2008 LEWIS AND CLARK CUP - ROGAINE ORIENTEERING LOUISVILLE WHEN: Saturday, October 11, 2008 WHERE: Bernheim Arboretum and Research Forest State Highway 245 Clermont, KY 40110 WHAT: A rogaining competition is a race between teams traveling on foot and limited by time. Competitors use maps, magnetic compasses and navigational skills to travel from a starting point pass
Muschealth.comBupropion SR Enhances Weight Loss:
A 48-Week Double-Blind, Placebo-
James W. Anderson,* Frank L. Greenway,† Ken Fujioka,‡ Kishore M. Gadde,§James McKenney,¶ and Patrick M. O’Neil** Abstract
0.0008) for placebo, bupropion SR 300, and 400 mg/d, ANDERSON, JAMES W., FRANK L. GREENWAY, KEN respectively. Withdrawals, changes in pulse and blood pres- FUJIOKA, KISHORE M. GADDE, JAMES MCKENNEY, sure did not differ significantly from placebo at 24 weeks.
AND PATRICK M. O’NEIL. Bupropion SR enhances Subjects who completed 48 weeks maintained mean losses weight loss: a 48-week double-blind, placebo-controlled trial.
of initial body weight of 7.5% and 8.6% for bupropion SR Obes Res. 2002;10:633– 641.
Objective: To critically examine the efficacy of bupropion
Discussion: Bupropion SR 300 and 400 mg/d were well-
tolerated by obese adults and were associated with a 24- Research Methods and Procedures: This 24-week multi-
week weight loss of 7.2% and 10.1% and sustained weight center, double-blind, placebo-controlled study randomized obese adults to placebo, bupropion SR 300, or 400 mg/d.
Subjects were counseled on energy-restricted diets, meal Key words: weight loss, pharmacotherapy, bupropion
replacements, and exercise. During a 24-week extension, SR, lifestyle, pedometer, meal replacements
placebo subjects were randomized to bupropion SR 300 or400 mg/d in a double-blinded manner.
Results: Of 327 subjects enrolled, 227 completed 24 weeks;
Obesity is a major global health problem (1,2) that con- 192 completed 48 weeks. Percentage losses of initial body tributes significantly to risk for developing coronary artery weight for subjects completing 24 weeks were 5.0%, 7.2%, disease, diabetes, hypertension, as well as premature dis- and 10.1% for placebo, bupropion SR 300, and 400 mg/d, ability and death (3,4). Current therapies are limited and respectively. Compared with placebo, net weight losses maintenance of weight loss may be suboptimal (5). Al- were 2.2% (p ϭ 0.0468) and 5.1% (p Ͻ 0.0001) for bupro- though there is a growing consensus that pharmacotherapy pion SR 300 and 400 mg/d, respectively. The percentages of is appropriate for many individuals who are unable to lose subjects who lost Ն5% of initial body weight were 46%, weight through less intensive measures, effective pharma- 59%, and 83% (p vs. placebo Ͻ 0.0001) for placebo, bu- cotherapy is not available for many patients. Only two propion SR 300, and 400 mg/d, respectively; weight losses agents—sibutramine and orlistat—are Food and Drug Ad- of Ն10% were 20%, 33%, and 46% (p vs. placebo ϭ ministration (FDA)-approved for long-term pharmacother-apy of obesity in the United States. New therapeutics areneeded because medical contraindications or intolerable Submitted for publication December 17, 2001.
side effects may prevent use of one or both of these agents Accepted for publication in final form February 12, 2002.
*Department of Internal Medicine, Veterans Affairs Medical Center, University of Ken- for some individuals (6 –9). Additional pharmacotherapeu- tucky, Lexington, Kentucky; †Pennington Biomedical Research Center, Baton Rouge, tic agents would serve to address this problem.
Louisiana; ‡Nutrition and Metabolic Research Center, Scripps Clinic Del Mar, San Diego,California; §Department of Psychiatry, Duke University Medical Centre, Durham, North Sustained-release bupropion (bupropion SR) is an FDA- Carolina; ¶National Clinical Research, Inc., Virginia Commonwealth University, Richmond, approved agent for treatment of major depression and for Virginia; and **Weight Management Center, Medical University of South Carolina, smoking cessation. Bupropion SR seems to have a weight- Charleston, South Carolina.
