From the Guidelines
Contrave can be a safe weight loss medication for many people when used as prescribed, but it's not suitable for everyone. Contrave combines two medications: naltrexone (an opioid antagonist) and bupropion (an antidepressant), which works by affecting brain pathways involved in hunger and food cravings, as shown in a 56-week multicenter, randomized, double-blind, placebo-controlled trial 1. The typical dosing starts with one tablet in the morning for the first week, then gradually increases to the maintenance dose of two tablets twice daily by week four. Common side effects include nausea, constipation, headache, dizziness, insomnia, and dry mouth 1.
Importantly, Contrave carries a black box warning for increased risk of suicidal thoughts and behaviors, particularly in young adults and adolescents 1. It's contraindicated for people with uncontrolled hypertension, seizure disorders, eating disorders, or those taking certain medications including MAOIs and opioids 1. Ideal candidates for naltrexone/bupropion may include patients that have concomitant depression because the bupropion component can assist in the treatment of this condition, as well as patients who are trying to quit smoking or reduce alcohol intake 1.
Key benefits of Contrave include its ability to help patients lose a significant amount of weight, with 44.5% of patients receiving naltrexone/bupropion losing 5% of their body weight after 56 weeks compared to 18.9% of patients receiving placebo 1. Additionally, patients using naltrexone/bupropion demonstrated a 0.6% reduction in hemoglobin A1c from baseline, compared to a 0.1% reduction in placebo 1. For safety, Contrave should only be used under medical supervision with regular follow-up appointments to monitor blood pressure, heart rate, and mental health status.
From the Research
Safety of Contrave for Weight Loss
- Contrave, a combination of naltrexone and bupropion, is a FDA-approved medication for weight loss, with clinical trials reporting approximately 6% loss of starting total body weight and improvement in metabolic health factors 2.
- The medication works by inhibiting the rewarding and reinforcing effects of food consumption, and may also improve a woman's ability to conceive by mitigating the effects of PCOS and endometriosis and reducing the drive for alcohol and smoking 2.
- Studies have shown that Contrave can result in significant weight loss, with an average weight loss of 11-22 lbs (5-9 kg) from baseline across four Phase III clinical trials 3.
- However, the safety and efficacy of Contrave should be weighed against its potential risks, including adverse events such as nausea, headache, and dizziness 4, 5.
Comparison with Other Weight Loss Medications
- Contrave has been compared to other FDA-approved weight loss medications, including orlistat, phentermine/topiramate, and liraglutide, with varying degrees of efficacy and safety 4, 5.
- Orlistat has been shown to reduce body weight and improve cardiometabolic markers, but may have gastrointestinal side effects 5.
- Phentermine/topiramate has been shown to result in greater weight loss than Contrave, but may have a higher risk of adverse events and is not recommended for use in the acute preconception period due to its teratogenic effects 2, 5.
Long-Term Efficacy and Safety
- Long-term studies have shown that Contrave can result in significant weight loss and improvement in cardiometabolic markers, but may also have adverse effects such as increased risk of adverse events 4, 5.
- The European Medicines Agency has refused marketing authorization for phentermine/topiramate due to safety concerns, and lorcaserin was withdrawn from the US market in 2020 due to an increased risk of cancer 5.
- Contrave has been shown to be effective for chronic weight management in obese adults, but its safety and efficacy should be carefully monitored and weighed against its potential risks 6.