Bipolar Disorder Center for Pennsylvanians: Implementing an Effectiveness Trial to Improve Treatment for At-Risk Patients

Enrollment in the study began in November 2003 and ended on October1, 2005. Enrolled participants were followed until the study ended in February 2007. A total of 626 individuals across the four study sites consented to be screened for participation. Of these, 515 individuals (82%) met inclusion criteria, enrolled in the BDCP study, and received regular clinical visits with a study psychiatrist. Table 1 shows the reasons that the 111 screened individuals did not enter the study.

The remaining data are presented for the 515 participants who enrolled in the study. Table 2 summarizes the referral sources of these patients and provides comparisons between referral sources of African-American participants and non-African-American participants. Although a substantial number of participants were referred by existing programs at WPIC, more than half of the study participants were referred from external sources. Table 3 summarizes data on site, age, gender, race, marital status, education, employment, and income. The three University of Pittsburgh sites accounted for 416 of the 515 total participants (54% in the adult clinic, 16% in the adolescent clinic, and 11% in the clinic for elderly persons), and the DuBois clinic accounted for 99 participants (19%). The mean±SD age of the 515 participants was 40.2±17.5 years. A total of 295 participants (57%) belonged to populations at high risk of health disparities (adolescents, elderly persons, African Americans, or patients living in a rural area). Eighty-four participants (16%) were aged 12 to 18 years, and 41 participants (8%) were 65 years or older; 89 (17%) participants identified themselves as members of racial or ethnic minority groups: 69 (13%) were African American, 14 (3%) were biracial, three (1%) were Asian, two (<1%) were Pacific Islander, and one (<1%) was Native American. The 99 participants treated at the DuBois site all lived in a rural area.

Table 4 shows diagnostic and illness characteristics for the cohort. Two-thirds of the patients were diagnosed as having bipolar I disorder. The average age at onset of bipolar disorder was in the early twenties. Eighty-three percent of the sample had some lifetime comorbidity of other psychiatric illness. Almost 40% of the sample reported a history of attempted suicide. The mean CGI score for the sample was 2.5 (possible scores range from 1 to 7, with higher scores indicating more severe illness). Eighty percent of the sample had a mother, father, or sibling with a history of bipolar, unipolar, schizophrenic, or anxiety disorder. As Table 4 indicates, age at bipolar disorder onset was lower among African Americans than among non-African Americans; however, because African Americans were younger, there was no significant difference between the races for the duration of the illness. There was a trend (p=.06) for African-American participants to more frequently report a history of suicide attempt (49% versus 37%). In order to explore this finding further, a logistic model was performed. Household income ( χ ² =8.23, df=1, p=.004) and anxiety disorder ( χ ² =3.88, df=1, p=.049) were found to be significant predictors of having made a suicide attempt; race was not a significant predictor.

Table 5 shows psychotropic medication status at entry to the study. Only 9% of the sample was not taking any medication at entry to the study, while 70% of the sample was taking two or more medications, and 50% was taking three or more medications. African Americans had fewer psychotropic medications than non-African-Americans (p=.004), mostly accounted for by fewer African-American participants taking lamotrigine, newer antidepressants, and hypnotics and anxiolytics.

