Contrave is a medication approved by FDA in 2014 for chronic weight management in overweight (BMI ≥27 kg/m2) and obese (BMI ≥ 30 kg/m2) patients with at least one weight-related comorbidity. Qualifying weight-related comorbidities include cardiovascular disease (consisting of hypertension, dyslipidemia, or heart failure), prediabetes, type 2 diabetes mellitus, osteoarthritis, polycystic ovarian syndrome and infertility, sleep apnea, and asthma. We will start by exploring Contrave.
Contrave is a combination of two different drugs, naltrexone and bupropion. Naltrexone is an opioid antagonist approved by the FDA to treat alcohol and opioid dependence. Bupropion is a dopamine and norepinephrine reuptake inhibitor approved by the FDA for depression and smoking cessation. The exact mechanism of how this medication causes weight loss is not fully understood, however, both medications cause a reduction in appetite which helps people who are overweight to stop overeating. It is thought that appetite suppression occurs via bupropion stimulating the hypothalamus to release alpha-MSH, and naltrexone inhibiting endogenous opioids, or opioids produced naturally in the hypothalamus.
Clinical trials demonstrate that when used in combination with lifestyle changes and a reduced-calorie diet, Contrave is significantly more effective than placebo at helping patients lose weight. After one year of treatment, patients from four randomized, placebo-controlled clinical trials lost an average of 16 pounds. Nondiabetic patients also receiving intensive behavior modification therapy lost even more weight, averaging 21 pounds lost over one year.
As a patient, you can expect to start out taking one table (8-mg naltrexone/90-mg bupropion) per day. Gradually, over the course of four weeks, you will increase the dose from one tablet per day to four tablets per day, consisting of a regimen of two tablets in the morning and two tablets in the evening. It is not recommended to take more than four tablets per day (i.e. 32 mg of naltrexone and 360 mg of bupropion).
Source: Sheehan A, Chen JT, Yanovski JA. Obesity. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw Hill; 2020. Accessed March 05, 2023.
What are the side effects of Contrave?
The most common side effect that Contrave causes is nausea. In preliminary clinical trials, approximately 25% of subjects had to discontinue use due to the nausea that they experienced. Other commonly cited gastrointestinal symptoms include constipation, vomiting, dry mouth, and diarrhea. It is also common for patients to experience abnormal neurological/psychological sensations such as headache, dizziness, and insomnia.
Contrave also has a statistically significant effect of elevating heart rate and blood pressure when compared to placebo. Clinical trials revealed that average heart rate increases by 2.1 beats per minute, systolic blood pressure increases by 1.8-2.3 mm Hg, and diastolic blood pressure increases by 1.7-2.1 mm Hg specifically during the first 3 months of therapy when compared to placebo. There is no evidence that this increase in heart rate or blood pressure has any significant clinical effect such as hypertensive emergency or increased rates of heart attack or stroke. Nonetheless, it is important that your healthcare provider monitor your pulse and blood pressure before taking the medication, and at regular intervals after starting the medication. Due to the known effect that Contrave has on blood pressure, it should not be taken in patients who have uncontrolled hypertension for risk of precipitating hypertensive crises.
In rare instances, when used as a monotherapy, naltrexone has been known to be toxic to the liver. Signs and symptoms of hepatitis that patients should be aware of that might indicate a toxic overdose affecting the liver includes fever, fatigue, nausea, vomiting, light-colored stool, muscle/joint aches, and dark brown urine. Bupropion monotherapy is known to increase the likelihood of seizures in patients who are at elevated risk of developing seizures, such as epilepsy or alcohol withdrawal. Therefore, Contrave should not be taken by anyone who is prone to having seizures. Being an antidepressant, bupropion has a black box warning for increasing suicidal ideation in children and adolescents who are suffering from major depressive disorder. Contrave should not be taken by anyone under the age of 18. Bupropion use is also associated with activating manic episodes in patients with bipolar disorder as well as exacerbating angle-closure glaucoma. Patients with bipolar disorder and glaucoma should not take Contrave.
Sources:Sheehan A, Chen JT, Yanovski JA. Obesity. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw Hill; 2020. Accessed March 05, 2023.
- Contrave is an FDA-approved medication for chronic weight management in overweight and obese patients with qualifying weight-related comorbidities.
- It is a combination of naltrexone and bupropion, two drugs with different mechanisms of action.
- The exact mechanism of weight loss with Contrave is not fully understood but is believed to involve appetite suppression.
- Qualifying weight-related comorbidities include cardiovascular disease, prediabetes, type 2 diabetes mellitus, osteoarthritis, polycystic ovarian syndrome, infertility, sleep apnea, and asthma.
- Clinical trials demonstrate that Contrave, when combined with lifestyle changes and a reduced-calorie diet, is significantly more effective than placebo in promoting weight loss.
- Patients in clinical trials lost an average of 16 pounds over one year, with even greater weight loss observed in non-diabetic patients receiving intensive behavior modification therapy.
- Contrave is initiated at a lower dose and gradually increased over four weeks to reach the recommended dose of four tablets per day.
- It is important not to exceed the maximum daily dose of four tablets.
- Section 3: Common Side Effects and Precautions
- The most common side effect of Contrave is nausea, which may cause discontinuation in some patients.
- Other gastrointestinal symptoms and neurological/psychological sensations may occur, including constipation, vomiting, dry mouth, headache, dizziness, and insomnia.
- Contrave can elevate heart rate and blood pressure, requiring monitoring and caution in patients with uncontrolled hypertension.
- Rare instances of liver toxicity, seizures (in susceptible individuals), suicidal ideation (in children and adolescents), activation of manic episodes (in bipolar disorder patients), and exacerbation of angle-closure glaucoma are associated with the individual components of Contrave.
- Conclusion: Contrave is an FDA-approved medication that can aid in weight management when used in conjunction with lifestyle changes and a reduced-calorie diet. However, it is crucial to consider the potential side effects and precautions associated with Contrave and consult with a healthcare provider to determine if it is suitable for individual circumstances.
April 8, 2023
This article has been reviewed by Dr. Jim Liu, MD and Ms. Deb Dooley, APRN.
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