By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv

Mysimba for weight loss: what you need to know

Mysimba for weight loss is a pill that combines two well-established active ingredients: naltrexone and bupropion. It acts on the hunger and reward centers in the brain, reducing appetite and food cravings. In clinical trials, average weight loss was moderate. As a result, it suits some patients, but not everyone.

In this article, I explain how the drug works, who it is for, how effective it is and what the risks are.

What the drug contains and how it works

The drug has two components. Naltrexone blocks opioid receptors and has been used for years to treat addiction. Bupropion is an antidepressant that also helps people quit smoking.

On its own, each component has only a small effect on weight. However, the combination acts on two mechanisms in the brain. First, it targets the hunger center in the hypothalamus, which regulates appetite. Second, it acts on the reward system, which drives the urge to eat tasty food. In practice, patients describe fewer cravings and fewer thoughts about food. I wrote about this phenomenon in detail in my article on food noise.

Who is Mysimba weight loss treatment for?

According to the European Medicines Agency (EMA), the European Union approved the drug in March 2015. It is intended for adults, alongside a reduced-calorie diet and physical activity, who have:

• A body mass index (BMI) of 30 or higher.
• Or a BMI of 27 to 30 with a related condition, such as type 2 diabetes, high blood lipids or controlled high blood pressure.

The drug may be especially suitable for people who struggle with strong cravings and emotional eating. In addition, it offers a pill option for those who don’t want injections. Even so, a doctor can decide whether it fits only after a full medical evaluation.

How to take the drug

You start at a low dose and increase it gradually over four weeks:

• First week: one tablet in the morning.
• Second week: one tablet in the morning and one in the evening.
• Third week: two tablets in the morning and one in the evening.
• From week 4: two tablets in the morning and two in the evening.

Swallow each tablet whole, without splitting or chewing it. It is best to take it with food, but not with a high-fat meal. The gradual increase reduces nausea and also lowers the risk of seizures.

How effective is Mysimba for weight loss?

Researchers tested the drug in four main trials that included about 4,500 patients. According to the EMA summary, average weight loss in three of them was 3.7% to 5.7% of body weight. In the placebo groups, weight loss was 1.3% to 1.9%. Put simply, a person weighing 100 kg lost about 4 to 6 kg on average with the drug.

In the fourth trial, which added intensive behavioral support, weight loss reached 8.1%, compared with 4.9% on placebo. Moreover, 28% to 42% of patients lost at least 5% of their weight, compared with 12% to 14% on placebo. The conclusion is clear: the drug works much better when you combine it with lifestyle change.

That is why there is a stopping rule. If you have not lost at least 5% of your weight after 16 weeks, you stop treatment.

Side effects of Mysimba weight loss treatment

The US prescribing information for the drug, which is sold in the United States as Contrave, lists the common side effects:

• Nausea: 32.5% of patients, compared with 6.7% on placebo.
• Constipation: 19.2%, compared with 7.2%.
• Headache: 17.6%, compared with 10.4%.
• Vomiting: 10.7%, compared with 2.9%.
• Dizziness, insomnia and dry mouth.

Most side effects appear early in treatment and fade over time. However, some less common effects are important to know about. The drug can slightly raise blood pressure and heart rate, so your doctor will measure them regularly. In addition, seizures occurred in about 0.1% of patients. Because of the bupropion component, the US label also carries a prominent warning about suicidal thoughts, especially in young people. Any change in mood calls for contacting your doctor right away.

Who should not take the drug

In some situations, you must not use this drug:

• Uncontrolled high blood pressure.
• Epilepsy or a history of seizures.
• An eating disorder such as anorexia or bulimia.
• Regular use of opioid painkillers, because naltrexone blocks their effect.
• Abrupt withdrawal from alcohol or sedatives.
• Use of MAOI medications.
• Severe liver or kidney failure.

You also should not use the drug during pregnancy. Before surgery, or whenever you need pain relief, be sure to tell your medical team that you are taking it.

Heart safety: the European regulator’s review

In 2023, the European Medicines Agency opened a new review of the drug because of questions about its long-term heart safety. In March 2025, its scientific committee concluded that the benefits still outweigh the risks. According to the findings, there is no sign of a heart problem with use of up to 12 months. After one year, however, the data are insufficient.

As a result, the EMA set new rules. Every year, your doctor reassesses whether the treatment is still helping. If, after a year, you have not maintained a loss of at least 5%, you stop. Meanwhile, the company must complete a large cardiovascular study called INFORMUS, with results expected in 2028.

Mysimba weight loss vs. other medications

GLP-1 drugs, such as Wegovy and Mounjaro, led to much greater average weight loss in clinical trials. It is worth knowing that all four of Israel’s health funds (HMOs) provide Wegovy and Mounjaro through their supplementary insurance plans at a discount of about 50%, and they publish the prices on their websites. The Wegovy pill and Rybelsus also offer the advantage of being taken by mouth.

Still, Mysimba has its place. For example, it can help when cravings are strong, when GLP-1 drugs are not tolerated or when you prefer a different mechanism. Other options include Razin, a mechanical weight loss capsule and the Epitomee capsule. You will find an overview of all the options on my page about medications for obesity. At our clinic, we choose treatment based on each patient’s goals, underlying conditions and preferences.

The bottom line on Mysimba for weight loss

Mysimba for weight loss is a pill that acts on hunger and cravings. In trials, average weight loss was 3.7% to 5.7%, and up to 8.1% with intensive support. It requires monitoring of blood pressure and mood, and it is not right for everyone. If you have not lost 5% after 16 weeks, you stop.

The information in this article is general and does not replace personal medical advice.

Questions and answers

How long does it take to see results?

You and your doctor decide after 16 weeks. If you have not lost at least 5% of your weight, you stop treatment.

Is Mysimba for weight loss addictive?

No. Neither component is addictive. In fact, doctors use naltrexone to treat addiction.

Can I drink alcohol during treatment?

It is best to avoid it, because alcohol increases the risk of seizures. Suddenly stopping heavy drinking is also dangerous, so talk to your doctor about it.

How long does treatment last?

There is no fixed limit, but every year your doctor reassesses whether the treatment is helping and whether you are maintaining the weight loss.

Sources

Mysimba – EPAR, European Medicines Agency

Mysimba – referral, European Medicines Agency

CONTRAVE (naltrexone HCl and bupropion HCl) Extended-Release Tablets – Prescribing Information