We examined the cohort for gender differences and found that women were more likely than men to have diagnoses of bipolar II disorder and schizoaffective disorder bipolar type (113 of 315 women, or 36%, versus 56 of 200 men, or 28%; χ ² =10.20, df=3, p=.017). Women had less education ( χ ² =13.17, df=4, p=.010) and lower personal income ( χ ² =18.19, df=7, p=.011). Women were more depressed than men (t=2.29, df=509, p=.022) and were more likely to have mothers with a history of psychiatric disorders (164 of 284 women, or 58%, versus 77 of 180 men, or 43%; χ ² =9.89, df=1, p=.002), siblings with a history of psychiatric disorders (162 of 281 women, or 58%, versus 67 of 173 men, or 39%; χ ² =15.34, df=1, p=.001), and more family history of psychiatric disorders (253 of 298 women, or 85%, versus 131 of 185 men, or 71%; χ ² =13.90, df=1, p=.001). Women were more likely than men to have comorbid anxiety disorders (159 of 273 women, or 58%, versus 70 of 157 men, or 45%; χ ² =7.47, df=1, p=.006) and eating disorders (63 of 273 women, or 23%, versus 15 of 157 men, or 10%; χ ² =12.28, df=1, p=.001). A greater proportion of men than women had never been married (126 of 314 women, or 40%, versus 100 of 197 men, or 51%; χ ² =9.29, df=3, p=.026) and had substance abuse diagnoses (132 of 273 women, or 48%, versus 94 of 157 men, or 60%; χ ² =5.31, df=1, p=.021). Finally, in this study the participation of African Americans was higher among women than among men (52 of 315 women, or 17%, versus 17 of 200 men, or 9%; χ ² =8.48, df=2, p=.014).

In the BDCP study we demonstrated that it is feasible to implement, in settings other than intensive research environments, extensive intake and screening procedures for patients with bipolar disorder that approach the quality of a rigorous research protocol. It was possible to recruit a cohort of patients who were diverse in terms of age and race and to implement the same protocol in various settings regardless of whether there was a history of routinely conducting research protocols and in urban as well as rural mental health provider agencies.

The patients in this study had baseline characteristics similar to those reported by patients in other large clinical studies of bipolar disorder. In our study, 61% of the participants were female, similar to several other recently published large studies, which found rates from 55% to 70% ( 19, 22, 23, 24, 25, 26 ). The BDCP participants' mean age at onset of bipolar disorder was 20.8 years, which matches nationwide epidemiologic studies, such as the Epidemiologic Catchment Area study, the National Comorbidity Survey replication, and other studies, all of which found a mean age at onset between 19.8 and 22.9 years ( 22, 24, 25, 27, 28, 29 ).

Because one of the aims of the BDCP study was to collect data on bipolar disorder among patients across the life span, different age groups are well represented in our sample. Eight percent of the patients in the study were 65 years or older, a rate higher than reported in other large studies, which range from .2% in the TMAP study ( 26 ) to 5.4% in the Stanley Foundation Bipolar Treatment Outcome Network (SFBN) study ( 25 ), yet consistent with the relative proportion of such elderly persons within the general population (9.7%) ( 30 ).

In the BDCP study we also made efforts to recruit a significant proportion of African-American participants, resulting in their constituting 13% of our total sample. Specific enrollment efforts in the BDCP study led to the proportion of African Americans in our study being higher than the proportion of African Americans in the Pittsburgh metropolitan statistical area (MSA) (8.1%), the area of western Pennsylvania served by WPIC where three of the study sites were located. Of note, the BDCP study recruited more than twice the proportion of African-American patients recruited in our earlier Maintenance Therapies in Bipolar Disorder study despite the fact that the BDCP study included a site in the DuBois area, where the percentage of African Americans in the general population is .3% ( 31 ). Other large studies reported variable rates of persons from racial or ethnic minority groups, from 37.5% in the TMAP study, conducted in an area with a high percentage of Latinos, to approximately 3% of African Americans reported in the Systematic Treatment Enhancement Program for Bipolar Disorder study (STEP-BD) and in the SFBN study.

It is worth noting that clinical characteristics, such as bipolar subtype, onset state, and lifetime comorbidity, differed very little between African Americans and non-African Americans in the BDCP study. However, the pathway into treatment differed significantly for African-American participants, who were referred more often from inpatient care, community presentations, and media outlets, compared with non-African-American participants. This difference may be attributable to the fact that we made planned, concerted efforts to do community outreach in African-American communities in the Pittsburgh MSA. In addition, to ensure continuity of care for inpatients with bipolar disorder once they were discharged, a study team member visited the inpatient units daily to discuss the BDCP study with patients, their family members, and inpatient staff. In addition, before study entry the African Americans in this sample were generally receiving less intensive treatment.

