***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This 56-week , r and omized , placebo-controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification ( BMOD ) . A total of 793 participants ( BMI = 36.5 ± 4.2 kg/m² ) was r and omly assigned in a 1:3 ratio to : ( i ) placebo + BMOD ( N = 202 ) ; or ( ii ) naltrexone sustained-release ( SR , 32 mg/day ) , combined with bupropion SR ( 360 mg/day ) plus BMOD ( i.e. , NB32 + BMOD ; N = 591 ) . Both groups were prescribed an energy-reduced diet and 28 group BMOD sessions . Co- primary end points were percentage change in weight and the proportion of participants who lost ≥5 % weight at week 56 . Efficacy analyses were performed on a modified intent-to-treat population ( ITT ; i.e. , participants with ≥1 postbaseline weight while taking study drug ( placebo + BMOD , N = 193 ; NB32 + BMOD , N = 482 ) ) . Missing data were replaced with the last observation obtained on study drug . At week 56 , weight loss was 5.1 ± 0.6 % with placebo + BMOD vs. 9.3 ± 0.4 % with NB32 + BMOD ( P < 0.001 ) . A completers analysis revealed weight losses of 7.3 ± 0.9 % ( N = 106 ) vs. 11.5 ± 0.6 % ( N = 301 ) , respectively ( P < 0.001 ) . A third analysis , which included all r and omized participants , yielded losses of 4.9 ± 0.6 vs. 7.8 ± 0.4 % , respectively ( P < 0.001 ) . Significantly more NB32 + BMOD- vs. placebo + BMOD-treated participants lost ≥5 and ≥10 % of initial weight , and the former had significantly greater improvements in markers of cardiometabolic disease risk . NB32 + BMOD was generally well tolerated , although associated with more reports of nausea than placebo + BMOD . The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity To investigate the effects of the long-acting opiate antagonist naltrexone on spontaneous human eating behavior , eight moderately obese male paid volunteers were housed in a hospital metabolic unit for 28 days and offered palatable foods ad lib by a platter service method . Under double-blind conditions , equally divided doses of 100 , 200 and 300 mg naltrexone , or an acetaminophen placebo , were administered twice daily in tablet form for 3-day periods each , according to a Latin Square design . The doses of naltrexone result ed in decreases of daily caloric intake from placebo level , but these reductions were neither statistically significant nor dose-related . When the averaged effects of the doses were compared to placebo , five subjects showed intake reductions but the overall intake reduction of 301.5 + /- 198.1 kcal/day ( mean + /- SEM ) was not statistically significant . Naltrexone administration failed to selectively alter intakes of individual meals and snacks or macronutrient consumption patterns . During active drug periods , subjects lost 0.62 + /- 0.22 lb over 3 days , while during the placebo period , subjects gained 0.46 + /- 0.68 lb . However , there was no reliable change of basal metabolic rate as a function of naltrexone administration . The present results , which indicate that naltrexone administration is relatively ineffective in reducing food intake and inducing body weight loss in obese humans , are thus in contrast with reports that administration of opiate antagonist agents promote significant reductions of food intake and attenuations of body weight gain in experimental animals Objective To examine the effects of naltrexone/bupropion ( NB ) combination therapy on weight and weight-related risk factors in overweight and obese participants . Design and Methods CONTRAVE Obesity Research -II ( COR-II ) was a double-blind , placebo-controlled study of 1,496 obese ( BMI 30 - 45 kg/m2 ) or overweight ( 27 - 45 kg/m2 with dyslipidemia and /or hypertension ) participants r and omized 2:1 to combined naltrexone sustained-release ( SR ) ( 32 mg/day ) plus bupropion SR ( 360 mg/day ) ( NB32 ) or placebo for up to 56 weeks . The co- primary endpoints were percent weight change and proportion achieving ≥5 % weight loss at week 28 . Results Significantly ( P < 0.001 ) greater weight loss was observed with NB32 versus placebo at week 28 ( −6.5 % vs. −1.9 % ) and week 56 ( −6.4 % vs. −1.2 % ) . More NB32-treated participants ( P < 0.001 ) experienced ≥5 % weight loss versus placebo at week 28 ( 55.6 % vs. 17.5 % ) and week 56 ( 50.5 % vs. 17.1 % ) . NB32 produced greater improvements in various cardiometabolic risk markers , participant-reported weight-related quality of life , and control of eating . The most common adverse event with NB was nausea , which was generally mild to moderate and transient . NB was not associated with increased events of depression or suicidality versus placebo . Conclusion NB represents a novel pharmacological approach to the treatment of obesity , and may become a valuable new therapeutic option A combination of sustained release ( SR ) naltrexone ( 32 mg/day ) and bupropion SR ( 360 mg/day ) plus behavioral counseling was evaluated for the treatment of smoking cessation and mitigation of nicotine withdrawal and weight gain .  