An Open-Label Study Evaluating the Naltrexone SR/Bupropion SR Combination Therapy in Overweight or Obese Subjects with Major Depression
Abstract Number: 1851-P
Authors: SUSAN L. MCELROY, ANNA I. GUERDJIKOVA, AMY ROSEN, DENNIS D. KIM, RONALD LANDBLOOM, EDUARDO DUNAYEVICH
Institutions: Mason, OH, Cincinnati, OH, Quincy, IL, La Jolla, CA
Results: Obesity and depression are highly comorbid conditions. Combined sustained-release (SR) naltrexone/bupropion SR (NB), in development for obesity, results in clinically significant weight loss in overweight/obese adults. NB contains bupropion at a dose used to treat depression. This 24-week open-label study was conducted to evaluate the effect of 32 mg/day naltrexone SR /360 mg/day bupropion SR in 25 subjects with major depressive disorder by DSM-IV criteria and BMI ≥27 and ≤43 kg/m2 on depressive symptoms, body weight, and measures of eating behavior. Subjects also received mild diet/exercise instruction. The primary endpoint was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 12 weeks (modified ITT-LOCF: subjects with ≥1 post-baseline MADRS total score on study drug; N=23). Mean baseline characteristics: age 47y, 100% female, 92% Caucasian, weight 95kg, BMI 35kg/m2, MADRS total score 24, IDS-SR total score 43 (consistent with moderately severe depression), and Binge Eating Scale (BES) total score 28 (indicating severe binge eating). Week 12 and 24 completion rates were 56% and 48%, respectively. Mean MADRS total score was reduced from 23.6 at baseline to 10.5 at Week 12 (-13.1; P<0.001) and to 8.4 at Week 24 (-15.3; P<0.001), as was Week 24 mean IDS-SR total score (-22.5; P<0.001). At Week 24, there was a reduction in body weight (-5.4%; P<0.001). The Week 24 response rate (defined by Clinical Global Impression-I [CGI-I] score ≤2) was 95%; 70% of subjects were in remission (CGI-I score of 1). Measures of eating behavior (Control of Eating Questionnaire and BES) showed reduced binge eating; hunger, frequency and strength of food cravings; improved ability to resist food cravings; and control of eating behavior (all P<0.01). There were no serious adverse events and the most common adverse events were nausea, constipation, headache and insomnia. In summary, 24 weeks of NB therapy was associated with significant improvements in depressive symptoms, reduced body weight and improved eating behavior measures in overweight and obese women with comorbid major depressive disorder.