contrave
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Synonyms | |||
Contrave represents one of the more interesting pharmacological approaches to chronic 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’s fascinating clinically isn’t just the weight loss numbers—which are decent—but the behavioral changes we observe in patients. I’ve been prescribing it since its approval and have watched the evolution from skepticism to cautious acceptance in our bariatric medicine community.
Key Components and Bioavailability of Contrave
The formulation contains two well-established drugs: naltrexone (8 mg) and bupropion (90 mg) in each tablet. The extended-release mechanism is crucial here—it’s not just about convenience but about maintaining steady-state concentrations that modulate the reward pathways without the peaks and troughs that would cause side effect issues or reduce compliance.
Naltrexone’s bioavailability is actually enhanced when administered with food, which creates an interesting dosing consideration many clinicians miss. Bupropion undergoes extensive first-pass metabolism primarily via CYP2B6, which explains the significant interpatient variability we see in efficacy and side effects. The formulation uses a proprietary osmotic delivery system that maintains consistent release over approximately 10 hours, which aligns well with the hypothalamic hunger-satiety cycle patterns.
Mechanism of Action: Scientific Substantiation
The dual mechanism targets both the mesolimbic dopamine pathway (reward system) and the hypothalamic feeding centers. Bupropion increases dopamine and norepinephrine activity in the hypothalamus, which reduces appetite and increases energy expenditure. Naltrexone blocks opioid receptors, which paradoxically enhances melanocortin pathway activity—essentially removing the “brake” on our natural appetite suppression system.
What’s clinically relevant is how these mechanisms interact—the combination appears to create a synergistic effect on POMC neurons that neither component achieves alone. We’re seeing evidence that it specifically targets food cravings rather than creating generalized appetite suppression, which explains why patients report reduced “food noise” without feeling medically starved.
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, or 27 kg/m² or greater with at least one weight-related comorbidity. The real-world effectiveness extends beyond the numbers—we consistently see improvements in eating behaviors and psychological relationship with food.
Contrave for Reduction of Food Cravings
This is where the clinical experience diverges somewhat from the trial data. While the studies focused on weight metrics, many of my patients report the most significant benefit is the reduction in obsessive food thoughts and binge eating tendencies. Several patients with previous bariatric surgery who experienced weight regain have responded remarkably well to low-dose Contrave when other options failed.
Contrave for Metabolic Syndrome Components
The indirect benefits on glycemic parameters and lipids, while not primary endpoints, are clinically meaningful. We’re observing HbA1c reductions of 0.5-0.7% in prediabetic patients, which aligns with the known metabolic effects of sustained weight loss.
Instructions for Use: Dosage and Course of Administration
The titration schedule is critical for tolerability:
| Week | Morning Dose | Evening Dose | Total Daily Dose |
|---|---|---|---|
| 1 | 1 tablet | 0 tablets | 1 tablet |
| 2 | 1 tablet | 1 tablet | 2 tablets |
| 3 | 2 tablets | 1 tablet | 3 tablets |
| 4+ | 2 tablets | 2 tablets | 4 tablets |
Administration should be with food to reduce nausea risk, and the evening dose should be taken at least 8 hours after the morning dose to minimize insomnia. The gradual escalation dramatically improves compliance compared to starting at full dose.
Maximum daily dose is 32 mg naltrexone/360 mg bupropion (two tablets twice daily). We typically assess efficacy at 12-16 weeks—if patients haven’t lost at least 5% of baseline body weight by that point, discontinuation should be considered.
Contraindications and Drug Interactions
Absolute contraindications include uncontrolled hypertension, seizure disorders, anorexia/bulimia, concurrent MAOI use, and opioid dependence (due to naltrexone component). The bupropion component carries the black box warning for suicidal ideation in young adults, which requires careful monitoring.
Significant drug interactions occur with:
- CYP2D6 substrates (dose adjustments needed for certain antidepressants, antipsychotics)
- Drugs that lower seizure threshold
- Opioid analgesics (rendered ineffective)
- Alcohol (increased neuropsychiatric effects)
Pregnancy category C—we recommend effective contraception during treatment. The lactation safety profile is unknown.
