To our knowledge, this is the first investigation to examine baseline characteristics and prospective functional outcome across a large group of well-characterized patients with bipolar disorder experiencing sustained recovery, depressive episodes, and chronic subsyndromal symptoms.
Our findings are consistent with previous work that suggests that continued subsyndromal symptoms after a major depressive episode adversely affect functional recovery in patients with bipolar disorder (Gitlin et al., 1995
; Bauer et al., 2001
; Shapira et al., 1991; Cooke et al., 1996
; Altshuler et al., 2002
) and unipolar major depression (Rapaport et al., 2002
, Howland et al., in press
, Judd et al., 1998
). More specifically, patients with sustained continued symptoms experience essentially the same functional burden as those experiencing a full episode of depression. Particularly salient symptoms that appear to correlate with impairment in individuals with persistent subsyndromal symptoms are reported sadness, anhedonia and lassitude. This suggests that clinicians should be particularly mindful of the persistence of these symptoms and any associated impairment should be the focus of continued aggressive treatment.
While group status (recovered, depressed, subsyndromal) was defined by prospective observation of a sustained clinical status rating over at least 2 years of observation in STEP-BD, the groups did differ on multiple baseline characteristics. Generally, the subsyndromal and depressed groups were more similar, and differed from those in the recovered group. Those who ultimately achieved recovered status had a shorter duration of bipolar disorder, fewer total episodes, less evidence of personality disorder, and were less likely to have comorbidity and rapid cycling than those who were in the depressed and continued symptomatic groups. Similar to rates observed in other studies, 54% of those in the subsyndromal group met criteria for a comorbid anxiety disorder (MacQueen et al., 2003
). Compared to the recovered and depressed groups, the subsyndromal group had the highest levels of comorbidity overall, and the greatest number of comorbid diagnoses of ADHD, anxiety, and substance use disorders.
Across bipolar subtypes, patients diagnosed with bipolar I, II, or other bipolar diagnoses were similarly likely to experience sustained periods of recovery, subsyndromal symptoms, or depression. This is consistent with recent work from the Collaborative Depression study (Judd et al., 2008
), and highlights the chronicity, severity and functional burden associated with all bipolar spectrum diagnoses. Interestingly, more individuals in the recovered group reported a previous diagnosis of a psychotic disorder. This history may have resulted in more aggressive treatment for these individuals, or may be a marker for a more treatment responsive phenotype.
However, functional outcomes remained significantly different across the three groups after accounting for these baseline differences. As expected, the recovered and depressed groups differed on almost all measures, with the exception of mean YMRS score. Interestingly, those in the subsyndromal group presented with the highest adjusted YMRS score. It is possible that patients who are likely to experience sustained periods of subsyndromal symptoms are prone to mixed episodes, or to a mixed symptom presentation, complicating treatment course and decisions (Goodwin et al., 2004
; Keller et al., 1986
; Strakowski et al., 1996
). In a recent analysis, 26.7% of those experiencing subsyndromal symptoms after recovery from a major affective disorder had symptoms of mixed polarity (Judd et al., 2008
), a pattern that has been observed elsewhere (Bauer et al., 2005
; Suppes et al., 2005
). It is possible that antidepressant exposure contributes to the experience of mixity in these patients (Goldberg et al., 2007
). Further work may help establish the frequency and characteristics of those likely to experience of subsyndromal mixed depressive and hypomanic/manic symptoms, and the relationship of these symptoms to clinical and functional outcomes.
Similar to patients in sustained depressive episodes, those patients with prolonged periods of subsyndromal symptoms separated from those in the recovered group on almost all of the functional outcome measures. They reported greater functional impairment on the total LIFE-RIFT and within each individual domain of Satisfaction, Recreation, Work, and Relationships, more impaired work days than those in the recovered group, and less overall satisfaction with the quality of their daily life.
The only exception was the measure of the number of work days missed. Those in a depressive episode were most likely to miss work due to symptoms, compared to those with continued symptoms or those who were recovered. However, though improvement may allow patients with continued symptoms to work, they perform consistently at lower levels, a problem described as “presenteeism” (Adler et al, 2006
The strengths of this analysis include the large, “real world” nature of the sample. One of the weaknesses is the cross-sectional nature of this initial work. Longitudinal outcome data would be beneficial in the future. Rapaport has reported that symptom severity, comorbid diagnoses, and other relevant clinical factors account for no more than a quarter of the variance in quality of life in any DSM IV mood and anxiety disorders previously evaluated (Rapaport et al., 2005
). Since the major focus of this paper is the relationship of subsyndromal symptoms to functioning rather than quality of life in bipolar disorder, we did not focus our analyses on the relationships between quality of life and symptom status across the range of mood states.
In conclusion, patients with sustained subsyndromal symptoms were indistinguishable from those in a full depressive episode on all measures of functional outcomes. The current work reinforces the need to attempt multiple trials of medication and medication combinations to strive toward full recovery in all patients and to include subsyndromal symptoms and/or functional outcomes in clinical trials.