Address correspondence to Dr. James W. Anderson, Medical Service, 111C, Veterans neutral effect for most depressed individuals of normal Affairs Medical Center, Lexington, KY 40511.
weight. However, controlled trials with depressed individ- E-mail: firstname.lastname@example.orgCopyright 2002 NAASO uals suggest that bupropion SR may be associated with Bupropion SR Enhances Weight Loss, Anderson et al.
weight loss in overweight or obese subjects (10,11). In Zyban) 300 mg/d, or 400 mg/d for the initial 24-week addition, weight gain after treatment for smoking cessation treatment period and began a lifestyle-intervention program was less in bupropion SR-treated subjects than in placebo- of mild to moderate intensity. At randomization a dietitian treated subjects (12). A small randomized, controlled study instructed subjects in energy-restricted diets with a deficit of suggested that bupropion SR may enhance weight loss for 600 kcal/d based on recommendations of the World Health nondepressed, obese subjects prescribed an energy-re- Organization (14). The recommended menu plan included mandatory use of two servings daily of canned, liquid meal This randomized, placebo-controlled trial was designed replacements (220 kcal/serving) in the form of Slim-Fast for to study the efficacy, safety, and tolerability of bupropion the first 24 weeks and one serving daily for the last 24 SR for weight loss in nondepressed obese adults as part of weeks. We encouraged subjects to use meal replacements a basic lifestyle-intervention program that included dietetic for breakfast and lunch and to consume an energy-restricted and lifestyle counseling, daily meal replacements, an exer- evening meal. Also, at randomization, subjects were pre- cise prescription, and self-monitoring of food intake and scribed exercise goals of 1000 kcal increase/wk of expended exercise. The primary objective was to assess weight loss energy by walking or equivalent activity compared with during the 24-week placebo-controlled period and the sec- pedometer readings. Subjects maintained daily records of ondary objective was to study weight changes over the next food intake and physical activity assessed by pedometer.
Specific weight loss goals were established for each subjectencouraging loss of initial body weight as follows: 2% at 4weeks, 3.5% at 8 weeks, and 5% at 12 weeks. These Research Methods and Procedures
lifestyle goals were reinforced at 12 subsequent visits Subjects
Six medical centers in the United States recruited obese Subjects visited the clinic at randomization (0), 2, 4, 8, individuals from their practices and the community. Eligible 12, 16, 20, 24, 26, 30, 36, 42, and 48 weeks. After medical subjects were women and men 18 to 65 years old with a histories and review of inclusion criteria, study physicians body mass index (BMI) of 30 to 44 kg/m2. Women were performed physical examinations and evaluated the Beck either infertile or used appropriate contraceptive measures.
Depression Index (BDI) (15), electrocardiograms, and lab- Subjects were excluded if they had predisposition to sei- oratory studies. Baseline measurements were made at ran- zures; history of bulimia or anorexia nervosa; significant domization. Concurrent medications, adverse events, drug cardiovascular disease; current depression; uncontrolled hy- accountability, weight, and blood pressure measurements pertension; diabetes; untreated hypothyroidism; addiction to were done at each visit. Waist circumference, chemistry nicotine (current smoker) or recent cessation of smoking; panel, complete blood count, urinalysis, lipid profile, serum use of weight loss agents in the past 3 months; history of glucose measurements, and serum pregnancy test were per- significant hepatic, renal, gastrointestinal, or psychiatric formed at 0, 24, and 48 weeks. At each visit a dietitian disease; history of alcohol or substance abuse; or history of provided brief individual lifestyle counseling that included a bupropion SR use in the past 12 months.
