Even with psychiatry’s most effective and best studied agents, many patients with bipolar disorder are inadequately treated and respond insufficiently to available psychopharmacologic agents. To address this problem, the Stanley Foundation Bipolar Network (SFBN) was created to explore acute and long-term response to treatment of bipolar disorder.
For the past 6 years, our group (Box) has followed an international cohort of patients with bipolar disorder and offered them opportunities to participate in clinical trials at seven field centers. We have made considerable progress as we focused on the longitudinal course of bipolar illness and evaluated various combinations of psychopharmacologic therapies. The SFBN also has explored factors that increase the risk of suicide, quantified the incidence of anxiety disorder and substance abuse, and looked at other variables that may affect treatment outcome.
This report for the readers of Current Psychiatry provides a brief state-of-the-art overview of what we have learned about the course and management of bipolar disorder. It brings together and summarizes the findings from studies published, in press, or under review. Our goal is to update current findings, which may help you provide optimum care for these at-risk patients.
ORIGINS AND METHODS OF THE STANLEY FOUNDATION BIPOLAR NETWORK
Since Robert Prien’s pioneering studies in the 1970s, the National Institute of Mental Health (NIMH) had funded little work on prophylaxis of bipolar disorders or acute bipolar depression. Following two NIMH conferences on bipolar illness in 1989 and 1994, the Stanley Foundation Bipolar Network (SFBN) was established to help overcome these research deficiencies, with funding provided by the Theodore and Vada Stanley Foundation.
Patients were recruited into the network from the general community and with the use of newspaper and newsletter advertisements. In contrast to many other clinical populations, few who wished to enter the network were excluded. It was clear, however, that filling out demographic, clinical, and rating forms would require considerable effort from each patient. All patients gave written informed consent to participate in the naturalistic part of the study, and were reconsented for any open or blind randomized clinical trial.
Patients provided daily self-ratings on the National Institute of Mental Health Life Chart Method (NIMH-LCM), a unique longitudinal instrument. Clinicians then completed their own separate LCMs, as more severely ill patients often could not complete their self-ratings, and patients often underestimated the severity and functional disability associated with the hypomanic and manic phases of bipolar illness. With the use of the NIMH-LCM, network investigators were able, for the first time, to assess the details of mood fluctuations associated with bipolar illness and to more precisely delineate the qualitative and quantitative aspects of response to psychopharmacologic interventions.
The SFBN includes seven research field centers in the United States, the Netherlands, and Germany. The leaders of those centers collaborated with Robert M. Post, MD, to prepare this report of the network findings. The collaborators are:
| Gabriele S. Leverich, MSW, and Kirk D. Denicoff, MD Biological Psychiatry Branch National Institute of Mental Health Bethesda, MD | Paul E. Keck, Jr., MD, and Susan L. McElroy, MD Biological Psychiatry Program University of Cincinnati College of Medicine Cincinnati, OH |
| Lori L. Altshuler, MD, and Mark A. Frye, MD UCLA Mood Disorders Research Program VA Medical Center Los Angeles, CA | Willem A. Nolen, MD, and Ralph Kupka, MD Altrecht Institute for Mental Health Care University Medical Center Utrecht, The Netherlands |
| John Rush, MD, and Trisha Suppes, MD Department of Psychiatry Southwest Medical Center University of Texas, Dallas | Joerg Walden, MD Department of Psychiatry University of Freiburg Freiburg, Germany |
| Keith Kramlinger, MD Mayo Clinic, Rochester, MN (Administrative center) | Heinz Grunze, MD Psychiatrische Klinik der LMU Munich, Germany |
In part one, we discuss the demographics of our cohort of 676 community-based bipolar patients, including risk factors for suicide attempts, frequency of comorbid psychiatric diagnoses, problems of overweight and obesity, and preliminary findings about thyroiditis.
In part two, we describe our clinical trials assessing mood stabilizers and adjunctive agents such as atypical antipsychotics, second-generation antidepressants, and anticonvulsants. We also will address a soon-to-be analyzed study of omega-3 fatty acids.
Table 1
CHARACTERISTICS OF THE 676 BIPOLAR OUTPATIENTS
| Mean age | 41 | |
| % Female | 43 | |
| Diagnosis (%) | ||
| Bipolar I | 79 | |
| Bipolar II | 16 | |
| Bipolar NOS | 4 | |
| Marital status (%) | ||
| Married/cohabitating | 44 | |
| Divorced/separated | 22 | |
| Income (%) | ||
| <$20,000 | 37 | |
| $20,000-40,000 | 22 | |
| $40,000-100,000 | 32 | |
| >$100,000 | 9 | |
| Education (completed, %) | ||
| High school | 34 | |
| Jr. college/technical | 13 | |
| College, 4-year | 27 | |
| Graduate degree | 16 | |
| Positive family history (1st-degree relatives, %) | ||
| Bipolar disorder | 56 | |
| Unipolar disorder | 64 | |
| Schizophrenia | 24 | |
| Drug dependence | 44 | |
| Other psychiatric disorder | 52 | |
| Alcohol abuse/dependence | 52 | |
| Suicide (complete or serious attempt) | 38 | |
| Environmental adversity (%): | Child/adolescent | Adult |
| Physical abuse | 29 | 8 |
| Sexual abuse | 30 | 8 |
| Illness course and treatment (age in yrs) | ||
| Age of onset (symptoms) | 19 | |
| Early onset (age <14) | 34 | |
| Age at first treatment | 29 | |
| Age at first hospitalization | 30 | |
| Cycling pattern (n = 643, %) | ||
| Rapid (or faster cycling) | 47 | |
| Ultrarapid (or faster cycling) | 30 | |
| Rapid-cycling only | 17 | |
| Ultrarapid cycling only | 10 | |
| Ultradian cycling | 20 | |
Study population
The SFBN recruited outpatients with bipolar disorders I, II, or not otherwise specified (NOS). We did not exclude patients with comorbid illnesses, except those with active substance abuse disorder requiring treatment in another setting.1 Patients were recruited almost exclusively from the community and rarely from inpatient hospitalization. The average age was 41, and 43% were college graduates. Most were employed but indicated that their illness limited their employment level or ability to function at work (Table 1).