Thirty overweight or obese nicotine-dependent subjects were enrolled in a 24-week , open-label study ; 85 % and 63 % completed 12 and 2 4weeks , respectively . The target quit date was Week 4 . Week 4 - 12 continuous abstinence rate was 48 % , 78 % of subjects achieved CO < or = 10 ppm , serum cotinine decreased from 185 to 48 microg/L , and tobacco use decreased from 129 to 14 cigarettes/week . Similar results were seen at Week 24 . Body weight was essentially unchanged ( Week 12 : -0.1 % ; Week 24 : + 0.4 % ) . Except for a transient significant increase 1 week after the target quit date ( p<0.05 ) , nicotine withdrawal scores did not change . The most common adverse events were nausea , insomnia , and constipation . These tended to be transient and mild or moderate in severity . In overweight or obese smokers , naltrexone/bupropion combination therapy with behavioral counseling was associated with decreased nicotine use , limited nicotine withdrawal symptoms , and no significant weight gain Eight healthy nonobese volunteers were asked to rate , on a pleasure-displeasure scale , sucrose and salty solutions as well as alimentary and nonalimentary odors . Effects of intragastric glucose load ( vs. water load ) and naltrexone ( vs. placebo ) were tested . Naltrexone produces a significant decrease for sweetened solution on the pleasure scale , a shift even stronger than that of the glucose load itself . Such a decrease is also observed for alimentary odors but not for responses to nonalimentary stimuli . Thus the opioid system is involved in ingestive behavior in humans , and this action is perhaps specific Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau . Here , we explore combination therapy with bupropion ( BUP ) , a putative stimulator of melanocortin pathways , and an opioid antagonist , naltrexone ( NAL ) , to antagonize an inhibitory feedback loop that limits sustained weight reduction . In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro-opiomelanocortin ( POMC ) neurons in mouse brain . A subsequent study further characterized the effect of combination BUP+NAL treatment on food intake in lean and obese mice . Finally , a r and omized , blinded , placebo-controlled trial in obese adult subjects was conducted . R and omization included : BUP ( 300 mg ) + NAL ( 50 mg ) , BUP ( 300 mg ) + placebo ( P ) , NAL ( 50 mg ) + P or P+P for up to 24 weeks . BUP+NAL stimulated murine POMC neurons in vitro and caused a greater reduction in acute food intake than either monotherapy , an effect consistent with synergism . Combined BUP+NAL provided sustained weight loss without evidence of an efficacy plateau through 24 weeks of treatment . BUP+NAL completers diverged from NAL+P ( P < 0.01 ) and P+P ( P < 0.001 ) at week 16 and from BUP+P by week 24 ( P < 0.05 ) . The combination was also well tolerated . Translational studies indicated that BUP+NAL therapy produced synergistic weight loss which exceeded either BUP or NAL alone . These results supported the hypothesis that NAL , through blockade of beta-endorphin mediated POMC autoinhibition , prevents the classic weight loss plateau observed with monotherapies such as BUP . This novel treatment approach ( BUP+NAL ) holds promise for the treatment of Based on reports that opiate antagonists can curtail short-term eating in several species including humans , the efficacy of naltrexone in promoting weight loss by obese subjects was examined . Naltrexone , a long-acting oral opiate antagonist , was studied in a r and omized parallel double-blind placebo controlled ten week trial in 27 females and 14 males who were 30 - 100 percent overweight . Subjects on naltrexone  lost an average of 1.8 kg and  placebo subjects lost 1.5 kg , with no significant difference between groups . Three subjects who took naltrexone had elevations of liver transaminases , two times higher than normal . In the present study naltrexone at a daily dosage of 200 mg did not appear to have efficacy in producing weight loss after eight weeks of treatment . Studies of the effects of naltrexone at higher dosage or for longer periods should monitor hepatic function OBJECTIVE To critically examine the efficacy of bupropion SR for weight loss . RESEARCH METHODS AND PROCEDURES This 24-week multicenter , double-blind , placebo-controlled study r and omized obese adults to placebo , bupropion SR 300 , or 400 mg/d . Subjects were counseled on energy-restricted diets , meal replacements , and exercise . During a 24-week extension , placebo subjects were r and omized to bupropion SR 300 or 400 mg/d in a double-blinded manner . RESULTS Of 327 subjects enrolled , 227 completed 24 weeks ; 192 completed 48 weeks .  Percentage losses of initial body weight for subjects completing 24 weeks were 5.0 % , 7.2 % , and 10.1 % for placebo , bupropion SR 300 , and 400 mg/d , respectively . Compared with placebo , net weight losses were 2.2 % ( p = 0.0468 ) and 5.1 % ( p < 0.0001 ) for bupropion SR 300 and 400 mg/d , respectively . The percentages of subjects who lost > or=5 % of initial body weight were 46 % , 59 % , and 83 % ( p vs. placebo < 0.0001 ) for placebo , bupropion SR 300 , and 400 mg/d , respectively ; weight losses of > or=10 % were 20 % , 33 % , and 46 % ( p vs. placebo = 0.0008 ) for placebo , bupropion SR 300 , and 400 mg/d , respectively . Withdrawals , changes in pulse and blood pressure did not differ significantly from placebo at 24 weeks . Subjects who completed 48 weeks maintained mean losses of initial body weight of 7.5 % and 8.6 % for bupropion SR 300 and 400 mg/d , respectively . DISCUSSION Bupropion SR 300 and 400 mg/d were well-tolerated by obese adults and were associated with a 24-week weight loss of 7.2 % and 10.1 % and sustained weight losses at 48 weeks BACKGROUND Despite increasing public health concerns regarding obesity , few safe and effective drug treatments are available . Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight . The Contrave Obesity Research I ( COR-I ) study assessed the effect of such treatment on bodyweight in overweight and obese participants . METHODS Men and women aged 18 - 65 years who had a body-mass index ( BMI ) of 30 - 45 kg/m(2 ) and uncomplicated obesity or BMI 27 - 45 kg/m(2 ) with dys 
    Output:
    
This weight reduction is moderate but similar to other antiobesity drugs .