Clinical Studies and Evidence Base
The COR trials demonstrated consistent results: approximately 5-8% greater weight loss versus placebo at 56 weeks when combined with lifestyle intervention. The COR-II extension showed maintenance of effect through 104 weeks, which addresses the chronic nature of obesity management.
What the numbers don’t capture is the qualitative improvement in eating behaviors. In my practice, the Food Craving Inventory scores improve more dramatically than the weight metrics in the first 12 weeks. The neurobehavioral effects appear to precede the significant weight changes, which is fascinating from a mechanistic perspective.
Comparing Contrave with Similar Products and Choosing Quality
Versus phentermine-topiramate (Qsymia): Contrave has slower onset but better behavioral effect profile. Versus liraglutide (Saxenda): Different mechanisms—Contrave targets reward pathways while GLP-1 agonists work through gastric emptying and central appetite centers. The choice often comes down to patient phenotype—those with significant emotional eating or binge tendencies tend to respond better to Contrave.
Quality considerations: There’s no generic available currently, and the fixed-dose combination is protected. Compounded versions lack the controlled-release properties and shouldn’t be substituted.
Frequently Asked Questions about Contrave
What is the recommended course of Contrave to achieve results?
We typically continue for 16 weeks if 5% weight loss is achieved. Many patients require ongoing treatment—obesity is a chronic disease requiring chronic management.
Can Contrave be combined with diabetes medications?
Yes, with monitoring. We’ve used it successfully with metformin, SGLT2 inhibitors, and GLP-1 agonists, though dose adjustments may be needed for hypoglycemia risk.
How long until patients notice reduced food cravings?
Most report changes within 2-4 weeks, often before significant weight loss occurs. The behavioral effects frequently precede the metabolic changes.
Is the weight regain significant after discontinuation?
Like most obesity pharmacotherapies, weight typically returns after discontinuation unless intensive lifestyle interventions are maintained.
Conclusion: Validity of Contrave Use in Clinical Practice
The risk-benefit profile favors use in appropriate patients with adequate monitoring. It fills an important niche in our obesity treatment arsenal—specifically for patients with significant reward-driven eating behaviors. The dual mechanism addresses both biological and psychological components of obesity.
I remember when Sarah, a 42-year-old teacher with BMI 38 and prediabetes, came to me after failing multiple weight loss attempts. She described her relationship with food as “constant negotiation”—always thinking about her next meal, fighting cravings, feeling guilty after eating. We started Contrave with the standard titration. By week 3, she reported the “food noise” had quieted significantly—she could actually forget about eating until mealtimes. Her 6-month follow-up showed 12% body weight reduction and normalization of her glucose tolerance test. What struck me wasn’t just the numbers but her comment: “For the first time in twenty years, food doesn’t control my thoughts.”
Then there was Mark, 58, with osteoarthritis and metabolic syndrome. He lost only 3% of body weight at 16 weeks but reported dramatic reduction in his compulsive evening snacking—his wife confirmed he’d stopped the nighttime refrigerator visits that had persisted through decades of dieting. We continued treatment despite the modest weight loss because the behavioral change was so meaningful to his quality of life.
The development team actually debated whether to pursue the combination—some argued both components were too old, too familiar to be patentable or interesting. The pharmacodynamic synergy wasn’t fully appreciated until mid-stage trials. We’ve since learned that the sequencing matters—starting with behavioral therapy first, then adding Contrave, yields better long-term outcomes than medication alone.
The unexpected finding across my patient cohort has been the improvement in depressive symptoms even in patients without formal depression diagnoses. The bupropion effect seems to extend beyond weight management to general anhedonia improvement. We’re tracking this systematically now—preliminary data suggests about 30% of patients report meaningful mood improvement independent of weight changes.
Five-year follow-up on my initial cohort shows about 60% maintenance of weight loss with continuous treatment, compared to 15% with intermittent use. The patients who do best are those who view it as part of comprehensive lifestyle change rather than a magic bullet. The ones who struggle often expect the medication to do all the work without addressing underlying eating behaviors.
Maria, now 3 years into treatment, recently told me: “I don’t think about taking it as a weight loss drug anymore—it’s just part of my daily routine, like my blood pressure medication. The difference is I’m not constantly fighting with myself about food.” That shift in perspective—from weight-focused to behavior-focused—might be the most valuable outcome we can achieve with this medication.