Forty-four percent of our BDCP sample had never been married, whereas other clinical studies reported a 30% to 35% rate ( 22, 23, 24, 25, 26 ). Twenty-one percent of our sample was separated or divorced, which is similar to the rates found in other studies of bipolar disorder and is as expected from a population with bipolar disorder, which displays the highest rates of separation and divorce among those with psychiatric disorders ( 32 ).

In the BDCP study two-thirds of the patients had bipolar I disorder, which is slightly below the rates reported in other studies (71% to 87%) ( 19, 23, 24, 25 ). This lower rate of participants with bipolar I disorder is consistent with our effort to improve the diagnosis of bipolar II disorder, which is more frequent than bipolar I disorder in the general population ( 30 ), albeit less frequently diagnosed in clinical settings.

Our patients reported considerable levels of psychiatric comorbidity, with a high rate of lifetime anxiety and substance use disorders (50% and 46%, respectively). Such findings are highly consistent with other large clinical studies reporting comorbid lifetime anxiety disorders at rates of 42% to 47.5% ( 23, 25, 33 ) and comorbid lifetime substance use disorders at rates of 40% to 43.7% ( 22, 23, 25 ). Finally, 39% of our patients reported a history of suicide attempts, which is slightly higher than the 31.8% found in the National Comorbidity Survey samples ( 34 ) and the 30% and 35.7% reported by the SFBN and STEP-BD studies, respectively. Similarly, both the Department of Veterans Affairs cooperative study and the Bipolar Disorder Case Registry reported rates of lifetime suicide attempts up to 65% within populations of patients with high unemployment and homelessness ( 24, 27 ). Several differences in demographic characteristics, treatment history, and clinical characteristics were found between African-American and non-African-American patients ( Tables 3, 4, and 5 ). For instance, African-American patients were less likely to be taking a psychotropic medication or an antidepressant at the time of study entry. Also, they tended to be more likely to report a history of suicide attempts (p=.061). However, in a logistic model of suicide attempts, household income and anxiety were strong predictors while African-American race was not, thus suggesting that socioeconomic status and comorbid anxiety have more of an influence than race on poorer outcomes among African-American patients.

Finally, African-American study participants were more likely to have been referred from inpatient services than their non-African-American counterparts. We suspect that this is because often African-American patients must reach a higher level of acuity before being willing to seek treatment for their bipolar disorder. This may have to do with the greater stigma associated with help seeking, particularly among African-American women, or with an inherent distrust of the medical establishment. Whatever the source of this difference, we found that with extensive community outreach, we were able to recruit the majority of the African Americans who participated in our study without their having to reach a level of symptom severity that required inpatient hospitalization.

One limitation to the interpretation of the results is that because the study intake criteria included individuals of all races, we felt that it was important to report on all people who participated in the study regardless of race, even though traditionally some studies compare African Americans to Caucasians. Therefore, the non-African-American group included 20 individuals who self-identified as Asian or American Indian, among other races. However, in the interest of completeness, we also compared the African-American group to the Caucasian group (for which we omitted the 20 individuals who were neither African American nor Caucasian) and still found no differences.

Another limitation to the study is that we cannot determine which of the procedures were most relevant to improved enrollment. Because the BDCP study was a research study supported by an outside agency, we had the funds to conduct extensive community outreach through in-person visits and presentations and through announcements of the availability of free treatment in various public media and to offer screening and treatment at no cost to participants. Reducing health disparities in terms of bipolar disorder treatment for patients in racial or ethnic minority groups, children and adolescents, and elderly persons may require this kind of community outreach because these patient subgroups are less likely to present voluntarily for treatment for a wide variety of reasons. Providing specialized bipolar disorder services that are of high quality undoubtedly helps with the retention of all patients, including these difficult-to-retain subpopulations. Although such efforts may not currently occur in many community settings, our results suggest that when such efforts are made, they have the potential to bear fruit in terms of reducing health disparities.

