Advancing bipolar disorder: key lessons from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

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 suicidality. 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.