contrave
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Synonyms | |||
Contrave represents one of the more interesting pharmacological approaches to weight management we’ve seen in recent years. It’s not a single molecule but rather a fixed-dose combination product containing naltrexone HCl and bupropion HCl in an extended-release formulation. What makes it particularly noteworthy is how it targets two separate neurological pathways involved in hunger regulation and food reward—something most previous weight loss medications never attempted. I remember when it first came across my desk, I was skeptical about combining these two particular agents, but the clinical data eventually won me over.
Key Components and Bioavailability of Contrave
The formulation contains 8 mg naltrexone and 90 mg bupropion in each tablet, designed for twice-daily administration. Both components utilize extended-release technology, which is crucial for maintaining steady plasma concentrations throughout the day while minimizing peak-trough fluctuations that could lead to side effects or reduced efficacy.
Naltrexone’s bioavailability is approximately 5-40% orally, with considerable interindividual variation, while bupropion exhibits about 5-20% absolute bioavailability due to extensive first-pass metabolism. The extended-release mechanism helps mitigate some of this variability by providing more consistent drug delivery. Interestingly, food doesn’t significantly affect the overall absorption of either component, though we generally recommend taking it with food to reduce potential gastrointestinal discomfort.
What many clinicians don’t realize is that the specific ratio of these components matters tremendously. Early development trials experimented with various ratios before settling on the current formulation. The 8mg/90mg combination demonstrated optimal synergy in clinical testing—enough naltrexone to effectively block opioid receptors without causing excessive side effects, paired with sufficient bupropion to enhance POMC neuron activity without significant cardiovascular risk.
Mechanism of Action: Scientific Substantiation
The beauty of Contrave’s mechanism lies in its dual approach to appetite regulation. Bupropion stimulates pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, increasing secretion of α-MSH, which activates melanocortin-4 receptors to reduce appetite and increase energy expenditure. Simultaneously, naltrexone blocks opioid receptors that would normally inhibit these same POMC neurons, creating a synergistic effect that enhances and sustains appetite suppression.
I’ve found this mechanism particularly effective for patients who describe “food noise”—that constant mental preoccupation with eating that doesn’t necessarily correlate with physical hunger. The combination seems to quiet this background chatter in ways that neither component achieves alone. One of my patients, Sarah, a 42-year-old teacher, described it as “finally being able to walk past the breakroom donuts without that internal debate.”
The medication also appears to reduce the rewarding aspects of highly palatable foods. Functional MRI studies have shown decreased activation in brain regions associated with food reward, including the insula and orbitofrontal cortex, when subjects taking Contrave were shown images of appetizing foods. This might explain why patients often report diminished cravings for specific comfort foods.
Indications for Use: What is Contrave Effective For?
Contrave for Chronic Weight Management
The primary indication is as an adjunct to reduced-calorie diet and increased physical activity for chronic weight management in adults with initial BMI of 30 kg/m² or greater (obesity), or 27 kg/m² or greater (overweight) with at least one weight-related comorbidity such as hypertension, type 2 diabetes, or dyslipidemia.
In my practice, I’ve found it works best for patients who’ve struggled with emotional eating or binge eating tendencies. Mark, a 55-year-old with hypertension and prediabetes, had failed multiple previous weight loss attempts despite good compliance with diet and exercise. After starting Contrave, he lost 8% of his body weight over six months and, more importantly, reported that he no longer felt compelled to eat when stressed.
Contrave for Reducing Weight-Related Comorbidity Risk
While not an official indication, the weight loss achieved with Contrave often leads to improvements in obesity-related conditions. I’ve consistently seen reductions in HbA1c (typically 0.5-0.7%), blood pressure (3-5 mmHg systolic), and triglycerides (15-20%) in responsive patients. These metabolic improvements frequently occur even before substantial weight loss is evident, suggesting possible direct metabolic benefits beyond simple calorie restriction.
Instructions for Use: Dosage and Course of Administration
The dosing schedule requires careful titration to improve tolerability:
| Week | Morning Dose | Evening Dose | Special Instructions |
|---|---|---|---|
| 1 | 1 tablet | None | Take with food to reduce nausea |
| 2 | 1 tablet | 1 tablet | Space doses at least 8 hours apart |
| 3 | 2 tablets | 1 tablet | Avoid evening dose if experiencing insomnia |
| 4+ | 2 tablets | 2 tablets | Maximum daily dose |
I typically assess response after 12-16 weeks of treatment at the maintenance dose. If patients haven’t lost at least 5% of baseline body weight by this point, discontinuation should be considered, as further weight loss is unlikely. For responders, treatment can continue as long as benefits are maintained and the medication is well-tolerated.
The most common side effects include nausea (which usually resolves within 4 weeks), constipation, headache, and dizziness. These are typically transient and manageable with dose adjustment or symptomatic treatment.
Contraindications and Drug Interactions
Contrave carries several important contraindications:
- Uncontrolled hypertension
- Seizure disorders or conditions predisposing to seizures
- Concomitant use of monoamine oxidase inhibitors (MAOIs)
- Chronic opioid use or opioid dependence
- Pregnancy and breastfeeding
The bupropion component significantly inhibits CYP2D6, which can increase concentrations of drugs metabolized by this pathway, including certain antidepressants (SSRIs, tricyclics), antipsychotics, beta-blockers, and antiarrhythmics. Dose adjustments of these medications may be necessary.
