Binge eating disorder (BED), the most prevalent formal eating disorder, is associated strongly with obesity and bio-psychosocial impairment. Improved treatments for patients with BED and obesity are needed that can produce sustained clinical outcomes. This study aims to perform a two-stage randomized controlled trial (RCT) to compare the effectiveness of two leading but distinct treatments — lisdexamfetamine (LDX) and cognitive behavioral therapy (CBT) — alone and in combination, for BED. LDX is the only FDA-approved medication for BED, has demonstrated short-term effectiveness relative to placebo, but comparative effectiveness to other active treatments and longer-term outcomes are unknown. The first stage RCT will provide new findings regarding the relative effectiveness of LDX, CBT, and combined CBT+LDX for obese patients with BED. The second stage RCT will provide novel findings from a controlled test, whether amongst Stage 1 patients who received acute pharmacotherapy with LDX (i.e., LDX or CBT+LDX) and showed a positive clinical response, continued LDX medication results in superior maintenance and longer-term outcomes than placebo. The second Stage RCT will also provide novel findings regarding whether amongst non-responders to Stage 1 pharmacotherapy, switching to an alternative medication (Naltrexone-Bupropion; FDA-approved for obesity) results in clinical improvements. This study addresses the dearth of research on longer-term outcomes of pharmacotherapy for BED, which is strikingly at odds with the public health significance of BED, including documented prevalence, strong association with obesity, and heightened bio-psychosocial morbidity. In Stage 1 RCT, N=180 obese patients with BED will be randomly assigned to one of three 12-week interventions: CBT, LDX, or CBT+LDX. In Stage 2, patients who received acute pharmacotherapy (LDX or CBT+LDX) and were “responders” (65% or greater reduction in binge eating) will be randomized in equal proportions (stratified blocked randomization with first treatment as stratifying variable) to LDX or placebo (double-blind) for 12 weeks. “Non-responders” to acute pharmacotherapy will be randomized to a second medication (Naltrexone-Bupropion or placebo; double-blind) for 12 weeks. Stage 1 patients receiving CBT will be followed without further intervening treatment. Independent outcome assessments will determine relative acute effectiveness, medication maintenance effectiveness, and longer-term maintenance through 18 months. Secondary aims are to contribute important new data regarding predictors of outcomes and moderators of treatment effects to inform prescription (i.e., for whom the LDX and CBT work best), exploration of mediators through which these two distinct methods work, exploration of alternmative pharmacotherapy for initial non- responders, and generation of cost-effectiveness estimates. This study will produce novel findings regarding “adaptive” SMART treatment methods for BED and obesity.