Contrave for Weight Loss

Weight loss medications have become a significant intervention to address the obesity epidemic within the United States. While lifestyle changes remain the foundation of treatment, several drugs are FDA-approved for chronic weight management. In September 2014, Contrave received FDA approval for chronic weight management. A few months later, the first GLP-1, Saxenda (liraglutide), was approved. It became available as a daily injectable offering weight loss benefits. However, Contrave provided another option to those who wanted to avoid injectables.

For nearly a decade, Contrave, Saxenda, orlistat, and Qsymia were among the primary options for chronic weight management. However, GLP1-type medications have been more effective in weight loss in recent years. Medications like Zepbound and Saxenda may not be covered or expensive, leaving patients with alternative options like Contrave. This article aims to provide a concise overview of Contrave for weight loss, how it works, what to expect, and possible alternatives.

What is Contrave?

Contrave is a brand-name prescription medication that contains two active ingredients, naltrexone (an opioid receptor antagonist) and bupropion (a norepinephrine-dopamine reuptake inhibitor). When used together, these medications work to regulate appetite and the reward system to reduce cravings and overall food intake. Contrave is now considered a second-line option, behind GLP-1 medications, given its lower efficacy than GLP-1 receptor agonists.

Contrave is FDA-approved for chronic weight management in the following individuals:

• BMI of 30 kg/m2 or greater
• BMI of 27 kg/m2 or greater with at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes, or dyslipidemia)

Contrave must be used alongside a reduced-calorie diet and increased physical activity.

How Contrave Works for Weight Loss

Contrave active ingredients include naltrexone and bupropion, which help regulate appetite in the hypothalamus and the reward system to reduce cravings. However, the complete mechanism behind Contrave’s effects on weight loss is not fully understood. It is thought that when these medications are administered together, it leads to increased activation of pro-opiomelanocortin (POMC) neurons in the hypothalamus, ultimately leading to an appetite suppression effect.

Naltrexone

Naltrexone is classified as an opioid antagonist because it blocks specific receptors (mu-opioid receptor) in the brain, reducing the rewarding sensation that occurs with eating. Naltrexone was originally used to treat alcohol use disorder and opioid dependence at higher doses (e.g., 50 mg/day), whereas in Contrave, the dose is lower (8 mg per tablet) and intended to modulate the reward system with bupropion. The FDA observed enough positive data demonstrating its efficacy for weight loss when used with bupropion.

Bupropion

Bupropion is considered an atypical antidepressant. It inhibits reuptake of dopamine and norepinephrine, meaning it stops the brain from reabsorbing the chemical too quickly, so it stays around and works longer. Dopamine and norepinephrine play a key role in regulating the reward system.

Dosage, Administration, and Contrave Contraindications

Contrave Dosing

The Contrave dose is slowly increased over 4 weeks to ensure the patient can tolerate the medication. Each Contrave tablet contains 90 mg of bupropion and 8 mg of naltrexone.

The dose of Contrave is reduced for those with moderate or severe kidney disease and moderate liver disease. If you have kidney or liver disease, consult your doctor to determine the appropriate dose based on your medical history.

Contrave Administration

Contrave should be taken twice daily with food to minimize stomach side effects. However, the meal should not be high in fats as this can increase the risk of seizures, particularly for those with a history of seizures. The manufacturer advises not to crush, chew, or split Contrave tablets.

Contrave Contraindications

Individuals with the following should not take Contrave:

• Uncontrolled hypertension (high blood pressure)
• Seizure disorders
• Anorexia nervosa or bulimia
• Sudden discontinuation of alcohol, benzodiazepines, barbiturates, and anti-seizure drugs
• Chronic opioid use
• Known allergies to either bupropion or naltrexone

Contrave Side Effects and Safety Concerns

At least 1 in 10 patients may experience:

• Nausea
• Vomiting
• Constipation
• Headache
• Insomnia
• Dry Mouth
• Dizziness

These side effects are typically mild to moderate and may lessen over time. However, Contrave can increase blood pressure and heart rate, so regular monitoring is recommended.

Contrave Alternatives: What Else Is Available?

If you cannot tolerate Contrave or if your doctor advises you to avoid it, there are alternatives to Contrave for chronic weight management.

Zepbound (tirzepatide)

Zepbound is a dual GIP/GLP-1 receptor agonist, most recently FDA-approved for weight loss. Based on the results of the SURMOUNT-1 trial, it has been shown to produce 20% or more weight loss. It is a weekly injectable medication that is also used to treat type 2 diabetes, under the brand name Mounjaro. Both contain the active ingredient tirzepatide. Between Contrave and Zepbound, Zepbound is much more effective, with Contrave producing only a 4-5% weight loss. Zepbound has similar side effects, such as nausea, vomiting, and constipation.

Wegovy (semaglutide)

Wegovy is an FDA-approved GLP-1 receptor agonist for weight loss. Similar to Zepbound, it is a once-weekly injectable that also helps with appetite suppression and delayed gastric emptying. Studies have shown a 15-20% weight loss with similar side effects to Zepbound, with the most common side effects being stomach-related.

Saxenda (liraglutide)

Saxenda is another GLP-1 receptor agonist, similar to Wegovy, but is considered lower in potency. It is a daily injectable medication approved for weight loss in adults and adolescents aged 12 and older. Saxenda produces slightly less weight loss than Zepbound and Wegovy, but more than Contrave, at roughly 5-10% weight loss. Saxenda may be preferred in those who cannot tolerate Contrave or other weekly GLP-1 injectables like Zepbound or Wegovy.

Qsymia (phentermine/topiramate)

Qsymia is an oral combination medication that contains phentermine, a stimulant, and topiramate, an anticonvulsant that suppresses the appetite. Studies have shown that taking Qsymia can result in 10-15% weight loss and may help with cravings and appetite. Common side effects include insomnia, dry mouth, and cognitive changes.

Orlistat

Orlistat is a lipase inhibitor that reduces fat absorption in the gut by approximately 30%. It is available over-the-counter (Alli) and produces a mild weight loss at around 5% with no effects on appetite. Orlistat can cause significant gastrointestinal side effects including oily stools, flatulence, and urgency. It should be used with a low-fat diet to minimize side effects.

Who Might Consider Contrave over GLP-1s?

Although Contrave may not be as effective for weight loss compared to other medications approved for chronic weight management, there may be scenarios where Contrave might be a better option:

• Patients who prefer oral medications
• Patients with emotional eating or binge eating behaviors
• Patients without diabetes or significant insulin resistance
• Patients who cannot tolerate GLP-1 side effects
• Patients with limited insurance coverage or affordability issues

Final Thoughts: Is Contrave Right For You?

Contrave offers a convenient, non-injectable option for individuals seeking help with chronic weight management. While its average weight loss benefit of 4–5% is less than that of GLP-1 or GIP/GLP-1 receptor agonists, it may still be clinically meaningful, especially for patients who respond well to behavioral modifications and struggle with food cravings or emotional eating. Its oral formulation and unique mechanism targeting the reward system make it a viable alternative for those hesitant about injections or who have difficulty adhering to injectable regimens.

In clinical practice, the decision to use Contrave should consider multiple factors, including patient comorbidities, cost and insurance coverage, risk of side effects (e.g., elevated blood pressure or seizure history), and personal preferences. Although newer injectable therapies are more effective overall, they are often cost-prohibitive or poorly tolerated by some patients. For these individuals, Contrave can offer a reasonable balance between effectiveness, convenience, and accessibility. Ultimately, a shared decision-making approach between the patient and healthcare provider can help tailor weight loss strategies that align with each person’s goals, values, and medical profile.

Frequently Asked Questions