The purpose of this study is to determine whether a combination of naltrexone SR and bupropion SR is safe and effective in the treatment of major depression in overweight or obese subjects.

Inclusion Criteria:

• Female and male subjects must be 18 to 65 years of age;
• Have body mass index (BMI) greater or equal to 27 and less than or to equal 43kg/m2;
• Meet criteria for major depression
• Women of child-bearing potential, must be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drug;
• Able to comply with all required study procedures and schedule;
• Able to speak and read English;
• Willing and able to give written informed consent

Exclusion Criteria:

• Obesity of known endocrine origin
• Serious medical condition
• History of drug or alcohol abuse or dependence
• Use of excluded concomitant medications
• History of surgical or device (e.g. gastric banding) intervention for obesity;
• History or predisposition to seizures
• Pregnant or breast-feeding women or planning to become pregnant during the study period or within 30 days of discontinuing study drug;
• Planned surgical procedure that can impact the conduct of the study;
• Use of investigational drug, device or procedure within 30 days prior to Screening;
• Participation in any previous clinical trial conducted by Orexigen Therapeutics;
• Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in the study.