Participants and length of follow-up
displays the sociodemographic and clinical characteristics at study intake (online Table DS1 shows the complete results). The mean (s.d.) length of follow-up was 17.3 (7.9) years and the median was 20 years. Of the 219 participants, 196 (90%) were followed for at least 5 years, 169 (77%) for at least 10 years, 144 (66%) for at least 15 years, and 122 (56%) were followed for at least 20 years. Compared with participants followed for fewer than 20 years, those followed for 20 or more years were significantly younger both at study intake and at onset of bipolar I disorder (as expected); they were also significantly more likely to be female.
Sociodemographic and clinical characteristics at study intake for participants with bipolar I disorder (n = 219)
Number of mood episodes
A total of 1208 recurrent mood episodes were prospectively observed. The median number of mood episodes observed per participant was 4 (range 1–21). The mean (s.d.) number of episodes per participant was 5.5 (4.6). The mean (s.d.) number of observed episodes per participant per year of follow-up was 0.4 (0.3).
shows the frequency of each type of mood episode observed during follow-up. Major depression was most common.
Typology of mood episodes observed in 219 participants with bipolar I disordera
Episodes consisting of a single pole of psychopathology (major depression, minor depression, mania, or hypomania) comprised 902 (75%) of the mood episodes. Of these 902 episodes, 578 occurred in female participants (n = 122), and consisted of 336 (58%) depressive episodes (major or minor depression) and 242 (42%) mood-elevated episodes (mania or hypomania). The 324 remaining episodes that occurred in male participants (n = 97) and consisted of 194 (60%) depressive episodes and 130 (40%) mood-elevated episodes. A mixed-effects logistic regression model (which accounted for the correlation among multiple, within-participant mood episodes) showed that gender was not significantly associated with the polarity of episode (depressive v. mood elevated; odds ratio (OR) = 0.76, 95% CI 0.37–1.58, Z = –0.73, P = 0.46).
Mixed states occurred as part of mixed major cycling episodes, which comprised 8% (n = 94) of the mood episodes. In addition, only two mixed episodes (major depression or minor depression concurrent with mania or hypomania throughout the entire episode, with at least one major pole) were observed.
There were 151 mood episodes prospectively observed in the subgroup with a diagnosis of schizoaffective disorder, mainly affective subtype, and 1057 observed in the subgroup with bipolar I disorder. The typologies of the two subgroups were similar.
Cycling mood episodes
shows the sequence of component mood states for 296 cycling episodes (major cycling, mixed major cycling, or minor cycling). In the 153 cycling episodes that began with depression (either major depression or minor depression), the depressive state was followed by an immediate switch to mood elevation or a mixed state in 64% of the episodes. In the 143 cycling episodes that began with mood elevation (either mania or hypomania), the elevated state was followed by an immediate switch to depression or a mixed state in 56% of the episodes.
Sequence of component mood states for 296 cycling episodesa
Change of mood episodes over time
Online Table DS2 displays the typology of the mood episodes that occurred from 1978 to 1991 and from 1992 to 2006. A mixed-effects logistic regression model showed that mood episodes from 1978 to 1991 were 37% less likely to be an episode of major depression, compared with mood episodes that occurred from 1992 to 2006 (OR = 0.63, 95% CI 0.44–0.90, Z = –2.55, P = 0.01).
We examined the somatic therapy received during mood episodes. Of the 1208 mood episodes, 85% (n = 1026) were treated with a mood stabiliser and/or an antidepressant for at least 1 week during prospective follow-up.
Online Table DS3 displays in greater detail the treatment that occurred. Of the 843 mood episodes selected for analysis, many were not treated with a mood stabiliser, including 40% (131/326) of the major depressive episodes, 39% (57/145) of the minor depressive episodes, 12% (30/246) of the manic episodes, and 24% (30/126) of the hypomanic episodes. Of the depressive (major or minor) episodes selected for analysis, 28% (134/471) were treated with an antidepressant in the absence of a mood stabiliser.