Course of illness following prospectively observed mania or hypomania in individuals presenting with unipolar depression.

OBJECTIVES: In a well-defined sample, we sought to determine which clinical variables, some of potential nosological relevance, influence subsequent course following prospectively observed initial episodes of hypomania or mania (H/M).
METHODS: We identified 108 individuals in the National Institute of Mental Health Collaborative Depression Study diagnosed with unipolar major depression at intake who subsequently developed H/M. We assessed time to repeat H/M based on whether one had been started on an antidepressant or electroconvulsive therapy within eight weeks of developing H/M, had longer episodes, or had a family history of bipolar disorder.
RESULTS: Modeling age of onset, treatment-associated H/M, family history of bipolar disorder, duration of index H/M episode, and psychosis in Cox regression analysis, family history of bipolar disorder (n=21) was strongly associated with repeat episodes of H/M [hazard ratio (HR)=2.01, 95% confidence interval (CI): 1.06-3.83, p=0.03]. Those with treatment-associated episodes (n=12) were less likely to experience subsequent episodes of H/M, although this was not significant in the multivariate model (HR=0.25, 95% CI: 0.06-1.05, p=0.06). These individuals also had a later age of onset for affective illness and were more likely to be depressed. Duration of illness with a temporal resolution of one week, psychosis, and age of onset were not associated with time to repeat H/M episode.
CONCLUSIONS: A family history of bipolar disorder influences the course of illness, even after an initial H/M episode. In this select sample, treatment-associated H/M did not appear to convey the same risk for a course of illness characterized by recurrent H/M episodes.