review of self-monitoring (meal replacement use, dietary The institutional review board for human studies at each intake, pedometer readings, and other physical activity) institution approved the study and all subjects signed in- and reiteration of diet and physical activity goals for At 24 weeks, subjects on bupropion SR continued their assigned treatment without interruption. Subjects on pla- Protocol
cebo were randomly assigned to bupropion SR 300 mg/d or This was a 24-week multicenter, randomized, double- 400 mg/d. The 26-week visit was used to reassess subjects, blind, placebo-controlled, parallel-group study. After 24 although double-blinded, after the placebo group had been weeks, the placebo group was randomized to active drug treatment with maintenance of double-blinding and all sub-jects participated in the 24-week extension. The allocationof placebo-treated subjects to active treatment during the Assignment and Masking
second half of the study was done to facilitate subject Subjects were randomly assigned to placebo, bupropion recruitment and to enhance retention of placebo-treated SR 300 mg/d, and 400 mg/d in a 1:1:1 ratio for 24 weeks subjects for the duration of the study. After meeting screen- of treatment. To mask treatment assignments despite the ing criteria, subjects were weighed, measured, and pre- different sizes of the 100-mg and 150-mg tablets, all sub- sented for venipuncture after a 14-hour fast. Subjects par- jects took six tablets of placebo or bupropion SR tablets ticipated in a 2-week run-in period to assess their ability to daily. Subjects randomized to bupropion SR 300 mg/d re- keep records and use a pedometer. Subjects were then ceived 150 mg/d for 3 days and then 300 mg/d; bupropion randomized to placebo, bupropion SR (Wellbutrin SR or SR 400 mg/d subjects received 150 mg/d for 3 days, 300 Bupropion SR Enhances Weight Loss, Anderson et al.
mg/d for the next 11 days, and subsequently 400 mg/d. At24 weeks when subjects taking placebos were randomized Table 1. Baseline characteristics of subjects
to active treatment, their dose was initiated and increased in Bupropion
Placebo SR, 300 mg/d SR, 400 mg/d
The primary endpoint was weight change—absolute (ki- lograms) and percentage—from baseline to week 24. Powercalculations were performed for this endpoint. Sample-size determination was based on the authors’ data and the sci- entific literature (5–9). The minimum sample size of 65 subjects per group was calculated to detect a difference in weight change between treatment groups of 2.5 kg, assum-ing SD of 5.1 kg. The significance level was set to be ␣ ϭ All continuous variables were analyzed as change from baseline. Three different types of analyses were performed: analysis of completers only; last-observation-carried-for- ward (LOCF) or intention-to-treat analysis; and multivariateanalysis of actual observations using the mixed model ap- proach. We consider the mixed model analysis to be themost accurate and appropriate for these data becausecompared with LOCF analysis we avoid artificial data im-putation beyond the time-point of subject withdrawal (16).
cantly among groups (Table 1). Subjects had an average Williamson (17) also criticized the LOCF analysis for BMI of 36.3 kg/m2 and a baseline weight of 100.2 kg. There weight-loss studies. For completers’ analyses, the response were no significant differences across treatment groups or variable was change from baseline at 24 and 48 weeks and gender for the following: fasting serum glucose, cholesterol, baseline values using analysis of covariance. To assess low-density lipoprotein-cholesterol, and triglycerides con- differences between treatment groups and differences over centrations; pulse; blood pressure; or waist circumference.
time, a mixed linear model was used with treatment as a Women had significantly higher high-density lipoprotein- fixed effect, site as a random effect, and the number of cholesterol concentrations than men. BDI scores did not weeks as a repeated factor. Lipid variables were analyzed in differ significantly among groups and averaged 8.8 (95% the same manner except the triglyceride values were loga- confidence intervals [CI]: 8.0 to 9.6) for all subjects.
Subjects in all groups lost weight steadily (Figure 1).
Because weight losses in percentages and kilograms were We screened 407 subjects and randomized 327 subjects almost identical, we have presented values as the percentage (278 women and 49 men) with sites randomizing from 51 to losses from initial body weights. Body weights differed 59 subjects. Participants included 245 whites, 71 blacks, significantly from baseline values at 2 through 48 weeks for and 11 with other ethnic/racial backgrounds; they were all groups. Weight loss with bupropion SR 300 mg/d dif- well-distributed across treatment groups. One hundred sub- fered significantly from placebo at 20 weeks. Weight loss jects (30.6%) withdrew over 24 weeks with this number per with bupropion SR 400 mg/d differed from 300-mg/d doses group: placebo, 32; bupropion SR 300 mg/d, 33; and 400 significantly at 24, 26, 30, 36, and 42 weeks and from mg/d, 35. Withdrawals did not differ significantly across placebo at 12, 16, 20, and 24 weeks.
