Clinical relevance of depressive symptom improvement in bipolar I depressed patients

Background emain between rating scale changes obtained in a clinical trial and what those results mean in clinical practice. ive ter understand the relevance of results from a clinical trial we examined the relationship between rating scale measures and the cliniciansʹ assessment of illness severity. s rom a randomized double-blind 8-week study of bipolar I depression were examined post hoc in patients who received placebo (PLA, n = 355), olanzapine (n = 351) (OLZ, 5 to 20 mg/d), or olanzapine–fluoxetine combination (n = 82) (OFC, 6 and 25, 6 and 50, or 12 and 50 mg/d). Principal components analysis identified related symptoms (factors) from Montgomery–Åsberg Depression Rating Scale (MADRS) item scores. Regression analysis examined baseline to endpoint changes in factor scores and Clinical Global Impression (CGI) scores. Mixed-effects model repeated measures analysis assessed differences between treatment groups. s factors identified were: sadness, negative thoughts, detachment, and neurovegetative symptoms. Factor and CGI scores were significantly reduced from baseline to endpoint (LOCF) in the combination therapy group as compared with placebo (p < .01). Changes in factor scores were highly correlated (p < .001) with changes in the CGI. Over 80% of this treatment effect was attributable to indirect effects of improvements in the MADRS factors, the remaining difference could not be explained even when changes in the YMRS and HAMA scores were included in the analytical model. sions anges in MADRS factors were closely aligned with the clinicianʹs assessment of overall depression severity, which may suggest a high degree of clinical relevance for differences observed between treatments.