The present findings indicate strongly that initial mixed-states of DSM-IV type-I BPD were not only followed by more weeks of illness during two-years of follow-up, but also much more mixed, depressive, and dysthymic illness, and much less mania, hypomania, or psychotic illness compared to patients presenting initially in relatively pure mania ( and ). The findings accord with suggestions in reports cited above that mixed-states are followed by more severe illnesses and more depressive morbidity than following initial mania. Moreover, the findings are based on systematic, prospective and detailed assessments from first-episodes. They strongly support the conclusion that the dissimilar presentations predicted markedly dissimilar future illness-courses, do not support the equivalence of mania and mixed-states, and indicate distinct clinical subtypes.
This study is limited by uncertainties involved in defining morbidity during follow-up with intermittent assessments, possibly biased by current mood or by characteristics of the private, university-affiliated, psychiatric hospital in which the study was conducted. Nevertheless, we made efforts to support the estimates of percent-of-weeks-ill by comparisons to results with frequently evaluated patients and by use of standard depression and mania symptom rating scales to verify current states: neither method of verification showed differences in morbidity estimates from the overall sample. It is also possible that illnesses, including depressive episodes, occurred in some cases prior to the index hospitalization, complicating estimates of onset-age, for example (Baldessarini et al., 2010
). Another potential confound is that patients were treated clinically by community standards during follow-up, and with lack of control over treatment. However, if treatment is a relevant factor, such a circumstance might suggest that patients presenting in mixed-states were less treatment-responsive. Indeed, this possibility is not ruled out and requires further testing (Berk et al., 2005
; Vieta et al., 2005
; González-Pinto et al., 2007
). It is also important to consider specifically the depressive component of long-term morbidity of patients presenting initially in mixed-states. This component of BPD is especially difficult to treat successfully without inducing destabilizing effects, such as with antidepressants (Ghaemi et al., 2008
; Tondo et al., 2009
; Baldessarini et al. 2010c
In conclusion, this study adds strong support to the hypothesis that DSM-IV type-I BPD patients with mixed-state first major episodes have a poorer prognosis than those presenting in mania, and that the type of illness involved includes much more recurrence of mixed-states as well as depression and dysthymia. In contrast, patients presenting in mania had less illness overall, and much more mania and hypomania, and tended to have more psychosis during follow-up. These findings encourage considering the two sub-groups separately in therapeutic trials and other studies, and underscore the challenge of treating the depressive components of BPD.