191 Background: Psychostimulant clinical trials on CRF in pts with advanced cancer suggest mixed effects on CRF. The aim of this study was to determine the effects of MP and placebo (PL) on the pts with clinically significant CRF and associated symptoms such as depression, sedation, or depression and sedation (couplets). Methods: Secondary analysis of pts who received MP as a part of 3 prospective controlled clinical trials on MP for CRF. Pts were categorized one of 4 groups, fatigue+depression (FD), fatigue+ drowsiness (FDR), fatigue+drowsiness+depression (FDDR) or fatigue only (F), and outcomes were change in FACIT-F subscale and ESAS -fatigue scores at Day 8 of treatment with MP and PL. Repeated measures analysis was applied to assess the effects of treatment over time (Day8 – Day0) among the 4 groups on FACIT-F subscale and ESAS fatigue. Results: Of the 322 evaluable pts (34 FD, 100 FDR, 78 FDDR, 107F), at Day 8 there was a significant improvement in the ESAS fatigue in MP compared to PL groups [median (IQR)-2 (-4, -1) vs 2 (-3.5,0),p = 0.03, but the difference in the change of FACIT-F between the groups was not significant [median(IQR) 8(2,17) VS7(0,12), p = 0.09). Repeated measures analysis on FACIT-F with pairwise interactions(Time X Baseline Group, Time X Treatment) shows that regardless of treatment, the increase of FACIT-F from Day0 to Day8 was significantly different between FD and F (p = 0.001) and between FDDR and F (p = 0.03).However the change over time was not significantly different between two treatment groups (p = 0.23). Furthermore, the repeated measure analysis including three term interactions(Time X Treatment X Baseline Group) indicates no significant the treatment effect on FACIT-F over time is not significantly different among the four groups (p = 0.89). Similarly, there is no significant treatment effect in ESAS fatigue score over time among the four groups. Conclusions: Although there was a general improvement in CRF (FACIT-F) scores over time, there was no significant treatment effect on this improvement over time among F or FD, or FDR, or FDDR groups defined by fatigue/depression/sedation in the whole study population. Further studies are needed.