What is the relationship between Bupropion (Wellbutrin) and obesity?

From the Guidelines

Bupropion, particularly in combination with naltrexone, is a viable treatment option for obesity management, as evidenced by significant weight loss in clinical trials. The mechanism of action involves bupropion stimulating hypothalamic proopiomelanocortin neurons, while naltrexone blocks opioid-mediated proopiomelanocortin autoinhibition, leading to reduced reactivity to food cues and improved eating control 1. This combination, known as Contrave, was FDA approved in 2014 for obesity treatment and has been shown to result in approximately 6% weight loss over 56 weeks, compared to 1% with placebo 1.

Key points to consider when prescribing bupropion for obesity management include:

• The typical dosing for weight management is not explicitly stated in the provided evidence, but the combination of naltrexone-bupropion is administered as 32/360 mg/d 1.
• Bupropion may be particularly beneficial for patients with obesity who also have comorbid depression or are seeking smoking cessation or alcohol use reduction 1.
• Weight loss effects are significant, but it is essential to use bupropion alongside dietary changes and increased physical activity for optimal results.
• Regular monitoring for side effects and effectiveness is crucial, with treatment typically continuing for at least 6-12 months to evaluate long-term benefits.

It is also important to note that bupropion is contraindicated in certain patient populations, such as those with seizure disorders, eating disorders, or those taking MAO inhibitors, although these specifics are not mentioned in the provided evidence 1. Overall, the combination of naltrexone-bupropion offers a promising approach to obesity management, particularly for patients with specific comorbidities.

From the FDA Drug Label

Table 5: Incidence of Weight Gain or Weight Loss (≥5 lbs) in MDD Trials Using Bupropion HCl Sustained-Release Weight Change Bupropion HCl Sustained- Release 300 mg/day (n=339) Bupropion HCl Sustained- Release 400 mg/day (n=112) Placebo (n=347) Gained >5 lbs 3% 2% 4% Lost >5 lbs 14% 19% 6%

Table 6: Incidence of Weight Gain or Weight Loss (≥5 lbs) in SAD Trials Using Bupropion HCl Extended-Release Weight Change Bupropion HCl Extended-Release 150 to 300 mg/day (n=537) Placebo (n=511) Gained >5 lbs 11% 21% Lost >5 lbs 23% 11%

Bupropion and Obesity: The relationship between bupropion and obesity is that bupropion may lead to weight loss.

• In MDD trials, a higher proportion of patients taking bupropion (14-19%) lost more than 5 pounds compared to the placebo group (6%).
• In SAD trials, 23% of patients taking bupropion lost more than 5 pounds, compared to 11% in the placebo group. 2

From the Research

Relationship Between Bupropion and Obesity

The relationship between Bupropion (Wellbutrin) and obesity is complex, with various studies examining its effects as a single agent and in combination with other medications, such as naltrexone.

• Bupropion is chemically related to certain amphetamines and has been used in combination with naltrexone, an opioid receptor antagonist, for weight loss in obese patients 3.
• Studies have shown that the combination of naltrexone and bupropion can lead to significant weight loss, with an average weight loss of a few additional kilograms compared to placebo after 6 months or one year of treatment 3, 4.
• However, the use of naltrexone and bupropion combination has also been associated with potentially severe adverse effects, including neuropsychiatric disorders, allergic reactions, and cardiovascular events 3.
• Other studies have compared the efficacy of different medications approved for chronic weight management, including bupropion/naltrexone, and found that while weight loss was limited to 5% to 10% of total body weight, patients were capable of losing more weight when using a cumulative approach of diet, exercise, and multiple medications 5.
• New-generation anti-obesity drugs, such as naltrexone/bupropion and liraglutide, have been shown to be effective in achieving clinically meaningful weight loss, especially when used in combination with lifestyle modification 6.
• A study examining the efficacy and tolerability of naltrexone/bupropion SR for treating altered eating behaviors and weight loss in binge eating disorder found that the combination was effective in improving pathological eating behavior and losing weight in obese-BED patients 7.

Efficacy and Safety of Bupropion for Weight Loss

The efficacy and safety of bupropion for weight loss have been evaluated in several studies, with results indicating that:

• Bupropion, in combination with naltrexone, can produce significant weight loss and improvements in cardiometabolic risk markers 4.
• The combination of naltrexone and bupropion has been associated with a higher percentage of patients achieving ≥ 5% weight loss compared to placebo 4.
• However, the use of bupropion, especially in combination with naltrexone, has also been linked to potential adverse effects, including nausea, neuropsychiatric disorders, and cardiovascular events 3, 4.