OBJECTIVES: To evaluate the effect of lisdexamfetamine dimesylate (LDX) and changes in binge eating (BE) days/week and BE episodes/week on disability in patients with protocol-defined moderate to severe binge eating disorder (BED) over 12 weeks. METHODS: : In two identically designed, 12-week, double-blind, placebo (PBO)-controlled trials, adults meeting DSM-IV-TR BED criteria were randomized (study 1, N=383; study 2, N=390) to PBO or LDX (50 or 70 mg). LDX was statistically superior to PBO in reducing the number of BE days/week (the primary endpoint) and showed numerical improvements in BE episodes/week (a secondary endpoint). The trials assessed disability with Sheehan Disability Scale (SDS) as an exploratory endpoint. Observations corresponding to visits from baseline to week 12 were analyzed; data were pooled across studies. The current post hoc analyses were performed using mixed-effect logistic regression models to determine the relationship between: (1) LDX therapy and disability, and (2) BE days/week and disability, and BE episodes/week and disability. P-values are unadjusted and presented for descriptive purposes only. RESULTS: LDX therapy showed a numeric improvement on disability as measured by SDS. The odds ratio (OR)/week for disability (>0 score) measured by SDS total score for LDX relative to placebo was 0.70 (P≤0.001). Higher BE frequency counteracted the improvement in disability which was significant in the lowest tertile of BE frequency (tertile 3). ORs/week for disability (>0 score) measured by SDS total score in BE days/week tertiles 1, 2 and 3 (relative to tertile 1) were 0.66, 1.37 and 1.72, and in BE episodes/week 0.66, 1.44 and 1.69, respectively (all P≤0.001). CONCLUSIONS: Findings of this longitudinal analysis indicate that LDX therapy has a positive effect on disability, as measured by SDS, of BED patients. The analysis also showed that reduction in both BE days/week and BE episodes/week is associated with improvement in disability over 12 weeks.