Prevalence and outcomes of real-world bipolar depression patients underrepresented in guideline RCTs.

BACKGROUND: The present study aimed to address the gap between treatment guidelines and real-world management of acute bipolar depression by examining the prevalence, clinical features, and patient-perceived improvement after pharmacotherapy among bipolar outpatients who would be ineligible for an average randomized controlled trial (RCT). METHODS: This cross-sectional study classified bipolar depressed outpatients as RCT-eligible or RCT-ineligible using the Trial Eligibility Index (TEI), while retaining the TEI as the primary continuous measure of RCT representativeness. Patient-perceived improvement after pharmacotherapy was assessed during routine clinical evaluation. Descriptive analyses were followed by multivariable regression and exploratory random-forest variable-importance analyses. RESULTS: At the prespecified TEI cutoff of 75, 53/122 patients (43.4%) were RCT-eligible. RCT-eligible patients had greater odds of reporting perceived improvement than RCT-ineligible patients (OR = 9.83, 95%CI 4.17-23.18; p < 0.001). Sensitivity analyses produced the same classification at a cutoff of 70 and preserved the direction of association at a cutoff of 80 (OR = 9.33, 95%CI 1.14-76.09; p = 0.013). The continuous TEI was associated with several psychiatric and medical characteristics in multivariable analysis. CONCLUSIONS: Targeted RCTs, broader eligibility criteria, subgroup analyses, and observational cohorts are needed to improve the evidence base for underrepresented patients with bipolar depression.