Objective: To review the overall clinical research findings from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), the world's largest study of BD.
Methods: STEP-BD was conducted from 1998 to 2005, enrolling participants (n = 4361) across 22 clinical sites in the United States. Each individual was followed for up to 2 years in naturalistic practice with blinded research assessments, while subgroups participated in randomized controlled trials (RCTs) for bipolar depression. The naturalistic database was used to examine the course of BD, comorbidity with other psychiatric disorders, and suicidally. Relevant studies in English, published from January 1, 1994, to May 31, 2009, were identified using computerized searches of electronic databases (PubMed, PsycINFO, and Cochrane Register of Clinical Trials), inspection of bibliographies, and review of other major reports.
Results: One large RCT involving the addition of either paroxetine or bupropion to mood stabilizers in acute depression found neither more effective than placebo in achieving sustained recovery
(8 weeks of euthymia). A second large RCT found intensive psychosocial interventions superior to a brief psychosocial intervention as an adjunct to medication in acute depression. A third small RCT found minimal effects of lamotrigine, risperidone, or inositol in refractory depression. Recovery was difficult to achieve, with subsyndromal symptoms or full relapse very common. Anxiety disorders and smoking in particular were treatable conditions that adversely affected the course of BD.
Conclusions: STEP-BD yielded numerous clinical and systems observations that provide fresh direction for research and treatment of BD, including setting new benchmarks for outcome and demonstrating the viability of large BD networks.
Can J Psychiatry. 2010;55(3):136-143.
* STEP-BD was the largest BD research program ever conducted, and included data from 3 major RCTs and findings from many observational studies.
* Few treatments were successful in bipolar depression, with psychosocial interventions combined with mood stabilizers the most positive.
* Comorbidity of BD with substance abuse and smoking were common and adversely affected clinical outcome, while comorbidity with adult attention-deficit hyperactivity disorder was modest.
Key Words: bipolar disorder, bipolar depression, antidepressants, mood stabilizers, mania, suicidality, Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), clinical trial, psychosocial treatment
Abbreviations used in this article
ADHD attention-deficit hyperactivity disorder
BD bipolar disorder
CC collaborative care
DSM Diagnostic and Statistical Manual of Mental Disorders
IPS Intensive Psychosocial Study
NIMH National Institute of Mental Health
RCT randomized controlled trial
SSRI specific serotonin reuptake inhibitor
STEP-BD Systematic Treatment Enhancement Program for BD
SUD substance use disorder
Evidence-based medicine postulates that RCTs are the ideal source of information regarding treatment. However, from a public health perspective, there are limitations to reliance on typical efficacy trials, where often small samples of so-called uncomplicated patients receive tightly circumscribed interventions. In response, the US NIMH in the 1 990s commissioned a series of effectiveness study programs to generate answers to treatment-effectiveness questions in so-called real-world settings,· for BD, this was known as the STEP-BD.1 Conducted from 1998 to 2005, this program enrolled participants (n = 4361) across 22 clinical sites in the United States, funded by an NIMH grant of US$26.8 million (with no pharmaceutical funding except for donated ADs for one study). To ensure generalizability, there were essentially no contraindications to enrolment in the overall program. …