To the Editor: After we submitted our article, two other research groups, using multivariate analyses, reported on manic subtypes (1, 2; Cassidy et al., 2001). Surprisingly, all reports, including ours, proposed almost the same subtypings. Similarities and minor differences between the Duke study (Cassidy et al., 2001) and ours are summarized by Drs. Cassidy and Carroll. Their letter calls into question our conclusion that atypical manic features, such as aggression, psychosis, and depression, are likely to separately characterize several manic subtypes since "the factor scores have extremely large standard deviations, denoting a wide overlap of scores among the identified clusters." It should be noted, however, that standardized factor scores were used in our study. The mean factor score and its standard deviation were set at 0.0 and 1.0, respectively. As shown in Table 2 of our article, it is not true that the factor scores reported "have extremely large standard deviations." Our factors, called depressive mood and psychomotor/thought inhibition, have relatively large standard deviations in our mixed subtype. This reflects a large variance of these syndromes within this subgroup, suggesting the possibility that this subtype consists of several lower-order subgroups. It would be interesting to determine whether these lower-order subtypes are similar to the two mixed subtypes proposed by Dr. Cassidy et al. and whether the depressive inhibition factor identified in our study plays a role in describing these lower-order subtypes. Until these issues are clarified, it is too early to state that our "cluster analysis does not positively support Kraepelin’s subclassification of mixed states."

Swann and colleagues (1, 2) proposed four manic subtypes that more strikingly resemble our subtypes. Their depressive, delusional, classical, and irritable subtypes appear exactly to correspond to our mixed, psychotic, pure, and aggressive subtypes, respectively. While the aggressive factor characterized several manic subtypes in the study by Dr. Cassidy et al., that factor was reported in the study by Swann et al. as only prominent in one subtype (irritable mania), as was found in our study. Furthermore, the report on their multicenter placebo-controlled trial implied that their four groups had differential treatment responses to placebo, divalproex, and lithium (2). This suggests that both their and our manic subtypes may be validated in terms of acute treatment response.

An agreement of results derived from cross-sectional phenomenological data is only the first step in identifying clinically meaningful manic subtypes, although this agreement was reached by three independent studies. Further studies are required to determine the differential long-term natural history of the proposed manic subtypes. Differential responses to available maintenance treatments should also be investigated.