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

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).

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.

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.

Targeted RCTs, broader eligibility criteria, subgroup analyses, and observational cohorts are needed to improve the evidence base for underrepresented patients with bipolar depression.