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Wait, an antidepressant could help with weight loss?

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Yes, it’s true. An FDA-approved medication for depression is now being used to treat obesity. We’re talking about bupropion. It might sound weird, but there’s good science behind it. Here’s the deal:

How bupropion works—and may help with weight care

An imbalance of certain chemicals in the brain called neurotransmitters—specifically dopamine and norepinephrine—can to lead to depression. Bupropion, also known by the brand name Wellbutrin, works by increasing levels of these chemicals and improving symptoms of depression.    

Researchers aren’t exactly sure how bupropion works for weight loss. But it’s known to increase activity in certain pathways of the brain that may increase levels of dopamine and lead to decreased appetite, reduced food cravings, and an increase in the number of calories you burn. Doctors can prescribe this medication off-label to expand their patients’ weight care options.  

Bupropion, like many weight loss medications, is intended for patients with a BMI of 30 or higher or a BMI of 27 or greater with at least one weight-related health condition such as high blood pressure or type 2 diabetes. They are also meant for those who have tried behavioral interventions—diet, exercise—and couldn’t achieve or maintain results. 

Is bupropion really effective?

Very. After researchers noticed that people prescribed bupropion for depression also tended to lose weight, it sparked an interest in exploring its use in obesity medicine. One study published in the journal Obesity looked at the effect of bupropion on weight by prescribing 300 mg to one group of participants, 400 mg of bupropion to another, and a placebo (dummy pill) to a third group. Each group received counseling on lifestyle weight care interventions. At the end of 24 weeks, those prescribed 400 mg of bupropion lost an average of 10% of their initial body weight, compared to 7% in the group prescribed 300 mg, and 5% in the placebo group. Both groups given bupropion also maintained their weight loss at the 48-week mark.

According to another study of obese adults with mild-to-moderate depression in the same journal, some depressive symptoms appeared to be related to weight alone. Participants prescribed bupropion dropped significantly more pounds than those given a placebo (an average of around 5% versus 2% of body weight). But while both groups reported decreased depressive symptoms, greater improvements were seen when total body weight loss was 5% or more. So while medication is a valuable tool in treating depression, it also appears that weight loss on its own may help as well.

Why is bupropion often prescribed in combo with other medications?

Some things are better together. And substantial evidence supports that for weight loss and maintenance, bupropion (also used for tobacco cessation) may be even more effective when paired with other drugs. These other drugs are naltrexone—a medication approved for the treatment of opioid and alcohol use disorder—and zonisamide—a drug approved for the treatment of seizures. You may notice improvements in other conditions when prescribed the combos. 

Bupropion + naltrexone

The combination of these two drug—also found in the brand name weight-loss medication Contrave—act on the hunger and reward centers of the brain and can reduce appetite and control cravings. 

In one study, people prescribed bupropion and naltrexone \in combination with lifestyle changes lost an average of 9% of their initial body weight, while the group that made lifestyle changes alone lost 5%.. Those prescribed this duo of medications were also more likely to keep the weight off at the 56-week mark. 

Bupropion + zonisamide

Together, these medications target all three major neurotransmitters that regulate appetite: Bupropion works on norepinephrine and dopamine, while zonisamide acts on serotonin anddopamine. 

Why not use one or the other? The two medications result in more weight loss, perhaps due to their ability to target more areas of the brain. In fact,  in a phase 2b clinical trial, those prescribed Empatic360 (a combination of bupropion and zonisamide) lost, on average, nearly 8% of their body weight after 24 weeks, compared to 2% in those prescribed bupropion alone and 5% for those given only zonisamide. 

The possible side effects of bupropion

Many people don’t experience any side effects when taking bupropion. However, as with any medication, there is a possibility. Common side effects include nausea, vomiting, dizziness, headache, dry mouth, difficulty sleeping, and constipation—although they usually resolve in a week or two. 

When exploring your medication options with your provider, it’s essential to be honest about your personal and family health history to reduce your risk of side effects. Certain prescription drugs may be more or less appropriate, depending on your history. 

Bottom line

Bupropion, a powerhouse medication for the treatment of depression, may reduce appetite and cravings—leading to more effective weight loss and maintenance.

Found offers a science-backed approach to weight care that's based on your unique biology, psychology, lifestyle, and prescription medication needs. Members receiving medication plus behavior change support from Found lost at least 13% more weight, and in some cases up to 229% more, compared to people receiving the same medication in clinical studies. To start your journey with Found, take our quiz.

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