Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo.
BACKGROUND
The efficacy of current centrally acting obesity pharmacotherapies is limited by compensatory mechanisms that mitigate weight loss.


OBJECTIVE
Our objective was to determine whether opioid receptor antagonism (naltrexone) plus pro-opiomelanocortin activation (bupropion) causes greater weight loss than placebo or monotherapy.


METHODS
A randomized, placebo- and monotherapy-controlled, double-blind, dose-finding trial was conducted from August 2005 to December 2006 in seven U.S. outpatient clinics.


METHODS
A total of 419 patients with uncomplicated obesity participated.


METHODS
Interventions included 24 wk of sustained-release bupropion (400 mg/d), immediate-release naltrexone (48 mg/d), placebo, and three combination therapy [naltrexone/bupropion (NB)] groups consisting of immediate-release naltrexone, 16, 32, or 48 mg/d, plus sustained-release bupropion (400 mg/d) with a 24-wk extension. A minimal diet and exercise component was also included.


METHODS
Percent weight change from baseline at wk 24 in the intent-to-treat population for NB48 vs. placebo and monotherapy was assessed. Other measurements included body mass index, waist circumference, fasting lipids, glycemic variables, safety, and tolerability.


RESULTS
At wk 24, placebo-subtracted weight loss was -4.62% [95% confidence interval (CI) -6.24 to -2.99; P < 0.001] for NB16, -4.65% (95% CI -6.20 to -3.09; P < 0.001) for NB32, and -3.53% (95% CI -5.15 to -1.90; P < 0.001) for NB48. Weight loss was statistically significant vs. monotherapy for all three NB combinations with the exception of NB48 vs. bupropion. Weight loss with NB continued after wk 24. The most common treatment-emergent adverse event was mild transient nausea.


CONCLUSIONS
NB caused gradual sustained weight loss over 48 wk; NB32 and NB16 demonstrated greater weight loss in the intent-to-treat population due to lower attrition rates. Further study is needed to demonstrate long-term efficacy and safety of NB.
Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, Louisiana 70808, USA. frank.greenway@pbrc.edu
Frank L
FL
Greenway
Eduardo
E
Dunayevich
Gary
G
Tollefson
Janelle
J
Erickson
Maria
M
Guttadauria
Ken
K
Fujioka
Michael A
MA
Cowley
D000293:Adolescent; D000328:Adult; D001066:Appetite / Q000187:drug effects; D016642:Bupropion / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D009765:Obesity / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000453:epidemiology; D049268:Positron-Emission Tomography; D012307:Risk Factors; D015431:Weight Loss / Q000187:drug effects; D055815:Young Adult
D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D016642:Bupropion; D009271:Naltrexone