The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) is one of the largest studies to have evaluated treatments for bipolar disorder. This chronic condition, which is characterized by repeated swings in mood between mania (a state of elation and high energy) and depression , can significantly affect quality of life if not properly treated.
STEP-BD investigated the most effective treatment methods for bipolar episodes (mania and depression), including medication, psychological therapies, and other modalities. The researchers evaluated treatments on the basis of cost-effectiveness, improvements in patients’ social functioning and quality of life, and preventing recurrence. As part of the study, the investigators also looked at the characteristics of patients with bipolar disorder.
The STEP-BD study was a $28-million, seven-year effort funded by the National Institutes of Mental Health (NIMH). It was conducted from September 1998 to September 2005, at 20 clinical treatment centers throughout the United States. Researchers followed 4,360 participants with bipolar disorder to determine which treatments were most effective for mania and depressive episodes, and for preventing recurrence.
The study offered two treatment arms, called pathways—a real-world, non-controlled Best Practice Pathway, and a randomized and controlled Randomized Care Pathway. Participants had the opportunity to join in both pathways. Researchers were able to compare the two pathways to see how the evaluated treatments worked both in clinical and real-world settings. In the “Best Practice Pathway,” participants were followed by a STEP-BD certified doctor and all treatment choices were individualized. Everyone enrolled in STEP-BD was able to participate in this pathway. Participants and their doctors worked together to decide on the best treatment plans and to change these plans if needed. Also, anyone who wished to stay on his or her current treatment upon entering STEP-BD was permitted do so in this pathway. Adolescents and adults age 15 years and older were eligible to participate in the Best Practice Pathway.
Patients ages 18 years and older had the option of entering the “Randomized Care Pathway” portion of the trial. Patients in this pathway remained on their mood-stabilizing medication, but some were also started on another medication or talk therapy . The patients were randomly assigned to treatments, and the study was double-blinded, meaning that neither the doctors nor their patients were aware of which treatment was given (double-blinding is done to prevent bias among both researchers and patients). Approximately 1,500 patients were involved in at least one Randomized Care Pathway. Patients remained with the same physician throughout the course of the study.
All researchers involved in STEP-BD were specially trained for the project in the treatment of bipolar disorder. The study was coordinated by Massachusetts General Hospital and the University of Pittsburgh School of Medicine.
The following research centers served as clinical sites for the study:
- Baylor College of Medicine
- Case Western Reserve University
- Cornell University
- Howard University
- Massachusetts General Hospital
- New York Presbyterian Hospital
- New York University
- Rush-Presbyterian-St. Luke’s Medical Center
- Stanford University
- State University of New York, Buffalo
- University of Arizona
- University of California, San Diego
- University of Colorado
- University of Louisville
- University of Massachusetts
- University of Missouri
- University of Oklahoma
- University of Pennsylvania
- University of Pittsburgh
- University of Texas, San Antonio
STEP-BD enrolled 4,360 patients with bipolar disorder in the United States. To enter the study, participants had to be at least 15 years of age and meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)criteria for bipolar I disorder, bipolar II disorder, cyclothymia, bipolar disorder not otherwise specified (BD-NOS), or schizoaffective disorder , bipolar subtype. The goal of STEP-BD was to evaluate all the best-practice treatment options used for bipolar disorder: mood-stabilizing medications, antidepressants , atypical antipsychotics, and psycho-social interventions—or “talk” therapies—including cognitive behavioral therapy, family-focused therapy, interpersonal and social rhythm therapy, and collaborative care (psychoeducation).
Some of the patients had already been treated for bipolar disorder before entering the study, whereas others had not received prior treatment. Many of the patients had other mental illnesses, such as anxiety or substance abuse problems. Doctors evaluated the participants upon entry (baseline) and monitored their progress throughout the study. Patients were considered to be recovering if they had no more than two moderate symptoms for at least one week. They were considered recovered if they had no more than two moderate symptoms for at least eight weeks.