Our sample of patients with bipolar disorder appears comparable to samples in other large recent studies of bipolar disorder. Furthermore, given that the design of the BDCP study was aimed at addressing the needs of patients across the life span and also the health needs of African Americans, our findings fit a broad range of individuals with bipolar disorder, with the different age classes and rates of African Americans mirroring their distribution within the U.S. general population. We demonstrated that highly rigorous intake, screening, diagnostic, and treatment procedures could be successfully implemented across different types of settings and within different cohorts of patients, thus facilitating increased access to high-quality treatment for individuals who do not frequently receive appropriate care for bipolar disorder. Future articles will report on a variety of outcome measures, including mediators and moderators of outcome, longitudinally from the point of randomization to the end point of the study.

Support for the research presented here was provided in whole or in part by grant ME-02385 from the Commonwealth of Pennsylvania Department of Mental Health and grant MH030915 from the National Institute of Mental Health.

Dr. Birmaher has participated in forums sponsored by Forest Laboratories, Shire Pharmaceuticals, and JAZZ Pharmaceuticals. Dr. Fagiolini has been a speaker and consultant for Bristol-Myers Squibb and Pfizer and a speaker for Ortho-McNeil-Janssen Pharmaceuticals. Dr. Frank has been on the advisory board for Servier International. Dr. Friedman has been a consultant for Pfizer. Dr. Mulsant has received grants or research support from Eli Lily and Company and Pfizer. Dr. Pollock has served as a consultant for Wyeth Pharmaceuticals. Dr. Swartz has received grant support from and has served on the advisory board for Bristol-Myers Squibb and has received honoraria from Eli Lilly and Company, AstraZeneca Pharmaceuticals, and Servier. Dr. Thase has provided scientific consultation for AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Medavante, Neuronetics, Novartis, Organon International, Sepracor, Shire Pharmaceuticals, Supernus Pharmaceuticals, Transcept Pharmaceuticals, and Wyeth-Ayerst Laboratories. He has also received grant support from Eli Lilly and Company and Sepracor and has served on speakers bureaus for AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly and Company, GlaxoSmithKline, Sanofi-Aventis, Schering-Plough Pharmaceuticals, and Wyeth-Ayerst Laboratories. Dr. Thase has also provided expert testimony for Jones Day and Philips Lyttle, L.L.P., and Pepper Hamilton, L.L.P. (law firms in which he provided an expert opinion on behalf of Wyeth Pharmaceuticals and Eli Lilly and Company). His spouse is senior medical director for Advogent. Dr. Whyte has received grants from Pfizer, Ortho-McNeil Pharmaceutical, and Eli Lilly and Company. The other authors report no competing interests.

Dr. Kupfer, Dr. Axelson, Dr. Birmaher, Dr. Brown, Mr. Curet, Dr. Frank, Dr. Friedman, Dr. Grochocinski, Ms. Houck, Dr. Reynolds, Ms. Stofko, Dr. Swartz, and Dr. Whyte are affiliated with the Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara St., Pittsburgh, PA 15213 (e-mail: [email protected]). Dr. Fagiolini is with the Department of Neuropsychiatry, University of Siena School of Medicine, Siena, Italy. Dr. Kilbourne is with the Department of Psychiatry, Serious Mental Illness Treatment Research and Evaluation Center, University of Michigan, Ann Arbor. Dr. Mulsant and Dr. Pollock are with the Department of Psychiatry, University of Toronto, Toronto, Ontario. Dr. Thase is with the Department of Psychiatry, University of Pennsylvania, Philadelphia. Dr. Turkin is with the Department of Psychiatry, DuBois Regional Medical Center, Behavioral Outpatient Clinic, DuBois, Pennsylvania.