookson and S. Ghalibseparate affective swings. In an investigation of the course of manic-depressivecycles, involving 434 bipolar patients, Koukopoulos et al. (1980) found thefollowing patterns. A total of 119 patients (28%) had a pattern of MDI and106 (25%) of DMI; there were 87 (20%) with rapid cycling, 83 (19%) with a CCcourse, and 39 (9%) with irregular patterns. Thus 28% had a depressive phaseimmediately following a manic phase, and may therefore have experienced atransitional mixed stage.Earlier intervention to treat or prevent the former state might prevent or reducethe subsequent severity of the later state. On the other hand, prompt treatment ofthe initial state might lead to earlier transition into the subsequent state thanwould occur without treatment, as in the apparent ‘‘triggering’’ of mania bytreatment of bipolar depression with tricyclic antidepressant drugs. Thus,Kukopulos and Reginaldi (1973) proposed that such a mechanism might accountfor the finding that lithium reduces the frequency and severity of depressiveepisodes in the prophylaxis of MDI disorder. The same could be applied to theuse of antipsychotic drugs in this condition. Drugs such as lithium and lamotriginemay have the advantage of treating or preventing the depressed phase of bipolardisorder with less risk of triggering secondary mania and may be particularly usefulin DMI (bipolar: BP-II) disorder.Faedda et al.(1991) analyzed the findings of five studies in which the response tolithium was considered in relation to clinical predictors of efficacy. They foundthat the MDI or hypomania with severe depression (mDI) pattern of episodespredicted better response to lithium than the other patterns. The sequence ofdeclining responsiveness was from this MDI pattern to irregular through CC,DMI, or severe depression with hypomania (DmI) to rapid cycling, which was theleast responsive pattern. The odds ratio for responding between MDI and DMIpatterns was 4.4, with 95% confidence intervals of 2.8–7.0.Mixed states in predominantly depressed bipolar patients (BP-II, Dm)Patients with recurrent depression who have hypomanic episodes (not requiringhospitalization), especially on recovery from depression, were described as BP-IIand those with a history of mania as BP-I (Dunner et al., 1976). There is extensiveoverlap between patients with the DMI pattern and those with BP-II, and betweenthose with the MDI pattern and BP-I. Koukopoulos (2002) reported that, of the119 DMI bipolars described above, 101 (85%) were BP-I and represented almosthalf of the total of 207 patients with BP-I. On the other hand, 80 (75%) of theDMI patients could be classified as BP-II.An average of 40% of BP-I patients develop a mixed state at some point duringthe course of their illness (Akiskal et al., 2000). In two recent clinical trials, the