SAN JUAN, P.R. — New data—especially on bipolar depression—are starting to emerge from randomized studies conducted within a bipolar disorder observational treatment study, according to an update presented at the annual meeting of the American College of Psychiatrists.
Researchers have been busy with analysis of three randomized trials embedded within the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study since recruitment ended in September 2005. With a total of 4,361 patients at 19 centers, STEP-BD is the largest prospective cohort study of this patient population.
One randomized study compares bupropion, paroxetine (Paxil), and placebo added to a standard mood stabilizer for acute bipolar depression. “It is not yet published. This probably will be the most interesting data to come out,” Dr. S. Nassir Ghaemi predicted.
Results of one study just published favor lamotrigine vs. inositol or risperidone (Risperdal) for treatment of resistant bipolar depression (Am. J. Psychiatry 2006;163:210–6). Researchers randomized 66 patients unresponsive to a mood stabilizer plus antidepressant to either lamotrigine (150–250 mg/day), inositol (10–25 g/day), or risperidone (up to 6 mg/day) for 16 weeks. They defined recovery as two or fewer DSM-IV mood criteria for 2 months, and “lamotrigine looked more favorable,” said Dr. Ghaemi, director of the Bipolar Disorder Research Program at Emory University, Atlanta.
The third randomized trial is not yet published. Researchers will compare psychosocial therapies for maintenance: cognitive-behavioral therapy, family-focused treatment, interpersonal and social rhythm therapy, and collaborative care/psychoeducation. “This is the hardest to conduct, getting people into psychosocial therapy and randomizing them,” said Dr. Ghaemi.
Many other researchers have mined the rich STEP-BD data to study the natural history, diagnosis, and treatment of bipolar disorder. For example, Dr. Ghaemi and his associates assessed treatment patterns among a cohort of 500 STEP-BD participants. They found that most were taking mood stabilizers (72%), and the next most common class of medication was antidepressants (41%). Anticonvulsants came in third, at 32%.
“We also looked at rapid vs. nonrapid cyclers,” Dr. Ghaemi said. “And we found no difference in medication use, including antidepressants.
“We're doing an open, randomized, long-term study of antidepressant outcome in bipolar disorder” based on a sample of STEP-BD participants, Dr. Ghaemi said. He presented an interim analysis based on 69 patients with acute bipolar depression who responded to a mood stabilizer and antidepressant for 2 months. Dr. Ghaemi and his associates then randomized participants to continue both agents or only the mood stabilizer for 1 year.
“On our clinical monitoring form, we found no difference between the two groups, meaning that continuing antidepressants had no effect on mood criteria, after adjusting for other variables,” Dr. Ghaemi said. In addition, there was no significant increased relapse to depression in the group that discontinued antidepressant therapy. “This conflicts with the Stanley Foundation [Bipolar Network] data published two years ago, but that was observational and this was randomized,” Dr. Ghaemi said (Bipolar Disord. 2003;5:396–406).
Predictors of increased morbidity in the study included rapid cycling, a negative patient attitude toward the regimen to which the patient was assigned, and prior psychosis. “Rapid cyclers who continued on antidepressants trended toward greater depressive morbidity, suggesting we should use these medications even less in this subpopulation,” Dr. Ghaemi said.
STEP-BD is sponsored by the National Institute of Mental Health.
Visit www.stepbd.org