sites or treatment groups. An additional 35 subjects with- Bupropion SR-treated subjects lost weight in a dose- drew over the last 24 weeks with this number per group: dependent manner (Table 2). For subjects who completed bupropion SR 300 mg/d, 10; bupropion SR 400 mg/d, 13; the 24-week study (completers), weight losses were as fol- placebo to bupropion SR 300 mg/d, 3; and placebo to lows: placebo, 5.0%; bupropion SR 300 mg/d, 7.2%; and bupropion SR 400 mg/d, 9. Withdrawals did not differ bupropion SR 400 mg/d, 10.1%. The net weight losses significantly among treatment groups.
(treatment Ϫ placebo) were 2.2% and 5.1% for bupropion Baseline Characteristics
SR 300 and 400 mg/d, respectively. Weight losses for The baseline characteristics of subjects randomized to LOCF, albeit smaller than those in the completers’ analyses, treatment groups were similar and did not differ signifi- nevertheless showed differences among groups with values Bupropion SR Enhances Weight Loss, Anderson et al.
of 4.0%, 5.7%, and 7.7% for placebo, bupropion SR 300mg/d and 400 mg/d, respectively. For completers, weightloss with bupropion SR 300 mg/d was significantly greaterthan with placebo and weight losses with bupropion SR 400mg/d were greater than with placebo and with bupropionSR 300 mg/d.
After week 24, subjects on placebo were randomized to active treatment and subsequently lost additional weight;they had weights at 48 weeks, Ϫ6.4% and Ϫ7.2% of initialvalues, for bupropion SR 300 mg/d and 400 mg/d, respec-tively, with the completers’ analyses. These values did notdiffer significantly from values for 48 weeks of treatmentwith bupropion SR 300 or 400 mg/d (Table 2). Weight lossin 48-week bupropion-treated subjects reached a nadir at 32 Figure 1: The percentage weight loss over 48 weeks. Values are or 36 weeks and body weight increased nonsignificantly mean Ϯ SEM for the percentage weight loss from baseline. Sub- during subsequent weeks. Weight losses as the percentage jects treated with bupropion SR 300 mg/d had significantly greater of initial body weights at 48 weeks were 7.5% and 8.6% for weight losses than subjects treated with placebo at 20 weeks (p Ͻ bupropion SR 300 mg/d and 400 mg/d, respectively with the 0.05). Subjects treated with bupropion SR 400 mg/d had signifi-cantly greater weight loss than those treated with bupropion SR completers’ analyses. Weight losses for the LOCF did not 300 mg/d at 24, 26, 30, 36, and 42 weeks (p Ͻ 0.05) and with placebo at 12, 16, 20, and 24 weeks (p Ͻ 0.0001). }, placebo; Œ,bupropion SR 300 mg/d; ■, bupropion SR 400 mg/d.
Table 2. Weight changes for LOCF and completers’ analyses
Significant differences are shown.
LOCF, last observed carried forward; CI, confidence interval; NA, not applicable.
* p ϭ 0.08; † p ϭ 0.047; ‡ p Ͻ 0.0001; § p ϭ 0.007.
Bupropion SR Enhances Weight Loss, Anderson et al.
significantly from placebo only for bupropion SR 300 mg/dat 16 weeks. The changes in pulse rates for bupropion SR400 mg/d did not differ significantly at any visit from valuesfor either bupropion SR 300 mg/d or placebo. Systolic anddiastolic blood pressure decreased in all three groups andthere were no significant differences between bupropion SR300 mg/d and placebo or between bupropion SR 400 mg/dand either treatment group at any weekly visit. Waist cir-cumference decreased significantly (p Ͻ 0.001) in all treat-ment groups with no significant differences among groups.
The BDI score decreased significantly in all groups with the following decreases: placebo, 1.5 (95% CI: 2.7 to 0.4);bupropion SR 300 mg/d, 3.9 (95% CI: 5.1 to 2.7); and 400mg/d, 2.8 (95% CI: 4.1 to 1.5). With bupropion SR 300 Figure 2: The percentage of subjects losing Ն5% (dark bars) or mg/d, the decrease in the BDI score was significantly Ն10% (light bars) of initial body weight.
greater than with placebo (p ϭ 0.033).
