LEP and major depressive disorder: 83% adherence rate for the 6-month study period. Significant reductions in fat mass. ~50% decline in self-reported fatigue and depression. Improved MS QoL physical health (67±16 vs 79±12, p<0.001) and mental health (71±17 vs 82±11, p<0.001). Improved EDSS scores (2.3±0.9 vs. 1.9±1.1, p<0.001). Improved 6-minute walk (1631±302 vs. 1733±330 ft, p<0.001). Improved Nine-Hole Peg Test (21.5±3.6 vs. 20.3±3.7 s, p<0.001). Reduced serum leptin (25.5±15.7 vs. 14.0±11.7 ng/mL, p<0.001). Increased adiponectin (11.4±7.8 vs. 13.5±8.4 μg/mL, p=0.002).