title: Naltrexone/Bupropion combination therapy in overweight or obese patients with major depressive disorder: results of a pilot study.
abstract: OBJECTIVE
  To evaluate the effect of 32-mg/d naltrexone sustained release and 360-mg/d bupropion sustained release (NB32) in overweight and obese patients with major depressive disorder (MDD).
  
  
  METHODS
  Twenty-five female patients with a DSM-IV diagnosis of MDD, an Inventory of Depressive Symptomatology-Self-Report score > 26, and a body mass index ≥ 27 and ≤ 43 kg/m(2) received up to 24 weeks of open-label treatment with NB32 with dietary and behavioral counseling (data collection: March 2008-July 2009). The primary endpoint was change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 12 weeks; secondary endpoints included MADRS total score at week 24, change in weight, and Clinical Global Impressions-Improvement scale responder status (CGI-I score ≤ 2) at weeks 12 and 24 (modified intent-to-treat [mITT]: patients with ≥ 1 postbaseline MADRS total score on study drug; N = 23).
  
  
  RESULTS
  MADRS scores showed significant reductions at weeks 12 and 24 (mITT-last observation carried forward [LOCF]: -13.1 ± 7.1 and -15.3 ± 8.1, respectively, P < .001 vs baseline for all). Mean ± SD weight loss was -4.0% ± 4.6% (mITT-LOCF) and -6.1% ± 4.7% (observed cases) at week 12 and -5.3% ± 6.5% (mITT-LOCF) and -9.2% ± 6.2% (observed cases) at week 24 (P < .001 vs baseline for all). By week 24, 95% of patients (mITT-LOCF) were responders (CGI-I score ≤ 2) and 70% were in remission (CGI-I score = 1). The safety/tolerability profile of NB32 was consistent with its individual components; the most common adverse events were nausea, constipation, headache, and insomnia, with no serious adverse events attributed to NB32.
  
  
  CONCLUSIONS
  Twenty-four weeks of open-label NB32 therapy with dietary and behavioral counseling was associated with improvement in depressive symptoms and reduced body weight in overweight/obese women with MDD.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00624858.
authors.affiliation: Research Institute, Lindner Center of HOPE, Mason, Ohio (Dr McElroy); Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio (Drs McElroy and Guerdjikova); and Orexigen Therapeutics, Inc, La Jolla, California (Drs Burns, Kim, Harris-Collazo, Landbloom, and Dunayevich). Dr Kim is currently employed by Zafgen. Dr Harris-Collazo is currently employed by Santarus. Dr Landbloom is currently employed by Merck. Dr Dunayevich is currently employed by Amgen.
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.forename: Anna I
authors.initials: AI
authors.lastname: Guerdjikova
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Kim
authors.forename: Colleen
authors.initials: C
authors.lastname: Burns
authors.forename: Raúl
authors.initials: R
authors.lastname: Harris-Collazo
authors.forename: Ronald
authors.initials: R
authors.lastname: Landbloom
authors.forename: Eduardo
authors.initials: E
authors.lastname: Dunayevich