Adherence to Medication and Lifestyle Procedures
Five and Ten Percentage Weight Losses
Adherence was assessed at 24 weeks; 92% of subjects Significantly greater numbers of subjects achieved took Ն80% of their medication and this did not differ weight losses of 5% and 10% with bupropion SR 400 mg/d significantly across groups. At least 80% of recommended than with placebo at 24 weeks (Figure 2). For completing meal replacements (two daily) were consumed by 96% of subjects the percentages of subjects who lost Ն5% of initial all subjects over the 24 weeks; differences among groups body weight were as follows: placebo, 46.3%; bupropion were not significant. All groups of subjects significantly SR 300 mg/d, 59.2%; and bupropion SR 400 mg/d, 82.9% (p Ͻ 0.0001) increased their physical activity and ap- (p vs. placebo Ͻ 0.001). The percentages of subjects who proached or exceeded the recommended increase in physi- lost Ն10% of initial body weight were as follows: placebo, cal activity (100%) as measured by pedometers with the 20.0%; bupropion SR 300 mg/d, 32.9%; and bupropion SR following increases: placebo, 85%; bupropion SR 300 mg/d, 400 mg/d, 45.7% (p vs. placebo ϭ 0.0008). At 48 weeks, 97%; and 400 mg/d, 135% (p vs. placebo Ͻ 0.031).
the percentages of subjects in 5% and 10% weight-lossgroups did not differ significantly across groups with these Withdrawals and Adverse Events
values: placebo to bupropion SR 300 mg/d, 51.4% and The numbers of adverse events (those exceeding 5% for 21.6%; placebo to bupropion SR 400 mg/d, 58.1% and any group) for each treatment group for 24 weeks of pla- 35.5%; bupropion SR 300 mg/d, 58.2% and 25.9%; and cebo-controlled treatment are summarized in Table 4. There bupropion SR 400 mg/d, 64.9% and 40.4%, for 5% and 10% were no significant differences in the occurrence of adverse events across groups. The 23 subjects who had early exits(withdrawals) related to adverse events were in these cate- Secondary Outcomes
gories (major adverse events only listed in parenthesis): Changes in fasting plasma values, pulse, blood pressure, placebo, 6 subjects (decreased concentration, 1; dizziness, and waist circumference at 24 weeks are summarized in 1; palpitations, 1; and abnormal laboratory values, 1); bu- Table 3. Fasting serum glucose concentrations decreased propion SR 300 mg/d, 8 subjects (insomnia, 2; palpitations, significantly from baseline with bupropion SR 400 mg/d.
1; and anxiety, 1); and bupropion SR 400 mg/d, 9 subjects Changes in total serum cholesterol and low-density lipopro- (anxiety, 4; hypertension, 1; and abnormal laboratory val- tein-cholesterol concentrations were similar across groups.
ues, 1). The one subject who withdrew because of hyper- High-density lipoprotein-cholesterol concentrations in- tension was concerned about slight increases in her blood creased significantly with bupropion SR 300 mg/d and 400 pressure readings at home, but had stable normal values at mg/d. Fasting serum triglycerides concentrations decreased clinic. Anxiety or insomnia led to withdrawal more often significantly with bupropion SR 300 mg/d and approached with bupropion SR treatment than with placebo but these statistical significance with bupropion SR 400 mg/d.
differences were not statistically significant.
Bupropion SR treatment was associated with an increase in pulse rate of 1.8 beats/min at 24 weeks but these changeswere not significant. Between 4 and 20 weeks, pulse rates Discussion
increased significantly from baseline by 2.4 to 5.2 beats/min In this study bupropion SR significantly facilitated with both doses of bupropion SR; these changes differed weight loss in a dose-dependent manner when used with a Bupropion SR Enhances Weight Loss, Anderson et al.
Table 3. Baseline values and changes from baseline at 24 weeks for fasting serum glucose and lipid values, blood
pressure, pulse, and waist circumference*
Bupropion SR 300 mg/d
Bupropion SR 400 mg/d
Placebo (n ؍ 112)
(n ؍ 110)
(n ؍ 105)
Values are means and SEM.
