PMH51 BREXANOLONE INJECTION FOR THE TREATMENT OF POSTPARTUM DEPRESSION: MINIMAL IMPORTANT DIFFERENCE AND MEANINGFUL CHANGE

Abstract

Brexanolone injection (BRX) is the first FDA-approved postpartum depression (PPD)-specific treatment, based on a primary endpoint supported by the Hamilton Rating Scale for Depression (HAM-D) total score at hour 60. The most common adverse events (≥10%) with BRX were headache, dizziness, and somnolence. While BRX has shown significant improvement over placebo (-4.1, 95% CI: -6.0, -2.3, p<0.0001) little is known about the interpretation of the HAM-D in a PPD population. Thus, the objectives of the analysis were to: (1) establish a HAM-D minimal important difference (MID) and patient-level meaningful change thresholds (MCT) for PPD, and (2) calculate the proportion of BRX and placebo patients who met the MCTs at hour 60. The HAM-D MID was estimated based on two distribution-based methods: one-half standard deviation (SD) for the pooled sample at baseline and one standard error of measurement (SEM; using a test re-test intra-class correlation coefficient). Thresholds for HAM-D MCTs (minimal, moderate, and large) were estimated based on Clinician Global Impression of Improvement (CGI-I) response category (minimally improved, much improved, and very much improved, respectively). 209 subjects were included at baseline. The HAM-D MID estimates were -1.8 and -2.4 based on one-half SD and one SEM, respectively. Integrated analysis estimates of least-squared mean difference between BRX and placebo at hour 60 exceeded both MID estimates. Minimal, moderate and large MCTs were estimated to be -9, -15 and -20 points, respectively. Significantly more BRX-treated patients achieved minimal (87% vs 68%, p<0.01), moderate (67% vs 42% p<0.001), and large change (30% vs 15%, p<0.05) at hour 60. HAM-D total score improvements at hour 60 with BRX were both statistically significant and clinically importantly different from placebo. This analysis has provided the first estimates of PPD-specific MID and MCTs for the HAM-D in this clinically important outcome.