I learned this interaction the hard way with a patient who was on metoprolol for hypertension. After starting Contrave, she developed significant bradycardia and dizziness. We had to reduce her metoprolol dose by nearly 50% to maintain her heart rate within normal limits.
Clinical Studies and Evidence Base
The COR (Contrave Obesity Research) program included four 56-week phase 3 trials involving over 4,500 patients. These demonstrated consistent weight loss superiority compared to placebo, with mean weight loss ranging from 6.1% to 9.3% versus 1.3% to 5.1% with placebo.
The LIGHT trial, while ultimately terminated early due to sponsor decision, initially showed promising cardiovascular safety data with a hazard ratio of 0.50 for major adverse cardiovascular events. However, these results should be interpreted cautiously given the trial’s premature termination.
What the published literature doesn’t fully capture is the variability in individual response. In my experience, about 60-70% of patients achieve clinically meaningful weight loss (≥5%), while the remainder show minimal response. We haven’t identified reliable predictors of response yet, though anecdotally, patients with strong emotional eating components seem to benefit most.
Comparing Contrave with Similar Products and Choosing Quality
When comparing Contrave to other prescription weight loss medications, several distinctions emerge:
- Unlike phentermine-topiramate (Qsymia), Contrave has minimal cognitive side effects and doesn’t require gradual titration over many weeks
- Compared to liraglutide (Saxenda), Contrave offers oral administration and lower cost, though possibly slightly less weight loss efficacy
- Versus orlistat (Xenical), Contrave works centrally rather than peripherally, resulting in fewer gastrointestinal side effects but requiring more monitoring for psychiatric and cardiovascular effects
The manufacturer (Currax Pharmaceuticals) maintains consistent quality control, and I’ve never encountered bioavailability issues between lots. Generic versions aren’t yet available, so patients should ensure they’re receiving the branded product to guarantee consistent delivery of both active components.
Frequently Asked Questions about Contrave
What is the recommended course of Contrave to achieve results?
Most patients begin seeing weight loss within 4 weeks of reaching the maintenance dose, with maximal effects typically apparent by 6 months. Treatment should be continued as long as benefits are maintained, though I recommend reassessing need annually.
Can Contrave be combined with antidepressants?
This requires careful consideration. While bupropion is itself an antidepressant, combining it with other serotonergic agents increases seizure risk. I typically avoid concomitant use with SSRIs or SNRIs unless absolutely necessary and under close monitoring.
Is weight regain common after stopping Contrave?
Unfortunately, yes. Like most chronic disease medications, discontinuation typically leads to return of symptoms—in this case, weight regain. I view Contrave as a long-term management tool rather than a short-term solution.
How does alcohol consumption affect Contrave treatment?
Alcohol can increase seizure risk with bupropion and may reduce adherence to dietary recommendations. I advise moderation and caution patients that alcohol might diminish their weight loss results.
Conclusion: Validity of Contrave Use in Clinical Practice
When used appropriately in selected patients, Contrave represents a valuable addition to our weight management toolkit. Its dual mechanism addresses both physiological and psychological aspects of appetite regulation, filling a niche that single-agent approaches cannot.
The risk-benefit profile favors use in patients without contraindications who have failed lifestyle intervention alone. Regular monitoring of blood pressure, mood, and adherence is essential throughout treatment.
I’ve been using Contrave in my practice since its approval in 2014, and it’s transformed my approach to weight management. The combination often works where single agents have failed, particularly for patients with significant emotional eating components.
I’ll never forget my patient Maria, who came to me after decades of yo-yo dieting. At 68 with osteoarthritis and hypertension, she needed to lose weight but couldn’t tolerate the side effects of phentermine. We started Contrave cautiously, and what surprised me was how quickly her relationship with food changed. “It’s like the volume got turned down on my cravings,” she told me at her 3-month follow-up. She lost 28 pounds over 9 months—not our most dramatic result, but what mattered was her knee pain diminished enough that she could resume gardening, and her blood pressure medications were reduced. Her husband mentioned she seemed “lighter in spirit too.”
We did hit a rough patch around month 6 when her nausea returned briefly—turned out she’d started taking her doses on an empty stomach to “get it over with” before her morning walk. A simple adjustment to taking it with breakfast resolved the issue. These practical nuances never make it into the clinical trials but matter tremendously in real-world use.
What continues to surprise me is how individual the response patterns are. Some patients experience immediate appetite suppression, others notice reduced food preoccupation first, and a subset only see effects after several weeks. The team at my clinic actually had heated debates about whether we should develop our own prediction tool for response—the endocrinologists were all for it, while the behavioral health folks argued we’d risk creating self-fulfilling prophecies. We settled on a 3-month therapeutic trial for most appropriate candidates.
Five years into using this medication, I’ve followed over 80 patients on long-term Contrave therapy. About 40% maintain significant weight loss at 3 years, which compares favorably to other interventions. The ones who do best tend to be those who continue regular follow-up and haven’t viewed the medication as a “magic bullet” but rather one component of comprehensive lifestyle change. James, a 47-year-old chef, put it well: “The medication stops the urgent screaming for food, but I still have to choose the broccoli over the fries.”