* p vs. baseline: † 0.0316; ‡ 0.0282; § 0.0014; ¶ 0.0178; 0.0529; ** Ͻ0.001.
There were no significant differences between treatment groups.
LDL, low-density lipoprotein; HDL, high-density lipoprotein; BP, blood pressure.
basic lifestyle intervention program. The lifestyle interven- mg/d and from ϩ0.8 to ϩ1.5% with bupropion SR 400 tion program was designed to enable subjects to lose Ն5% mg/d— between 24 and 48 weeks are consistent with the of their initial body weight over 24 weeks with placebo weight change reported by a number of other clinical trials treatment; subjects, on average, exceeded this goal. Subjects with dexfenfluramine (21), sibutramine (20), and orlistat who completed 24 weeks of treatment with bupropion SR (8,22). The failure to lose further weight during the last 24 400 mg/d lost 10.1% of their initial body weight loss and weeks may relate to decreased intensity of the interven- had a net weight loss (compared with placebo) of 5.1%.
tion— use of only one meal replacement daily and de- These weight losses are consistent with the guidelines for creased frequency of visits—in our study. This loss of effect approval of antiobesity agents by the U.S. FDA (18) and the on weight or other outcome variables with nutrition inter- European Agency (19). The weight losses we observed for ventions over time is commonly seen and may relate to diet the LOCF analysis with bupropion SR 400 mg/d are com- fatigue and decreased adherence to the prescribed diet (23), parable to those reported with the two agents approved for to regression to the mean, or to other factors.
long-term treatment of obesity (6 –9). However, it is diffi- The precise mechanism for bupropion SR that is respon- cult to compare different agents across clinical trials be- sible for effects on weight loss is unknown. Bupropion has cause of differences in experimental design. Many previous dual neurotransmitter properties as a norepinephrine and studies (8,9,20) used a weight-loss run-in period that en- dopamine reuptake inhibitor (24). Bupropion has no clini- hances total weight loss and may affect net weight loss.
cally significant effect on serotonin neurotransmission and The weight losses at 48 weeks did not differ significantly essentially no affinity for muscarinic, histaminergic or from those at 24 weeks. The weight changes—from ϩ0.3% ␣-adrenergic receptors (25). These effects on norepineph- to Ϫ0.3% of initial body weight with bupropion SR 300 rine and dopamine in the central nervous system may con- Bupropion SR Enhances Weight Loss, Anderson et al.
Table 4. Number of adverse events reported by subjects in different treatment groups
There were no significant differences between groups.
tribute to weight loss (26). Human studies suggest that have contributed to compliance to physical activity recom- dopamine D receptor density is significantly lower in mor- mendations. Racette et al. (31) and Pronk and Wing (32) bidly obese individuals (BMI Ͼ 40 kg/m2) than in lean suggest that exercise is the cornerstone for long-term main- control subjects (27). Agents having norepinephrine effects can affect blood pressure and pulse rates (26). The effects Meal replacements—shakes, bars, or entre´es— can have a of bupropion SR on blood pressure and pulse were tran- significant adjunctive role in weight loss and maintenance sient and do not seem clinically important in this study.
of weight loss (33,34). The recent reports of Rothacker (35) Whereas modest increases in systolic and diastolic blood and Ashley et al. (36) highlight this growing interest. In pressure are noted with sibutramine treatment (6,7), we controlled trials, meal replacement use is associated with observed no significant changes from baseline in blood significantly more weight loss than control diets (33,34,36).
pressure among any treatment group at 24 weeks. Although Use of two meal replacements daily in our trial probably sibutramine 15 mg/d significantly increases the pulse rate contributed importantly to the effectiveness of our interven- by ϳ6 beats/min (6,7), bupropion SR did not significantly tion. Hill (37) suggests that meal replacements may help affect pulse rate at 24 weeks. Overall, the safety of bupro- individuals to make transitions from their usual diet to a pion SR at the doses we used seems comparable to the other health-promoting diet. Thus, meal replacements, like phys- two agents approved for long-term treatment of obesity.