The following treatments were used in the STEP-BD study:
- Lithium: A mood-stabilizing medication
- Valproate: An anti-convulsant medication that has mood-stabilizing effects
- Lamotrigine: A newer anti-convulsant medication
- Risperidone: A newer, atypical antipsychotic medication
- Bupropion: An antidepressant
- Paroxetine: A type of antidepressant called a selective serotonin reuptake inhibitor (SSRI)
- Tranylcypromine: A type of antidepressant known as a monoamine oxidase inhibitor
- Inositol:A natural substance that acts as a chemical messenger
- Cognitive behavioral therapy
- Family-focused therapy
- Interpersonal and social rhythms therapy
In addition to evaluating treatment outcomes, the STEP-BD study looked at the coexistence of other mental disorders, types of medications commonly prescribed for bipolar disorder, and recurrence rates, among other areas of study.
The following were some of the research findings to come out of the STEP-BD study:
- Coexistence of other mental disorders: Among a subgroup of the first 500 patients in the STEP-BD study, more than 50% had a lifetime history of anxiety disorder, 38% had a history of alcohol abuse or dependence, and 26% had a history of substance of abuse or dependence.
- Most common existing treatments for bipolar disorder: Researchers looked at the first 500 patients entering the study and found that the majority (72%)were taking mood-stabilizer medications, such as lithium or carbamazepine, when they began STEP-BD. The next most common class of medications taken was antidepressants (40%), followed by anticonvulsants (32%) and antipsychotic agents (31%).
- Treatment-resistant bipolar depression: Researchers tested three different medications, lamotrigine, ino-sitol, and risperidone, on a subgroup of 66 participants with bipolar depression who had not previously responded to treatment. The recovery rate was 24% with lamotrigine, 17% with inositol, and 4.6% with risperidone. The researchers said their results suggested that lamotrigine may be superior to inositol and risperidone for improving symptoms of treatment-resistant bipolar depression.
- The effectiveness of psychotherapy on bipolar disorder: Researchers looked at a subgroup of the first 1,000 people enrolled in the STEP-BD study. About 60% of these patients had at least one psychotherapy session during the first year of the study. Among participants with more severe depressive symptoms at the outset of the study, more frequent psychotherapy sessions were associated with less severe mood symptoms and better functioning. The researchers said these results suggest that patients with more severe bipolar disorder might benefit from more frequent psychotherapy sessions.
- Bipolar disorder recurrence: In a prospective study of 1,469 STEP-BD participants, more than half of the patients (58%) achieved recovery. However, almost half of those who recovered experienced a
Atypical antipsychotics —A class of newer generation antipsychotic medications that are used to treat schizophrenia, bipolar disorder, and other mental disorders.
Bipolar I disorder —A subtype of bipolar disorder characterized by a manic or mixed episode that lasts for at least one week.
Bipolar II disorder —A subtype of bipolar disorder characterized by alternating depressive and hypo-manic (persistently elevated or irritable mood) episodes.
Bipolar disorder not otherwise specified —Cases of bipolar disorder that don’t meet the full criteria for the other two bipolar disorder subtypes but that involve an elevated or irritable mood, plus two or three bipolar symptoms (difficulty concentrating, sleep changes, and so on) that are severe enough to interfere with functioning.
Cognitive behavioral therapy —A treatment that helps patients control the negative thoughts that are leading to their depressive symptoms.
Cyclothymia —A milder form of bipolar disorder that persists for a long period of time.
Monoamine oxidase inhibitor —A type of antide-pressant that works by inhibiting the enzyme monoamine oxidase, which breaks down mood-regulating neurotransmitters such as serotonin and dopamine.
Schizoaffective disorder —A mental disorder in which depressive episodes occur, along with symptoms of schizophrenia, such as hallucinations.
Selective serotonin reuptake inhibitors (SSRIs) —A class of antidepressant medications that help improve mood by increasing the amount of the neurotransmitter serotonin in the brain.
recurrence during the two-year follow-up period. Researchers said these findings indicate that bipolar disorder has a strong likelihood of recurrence.
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Depression and Bipolar Support Alliance, 730 N. Franklin Street, Suite 501, Chicago, IL 60610-7224. Telephone: (800) 826-3632. Web site: http://www.dbsalliance.org
National Alliance on Mental Illness, 2107 Wilson Boulevard, Suite 300, Arlington, VA 22201-3042. Telephone: (800) 950-6264. Web site: http://www.nami.org
National Institute of Mental Health, 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. Telephone: (866) 615-6464. Web site: http://www.nimh.nih.gov
Stephanie N. Watson