The results of this study indicate a favorable clinical impact for the model of specialized care for the treatment of bipolar disorder used in the BDCP. Both participants assigned to SCBD alone and those assigned to SCBD + ECI experienced significant improvement over time in CGI and functioning. No significant differences in treatment outcomes were found between participants of different race and place of residence, except for a higher GAF improvement in late-life versus adult subjects and a lower risk of recurrence in adolescent participants. Several factors may have contributed to the generally positive outcomes observed, many of which may be implemented in different settings and possibly become the standard of care for patients with bipolar disorder. Although it remains to be established which and to what degree each specific factor played a role, we posit that the following conditions contributed to study outcomes and should be among the first to consider among the strategies that may be exported to other settings: a well-trained team specialized in the care of patients with bipolar disorder; highly standardized and thorough diagnostic and clinical monitoring strategies; relatively frequent visits to the clinic; reminder calls and immediate availability when there are changes in clinical status in the period between scheduled visits; collaborative care among centers / clinics that provide a specialized treatment for bipolar disorder; and standardized, yet not overly rigid pharmacotherapy protocols. We believe that all patients benefited from attendance at clinics structured as above. However, it is possible that patients with certain demographic or clinical characteristics may benefit more than others. For instance, our study model seemed particularly effective for the improvement in functioning in late-life patients.
We demonstrated that adding ECI to SCBD confers the additional benefit of greater improvement in quality of life. Quality of life has gained increasing attention as an important outcome in patients with severe and persistent mental disorders, including bipolar disorder. The efficacy of ECI in the improvement of quality of life is of particular importance, given that patients with bipolar disorder experience lower quality of life than the general population even during euthymic periods (25
). Several factors may have contributed to the efficacy of ECI, including its social and general support component. In fact, previous research has shown that the availability of social support plays an important role in enhancing quality of life in patients with bipolar disorder (25
Seventy-seven percent of our study participants completed one year of follow-up and 68.5% completed two years of follow-up, with no difference between the SCBD and the SCBD + ECI group, possibly because of the adoption of similar retention strategies in both groups. For example, reminder and follow-up calls were made to patients assigned to both groups by the office manager, study coordinators, or treating ECI therapist. Remarkably, no significant differences for retention rate were observed based on age, race, and place of residence.
Although statistical comparisons of our outcomes with those reported in other published studies conducted with different methodologies are not appropriate, it is noteworthy that: (i) 71% [versus 58% in the STEP-BD study (24
)] of the participants who were symptomatic at study entry (CGI > 2) achieved ‘recovery’ clinical status (at least eight weeks with CGI of 1 or 2) within 24 months; (ii) during this 24-month period, 40% [versus 48.5% of the STEP-BD study (24
)] of the subjects who had achieved ‘recovery’ met criteria for a new episode (CGI-D ≥ 4 for two weeks or CGI-M ≥ 4 for four or more days); (iii) the time until 25% of the participants experienced a depressive episode was 21.3 weeks [versus 21.4 weeks in the STEP-BD study (24
)], and less than 25% of our subjects experienced a manic recurrence.
In the present study, participants with bipolar I disorder were symptomatically ill (CGI ≥ 3) 33% of study weeks and those with bipolar II disorder were also symptomatically ill 33% of weeks. In a prospective follow-up of 146 patients with bipolar I disorder and 86 patients with bipolar II disorder who entered the National Institute of Mental Health Collaborative Depression Study, those with bipolar I disorder were symptomatically ill 47.3% of weeks and those with bipolar II disorder were symptomatically ill 53.9% of weeks (26
). The Course and Outcome of Bipolar Youth (COBY) study with children and adolescents yielded similar results (2
Although outcomes in the present study are somewhat better than those of the research mentioned above, the fact that 29% of our study participants were still symptomatic after two years of treatment and that 40% of those who recovered from an acute episode experienced a recurrence in a relatively short period of time clearly confirms that bipolar disorder remains a chronic, difficult-to-treat, and highly recurrent condition in a large number of affected individuals. Of interest, we found no significant difference for race or age between the patients who experienced a recurrence and those who did not. However, we found that patients living in a rural area were more likely to recur following the resolution of an acute episode, despite the absence of differences in the study protocol at the rural and urban sites.
Sixty-eight percent of our patients completed the study. Long-term studies conducted on patients with bipolar disorders have reported variable completion rates, strongly depending on the duration and type of treatment and follow-up that was provided, which makes it very difficult to perform any comparison. For instance, Miller and colleagues (27
) reported a 69% completion rate in patients with bipolar disorder followed for about two years; Keck and colleagues (28
) reported a much lower retention rate in a group of patients treated for 100 weeks under a very rigid protocol; and Judd and colleagues (26
) reported a very high completion rate (93%) in a follow-up nontreatment study that required a much lower level of commitment. Two studies have employed a design similar to ours. In the first study (20
), patients with bipolar disorder were randomized to usual treatment or to algorithm implementation and the retention rate was 81% after the first year of follow-up; two-year follow-up data were too sparse for reporting. The second study (29
) compared the long-term effectiveness of a systematic care program versus usual care: 381 of 441 patients (86.4%) completed the 12-month follow-up, yet the number of completers decreased to 335 (76%) at 24 months.
The present study demonstrated the utility of a long-term, standardized treatment protocol based on specialized care for bipolar disorder in which the procedures were designed to increase the probability of accurate diagnosis, increase adequacy of treatment, increase retention in treatment, and improve treatment outcomes for all patients, including those at higher risk for a poorer outcome, such as adolescent, elderly, and African American individuals with bipolar disorder. Among the limitations of this study, we would like to acknowledge the exclusion of patients with substance dependence, who represent a non-negligible proportion of patients with bipolar disorder. This fact clearly limits the generalizability of our results and calls for more studies that integrate the interventions that were tested in our study with the specialized interventions that are currently provided to patients with co-occurring substance dependence and bipolar disorder. Regrettably, the study also confirms that bipolar disorder is a difficult-to-treat, highly recurrent condition even when individuals receive consistent, high-quality treatment. We hope that the present study may provide a model for establishing or re-establishing treatment teams or clinics specialized in the diagnosis, assessment, and treatment of patients with bipolar disorder.