ical activity, may be an adjunct for making dietary changes Although seizures were not observed in this study or by and maintaining these changes over intermediate- or long- Gadde et al. (13), this agent is contraindicated for per- sons with history of seizures or bulimia (Wellbutrin SR In summary, bupropion SR in conjunction with a lifestyle intervention program was associated with a dose-related Physical activity has an important adjunctive role in reduction in body weight at 24 weeks. Subjects who com- facilitating weight loss for individuals on energy-restricted pleted 24 weeks of treatment with bupropion SR 400 mg/d diets (28). Increments in physical activity that expend 1000 lost 10.1% of their initial body weight and had a net loss of kcal/wk or walking one mile daily are commonly recom- 5.1% of their initial body weight compared with placebo.
mended (28), but increments that expend Ͼ2500 kcal/wk With LOCF analysis, weight loss was 7.7% with bupropion may be required to have a significant impact on the rate of SR 400 mg/d and the net decrease was 3.7%. The initial weight loss (29,30). Use of pedometers by our subjects may weight losses at 24 weeks were generally sustained at 48 Bupropion SR Enhances Weight Loss, Anderson et al.
weeks. Bupropion SR was well-tolerated, and the early exits 14. Beck AT, Steer RA, Brown GK. Beck Depression Inventory
and adverse events did not differ significantly from those of Manual. 2nd ed. San Antonio, TX: Psychological Corpora- placebo. The lifestyle intervention of increased physical activity, use of two meal replacements daily, and self- 15. World Health Organization. Diet, Nutrition and the Preven-
tion of Chronic Diseases. London, UK: Her Majesty’s Sta- monitoring may have enhanced weight loss. Because of its effectiveness and safety, bupropion SR warrants consider- 16. Little R. Missing data. In: Armitage P, Colton T, eds. Ency-
ation as an adjunct to lifestyle changes for enabling obese clopedia of Biostatistics. Chichester, NY: John Wiley; 1998, 17. Williamson D. Pharmacotherapy of obesity. J Am Med Assoc.
18. Food and Drug Administration. Guidance for the Clinical
Supported by the Obesity Research Network and Glaxo- Evaluation of Weight Control Drugs. Rockville, MD: Food 19. Committee for Proprietary Medicinal Products (CPMP).
Clinical Investigation of Drugs Used in Weight Control. Lon- 1. Mokdad A, Serdula M, Dietz W, Bowman B, Marks
don, UK: European Agency for the Evaluation of Medicinal J, Koplan J. The spread of the obesity epidemic in the
United States, 1991–1998. J Am Med Assoc. 1999;282: 20. Apfelbaum M, Vague P, Ziegler O, Hanotin C, Thomas F,
Leutenegger E. Long-term maintenance of weight loss after a
2. World Health Organization. Obesity: Preventing and Man-
very-low-calorie diet: a randomized blinded trial of the effi- aging the Global Epidemic: Report of a WHO Consultation on cacy and tolerability of sibutramine. Am J Med. 1999;106: Obesity. Geneva, Switzerland: World Health Organization; 21. Guy-Grand B, Apfelbaum M, Crepaldi H, Gries A, Lefeb-
3. Allison D, Fontaine K, Manson J, Stevens J, Van Itallie T.
vre P, Turner P. International trial of long-term dexfenflu-
Annual deaths attributable to obesity in the United States.
ramine in obesity. Lancet. 1989;2:1142–5.
J Am Med Assoc. 1999;282:1530 – 8.
22. James WPT, Avenell A, Broom J, Whitehead J. A one-year
4. Pi-Sunyer F. Medical hazards of obesity. Ann Intern Med.
trial to assess the value of orlistat in the management of obesity. Int J Obes Relat Metab Disord. 1997;21(suppl 3): 5. Anderson J, Konz E, Frederich R, Wood C. Long-term
weight maintenance: a meta-analysis of US studies. Am J Clin 23. Anderson JW, Davidson MH, Blonde L, et al. Long-term
cholesterol-lowering effects of psyllium as an adjunct to diet 6. Bray G, Blackburn G, Ferguson J, et al. Sibutramine
therapy in the treatment of hypercholesterolemia. Am J Clin produces dose-related weight loss. Obes Res. 1999;7:189 – 24. Ascher J, Cole J, Colin J, et al. Bupropion: a review of its
7. James W, Astrup A, Hilsted J, et al. Effect of sibutramine on
mechanisms of antidepressant activity. J Clin Psychiatry. weight maintenance after weight loss: a randomized trial.
25. Ferris R, Cooper B. Mechanisms of antidepressant activity of
8. Hollander P, Elbein S, Hirsch I, et al. Role of orlistat in the
bupropion. J Clin Psychiatry Monograph. 1993;11:2–14.
treatment of obese patients with Type 2 diabetes. Diabetes 26. Bray G, Greenway F. Current and potential drugs for treat-
ment of obesity. Endocr Rev. 1999;20:805–75.
9. Davidson M, Hauptman J, DiGirolamo M, et al. Weight
27. Wang G-J, Volkow N, Logan J, et al. Brain dopamine and
control and risk factor reduction in obese subjects treated for obesity. Lancet. 2001;357:354 –7.
2 years with orlistat: a randomized controlled trial. J Am Med 28. Grilo C. The role of physical activity in weight loss and
weight loss management. Med Exerc Nutr Health. 1995; 10. Settle E, Stahl S, Batey S, Johnson J, Ascher J. Safety
profile of sustained-release bupropion in depression: results of 29. Anonymous. The Practical Guide: Identification, Evaluation
three clinical trials. Clin Ther. 1999;21:455– 63.
and Treatment of Overweight and Obesity in Adults. Bethesda, 11. Croft H, Houser T, Jamerson B, et al. Lack of weight gain
MD: National Institutes of Health; 2000.
in patients taking bupropion SR: a 1-year placebo-controlled 30. Votruba S, Horvitz M, Schoeller D. The role of exercise in
study in patients with major depression. Obes Res. 2000; the treatment of obesity. Nutrition. 2000;16:179 – 88.
31. Racette S, Schoeller D, Kushner R, Neil K. Exercise en-
12. Jorenby D, Leischow S, Nides M, et al. A controlled trial of
hances dietary compliance during moderate energy restriction sustained-release bupropion, a nicotine patch, or both for in obese women. Am J Clin Nutr. 2001;62:345–9.
smoking cessation. N Engl J Med. 1999;340:685–92.
32. Pronk N, Wing R. Physical activity and long-term mainte-
13. Gadde K, Parker CB, Maner LG, Wagner HR, Drezner
nance of weight loss. Obes Res. 1994;2:587–99.
MK, Krishnan KRR. Bupropion for weight loss: an investi-
33. Heber D, Ashley JM, Wang H-J, Elashoff RM. Clinical
gation of efficacy and tolerability in overweight and obese evaluation of a minimal intervention meal replacement regi- women. Obes Res. 2001;9:544 –51.
men for weight reduction. J Am Coll Nutr. 1994;6:608 –14.
Bupropion SR Enhances Weight Loss, Anderson et al.
34. Ditschuneit H, Flechtner-Mors M, Johnson T, Adler G.
36. Ashley JM, St. Jeor ST, Schrage JP, et al. Weight control in
Metabolic and weight-loss effects of a long-term dietary in the physician’s office. Arch Intern Med. 2001;161:1599 – 604.
tervention in obese patients. Am J Clin Nutr. 1999;69: 37. Hill JO. Long-term weight control with meal replacements.
35. Rothacker D. Five-year self-management of weight using
38. Daly A, Konz E, Soler N, Anderson J, Yergler C, Carpenter
meal replacements: comparison with matched controls in rural P. Successful long-term management of substantial weight loss:
Wisconsin. Nutrition. 2000;16:344 – 8.
one program’s experience. J Am Diet Assoc. 2000;100:1456.
USE OF THE HOMEOPATHY FOR THE IMPROVEMENT OF THE AMOUNT AND QUALITY OF EMBRYOS IN BOVINE (BRAZIL). LOURENÇO, F.1 ; KOYAMA, R.2; LOPES, E.2 1 - Veterinary doctor - Veterinary Medicine School of the Paraná University. UNIPAR. INTRODUCTION: The use of homeopathic products in the cattle industry has increased considerably in the last years. Among the several available products in the m